ID HOP_HUMAN Reviewed; 73 AA. AC Q9BPY8; A8K0Z2; E9PB55; G3V294; Q8N0V6; Q96CI1; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 14-DEC-2022, entry version 160. DE RecName: Full=Homeodomain-only protein; DE AltName: Full=Lung cancer-associated Y protein; DE AltName: Full=Not expressed in choriocarcinoma protein 1; DE AltName: Full=Odd homeobox protein 1; GN Name=HOPX; Synonyms=HOD, HOP, LAGY, NECC1, OB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Heart; RX PubMed=14516659; DOI=10.1016/s0925-4773(03)00090-x; RA Adu J., Leong F.T., Smith N.R., Leek J.P., Markham A.F., Robinson P.A., RA Mighell A.J.; RT "Expression of mOb1, a novel atypical 73 amino acid K50-homeodomain RT protein, during mouse development."; RL Mech. Dev. 119:S43-S47(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE RP INVOLVEMENT IN CHORIOCARCINOMA. RX PubMed=12573257; DOI=10.1016/s0888-7543(02)00011-3; RA Asanoma K., Matsuda T., Kondo H., Kato K., Kishino T., Niikawa N., Wake N., RA Kato H.; RT "NECC1, a candidate choriocarcinoma suppressor gene that encodes a RT homeodomain consensus motif."; RL Genomics 81:15-25(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND POSSIBLE RP INVOLVEMENT IN LUNG CANCER. RX PubMed=12759545; DOI=10.1159/000070306; RA Chen Y., Petersen S., Pacyna-Gengelbach M., Pietas A., Petersen I.; RT "Identification of a novel homeobox-containing gene, LAGY, which is RT downregulated in lung cancer."; RL Oncology 64:450-458(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INVOLVEMENT IN HEAD AND NECK SQUAMOUS CELL CARCINOMA. RX PubMed=15213722; DOI=10.1038/sj.bjc.6601952; RA Lemaire F., Millon R., Muller D., Rabouel Y., Bracco L., Abecassis J., RA Wasylyk B.; RT "Loss of HOP tumour suppressor expression in head and neck squamous cell RT carcinoma."; RL Br. J. Cancer 91:258-261(2004). RN [8] RP INVOLVEMENT IN ORAL SQUAMOUS CELL CARCINOMA. RX PubMed=15381369; DOI=10.1016/j.cancergencyto.2004.01.026; RA Toruner G.A., Ulger C., Alkan M., Galante A.T., Rinaggio J., Wilk R., RA Tian B., Soteropoulos P., Hameed M.R., Schwalb M.N., Dermody J.J.; RT "Association between gene expression profile and tumor invasion in oral RT squamous cell carcinoma."; RL Cancer Genet. Cytogenet. 154:27-35(2004). RN [9] RP FUNCTION, AND INTERACTION WITH HSPA1A; HSPA1B AND HSPA8. RX PubMed=27708256; DOI=10.1038/ncomms12882; RA Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K., RA Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H., RA Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.; RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding RT and degradation."; RL Nat. Commun. 7:12882-12882(2016). CC -!- FUNCTION: Atypical homeodomain protein which does not bind DNA and is CC required to modulate cardiac growth and development. Acts via its CC interaction with SRF, thereby modulating the expression of SRF- CC dependent cardiac-specific genes and cardiac development. Prevents SRF- CC dependent transcription either by inhibiting SRF binding to DNA or by CC recruiting histone deacetylase (HDAC) proteins that prevent CC transcription by SRF. Overexpression causes cardiac hypertrophy (By CC similarity). May act as a tumor suppressor. Acts as a co-chaperone for CC HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated CC protein refolding (PubMed:27708256). {ECO:0000250|UniProtKB:Q8R1H0, CC ECO:0000269|PubMed:27708256}. CC -!- SUBUNIT: Interacts with serum response factor (SRF). Component of a CC large complex containing histone deacetylases such as HDAC2 (By CC similarity). Interacts with the acetylated forms of HSPA1A and HSPA1B. CC Interacts with HSPA8 (PubMed:27708256). {ECO:0000250|UniProtKB:Q8R1H0, CC ECO:0000269|PubMed:27708256}. CC -!- INTERACTION: CC Q9BPY8; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-10295883, EBI-79165; CC Q9BPY8; Q99081: TCF12; NbExp=3; IntAct=EBI-10295883, EBI-722877; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8R1H0}. Cytoplasm CC {ECO:0000250|UniProtKB:Q8R1H0}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=A; CC IsoId=Q9BPY8-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q9BPY8-2; Sequence=VSP_012659; CC Name=3; CC IsoId=Q9BPY8-3; Sequence=VSP_047290; CC Name=4; CC IsoId=Q9BPY8-4; Sequence=VSP_047290, VSP_012659; CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in the heart, brain, CC placenta, lung, skeletal and smooth muscles, uterus, urinary bladder, CC kidney and spleen. Down-regulated in some types of cancer such as lung CC cancer, choriocarcinoma, head and neck squamous cell carcinoma and oral CC squamous cell carcinoma. {ECO:0000269|PubMed:12573257, CC ECO:0000269|PubMed:12759545}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF492675; AAM46827.1; -; mRNA. DR EMBL; AF492676; AAM46828.1; -; mRNA. DR EMBL; AF492677; AAM46829.1; -; mRNA. DR EMBL; AF492678; AAM46830.1; -; mRNA. DR EMBL; AF492679; AAM46831.1; -; mRNA. DR EMBL; AF492680; AAM46832.1; -; mRNA. DR EMBL; AF492681; AAM46833.1; -; mRNA. DR EMBL; AB059408; BAB40926.1; -; mRNA. DR EMBL; AB059409; BAB40927.1; -; mRNA. DR EMBL; AB059410; BAB40928.1; -; mRNA. DR EMBL; AF454763; AAL56613.1; -; mRNA. DR EMBL; AK289707; BAF82396.1; -; mRNA. DR EMBL; AC108215; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014225; AAH14225.1; -; mRNA. DR CCDS; CCDS3507.1; -. [Q9BPY8-1] DR CCDS; CCDS47062.1; -. [Q9BPY8-3] DR CCDS; CCDS54767.1; -. [Q9BPY8-4] DR RefSeq; NP_001138931.1; NM_001145459.1. [Q9BPY8-1] DR RefSeq; NP_001138932.1; NM_001145460.1. [Q9BPY8-4] DR RefSeq; NP_115884.4; NM_032495.5. [Q9BPY8-3] DR RefSeq; NP_631957.1; NM_139211.4. [Q9BPY8-1] DR RefSeq; NP_631958.1; NM_139212.3. [Q9BPY8-1] DR RefSeq; XP_016864218.1; XM_017008729.1. DR RefSeq; XP_016864219.1; XM_017008730.1. [Q9BPY8-1] DR RefSeq; XP_016864220.1; XM_017008731.1. [Q9BPY8-1] DR RefSeq; XP_016864221.1; XM_017008732.1. [Q9BPY8-1] DR RefSeq; XP_016864222.1; XM_017008733.1. [Q9BPY8-1] DR RefSeq; XP_016864223.1; XM_017008734.1. [Q9BPY8-1] DR AlphaFoldDB; Q9BPY8; -. DR SMR; Q9BPY8; -. DR BioGRID; 124117; 34. DR IntAct; Q9BPY8; 7. DR MINT; Q9BPY8; -. DR STRING; 9606.ENSP00000450527; -. DR iPTMnet; Q9BPY8; -. DR PhosphoSitePlus; Q9BPY8; -. DR BioMuta; HOPX; -. DR DMDM; 60392394; -. DR jPOST; Q9BPY8; -. DR MassIVE; Q9BPY8; -. DR PaxDb; Q9BPY8; -. DR PeptideAtlas; Q9BPY8; -. DR ProteomicsDB; 19147; -. DR ProteomicsDB; 32566; -. DR ProteomicsDB; 78595; -. [Q9BPY8-1] DR ProteomicsDB; 78596; -. [Q9BPY8-2] DR Antibodypedia; 24043; 282 antibodies from 29 providers. DR DNASU; 84525; -. DR Ensembl; ENST00000317745.11; ENSP00000315198.7; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000337881.11; ENSP00000337330.7; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000381255.7; ENSP00000370654.3; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000381260.7; ENSP00000370659.2; ENSG00000171476.22. [Q9BPY8-2] DR Ensembl; ENST00000420433.6; ENSP00000396275.1; ENSG00000171476.22. [Q9BPY8-3] DR Ensembl; ENST00000503639.7; ENSP00000424101.2; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000508121.2; ENSP00000422175.2; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000553379.6; ENSP00000452340.1; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000554144.5; ENSP00000450527.1; ENSG00000171476.22. [Q9BPY8-4] DR Ensembl; ENST00000555760.6; ENSP00000452098.1; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000556376.6; ENSP00000451794.1; ENSG00000171476.22. [Q9BPY8-1] DR Ensembl; ENST00000556614.6; ENSP00000452003.1; ENSG00000171476.22. [Q9BPY8-1] DR GeneID; 84525; -. DR KEGG; hsa:84525; -. DR MANE-Select; ENST00000420433.6; ENSP00000396275.1; NM_032495.6; NP_115884.4. [Q9BPY8-3] DR UCSC; uc003hbz.3; human. [Q9BPY8-1] DR CTD; 84525; -. DR DisGeNET; 84525; -. DR GeneCards; HOPX; -. DR HGNC; HGNC:24961; HOPX. DR HPA; ENSG00000171476; Tissue enhanced (esophagus, skin). DR MIM; 607275; gene. DR neXtProt; NX_Q9BPY8; -. DR OpenTargets; ENSG00000171476; -. DR PharmGKB; PA162391564; -. DR VEuPathDB; HostDB:ENSG00000171476; -. DR eggNOG; KOG0490; Eukaryota. DR GeneTree; ENSGT00390000017143; -. DR HOGENOM; CLU_193231_0_0_1; -. DR InParanoid; Q9BPY8; -. DR OMA; EDSFKGC; -. DR OrthoDB; 1567787at2759; -. DR PhylomeDB; Q9BPY8; -. DR PathwayCommons; Q9BPY8; -. DR SignaLink; Q9BPY8; -. DR SIGNOR; Q9BPY8; -. DR BioGRID-ORCS; 84525; 9 hits in 1090 CRISPR screens. DR ChiTaRS; HOPX; human. DR GeneWiki; HOPX; -. DR GenomeRNAi; 84525; -. DR Pharos; Q9BPY8; Tbio. DR PRO; PR:Q9BPY8; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q9BPY8; protein. DR Bgee; ENSG00000171476; Expressed in upper leg skin and 195 other tissues. DR Genevisible; Q9BPY8; HS. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003166; P:bundle of His development; NAS:BHF-UCL. DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:CAFA. DR GO; GO:0016575; P:histone deacetylation; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0045596; P:negative regulation of cell differentiation; IDA:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:1903598; P:positive regulation of gap junction assembly; IEA:Ensembl. DR GO; GO:0043415; P:positive regulation of skeletal muscle tissue regeneration; IEA:Ensembl. DR GO; GO:0051155; P:positive regulation of striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:0008016; P:regulation of heart contraction; IEA:Ensembl. DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001829; P:trophectodermal cell differentiation; IDA:MGI. DR CDD; cd00086; homeodomain; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR039162; HOPX. DR PANTHER; PTHR21408; HOMEODOMAIN-ONLY PROTEIN; 1. DR Pfam; PF00046; Homeodomain; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR AGR; HGNC:24961; -. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Developmental protein; Homeobox; Nucleus; KW Proto-oncogene; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1..73 FT /note="Homeodomain-only protein" FT /id="PRO_0000049129" FT DNA_BIND 3..62 FT /note="Homeobox; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT VAR_SEQ 1 FT /note="M -> MLIFLGCYRRRLEERAGTM (in isoform 3 and isoform FT 4)" FT /evidence="ECO:0000305" FT /id="VSP_047290" FT VAR_SEQ 49..73 FT /note="KWFKQRLAKWRRSEGLPSECRSVTD -> GSDLISRSKIWHPESSPQREGYP FT HDSLPCLAFDYFSLLPPQCKEMV (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14516659" FT /id="VSP_012659" FT CONFLICT 72 FT /note="T -> I (in Ref. 6; AAH14225)" FT /evidence="ECO:0000305" FT CONFLICT Q9BPY8-2:76 FT /note="P -> L (in Ref. 1; AAM46830/AAM46831)" FT /evidence="ECO:0000305" SQ SEQUENCE 73 AA; 8260 MW; CE65E4D2A8972022 CRC64; MSAETASGPT EDQVEILEYN FNKVDKHPDS TTLCLIAAEA GLSEEETQKW FKQRLAKWRR SEGLPSECRS VTD // ID HOP2_HUMAN Reviewed; 217 AA. AC Q9P2W1; C5ILB7; Q14458; Q8WXG2; Q96HA2; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 14-DEC-2022, entry version 140. DE RecName: Full=Homologous-pairing protein 2 homolog; DE AltName: Full=Nuclear receptor coactivator GT198; DE AltName: Full=PSMC3-interacting protein; DE AltName: Full=Proteasome 26S ATPase subunit 3-interacting protein; DE AltName: Full=Tat-binding protein 1-interacting protein; DE Short=TBP-1-interacting protein; GN Name=PSMC3IP; Synonyms=HOP2, TBPIP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=7490091; DOI=10.1006/geno.1995.1185; RA Rommens J.M., Durocher F., McArthur J., Tonin P., Leblanc J.-F., Allen T., RA Samson C., Ferri L., Narod S., Morgan K., Simard J.; RT "Generation of a transcription map at the HSD17B locus centromeric to BRCA1 RT at 17q21."; RL Genomics 28:530-542(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH RP PSMC3. RX PubMed=10806355; DOI=10.1016/s0378-1119(00)00141-4; RA Ijichi H., Tanaka T., Nakamura T., Yagi H., Hakuba A., Sato M.; RT "Molecular cloning and characterization of a human homologue of TBPIP, a RT BRCA1 locus-related gene."; RL Gene 248:99-107(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND ALTERNATIVE SPLICING. RA Peng M., Ko L.; RT "Alternative splicing of GT198 in the BRCA1 locus."; RL Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RX PubMed=11739747; DOI=10.1128/mcb.22.1.357-369.2002; RA Ko L., Cardona G.R., Henrion-Caude A., Chin W.W.; RT "Identification and characterization of a tissue-specific coactivator, RT GT198, that interacts with the DNA-binding domains of nuclear receptors."; RL Mol. Cell. Biol. 22:357-369(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH MND1, AND FUNCTION. RX PubMed=16407260; DOI=10.1074/jbc.m506506200; RA Enomoto R., Kinebuchi T., Sato M., Yagi H., Kurumizaka H., Yokoyama S.; RT "Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex."; RL J. Biol. Chem. 281:5575-5581(2006). RN [8] RP INDUCTION. RX PubMed=17716379; DOI=10.1186/1477-7827-5-34; RA Pan Q., Luo X., Chegini N.; RT "Genomic and proteomic profiling I: leiomyomas in African Americans and RT Caucasians."; RL Reprod. Biol. Endocrinol. 5:34-34(2007). RN [9] RP FUNCTION, VARIANT ODG3 GLU-201 DEL, AND CHARACTERIZATION OF VARIANT ODG3 RP GLU-201 DEL. RX PubMed=21963259; DOI=10.1016/j.ajhg.2011.09.006; RA Zangen D., Kaufman Y., Zeligson S., Perlberg S., Fridman H., Kanaan M., RA Abdulhadi-Atwan M., Abu Libdeh A., Gussow A., Kisslov I., Carmel L., RA Renbaum P., Levy-Lahad E.; RT "XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes RT coactivation of estrogen-driven transcription."; RL Am. J. Hum. Genet. 89:572-579(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: Plays an important role in meiotic recombination. Stimulates CC DMC1-mediated strand exchange required for pairing homologous CC chromosomes during meiosis. The complex PSMC3IP/MND1 binds DNA, CC stimulates the recombinase activity of DMC1 as well as DMC1 D-loop CC formation from double-strand DNA. This complex stabilizes presynaptic CC RAD51 and DMC1 filaments formed on single strand DNA to capture double- CC strand DNA. This complex stimulates both synaptic and presynaptic CC critical steps in RAD51 and DMC1-promoted homologous pairing. May CC inhibit HIV-1 viral protein TAT activity and modulate the activity of CC proteasomes through association with PSMC3. Acts as a tissue specific CC coactivator of hormone-dependent transcription mediated by nuclear CC receptors. {ECO:0000269|PubMed:10806355, ECO:0000269|PubMed:16407260, CC ECO:0000269|PubMed:21963259}. CC -!- SUBUNIT: Interacts with the DNA-binding domain of the nuclear receptors CC NR3C1/GR, ESR2/ER-beta, THRB and RXRA (By similarity). Forms a stable CC heterodimer with MND1. Interacts with PSMC3/TBP1. {ECO:0000250, CC ECO:0000269|PubMed:10806355, ECO:0000269|PubMed:16407260}. CC -!- INTERACTION: CC Q9P2W1; Q9BWT6: MND1; NbExp=5; IntAct=EBI-9057595, EBI-11137441; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11739747}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9P2W1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P2W1-2; Sequence=VSP_030213; CC Name=3; CC IsoId=Q9P2W1-3; Sequence=VSP_047716; CC -!- TISSUE SPECIFICITY: Highly expressed in testis and colon. CC {ECO:0000269|PubMed:11739747, ECO:0000269|PubMed:7490091}. CC -!- INDUCTION: Overexpressed in leiomyomas compared to myometrium. CC {ECO:0000269|PubMed:17716379}. CC -!- PTM: PTM: Phosphorylated by PKA, PKC and MAPK. {ECO:0000250}. CC -!- DISEASE: Ovarian dysgenesis 3 (ODG3) [MIM:614324]: A disorder CC characterized by lack of spontaneous pubertal development, primary CC amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a CC result of streak gonads. {ECO:0000269|PubMed:21963259}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the HOP2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC41915.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L38933; AAC41915.1; ALT_FRAME; mRNA. DR EMBL; AB030304; BAA92872.1; -; mRNA. DR EMBL; AF440240; AAL33609.1; -; mRNA. DR EMBL; FJ952180; ACR46655.1; -; mRNA. DR EMBL; FJ952181; ACR46656.1; -; mRNA. DR EMBL; FJ952182; ACR46657.1; -; mRNA. DR EMBL; FJ952183; ACR46658.1; -; mRNA. DR EMBL; GQ851964; ACX30903.1; -; mRNA. DR EMBL; GQ851965; ACX30904.1; -; mRNA. DR EMBL; AC067852; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008792; AAH08792.1; -; mRNA. DR CCDS; CCDS11431.1; -. [Q9P2W1-2] DR CCDS; CCDS45688.1; -. [Q9P2W1-1] DR PIR; I68521; I68521. DR RefSeq; NP_001242943.1; NM_001256014.1. DR RefSeq; NP_001242944.1; NM_001256015.1. DR RefSeq; NP_001242945.1; NM_001256016.1. DR RefSeq; NP_037422.2; NM_013290.6. [Q9P2W1-2] DR RefSeq; NP_057640.1; NM_016556.3. [Q9P2W1-1] DR AlphaFoldDB; Q9P2W1; -. DR SMR; Q9P2W1; -. DR BioGRID; 118945; 38. DR ComplexPortal; CPX-6661; HOP2-MND1 complex. DR CORUM; Q9P2W1; -. DR IntAct; Q9P2W1; 16. DR MINT; Q9P2W1; -. DR STRING; 9606.ENSP00000377384; -. DR iPTMnet; Q9P2W1; -. DR PhosphoSitePlus; Q9P2W1; -. DR BioMuta; PSMC3IP; -. DR DMDM; 74719969; -. DR EPD; Q9P2W1; -. DR jPOST; Q9P2W1; -. DR MassIVE; Q9P2W1; -. DR MaxQB; Q9P2W1; -. DR PaxDb; Q9P2W1; -. DR PeptideAtlas; Q9P2W1; -. DR ProteomicsDB; 83901; -. [Q9P2W1-1] DR ProteomicsDB; 83902; -. [Q9P2W1-2] DR Antibodypedia; 29297; 72 antibodies from 22 providers. DR DNASU; 29893; -. DR Ensembl; ENST00000253789.9; ENSP00000253789.4; ENSG00000131470.15. [Q9P2W1-2] DR Ensembl; ENST00000393795.8; ENSP00000377384.2; ENSG00000131470.15. [Q9P2W1-1] DR Ensembl; ENST00000590760.5; ENSP00000466381.1; ENSG00000131470.15. [Q9P2W1-3] DR GeneID; 29893; -. DR KEGG; hsa:29893; -. DR MANE-Select; ENST00000393795.8; ENSP00000377384.2; NM_016556.4; NP_057640.1. DR UCSC; uc002iai.4; human. [Q9P2W1-1] DR CTD; 29893; -. DR DisGeNET; 29893; -. DR GeneCards; PSMC3IP; -. DR HGNC; HGNC:17928; PSMC3IP. DR HPA; ENSG00000131470; Tissue enhanced (testis). DR MalaCards; PSMC3IP; -. DR MIM; 608665; gene. DR MIM; 614324; phenotype. DR neXtProt; NX_Q9P2W1; -. DR OpenTargets; ENSG00000131470; -. DR Orphanet; 243; 46,XX gonadal dysgenesis. DR PharmGKB; PA143485584; -. DR VEuPathDB; HostDB:ENSG00000131470; -. DR eggNOG; KOG4603; Eukaryota. DR GeneTree; ENSGT00390000006890; -. DR HOGENOM; CLU_181023_0_0_1; -. DR InParanoid; Q9P2W1; -. DR OMA; IETDEDC; -. DR PhylomeDB; Q9P2W1; -. DR TreeFam; TF328666; -. DR PathwayCommons; Q9P2W1; -. DR Reactome; R-HSA-912446; Meiotic recombination. DR SignaLink; Q9P2W1; -. DR BioGRID-ORCS; 29893; 32 hits in 1083 CRISPR screens. DR ChiTaRS; PSMC3IP; human. DR GenomeRNAi; 29893; -. DR Pharos; Q9P2W1; Tbio. DR PRO; PR:Q9P2W1; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9P2W1; protein. DR Bgee; ENSG00000131470; Expressed in tendon of biceps brachii and 188 other tissues. DR ExpressionAtlas; Q9P2W1; baseline and differential. DR Genevisible; Q9P2W1; HS. DR GO; GO:0000794; C:condensed nuclear chromosome; IBA:GO_Central. DR GO; GO:0120231; C:DNA recombinase auxiliary factor complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IMP:UniProtKB. DR GO; GO:0120230; F:recombinase activator activity; IBA:GO_Central. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IDA:ComplexPortal. DR GO; GO:0000709; P:meiotic joint molecule formation; IBA:GO_Central. DR GO; GO:0010774; P:meiotic strand invasion involved in reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:0007131; P:reciprocal meiotic recombination; IDA:ComplexPortal. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR040461; Hop2. DR InterPro; IPR010776; Hop2_WH_dom. DR InterPro; IPR040661; LZ3wCH. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR PANTHER; PTHR15938; TBP-1 INTERACTING PROTEIN; 1. DR Pfam; PF18517; LZ3wCH; 1. DR Pfam; PF07106; TBPIP; 1. DR AGR; HGNC:17928; -. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Disease variant; DNA recombination; KW DNA-binding; Meiosis; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..217 FT /note="Homologous-pairing protein 2 homolog" FT /id="PRO_0000314135" FT REGION 118..182 FT /note="DNA-binding" FT /evidence="ECO:0000250" FT COILED 93..153 FT /evidence="ECO:0000255" FT VAR_SEQ 1..125 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_047716" FT VAR_SEQ 113..124 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030213" FT VARIANT 163 FT /note="Y -> N (in dbSNP:rs2292754)" FT /id="VAR_037841" FT VARIANT 201 FT /note="Missing (in ODG3; impairs function as estrogen FT receptor coactivator)" FT /evidence="ECO:0000269|PubMed:21963259" FT /id="VAR_066636" FT CONFLICT 8 FT /note="Missing (in Ref. 1; AAC41915)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="S -> T (in Ref. 1; AAC41915 and 5; AAL33609)" FT /evidence="ECO:0000305" FT CONFLICT 184 FT /note="S -> L (in Ref. 5; AAL33609)" FT /evidence="ECO:0000305" SQ SEQUENCE 217 AA; 24906 MW; 892B7D20CAA0A121 CRC64; MSKGRAEAAA GAAGILLRYL QEQNRPYSSQ DVFGNLQREH GLGKAVVVKT LEQLAQQGKI KEKMYGKQKI YFADQDQFDM VSDADLQVLD GKIVALTAKV QSLQQSCRYM EAELKELSSA LTTPEMQKEI QELKKECAGY RERLKNIKAA TNHVTPEEKE QVYRERQKYC KEWRKRKRMA TELSDAILEG YPKSKKQFFE EVGIETDEDY NVTLPDP // ID F10A1_HUMAN Reviewed; 369 AA. AC P50502; O14999; Q2TU77; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 14-DEC-2022, entry version 217. DE RecName: Full=Hsc70-interacting protein; DE Short=Hip; DE AltName: Full=Aging-associated protein 2; DE AltName: Full=Progesterone receptor-associated p48 protein; DE AltName: Full=Protein FAM10A1; DE AltName: Full=Putative tumor suppressor ST13; DE AltName: Full=Renal carcinoma antigen NY-REN-33; DE AltName: Full=Suppression of tumorigenicity 13 protein; GN Name=ST13; Synonyms=AAG2, FAM10A1, HIP, SNC6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. RX PubMed=8721986; DOI=10.1210/mend.10.4.8721986; RA Prapapanich V., Chen S., Nair S.C., Rimerman R.A., Smith D.F.; RT "Molecular cloning of human p48, a transient component of progesterone RT receptor complexes and an Hsp70-binding protein."; RL Mol. Endocrinol. 10:420-431(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Colon mucosa; RX PubMed=9387309; RA Mo Y., Zheng S., Shen D.; RT "Differential expression of HSU17714 gene in colorectal cancer and normal RT colonic mucosa."; RL Zhonghua Zhong Liu Za Zhi 18:241-243(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Colon mucosa; RX PubMed=9292708; DOI=10.1007/bf01372549; RA Cao J., Cai X., Zheng L., Geng L., Shi Z., Pao C.C., Zheng S.; RT "Characterization of colorectal-cancer-related cDNA clones obtained by RT subtractive hybridization screening."; RL J. Cancer Res. Clin. Oncol. 123:447-451(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Kim J.W.; RT "Identification of human aging-associated gene."; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 119-142; 147-153; 174-186 AND 211-222, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [10] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP PHOSPHORYLATION AT SER-346, AND INTERACTION WITH GRK5. RX PubMed=21728385; DOI=10.1021/bi2005202; RA Barker B.L., Benovic J.L.; RT "G protein-coupled receptor kinase 5 phosphorylation of Hip regulates RT internalization of the chemokine receptor CXCR4."; RL Biochemistry 50:6933-6941(2011). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: One HIP oligomer binds the ATPase domains of at least two CC HSC70 molecules dependent on activation of the HSC70 ATPase by HSP40. CC Stabilizes the ADP state of HSC70 that has a high affinity for CC substrate protein. Through its own chaperone activity, it may CC contribute to the interaction of HSC70 with various target proteins (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Homotetramer. Interacts with HSC70 as well as DNAJ homologs CC and HSP90 (By similarity). Interacts (via the C-terminus 303- 319 AA) CC with GRK5. {ECO:0000250, ECO:0000269|PubMed:21728385}. CC -!- INTERACTION: CC P50502; P02649: APOE; NbExp=3; IntAct=EBI-357285, EBI-1222467; CC P50502; Q9NNX6-10: CD209; NbExp=3; IntAct=EBI-357285, EBI-12300031; CC P50502; P42858: HTT; NbExp=13; IntAct=EBI-357285, EBI-466029; CC P50502; P29474: NOS3; NbExp=3; IntAct=EBI-357285, EBI-1391623; CC P50502; P49768: PSEN1; NbExp=3; IntAct=EBI-357285, EBI-297277; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. CC -!- SIMILARITY: Belongs to the FAM10 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U28918; AAB38382.1; -; mRNA. DR EMBL; U17714; AAC97526.1; -; mRNA. DR EMBL; AY513286; AAT08039.1; -; mRNA. DR EMBL; CR456586; CAG30472.1; -; mRNA. DR EMBL; Z98048; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471095; EAW60394.1; -; Genomic_DNA. DR EMBL; BC052982; AAH52982.1; -; mRNA. DR EMBL; BC071629; AAH71629.1; -; mRNA. DR EMBL; BC139724; AAI39725.1; -; mRNA. DR CCDS; CCDS14006.1; -. DR RefSeq; NP_003923.2; NM_003932.4. DR AlphaFoldDB; P50502; -. DR SMR; P50502; -. DR BioGRID; 112644; 147. DR CORUM; P50502; -. DR IntAct; P50502; 44. DR MINT; P50502; -. DR STRING; 9606.ENSP00000216218; -. DR GlyGen; P50502; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P50502; -. DR MetOSite; P50502; -. DR PhosphoSitePlus; P50502; -. DR SwissPalm; P50502; -. DR BioMuta; ST13; -. DR DMDM; 6686278; -. DR OGP; P50502; -. DR REPRODUCTION-2DPAGE; IPI00032826; -. DR EPD; P50502; -. DR jPOST; P50502; -. DR MassIVE; P50502; -. DR PaxDb; P50502; -. DR PeptideAtlas; P50502; -. DR ProteomicsDB; 56234; -. DR Antibodypedia; 3378; 389 antibodies from 33 providers. DR DNASU; 6767; -. DR Ensembl; ENST00000216218.8; ENSP00000216218.3; ENSG00000100380.15. DR GeneID; 6767; -. DR KEGG; hsa:6767; -. DR MANE-Select; ENST00000216218.8; ENSP00000216218.3; NM_003932.5; NP_003923.2. DR UCSC; uc003aze.5; human. DR CTD; 6767; -. DR DisGeNET; 6767; -. DR GeneCards; ST13; -. DR HGNC; HGNC:11343; ST13. DR HPA; ENSG00000100380; Low tissue specificity. DR MIM; 606796; gene. DR neXtProt; NX_P50502; -. DR OpenTargets; ENSG00000100380; -. DR PharmGKB; PA36167; -. DR VEuPathDB; HostDB:ENSG00000100380; -. DR eggNOG; KOG1308; Eukaryota. DR GeneTree; ENSGT00390000001347; -. DR InParanoid; P50502; -. DR OMA; TVLNMPQ; -. DR OrthoDB; 1282821at2759; -. DR PhylomeDB; P50502; -. DR TreeFam; TF313244; -. DR PathwayCommons; P50502; -. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR SignaLink; P50502; -. DR SIGNOR; P50502; -. DR BioGRID-ORCS; 6767; 36 hits in 1035 CRISPR screens. DR ChiTaRS; ST13; human. DR GeneWiki; ST13; -. DR GenomeRNAi; 6767; -. DR Pharos; P50502; Tbio. DR PRO; PR:P50502; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P50502; protein. DR Bgee; ENSG00000100380; Expressed in left ovary and 208 other tissues. DR ExpressionAtlas; P50502; baseline and differential. DR Genevisible; P50502; HS. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0030544; F:Hsp70 protein binding; IBA:GO_Central. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:ProtInc. DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central. DR GO; GO:0006457; P:protein folding; TAS:ProtInc. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR CDD; cd14438; Hip_N; 1. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR034649; Hip_N. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF18253; HipN; 1. DR Pfam; PF17830; STI1; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR AGR; HGNC:11343; -. PE 1: Evidence at protein level; KW Acetylation; Chaperone; Cytoplasm; Direct protein sequencing; KW Phosphoprotein; Reference proteome; Repeat; TPR repeat. FT CHAIN 1..369 FT /note="Hsc70-interacting protein" FT /id="PRO_0000190811" FT REPEAT 114..147 FT /note="TPR 1" FT REPEAT 148..181 FT /note="TPR 2" FT REPEAT 182..215 FT /note="TPR 3" FT DOMAIN 319..358 FT /note="STI1" FT REGION 38..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 256..300 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..71 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 256..273 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 346 FT /note="Phosphoserine; by GRK5" FT /evidence="ECO:0000269|PubMed:21728385" FT MOD_RES 353 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99L47" FT MOD_RES 360 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99L47" FT VARIANT 297 FT /note="M -> I (in dbSNP:rs710193)" FT /id="VAR_011900" FT CONFLICT 24 FT /note="H -> Y (in Ref. 1; AAB38382)" FT /evidence="ECO:0000305" FT CONFLICT 38 FT /note="M -> I (in Ref. 1; AAB38382)" FT /evidence="ECO:0000305" FT CONFLICT 50 FT /note="K -> I (in Ref. 1; AAB38382)" FT /evidence="ECO:0000305" SQ SEQUENCE 369 AA; 41332 MW; 98FCC65BEE14CDD7 CRC64; MDPRKVNELR AFVKMCKQDP SVLHTEEMRF LREWVESMGG KVPPATQKAK SEENTKEEKP DSKKVEEDLK ADEPSSEESD LEIDKEGVIE PDTDAPQEMG DENAEITEEM MDQANDKKVA AIEALNDGEL QKAIDLFTDA IKLNPRLAIL YAKRASVFVK LQKPNAAIRD CDRAIEINPD SAQPYKWRGK AHRLLGHWEE AAHDLALACK LDYDEDASAM LKEVQPRAQK IAEHRRKYER KREEREIKER IERVKKAREE HERAQREEEA RRQSGAQYGS FPGGFPGGMP GNFPGGMPGM GGGMPGMAGM PGLNEILSDP EVLAAMQDPE VMVAFQDVAQ NPANMSKYQS NPKVMNLISK LSAKFGGQA // ID STIP1_HUMAN Reviewed; 543 AA. AC P31948; B4DM70; F5H0T1; G3XAD8; Q3ZCU9; Q5TZU9; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 14-DEC-2022, entry version 224. DE RecName: Full=Stress-induced-phosphoprotein 1; DE Short=STI1; DE AltName: Full=Hsc70/Hsp90-organizing protein; DE Short=Hop; DE AltName: Full=Renal carcinoma antigen NY-REN-11; DE AltName: Full=Transformation-sensitive protein IEF SSP 3521; GN Name=STIP1 {ECO:0000312|HGNC:HGNC:11387}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1569099; DOI=10.1016/s0021-9258(18)42471-4; RA Honore B., Leffers H., Madsen P., Rasmussen H.H., Vandekerckhove J., RA Celis J.E.; RT "Molecular cloning and expression of a transformation-sensitive human RT protein containing the TPR motif and sharing identity to the stress- RT inducible yeast protein STI1."; RL J. Biol. Chem. 267:8485-8491(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 1-10; 110-118; 345-364; 382-389; 479-486 AND 534-543, RP ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (OCT-2004) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 33-44; 64-73; 79-87; 154-160; 253-272; 306-312; RP 352-364; 407-429; 454-462; 489-513 AND 534-543, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [10] RP PROTEIN SEQUENCE OF 101-109; 352-364 AND 374-381. RC TISSUE=Keratinocyte; RX PubMed=1286667; DOI=10.1002/elps.11501301199; RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., RA Vandekerckhove J.; RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein RT database of normal human epidermal keratinocytes."; RL Electrophoresis 13:960-969(1992). RN [11] RP INTERACTION WITH HSP90AA1. RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224; RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K., RA Chinkers M., Pratt W.B.; RT "Protein phosphatase 5 is a major component of glucocorticoid RT receptor.hsp90 complexes with properties of an FK506-binding RT immunophilin."; RL J. Biol. Chem. 272:16224-16230(1997). RN [12] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [13] RP INTERACTION WITH PACRG. RX PubMed=14532270; DOI=10.1074/jbc.m309655200; RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.; RT "A product of the human gene adjacent to parkin is a component of Lewy RT bodies and suppresses Pael receptor-induced cell death."; RL J. Biol. Chem. 278:51901-51910(2003). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-354, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8; LYS-301; LYS-312; LYS-325; RP LYS-344 AND LYS-446, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; THR-332 AND SER-481, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP INTERACTION WITH EEF1AKMT3. RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210; RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.; RT "A newly uncovered group of distantly related lysine methyltransferases RT preferentially interact with molecular chaperones to regulate their RT activity."; RL PLoS Genet. 9:E1003210-E1003210(2013). RN [24] RP INTERACTION WITH HSP90AB1. RX PubMed=24880080; DOI=10.1016/j.canlet.2014.05.014; RA Hamamoto R., Toyokawa G., Nakakido M., Ueda K., Nakamura Y.; RT "SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by RT regulating the chaperone complex formation."; RL Cancer Lett. 351:126-133(2014). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-123, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [27] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-123 AND LYS-210, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [28] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-123, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [30] RP FUNCTION, AND INTERACTION WITH HSP90AA1; FLCN; FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [31] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; PTGES3; CDC37; PPP5C; TSC1 RP AND TSC2. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [32] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-123 AND LYS-210, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 223-349. RX PubMed=10786835; DOI=10.1016/s0092-8674(00)80830-2; RA Scheufler C., Brinker A., Bourenkov G., Pegoraro S., Moroder L., RA Bartunik H., Hartl F.U., Moarefi I.; RT "Structure of TPR domain-peptide complexes: critical elements in the RT assembly of the Hsp70-Hsp90 multichaperone machine."; RL Cell 101:199-210(2000). CC -!- FUNCTION: Acts as a co-chaperone for HSP90AA1 (PubMed:27353360). CC Mediates the association of the molecular chaperones HSPA8/HSC70 and CC HSP90 (By similarity). {ECO:0000250|UniProtKB:O35814, CC ECO:0000303|PubMed:27353360}. CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Forms a complex with CC HSPA8/HSC70, HSPCA/HSP-86 and HSPCB/HSP-84 (By similarity). Interacts CC with PACRG (PubMed:14532270). Interacts with EEF1AKMT3 CC (PubMed:23349634). Interacts with HSP90/HSP90AA1; the interaction CC dissociates the PPP5C:HSP90AA1 interaction (PubMed:9195923, CC PubMed:27353360). Interacts with FLCN, FNIP1 and FNIP2 CC (PubMed:27353360). Interacts with HSPA8/HSC70 (By similarity). CC Interacts with HSP90AB1; upon SMYD2-dependent HSP90AB1 methylation CC (PubMed:24880080). {ECO:0000250|UniProtKB:O35814, CC ECO:0000250|UniProtKB:Q60864, ECO:0000269|PubMed:14532270, CC ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:24880080, CC ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, CC ECO:0000269|PubMed:9195923}. CC -!- INTERACTION: CC P31948; Q96AP0: ACD; NbExp=2; IntAct=EBI-1054052, EBI-717666; CC P31948; Q6DHV7-2: ADAL; NbExp=3; IntAct=EBI-1054052, EBI-18899653; CC P31948; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-1054052, EBI-18036948; CC P31948; Q8IWD4: CCDC117; NbExp=2; IntAct=EBI-1054052, EBI-3387963; CC P31948; Q7L3B6: CDC37L1; NbExp=2; IntAct=EBI-1054052, EBI-2841876; CC P31948; O95674: CDS2; NbExp=3; IntAct=EBI-1054052, EBI-3913685; CC P31948; P00533: EGFR; NbExp=3; IntAct=EBI-1054052, EBI-297353; CC P31948; O00423: EML1; NbExp=3; IntAct=EBI-1054052, EBI-751327; CC P31948; P04626: ERBB2; NbExp=2; IntAct=EBI-1054052, EBI-641062; CC P31948; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-1054052, EBI-8468186; CC P31948; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-1054052, EBI-6425864; CC P31948; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-1054052, EBI-9088619; CC P31948; P08238: HSP90AB1; NbExp=4; IntAct=EBI-1054052, EBI-352572; CC P31948; P01106: MYC; NbExp=3; IntAct=EBI-1054052, EBI-447544; CC P31948; Q14181: POLA2; NbExp=3; IntAct=EBI-1054052, EBI-712752; CC P31948; P53041: PPP5C; NbExp=4; IntAct=EBI-1054052, EBI-716663; CC P31948; Q09028: RBBP4; NbExp=3; IntAct=EBI-1054052, EBI-620823; CC P31948; Q9C004: SPRY4; NbExp=3; IntAct=EBI-1054052, EBI-354861; CC P31948; P54274-2: TERF1; NbExp=3; IntAct=EBI-1054052, EBI-711018; CC P31948; P04637: TP53; NbExp=4; IntAct=EBI-1054052, EBI-366083; CC P31948; O00463: TRAF5; NbExp=3; IntAct=EBI-1054052, EBI-523498; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60864}. Nucleus CC {ECO:0000250|UniProtKB:Q60864}. Dynein axonemal particle CC {ECO:0000250|UniProtKB:Q7ZWU1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P31948-1; Sequence=Displayed; CC Name=2; CC IsoId=P31948-2; Sequence=VSP_055034; CC Name=3; CC IsoId=P31948-3; Sequence=VSP_055035; CC -!- DOMAIN: The TPR 1 repeat interacts with the C-terminal of HSC70. The CC TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 CC repeats (also called TPR2B domain) interact with HSP90. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M86752; AAA58682.1; -; mRNA. DR EMBL; BT020010; AAV38813.1; -; mRNA. DR EMBL; BT020011; AAV38814.1; -; mRNA. DR EMBL; CR536512; CAG38750.1; -; mRNA. DR EMBL; AK297319; BAG59782.1; -; mRNA. DR EMBL; AP005668; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW74196.1; -; Genomic_DNA. DR EMBL; CH471076; EAW74197.1; -; Genomic_DNA. DR EMBL; BC002987; AAH02987.1; -; mRNA. DR EMBL; BC039299; AAH39299.1; -; mRNA. DR CCDS; CCDS60827.1; -. [P31948-2] DR CCDS; CCDS60828.1; -. [P31948-3] DR CCDS; CCDS8058.1; -. [P31948-1] DR PIR; A38093; A38093. DR RefSeq; NP_001269581.1; NM_001282652.1. [P31948-2] DR RefSeq; NP_001269582.1; NM_001282653.1. [P31948-3] DR RefSeq; NP_006810.1; NM_006819.2. [P31948-1] DR PDB; 1ELR; X-ray; 1.90 A; A=223-352. DR PDB; 1ELW; X-ray; 1.60 A; A/B=1-118. DR PDB; 2LNI; NMR; -; A=356-477. DR PDB; 2NC9; NMR; -; A=220-350. DR PDB; 3ESK; X-ray; 2.05 A; A=223-350. DR PDB; 3FWV; X-ray; 2.20 A; A/B=223-349. DR PDB; 7KW7; EM; 3.57 A; E=1-543. DR PDBsum; 1ELR; -. DR PDBsum; 1ELW; -. DR PDBsum; 2LNI; -. DR PDBsum; 2NC9; -. DR PDBsum; 3ESK; -. DR PDBsum; 3FWV; -. DR PDBsum; 7KW7; -. DR AlphaFoldDB; P31948; -. DR SMR; P31948; -. DR BioGRID; 116162; 383. DR DIP; DIP-41085N; -. DR IntAct; P31948; 189. DR MINT; P31948; -. DR STRING; 9606.ENSP00000351646; -. DR ChEMBL; CHEMBL4523216; -. DR DrugBank; DB09130; Copper. DR GlyGen; P31948; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P31948; -. DR MetOSite; P31948; -. DR PhosphoSitePlus; P31948; -. DR SwissPalm; P31948; -. DR BioMuta; STIP1; -. DR DMDM; 400042; -. DR REPRODUCTION-2DPAGE; IPI00013894; -. DR UCD-2DPAGE; P31948; -. DR EPD; P31948; -. DR jPOST; P31948; -. DR MassIVE; P31948; -. DR MaxQB; P31948; -. DR PaxDb; P31948; -. DR PeptideAtlas; P31948; -. DR ProteomicsDB; 25436; -. DR ProteomicsDB; 33721; -. DR ProteomicsDB; 54820; -. [P31948-1] DR TopDownProteomics; P31948-1; -. [P31948-1] DR Antibodypedia; 15273; 439 antibodies from 39 providers. DR DNASU; 10963; -. DR Ensembl; ENST00000305218.9; ENSP00000305958.5; ENSG00000168439.17. [P31948-1] DR Ensembl; ENST00000358794.9; ENSP00000351646.5; ENSG00000168439.17. [P31948-2] DR Ensembl; ENST00000538945.5; ENSP00000445957.1; ENSG00000168439.17. [P31948-3] DR GeneID; 10963; -. DR KEGG; hsa:10963; -. DR MANE-Select; ENST00000305218.9; ENSP00000305958.5; NM_006819.3; NP_006810.1. DR UCSC; uc010rnb.2; human. [P31948-1] DR CTD; 10963; -. DR DisGeNET; 10963; -. DR GeneCards; STIP1; -. DR HGNC; HGNC:11387; STIP1. DR HPA; ENSG00000168439; Tissue enhanced (brain). DR MIM; 605063; gene. DR neXtProt; NX_P31948; -. DR OpenTargets; ENSG00000168439; -. DR PharmGKB; PA36196; -. DR VEuPathDB; HostDB:ENSG00000168439; -. DR eggNOG; KOG0548; Eukaryota. DR GeneTree; ENSGT00940000154911; -. DR HOGENOM; CLU_000134_46_5_1; -. DR InParanoid; P31948; -. DR OMA; HYSKAWE; -. DR OrthoDB; 933764at2759; -. DR PhylomeDB; P31948; -. DR TreeFam; TF300478; -. DR PathwayCommons; P31948; -. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-9696273; RND1 GTPase cycle. DR SignaLink; P31948; -. DR SIGNOR; P31948; -. DR BioGRID-ORCS; 10963; 94 hits in 1086 CRISPR screens. DR ChiTaRS; STIP1; human. DR EvolutionaryTrace; P31948; -. DR GeneWiki; Hop_(protein); -. DR GenomeRNAi; 10963; -. DR Pharos; P31948; Tbio. DR PRO; PR:P31948; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P31948; protein. DR Bgee; ENSG00000168439; Expressed in adrenal tissue and 201 other tissues. DR ExpressionAtlas; P31948; baseline and differential. DR Genevisible; P31948; HS. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0120293; C:dynein axonemal particle; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR IDEAL; IID00449; -. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 2. DR Pfam; PF07719; TPR_2; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 2. DR SMART; SM00028; TPR; 9. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 9. DR PROSITE; PS50293; TPR_REGION; 2. DR AGR; HGNC:11387; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; TPR repeat; Ubl conjugation. FT CHAIN 1..543 FT /note="Stress-induced-phosphoprotein 1" FT /id="PRO_0000106372" FT REPEAT 4..37 FT /note="TPR 1" FT REPEAT 38..71 FT /note="TPR 2" FT REPEAT 72..105 FT /note="TPR 3" FT DOMAIN 130..169 FT /note="STI1 1" FT REPEAT 225..258 FT /note="TPR 4" FT REPEAT 259..292 FT /note="TPR 5" FT REPEAT 300..333 FT /note="TPR 6" FT REPEAT 360..393 FT /note="TPR 7" FT REPEAT 394..427 FT /note="TPR 8" FT REPEAT 428..461 FT /note="TPR 9" FT DOMAIN 492..531 FT /note="STI1 2" FT REGION 192..233 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 222..239 FT /note="Bipartite nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 208..233 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT MOD_RES 8 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 198 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 301 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 312 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 325 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 332 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 344 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 354 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 446 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 481 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT CROSSLNK 123 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 123 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 210 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 210 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..3 FT /note="MEQ -> MESGSPMGEVEISRTIRTNGRGQRGYDWQCKRPIRVAEVRSSLHS FT WSLRW (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055034" FT VAR_SEQ 74..97 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055035" FT CONFLICT 84 FT /note="F -> L (in Ref. 7; AAH39299)" FT /evidence="ECO:0000305" FT CONFLICT 364 FT /note="K -> E (in Ref. 4; BAG59782)" FT /evidence="ECO:0000305" FT CONFLICT 533 FT /note="K -> R (in Ref. 4; BAG59782)" FT /evidence="ECO:0000305" FT HELIX 3..16 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 20..33 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 38..51 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 54..67 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 72..84 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 88..99 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 106..117 FT /evidence="ECO:0007829|PDB:1ELW" FT HELIX 223..237 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 241..254 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 259..272 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 275..291 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 296..312 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 316..329 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 333..348 FT /evidence="ECO:0007829|PDB:1ELR" FT HELIX 359..372 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 377..387 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 394..404 FT /evidence="ECO:0007829|PDB:2LNI" FT TURN 405..408 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 410..423 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 428..440 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 444..457 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 459..462 FT /evidence="ECO:0007829|PDB:2LNI" FT HELIX 463..475 FT /evidence="ECO:0007829|PDB:2LNI" SQ SEQUENCE 543 AA; 62639 MW; 8E58ECA13825CB0E CRC64; MEQVNELKEK GNKALSVGNI DDALQCYSEA IKLDPHNHVL YSNRSAAYAK KGDYQKAYED GCKTVDLKPD WGKGYSRKAA ALEFLNRFEE AKRTYEEGLK HEANNPQLKE GLQNMEARLA ERKFMNPFNM PNLYQKLESD PRTRTLLSDP TYRELIEQLR NKPSDLGTKL QDPRIMTTLS VLLGVDLGSM DEEEEIATPP PPPPPKKETK PEPMEEDLPE NKKQALKEKE LGNDAYKKKD FDTALKHYDK AKELDPTNMT YITNQAAVYF EKGDYNKCRE LCEKAIEVGR ENREDYRQIA KAYARIGNSY FKEEKYKDAI HFYNKSLAEH RTPDVLKKCQ QAEKILKEQE RLAYINPDLA LEEKNKGNEC FQKGDYPQAM KHYTEAIKRN PKDAKLYSNR AACYTKLLEF QLALKDCEEC IQLEPTFIKG YTRKAAALEA MKDYTKAMDV YQKALDLDSS CKEAADGYQR CMMAQYNRHD SPEDVKRRAM ADPEVQQIMS DPAMRLILEQ MQKDPQALSE HLKNPVIAQK IQKLMDVGLI AIR // ID TEBP_HUMAN Reviewed; 160 AA. AC Q15185; A8K7D0; B4DHP2; B4DP11; B4DP21; Q8WU70; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 14-DEC-2022, entry version 210. DE RecName: Full=Prostaglandin E synthase 3; DE EC=5.3.99.3 {ECO:0000269|PubMed:10922363}; DE AltName: Full=Cytosolic prostaglandin E2 synthase; DE Short=cPGES; DE AltName: Full=Hsp90 co-chaperone; DE AltName: Full=Progesterone receptor complex p23; DE AltName: Full=Telomerase-binding protein p23; GN Name=PTGES3; Synonyms=P23, TEBP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROGESTERONE RECEPTOR-BINDING. RC TISSUE=Testis; RX PubMed=8114727; DOI=10.1128/mcb.14.3.1956-1963.1994; RA Johnson J.L., Beito T.G., Krco C.J., Toft D.O.; RT "Characterization of a novel 23-kilodalton protein of unactive progesterone RT receptor complexes."; RL Mol. Cell. Biol. 14:1956-1963(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4). RC TISSUE=Caudate nucleus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 13-65; 72-88 AND 96-122, PHOSPHORYLATION AT SER-113, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [7] RP INTERACTION WITH TERT, AND FUNCTION AS A CO-CHAPERONE IN TELOMERASE RP HOLOENZYME ASSEMBLY. RX PubMed=11274138; DOI=10.1074/jbc.c100055200; RA Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.; RT "Stable association of hsp90 and p23, but Not hsp70, with active human RT telomerase."; RL J. Biol. Chem. 276:15571-15574(2001). RN [8] RP FUNCTION AS A CHAPERONE. RX PubMed=12077419; DOI=10.1126/science.1073051; RA Freeman B.C., Yamamoto K.R.; RT "Disassembly of transcriptional regulatory complexes by molecular RT chaperones."; RL Science 296:2232-2235(2002). RN [9] RP FUNCTION AS A PROSTAGLANDIN SYNTHASE, BIOPHYSICOCHEMICAL PROPERTIES, RP CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=10922363; DOI=10.1074/jbc.m003504200; RA Tanioka T., Nakatani Y., Semmyo N., Murakami M., Kudo I.; RT "Molecular identification of cytosolic prostaglandin E2 synthase that is RT functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2 RT biosynthesis."; RL J. Biol. Chem. 275:32775-32782(2000). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-118; SER-148 AND RP SER-151, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Pituitary; RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x; RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.; RT "Phosphoproteomic analysis of the human pituitary."; RL Pituitary 9:109-120(2006). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-148 AND SER-151, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-148 AND SER-151, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [22] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-33, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113 AND SER-118, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [26] RP PROTEOLYTIC CLEAVAGE. RX PubMed=22451931; DOI=10.1073/pnas.1200934109; RA Boucher D., Blais V., Denault J.B.; RT "Caspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1 RT proteolysis."; RL Proc. Natl. Acad. Sci. U.S.A. 109:5669-5674(2012). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-85 AND SER-113, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [29] RP FUNCTION, AND INTERACTION WITH EGLN1. RX PubMed=24711448; DOI=10.1074/jbc.m113.541227; RA Song D., Li L.S., Arsenault P.R., Tan Q., Bigham A.W., Heaton-Johnson K.J., RA Master S.R., Lee F.S.; RT "Defective Tibetan PHD2 binding to p23 links high altitude adaption to RT altered oxygen sensing."; RL J. Biol. Chem. 289:14656-14665(2014). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-113; SER-148 AND RP SER-151, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130 (ISOFORM 4), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [32] RP INTERACTION WITH HSP90AA1; FLCN; FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [33] RP PROTEOLYTIC CLEAVAGE. RX PubMed=28863261; DOI=10.1021/acs.biochem.7b00298; RA Martini C., Bedard M., Lavigne P., Denault J.B.; RT "Characterization of Hsp90 co-chaperone p23 cleavage by caspase-7 uncovers RT a peptidase-substrate interaction involving intrinsically disordered RT regions."; RL Biochemistry 56:5099-5111(2017). RN [34] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; CDC37; PPP5C; TSC1 RP AND TSC2. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [35] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-35 AND LYS-65, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 1-125. RX PubMed=10811660; DOI=10.1074/jbc.m003410200; RA Weaver A.J., Sullivan W.P., Felts S.J., Owen B.A.L., Toft D.O.; RT "Crystal structure and activity of human p23, a heat shock protein 90 co- RT chaperone."; RL J. Biol. Chem. 275:23045-23052(2000). CC -!- FUNCTION: Cytosolic prostaglandin synthase that catalyzes the CC oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin CC E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to CC genomic response elements in a hormone-dependent manner and disrupts CC receptor-mediated transcriptional activation, by promoting disassembly CC of transcriptional regulatory complexes (PubMed:11274138, CC PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via CC interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 CC pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, CC ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, CC ECO:0000269|PubMed:24711448}. CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin H2 = prostaglandin E2; Xref=Rhea:RHEA:12893, CC ChEBI:CHEBI:57405, ChEBI:CHEBI:606564; EC=5.3.99.3; CC Evidence={ECO:0000269|PubMed:10922363}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=14 uM for PGH2 {ECO:0000269|PubMed:10922363}; CC Vmax=190 nmol/min/mg enzyme toward PGH2 CC {ECO:0000269|PubMed:10922363}; CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis. CC {ECO:0000269|PubMed:10922363}. CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Binds to the progesterone CC receptor (PubMed:8114727). Interacts with TERT; the interaction, CC together with HSP90AA1, is required for correct assembly and CC stabilization of the telomerase holoenzyme complex (PubMed:11274138). CC Interacts (via PXLE motif) with EGLN1/PHD2, recruiting EGLN1/PHD2 to CC the HSP90 pathway to facilitate HIF alpha proteins hydroxylation CC (PubMed:24711448). Interacts with HSP90AA1, FLCN, FNIP1 and FNIP2 CC (PubMed:27353360). {ECO:0000269|PubMed:11274138, CC ECO:0000269|PubMed:24711448, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:8114727}. CC -!- INTERACTION: CC Q15185; Q9UKV8: AGO2; NbExp=3; IntAct=EBI-1049387, EBI-528269; CC Q15185; P07900: HSP90AA1; NbExp=6; IntAct=EBI-1049387, EBI-296047; CC Q15185; P08238: HSP90AB1; NbExp=4; IntAct=EBI-1049387, EBI-352572; CC Q15185; O14654: IRS4; NbExp=2; IntAct=EBI-1049387, EBI-356594; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q3ZBF7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q15185-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15185-2; Sequence=VSP_055363; CC Name=3; CC IsoId=Q15185-3; Sequence=VSP_055364; CC Name=4; CC IsoId=Q15185-4; Sequence=VSP_055365; CC -!- DOMAIN: The PXLE motif mediates interaction with EGLN1/PHD2. CC {ECO:0000269|PubMed:24711448}. CC -!- PTM: Proteolytically cleaved by caspase-7 (CASP7) in response to CC apoptosis, leading to its inactivation. {ECO:0000269|PubMed:22451931, CC ECO:0000269|PubMed:28863261}. CC -!- SIMILARITY: Belongs to the p23/wos2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L24804; AAA18537.1; -; mRNA. DR EMBL; AK291945; BAF84634.1; -; mRNA. DR EMBL; AK295208; BAG58204.1; -; mRNA. DR EMBL; AK298147; BAG60423.1; -; mRNA. DR EMBL; AK298160; BAG60433.1; -; mRNA. DR EMBL; AC117378; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW96953.1; -; Genomic_DNA. DR EMBL; CH471054; EAW96958.1; -; Genomic_DNA. DR EMBL; BC003005; AAH03005.1; -; mRNA. DR EMBL; BC021167; AAH21167.1; -; mRNA. DR CCDS; CCDS31836.1; -. [Q15185-1] DR CCDS; CCDS61158.1; -. [Q15185-2] DR CCDS; CCDS61159.1; -. [Q15185-3] DR CCDS; CCDS61160.1; -. [Q15185-4] DR PIR; A56211; A56211. DR RefSeq; NP_001269530.1; NM_001282601.1. [Q15185-4] DR RefSeq; NP_001269531.1; NM_001282602.1. [Q15185-3] DR RefSeq; NP_001269532.1; NM_001282603.1. [Q15185-2] DR RefSeq; NP_001269533.1; NM_001282604.1. DR RefSeq; NP_001269534.1; NM_001282605.1. DR RefSeq; NP_006592.3; NM_006601.6. [Q15185-1] DR PDB; 1EJF; X-ray; 2.49 A; A/B=1-125. DR PDB; 7KRJ; EM; 2.56 A; C=1-160. DR PDB; 7L7I; EM; 3.30 A; E=1-160. DR PDB; 7L7J; EM; 3.10 A; C=1-160. DR PDBsum; 1EJF; -. DR PDBsum; 7KRJ; -. DR PDBsum; 7L7I; -. DR PDBsum; 7L7J; -. DR AlphaFoldDB; Q15185; -. DR BMRB; Q15185; -. DR SASBDB; Q15185; -. DR SMR; Q15185; -. DR BioGRID; 115952; 403. DR CORUM; Q15185; -. DR DIP; DIP-279N; -. DR ELM; Q15185; -. DR IntAct; Q15185; 97. DR MINT; Q15185; -. DR STRING; 9606.ENSP00000482075; -. DR ChEMBL; CHEMBL3341580; -. DR DrugBank; DB00316; Acetaminophen. DR DrugBank; DB09130; Copper. DR DrugBank; DB05036; Grn163l. DR SwissLipids; SLP:000000831; -. DR GlyGen; Q15185; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15185; -. DR PhosphoSitePlus; Q15185; -. DR SwissPalm; Q15185; -. DR BioMuta; PTGES3; -. DR EPD; Q15185; -. DR jPOST; Q15185; -. DR MassIVE; Q15185; -. DR MaxQB; Q15185; -. DR PaxDb; Q15185; -. DR PeptideAtlas; Q15185; -. DR PRIDE; Q15185; -. DR ProteomicsDB; 4234; -. DR ProteomicsDB; 4741; -. DR ProteomicsDB; 4744; -. DR ProteomicsDB; 60486; -. [Q15185-1] DR TopDownProteomics; Q15185-1; -. [Q15185-1] DR Antibodypedia; 28360; 763 antibodies from 38 providers. DR DNASU; 10728; -. DR Ensembl; ENST00000262033.11; ENSP00000262033.6; ENSG00000110958.16. [Q15185-1] DR Ensembl; ENST00000414274.7; ENSP00000405299.3; ENSG00000110958.16. [Q15185-3] DR Ensembl; ENST00000436399.6; ENSP00000402385.2; ENSG00000110958.16. [Q15185-2] DR Ensembl; ENST00000448157.6; ENSP00000414892.2; ENSG00000110958.16. [Q15185-4] DR GeneID; 10728; -. DR KEGG; hsa:10728; -. DR MANE-Select; ENST00000262033.11; ENSP00000262033.6; NM_006601.7; NP_006592.3. DR UCSC; uc001slu.6; human. [Q15185-1] DR CTD; 10728; -. DR DisGeNET; 10728; -. DR GeneCards; PTGES3; -. DR HGNC; HGNC:16049; PTGES3. DR HPA; ENSG00000110958; Low tissue specificity. DR MIM; 607061; gene. DR neXtProt; NX_Q15185; -. DR OpenTargets; ENSG00000110958; -. DR PharmGKB; PA142671118; -. DR VEuPathDB; HostDB:ENSG00000110958; -. DR eggNOG; KOG3158; Eukaryota. DR GeneTree; ENSGT00940000154256; -. DR InParanoid; Q15185; -. DR PhylomeDB; Q15185; -. DR TreeFam; TF315077; -. DR BioCyc; MetaCyc:HS03359-MON; -. DR PathwayCommons; Q15185; -. DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX). DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-3371511; HSF1 activation. DR Reactome; R-HSA-3371568; Attenuation phase. DR Reactome; R-HSA-8937144; Aryl hydrocarbon receptor signalling. DR Reactome; R-HSA-8939211; ESR-mediated signaling. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SABIO-RK; Q15185; -. DR SignaLink; Q15185; -. DR SIGNOR; Q15185; -. DR UniPathway; UPA00662; -. DR BioGRID-ORCS; 10728; 35 hits in 1009 CRISPR screens. DR ChiTaRS; PTGES3; human. DR EvolutionaryTrace; Q15185; -. DR GeneWiki; PTGES3; -. DR GenomeRNAi; 10728; -. DR Pharos; Q15185; Tbio. DR PRO; PR:Q15185; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q15185; protein. DR Bgee; ENSG00000110958; Expressed in secondary oocyte and 220 other tissues. DR ExpressionAtlas; Q15185; baseline and differential. DR Genevisible; Q15185; HS. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IC:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005697; C:telomerase holoenzyme complex; IDA:UniProtKB. DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central. DR GO; GO:0070182; F:DNA polymerase binding; IPI:BHF-UCL. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:CAFA. DR GO; GO:0050220; F:prostaglandin-E synthase activity; IDA:UniProtKB. DR GO; GO:0003720; F:telomerase activity; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB. DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IDA:UniProtKB. DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IMP:CAFA. DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome. DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl. DR GO; GO:0042921; P:glucocorticoid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:Ensembl. DR GO; GO:0060430; P:lung saccule development; IEA:Ensembl. DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL. DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL. DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0050821; P:protein stabilization; IMP:CAFA. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0043588; P:skin development; IEA:Ensembl. DR GO; GO:1905323; P:telomerase holoenzyme complex assembly; IDA:BHF-UCL. DR GO; GO:0000723; P:telomere maintenance; TAS:UniProtKB. DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:BHF-UCL. DR DisProt; DP00358; -. DR Gene3D; 2.60.40.790; -; 1. DR InterPro; IPR007052; CS_dom. DR InterPro; IPR008978; HSP20-like_chaperone. DR InterPro; IPR045250; p23-like. DR PANTHER; PTHR22932; TELOMERASE-BINDING PROTEIN P23 HSP90 CO-CHAPERONE; 1. DR Pfam; PF04969; CS; 1. DR SUPFAM; SSF49764; HSP20-like chaperones; 1. DR PROSITE; PS51203; CS; 1. DR AGR; HGNC:16049; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chaperone; Cytoplasm; KW Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; KW Isomerase; Isopeptide bond; Lipid biosynthesis; Lipid metabolism; KW Phosphoprotein; Prostaglandin biosynthesis; Prostaglandin metabolism; KW Reference proteome; Ubl conjugation. FT CHAIN 1..160 FT /note="Prostaglandin E synthase 3" FT /id="PRO_0000218952" FT DOMAIN 1..90 FT /note="CS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00547" FT REGION 124..160 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 157..160 FT /note="PXLE motif" FT /evidence="ECO:0000303|PubMed:24711448" FT COMPBIAS 135..160 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 142..143 FT /note="Cleavage; by caspase-7" FT /evidence="ECO:0000269|PubMed:28863261" FT MOD_RES 33 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 44 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 85 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 100 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9R0Q7" FT MOD_RES 113 FT /note="Phosphoserine" FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:16807684, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17487921, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 118 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231" FT MOD_RES 148 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:24275569" FT MOD_RES 151 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 35 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 63..95 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055363" FT VAR_SEQ 96..125 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055364" FT VAR_SEQ 126..146 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055365" FT STRAND 6..10 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 12..19 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 24..32 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 35..42 FT /evidence="ECO:0007829|PDB:1EJF" FT TURN 43..46 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 47..57 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 59..68 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 73..81 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 87..92 FT /evidence="ECO:0007829|PDB:1EJF" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:1EJF" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:1EJF" FT HELIX 120..130 FT /evidence="ECO:0007829|PDB:7KRJ" FT MOD_RES Q15185-4:130 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" SQ SEQUENCE 160 AA; 18697 MW; 23538BB9D7AFD73F CRC64; MQPASAKWYD RRDYVFIEFC VEDSKDVNVN FEKSKLTFSC LGGSDNFKHL NEIDLFHCID PNDSKHKRTD RSILCCLRKG ESGQSWPRLT KERAKLNWLS VDFNNWKDWE DDSDEDMSNF DRFSEMMNNM GGDEDVDLPE VDGADDDSQD SDDEKMPDLE // ID CD37L_HUMAN Reviewed; 337 AA. AC Q7L3B6; B1AL70; Q9NWS3; Q9NX16; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 1. DT 14-DEC-2022, entry version 102. DE RecName: Full=Hsp90 co-chaperone Cdc37-like 1; DE AltName: Full=Hsp90-associating relative of Cdc37; GN Name=CDC37L1; Synonyms=CDC37B, HARC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Signet-ring cell carcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP INTERACTION WITH FKBP4; HSP70; HSP90; PPID AND STIP1, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND PHOSPHORYLATION. RX PubMed=11413142; DOI=10.1074/jbc.m103889200; RA Scholz G.M., Cartledge K., Hall N.E.; RT "Identification and characterization of Harc, a novel Hsp90-associating RT relative of Cdc37."; RL J. Biol. Chem. 276:30971-30979(2001). RN [6] RP SELF-ASSOCIATION, AND INTERACTION WITH CDC37 AND HSP90. RX PubMed=15850399; DOI=10.1021/bi047406z; RA Roiniotis J., Masendycz P., Ho S., Scholz G.M.; RT "Domain-mediated dimerization of the Hsp90 cochaperones Harc and Cdc37."; RL Biochemistry 44:6662-6669(2005). RN [7] RP SELF-ASSOCIATION, AND INTERACTION WITH HSP70; HSP90 AND STIP1. RX PubMed=18052042; DOI=10.1021/bi701041p; RA Cartledge K., Elsegood C., Roiniotis J., Hamilton J.A., Scholz G.M.; RT "Importance of the C-terminal domain of harc for binding to hsp70 and hop RT as well as its response to heat shock."; RL Biochemistry 46:15144-15152(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Co-chaperone that binds to numerous proteins and promotes CC their interaction with Hsp70 and Hsp90. {ECO:0000250}. CC -!- SUBUNIT: Self-associates. Forms complexes with Hsp70 and Hsp90. CC Interacts with CDC37, FKBP4, PPID and STIP1. CC {ECO:0000269|PubMed:11413142, ECO:0000269|PubMed:15850399, CC ECO:0000269|PubMed:18052042}. CC -!- INTERACTION: CC Q7L3B6; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-2841876, EBI-2837444; CC Q7L3B6; P07900: HSP90AA1; NbExp=2; IntAct=EBI-2841876, EBI-296047; CC Q7L3B6; P08238: HSP90AB1; NbExp=5; IntAct=EBI-2841876, EBI-352572; CC Q7L3B6; Q6PK50: HSP90AB1; NbExp=2; IntAct=EBI-2841876, EBI-9356629; CC Q7L3B6; P31948: STIP1; NbExp=2; IntAct=EBI-2841876, EBI-1054052; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11413142}. CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, placenta CC and skeletal muscle. {ECO:0000269|PubMed:11413142}. CC -!- SIMILARITY: Belongs to the CDC37 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91206.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000497; BAA91206.1; ALT_SEQ; mRNA. DR EMBL; AK000646; BAA91304.1; -; mRNA. DR EMBL; AL136231; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58782.1; -; Genomic_DNA. DR EMBL; BC014133; AAH14133.1; -; mRNA. DR CCDS; CCDS6454.1; -. DR RefSeq; NP_060383.2; NM_017913.3. DR AlphaFoldDB; Q7L3B6; -. DR SMR; Q7L3B6; -. DR BioGRID; 120796; 31. DR IntAct; Q7L3B6; 26. DR STRING; 9606.ENSP00000371278; -. DR GlyGen; Q7L3B6; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q7L3B6; -. DR PhosphoSitePlus; Q7L3B6; -. DR BioMuta; CDC37L1; -. DR DMDM; 182705252; -. DR EPD; Q7L3B6; -. DR jPOST; Q7L3B6; -. DR MassIVE; Q7L3B6; -. DR MaxQB; Q7L3B6; -. DR PaxDb; Q7L3B6; -. DR PeptideAtlas; Q7L3B6; -. DR ProteomicsDB; 68770; -. DR Antibodypedia; 24046; 204 antibodies from 28 providers. DR DNASU; 55664; -. DR Ensembl; ENST00000381854.4; ENSP00000371278.3; ENSG00000106993.12. DR GeneID; 55664; -. DR KEGG; hsa:55664; -. DR MANE-Select; ENST00000381854.4; ENSP00000371278.3; NM_017913.4; NP_060383.2. DR UCSC; uc003zio.4; human. DR CTD; 55664; -. DR DisGeNET; 55664; -. DR GeneCards; CDC37L1; -. DR HGNC; HGNC:17179; CDC37L1. DR HPA; ENSG00000106993; Tissue enhanced (skeletal). DR MIM; 610346; gene. DR neXtProt; NX_Q7L3B6; -. DR OpenTargets; ENSG00000106993; -. DR PharmGKB; PA134982210; -. DR VEuPathDB; HostDB:ENSG00000106993; -. DR eggNOG; KOG2260; Eukaryota. DR GeneTree; ENSGT00390000013443; -. DR HOGENOM; CLU_046495_1_0_1; -. DR InParanoid; Q7L3B6; -. DR OMA; GKWTKDD; -. DR OrthoDB; 786744at2759; -. DR PhylomeDB; Q7L3B6; -. DR TreeFam; TF101059; -. DR PathwayCommons; Q7L3B6; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR SignaLink; Q7L3B6; -. DR BioGRID-ORCS; 55664; 14 hits in 1080 CRISPR screens. DR ChiTaRS; CDC37L1; human. DR GenomeRNAi; 55664; -. DR Pharos; Q7L3B6; Tbio. DR PRO; PR:Q7L3B6; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q7L3B6; protein. DR Bgee; ENSG00000106993; Expressed in gastrocnemius and 198 other tissues. DR ExpressionAtlas; Q7L3B6; baseline and differential. DR Genevisible; Q7L3B6; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031089; C:platelet dense granule lumen; TAS:Reactome. DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central. DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central. DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0050821; P:protein stabilization; IBA:GO_Central. DR Gene3D; 1.20.58.610; -; 1. DR InterPro; IPR004918; Cdc37. DR InterPro; IPR013874; Cdc37_Hsp90-bd. DR InterPro; IPR038189; Cdc37_Hsp90-bd_sf. DR PANTHER; PTHR12800; CDC37-RELATED; 1. DR Pfam; PF08565; CDC37_M; 1. DR SMART; SM01070; CDC37_M; 1. DR AGR; HGNC:17179; -. PE 1: Evidence at protein level; KW Chaperone; Coiled coil; Cytoplasm; Phosphoprotein; Reference proteome. FT CHAIN 1..337 FT /note="Hsp90 co-chaperone Cdc37-like 1" FT /id="PRO_0000318521" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..171 FT /note="Self-association" FT REGION 147..277 FT /note="Self-association and interaction with Hsp90" FT REGION 267..337 FT /note="Interaction with Hsp70" FT REGION 278..337 FT /note="Required for interaction with STIP1" FT COILED 84..122 FT /evidence="ECO:0000255" FT MOD_RES 32 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 88 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 291 FT /note="S -> F (in dbSNP:rs7036014)" FT /id="VAR_038755" FT CONFLICT 17 FT /note="E -> G (in Ref. 1; BAA91304)" FT /evidence="ECO:0000305" FT CONFLICT 159 FT /note="M -> V (in Ref. 1; BAA91206)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="N -> S (in Ref. 1; BAA91304)" FT /evidence="ECO:0000305" SQ SEQUENCE 337 AA; 38835 MW; 46ACDDCE5D07B587 CRC64; MEQPWPPPGP WSLPRAEGEA EEESDFDVFP SSPRCPQLPG GGAQMYSHGI ELACQKQKEF VKSSVACKWN LAEAQQKLGS LALHNSESLD QEHAKAQTAV SELRQREEEW RQKEEALVQR EKMCLWSTDA ISKDVFNKSF INQDKRKDTE DEDKSESFMQ KYEQKIRHFG MLSRWDDSQR FLSDHPYLVC EETAKYLILW CFHLEAEKKG ALMEQIAHQA VVMQFIMEMA KNCNVDPRGC FRLFFQKAKA EEEGYFEAFK NELEAFKSRV RLYSQSQSFQ PMTVQNHVPH SGVGSIGLLE SLPQNPDYLQ YSISTALCSL NSVVHKEDDE PKMMDTV // ID PPP5_HUMAN Reviewed; 499 AA. AC P53041; Q16722; Q53XV2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 14-DEC-2022, entry version 231. DE RecName: Full=Serine/threonine-protein phosphatase 5; DE Short=PP5; DE EC=3.1.3.16 {ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:30699359}; DE AltName: Full=Protein phosphatase T; DE Short=PP-T; DE Short=PPT; GN Name=PPP5C; Synonyms=PPP5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-499. RX PubMed=7925273; DOI=10.1002/j.1460-2075.1994.tb06748.x; RA Chen M.X., McPartlin A.E., Brown L., Chen Y.H., Barker H.M., Cohen P.T.W.; RT "A novel human protein serine/threonine phosphatase, which possesses four RT tetratricopeptide repeat motifs and localizes to the nucleus."; RL EMBO J. 13:4278-4290(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-499. RC TISSUE=Fetal brain; RX PubMed=8666404; DOI=10.1006/geno.1995.9972; RA Yong W.H., Ueki K., Chou D., Reeves S.A., von Deimling A., Gusella J.F., RA Mohrenweiser H.W., Buckler A.J., Louis D.N.; RT "Cloning of a highly conserved human protein serine-threonine phosphatase RT gene from the glioma candidate region on chromosome 19q13.3."; RL Genomics 29:533-536(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-37. RC TISSUE=Fetal brain; RX PubMed=8561788; DOI=10.1006/bbrc.1996.0092; RA Xu X., Lagercrantz J., Zickert P., Bajalica-Lagercrantz S., Zetterberg A.; RT "Chromosomal localization and 5' sequence of the human protein RT serine/threonine phosphatase 5' gene."; RL Biochem. Biophys. Res. Commun. 218:514-517(1996). RN [8] RP FUNCTION, ACTIVITY REGULATION, AND LIPID-BINDING. RX PubMed=9000529; DOI=10.1016/s0014-5793(96)01427-5; RA Chen M.X., Cohen P.T.; RT "Activation of protein phosphatase 5 by limited proteolysis or the binding RT of polyunsaturated fatty acids to the TPR domain."; RL FEBS Lett. 400:136-140(1997). RN [9] RP INTERACTION WITH CDC16 AND CDC27. RX PubMed=9405394; DOI=10.1074/jbc.272.51.32011; RA Ollendorff V., Donoghue D.J.; RT "The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two RT tetratricopeptide repeat-containing subunits of the anaphase-promoting RT complex."; RL J. Biol. Chem. 272:32011-32018(1997). RN [10] RP FUNCTION IN DNA DAMAGE RESPONSE, AND INTERACTION WITH ATM AND RAD17. RX PubMed=14871926; DOI=10.1101/gad.1176004; RA Ali A., Zhang J., Bao S., Liu I., Otterness D., Dean N.M., Abraham R.T., RA Wang X.F.; RT "Requirement of protein phosphatase 5 in DNA-damage-induced ATM RT activation."; RL Genes Dev. 18:249-254(2004). RN [11] RP FUNCTION IN DEPHOSPHORYLATION OF ESR1 AND ESR2. RX PubMed=14764652; DOI=10.1210/me.2003-0308; RA Ikeda K., Ogawa S., Tsukui T., Horie-Inoue K., Ouchi Y., Kato S., RA Muramatsu M., Inoue S.; RT "Protein phosphatase 5 is a negative regulator of estrogen receptor- RT mediated transcription."; RL Mol. Endocrinol. 18:1131-1143(2004). RN [12] RP FUNCTION IN DEPHOSPHORYLATION OF PRKDC. RX PubMed=14734805; DOI=10.1073/pnas.0307765100; RA Wechsler T., Chen B.P., Harper R., Morotomi-Yano K., Huang B.C., Meek K., RA Cleaver J.E., Chen D.J., Wabl M.; RT "DNA-PKcs function regulated specifically by protein phosphatase 5."; RL Proc. Natl. Acad. Sci. U.S.A. 101:1247-1252(2004). RN [13] RP FUNCTION, INTERACTION WITH HSP90AA1 AND HSPA1A, LIPID-BINDING, ACTIVITY RP REGULATION, SUBCELLULAR LOCATION, CLEAVAGE, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=15383005; DOI=10.1042/bj20040690; RA Zeke T., Morrice N., Vazquez-Martin C., Cohen P.T.; RT "Human protein phosphatase 5 dissociates from heat-shock proteins and is RT proteolytically activated in response to arachidonic acid and the RT microtubule-depolymerizing drug nocodazole."; RL Biochem. J. 385:45-56(2005). RN [14] RP FUNCTION IN DEPHOSPHORYLATION OF MAPT, BIOPHYSICOCHEMICAL PROPERTIES, AND RP TISSUE SPECIFICITY. RX PubMed=15546861; DOI=10.1074/jbc.m410775200; RA Liu F., Iqbal K., Grundke-Iqbal I., Rossie S., Gong C.X.; RT "Dephosphorylation of tau by protein phosphatase 5: impairment in RT Alzheimer's disease."; RL J. Biol. Chem. 280:1790-1796(2005). RN [15] RP FUNCTION IN DNA DAMAGE RESPONSE. RX PubMed=16260606; DOI=10.1128/mcb.25.22.9910-9919.2005; RA Zhang J., Bao S., Furumai R., Kucera K.S., Ali A., Dean N.M., Wang X.F.; RT "Protein phosphatase 5 is required for ATR-mediated checkpoint RT activation."; RL Mol. Cell. Biol. 25:9910-9919(2005). RN [16] RP FUNCTION IN MAPK SIGNALING, IDENTIFICATION BY MASS SPECTROMETRY, AND RP MUTAGENESIS OF LYS-97 AND HIS-304. RX PubMed=16892053; DOI=10.1038/ncb1465; RA von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.; RT "Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5."; RL Nat. Cell Biol. 8:1011-1016(2006). RN [17] RP FUNCTION IN DEPHOSPHORYLATION OF CSNK1E, INTERACTION WITH CRY1 AND CRY2, RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-304. RX PubMed=16790549; DOI=10.1073/pnas.0604138103; RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.; RT "Posttranslational regulation of the mammalian circadian clock by RT cryptochrome and protein phosphatase 5."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [19] RP FUNCTION IN DEPHOSPHORYLATION OF TP53BP1. RX PubMed=19176521; DOI=10.1074/jbc.m809272200; RA Kang Y., Lee J.H., Hoan N.N., Sohn H.M., Chang I.Y., You H.J.; RT "Protein phosphatase 5 regulates the function of 53BP1 after RT neocarzinostatin-induced DNA damage."; RL J. Biol. Chem. 284:9845-9853(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [21] RP FUNCTION AS PHOSPHATASE, INTERACTION WITH RAC1, ACTIVITY REGULATION, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-93 AND HIS-304. RX PubMed=19948726; DOI=10.1074/jbc.m109.088427; RA Chatterjee A., Wang L., Armstrong D.L., Rossie S.; RT "Activated Rac1 GTPase translocates protein phosphatase 5 to the cell RT membrane and stimulates phosphatase activity in vitro."; RL J. Biol. Chem. 285:3872-3882(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [23] RP FUNCTION IN DNA DAMAGE RESPONSE. RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005; RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y., RA You H.J.; RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair."; RL Biochem. Biophys. Res. Commun. 404:476-481(2011). RN [24] RP FUNCTION IN TGF-BETA SIGNALING, AND INTERACTION WITH SMAD2 AND SMAD3. RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003; RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.; RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth RT factor-beta pathway."; RL Cell. Signal. 24:1999-2006(2012). RN [25] RP FUNCTION AS PHOSPHATASE, INTERACTION WITH S100A1; S100A2; S100A6 AND S100B, RP ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-32; ARG-74; LYS-97 AND ARG-101. RX PubMed=22399290; DOI=10.1074/jbc.m111.329771; RA Yamaguchi F., Umeda Y., Shimamoto S., Tsuchiya M., Tokumitsu H., Tokuda M., RA Kobayashi R.; RT "S100 proteins modulate protein phosphatase 5 function: a link between CA2+ RT signal transduction and protein dephosphorylation."; RL J. Biol. Chem. 287:13787-13798(2012). RN [26] RP FUNCTION IN DEPHOSPHORYLATION OF MAP3K5, INTERACTION WITH KLHDC10, AND RP CLEAVAGE. RX PubMed=23102700; DOI=10.1016/j.molcel.2012.09.018; RA Sekine Y., Hatanaka R., Watanabe T., Sono N., Iemura S., Natsume T., RA Kuranaga E., Miura M., Takeda K., Ichijo H.; RT "The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 RT activation by suppressing PP5."; RL Mol. Cell 48:692-704(2012). RN [27] RP INTERACTION WITH HSP90AA1 AND FLCN. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [28] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; CDC37; PTGES3; TSC1; RP TSC2; AKT; CDK4; RAF1 AND NR3C1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [29] RP FUNCTION. RX PubMed=30699359; DOI=10.1016/j.celrep.2019.01.018; RA Sager R.A., Woodford M.R., Backe S.J., Makedon A.M., Baker-Williams A.J., RA DiGregorio B.T., Loiselle D.R., Haystead T.A., Zachara N.E., Prodromou C., RA Bourboulia D., Schmidt L.S., Linehan W.M., Bratslavsky G., Mollapour M.; RT "Post-translational regulation of FNIP1 creates a rheostat for the RT molecular chaperone Hsp90."; RL Cell Rep. 26:1344-1356(2019). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 19-177. RX PubMed=9482716; DOI=10.1093/emboj/17.5.1192; RA Das A.K., Cohen P.T.W., Barford D.; RT "The structure of the tetratricopeptide repeats of protein phosphatase 5: RT implications for TPR-mediated protein-protein interactions."; RL EMBO J. 17:1192-1199(1998). RN [31] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 169-499 IN COMPLEX WITH SUBSTRATE RP AND MAGNESIUM OR MANGANESES, ACTIVE SITE, AND MAGNESIUM OR RP MANGANESE-BINDING SITES. RX PubMed=15155720; DOI=10.1074/jbc.m402855200; RA Swingle M.R., Honkanen R.E., Ciszak E.M.; RT "Structural basis for the catalytic activity of human serine/threonine RT protein phosphatase-5."; RL J. Biol. Chem. 279:33992-33999(2004). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 23-499 IN COMPLEX WITH MANGANESE RP IONS, INTERACTION WITH HSP90AA1, LIPID-BINDING, MAGNESIUM OR RP MANGANESE-BINDING SITES, AND ACTIVITY REGULATION. RX PubMed=15577939; DOI=10.1038/sj.emboj.7600496; RA Yang J., Roe S.M., Cliff M.J., Williams M.A., Ladbury J.E., Cohen P.T., RA Barford D.; RT "Molecular basis for TPR domain-mediated regulation of protein phosphatase RT 5."; RL EMBO J. 24:1-10(2005). RN [33] RP STRUCTURE BY NMR OF 19-147 IN COMPLEX WITH HSP90AA1 PEPTIDE, INTERACTION RP WITH HSP90AA1, AND MUTAGENESIS OF GLY-83. RX PubMed=16531226; DOI=10.1016/j.str.2005.12.009; RA Cliff M.J., Harris R., Barford D., Ladbury J.E., Williams M.A.; RT "Conformational diversity in the TPR domain-mediated interaction of protein RT phosphatase 5 with Hsp90."; RL Structure 14:415-426(2006). RN [34] RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 176-490 IN COMPLEX WITH RP INHIBITORS AND MANGANESE, MANGANESE-BINDING SITES, AND ACTIVITY REGULATION. RX PubMed=19601647; DOI=10.1021/jm900610k; RA Bertini I., Calderone V., Fragai M., Luchinat C., Talluri E.; RT "Structural basis of serine/threonine phosphatase inhibition by the RT archetypal small molecules cantharidin and norcantharidin."; RL J. Med. Chem. 52:4838-4843(2009). CC -!- FUNCTION: Serine/threonine-protein phosphatase that dephosphorylates a CC myriad of proteins involved in different signaling pathways including CC the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors CC NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT CC (PubMed:14734805, PubMed:14764652, PubMed:14871926, PubMed:15383005, CC PubMed:15546861, PubMed:16260606, PubMed:16790549, PubMed:16892053, CC PubMed:19176521, PubMed:19948726, PubMed:21144835, PubMed:22399290, CC PubMed:22781750, PubMed:23102700, PubMed:9000529, PubMed:30699359). CC Implicated in wide ranging cellular processes, including apoptosis, CC differentiation, DNA damage response, cell survival, regulation of ion CC channels or circadian rhythms, in response to steroid and thyroid CC hormones, calcium, fatty acids, TGF-beta as well as oxidative and CC genotoxic stresses (PubMed:14734805, PubMed:14764652, PubMed:14871926, CC PubMed:15383005, PubMed:15546861, PubMed:16260606, PubMed:16790549, CC PubMed:16892053, PubMed:19176521, PubMed:19948726, PubMed:21144835, CC PubMed:22399290, PubMed:22781750, PubMed:23102700, PubMed:9000529, CC PubMed:30699359). Participates in the control of DNA damage response CC mechanisms such as checkpoint activation and DNA damage repair through, CC for instance, the regulation ATM/ATR-signaling and dephosphorylation of CC PRKDC and TP53BP1 (PubMed:14871926, PubMed:16260606, PubMed:21144835). CC Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress CC (PubMed:23102700). Plays a positive role in adipogenesis, mainly CC through the dephosphorylation and activation of PPARG transactivation CC function (By similarity). Also dephosphorylates and inhibits the anti- CC adipogenic effect of NR3C1 (By similarity). Regulates the circadian CC rhythms, through the dephosphorylation and activation of CSNK1E CC (PubMed:16790549). May modulate TGF-beta signaling pathway by the CC regulation of SMAD3 phosphorylation and protein expression levels CC (PubMed:22781750). Dephosphorylates and may play a role in the CC regulation of TAU/MAPT (PubMed:15546861). Through their CC dephosphorylation, may play a role in the regulation of ions channels CC such as KCNH2 (By similarity). Dephosphorylate FNIP1, disrupting CC interaction with HSP90AA1/Hsp90 (PubMed:30699359). CC {ECO:0000250|UniProtKB:P53042, ECO:0000250|UniProtKB:Q60676, CC ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, CC ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005, CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16260606, CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:16892053, CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:19948726, CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22399290, CC ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:23102700, CC ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:9000529}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + CC phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:83421; EC=3.1.3.16; CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700, CC ECO:0000269|PubMed:30699359}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20630; CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700, CC ECO:0000269|PubMed:30699359}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + CC phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:61977; EC=3.1.3.16; CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47005; CC Evidence={ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:14764652, CC ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549, CC ECO:0000269|PubMed:19176521, ECO:0000269|PubMed:23102700}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Note=Binds 2 Mg(2+) or Mn(2+) cations per subunit.; CC -!- ACTIVITY REGULATION: Autoinhibited. In the autoinhibited state, the TPR CC domain interacts with the catalytic region and prevents substrate CC access to the catalytic pocket. Allosterically activated by various CC polyunsaturated fatty acids, free long-chain fatty-acids and long-chain CC fatty acyl-CoA esters, arachidonic acid being the most effective CC activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release CC the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and CC GNA13 is synergistic with the one produced by fatty acids binding. CC Inhibited by okadaic acid. {ECO:0000269|PubMed:15383005, CC ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, CC ECO:0000269|PubMed:19948726, ECO:0000269|PubMed:22399290, CC ECO:0000269|PubMed:9000529}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.847 uM for CSNK1E (at 30 degrees Celsius) CC {ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549}; CC KM=13.2 uM for MAPT/TAU (at pH 7.4 and 30 degrees Celsius) CC {ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16790549}; CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Probably forms a complex CC composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, CC TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex CC does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Part of a complex with HSP90/HSP90AA1 and steroid CC receptors (By similarity). Interacts (via TPR repeats) with HSP90AA1 CC (via TPR repeat-binding motif) or HSPA1A/HSPA1B; the interaction is CC direct and activates the phosphatase activity (PubMed:15383005, CC PubMed:15577939, PubMed:16531226). Dissociates from HSPA1A/HSPA1B and CC HSP90AA1 in response to arachidonic acid (PubMed:15383005). Interacts CC with CPNE1 (via VWFA domain) (By similarity). Interacts with CDC16, CC CDC27 (PubMed:9405394). Interacts with KLHDC10 (via the 6 Kelch CC repeats); inhibits the phosphatase activity on MAP3K5 CC (PubMed:23102700). Interacts with ATM and ATR; both interactions are CC induced by DNA damage and enhance ATM and ATR kinase activity CC (PubMed:14871926). Interacts with RAD17; reduced by DNA damage CC (PubMed:14871926). Interacts with nuclear receptors such as NR3C1/GCR CC and PPARG (activated by agonist); regulates their transactivation CC activities (By similarity). Interacts (via TPR repeats) with S100 CC proteins S100A1, S100A2, S100A6, S100B and S100P; the interactions are CC calcium-dependent, strongly activate PPP5C phosphatase activity and CC compete with HSP90AA1 and MAP3K5 interactions (PubMed:22399290). CC Interacts with SMAD2 and SMAD3 but not with SMAD1; decreases SMAD3 CC phosphorylation and protein levels (PubMed:22781750). Interacts (via CC TPR repeats) with CRY1 and CRY2; the interaction with CRY2 down- CC regulates the phosphatase activity on CSNK1E (PubMed:16790549). CC Interacts (via TPR repeats) with the active form of RAC1, GNA12 or CC GNA13; these interactions activate the phosphatase activity and CC translocate PPP5C to the cell membrane (PubMed:19948726). Interacts CC with FLCN (PubMed:27353360). {ECO:0000250|UniProtKB:Q60676, CC ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15383005, CC ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:16531226, CC ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:19948726, CC ECO:0000269|PubMed:22399290, ECO:0000269|PubMed:22781750, CC ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:9405394}. CC -!- INTERACTION: CC P53041; Q9UL18: AGO1; NbExp=2; IntAct=EBI-716663, EBI-527363; CC P53041; Q9H9G7: AGO3; NbExp=2; IntAct=EBI-716663, EBI-2267883; CC P53041; Q16543: CDC37; NbExp=5; IntAct=EBI-716663, EBI-295634; CC P53041; P50750: CDK9; NbExp=3; IntAct=EBI-716663, EBI-1383449; CC P53041; Q49AN0: CRY2; NbExp=3; IntAct=EBI-716663, EBI-2212355; CC P53041; P03372: ESR1; NbExp=4; IntAct=EBI-716663, EBI-78473; CC P53041; Q92731: ESR2; NbExp=4; IntAct=EBI-716663, EBI-78505; CC P53041; P07900: HSP90AA1; NbExp=12; IntAct=EBI-716663, EBI-296047; CC P53041; P08238: HSP90AB1; NbExp=8; IntAct=EBI-716663, EBI-352572; CC P53041; Q5SY16: NOL9; NbExp=2; IntAct=EBI-716663, EBI-1055462; CC P53041; P30153: PPP2R1A; NbExp=3; IntAct=EBI-716663, EBI-302388; CC P53041; P53041: PPP5C; NbExp=2; IntAct=EBI-716663, EBI-716663; CC P53041; P31948: STIP1; NbExp=4; IntAct=EBI-716663, EBI-1054052; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15383005}. Cytoplasm CC {ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:19948726}. Cell CC membrane {ECO:0000269|PubMed:19948726}. Note=Predominantly nuclear CC (PubMed:15383005). But also present in the cytoplasm (PubMed:15383005). CC Translocates from the cytoplasm to the plasma membrane in a RAC1- CC dependent manner (PubMed:19948726). {ECO:0000269|PubMed:15383005, CC ECO:0000269|PubMed:19948726}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:15546861}. CC -!- PTM: Activated by at least two different proteolytic cleavages CC producing a 56 kDa and a 50 kDa form. {ECO:0000269|PubMed:15383005, CC ECO:0000269|PubMed:23102700}. CC -!- SIMILARITY: Belongs to the PPP phosphatase family. PP-5 (PP-T) CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BT007275; AAP35939.1; -; mRNA. DR EMBL; X89416; CAA61595.1; -; mRNA. DR EMBL; U25174; AAB60384.1; -; mRNA. DR EMBL; AC007193; AAD22669.1; -; Genomic_DNA. DR EMBL; CH471126; EAW57416.1; -; Genomic_DNA. DR EMBL; BC001970; AAH01970.1; -; mRNA. DR EMBL; X92121; CAA63089.1; -; mRNA. DR CCDS; CCDS12684.1; -. DR PIR; S52570; S52570. DR RefSeq; NP_006238.1; NM_006247.3. DR PDB; 1A17; X-ray; 2.45 A; A=16-181. DR PDB; 1S95; X-ray; 1.60 A; A/B=169-499. DR PDB; 1WAO; X-ray; 2.90 A; 1/2/3/4=23-499. DR PDB; 2BUG; NMR; -; A=19-147. DR PDB; 3H60; X-ray; 2.00 A; A/B=176-490. DR PDB; 3H61; X-ray; 1.45 A; A/D=176-490. DR PDB; 3H62; X-ray; 1.40 A; B/C=176-490. DR PDB; 3H63; X-ray; 1.30 A; A/C=176-490. DR PDB; 3H64; X-ray; 1.90 A; A/D=176-490. DR PDB; 3H66; X-ray; 2.59 A; A/B=176-490. DR PDB; 3H67; X-ray; 1.65 A; A/D=176-490. DR PDB; 3H68; X-ray; 1.50 A; A/D=176-490. DR PDB; 3H69; X-ray; 2.10 A; A/D=176-490. DR PDB; 4ZVZ; X-ray; 2.00 A; A/B/C/D=169-499. DR PDB; 4ZX2; X-ray; 1.23 A; A=169-499. DR PDB; 5HPE; X-ray; 2.27 A; A=175-499. DR PDB; 5UI1; X-ray; 1.96 A; A/B/C/D=169-499. DR PDB; 5WG8; X-ray; 1.65 A; A=169-499. DR PDBsum; 1A17; -. DR PDBsum; 1S95; -. DR PDBsum; 1WAO; -. DR PDBsum; 2BUG; -. DR PDBsum; 3H60; -. DR PDBsum; 3H61; -. DR PDBsum; 3H62; -. DR PDBsum; 3H63; -. DR PDBsum; 3H64; -. DR PDBsum; 3H66; -. DR PDBsum; 3H67; -. DR PDBsum; 3H68; -. DR PDBsum; 3H69; -. DR PDBsum; 4ZVZ; -. DR PDBsum; 4ZX2; -. DR PDBsum; 5HPE; -. DR PDBsum; 5UI1; -. DR PDBsum; 5WG8; -. DR AlphaFoldDB; P53041; -. DR BMRB; P53041; -. DR SMR; P53041; -. DR BioGRID; 111528; 154. DR DIP; DIP-29043N; -. DR IntAct; P53041; 83. DR MINT; P53041; -. DR STRING; 9606.ENSP00000012443; -. DR BindingDB; P53041; -. DR ChEMBL; CHEMBL3425389; -. DR DrugBank; DB00171; ATP. DR DEPOD; PPP5C; -. DR GlyGen; P53041; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P53041; -. DR MetOSite; P53041; -. DR PhosphoSitePlus; P53041; -. DR SwissPalm; P53041; -. DR BioMuta; PPP5C; -. DR DMDM; 1709744; -. DR EPD; P53041; -. DR jPOST; P53041; -. DR MassIVE; P53041; -. DR MaxQB; P53041; -. DR PaxDb; P53041; -. DR PeptideAtlas; P53041; -. DR ProteomicsDB; 56568; -. DR Antibodypedia; 31446; 700 antibodies from 31 providers. DR DNASU; 5536; -. DR Ensembl; ENST00000012443.9; ENSP00000012443.4; ENSG00000011485.15. DR GeneID; 5536; -. DR KEGG; hsa:5536; -. DR MANE-Select; ENST00000012443.9; ENSP00000012443.4; NM_006247.4; NP_006238.1. DR UCSC; uc002pem.4; human. DR CTD; 5536; -. DR DisGeNET; 5536; -. DR GeneCards; PPP5C; -. DR HGNC; HGNC:9322; PPP5C. DR HPA; ENSG00000011485; Low tissue specificity. DR MIM; 600658; gene. DR neXtProt; NX_P53041; -. DR OpenTargets; ENSG00000011485; -. DR PharmGKB; PA33686; -. DR VEuPathDB; HostDB:ENSG00000011485; -. DR eggNOG; KOG0376; Eukaryota. DR GeneTree; ENSGT00940000158785; -. DR InParanoid; P53041; -. DR OMA; NHFFMSR; -. DR OrthoDB; 671536at2759; -. DR PhylomeDB; P53041; -. DR TreeFam; TF105562; -. DR BRENDA; 3.1.3.16; 2681. DR PathwayCommons; P53041; -. DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway. DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-HSA-8939211; ESR-mediated signaling. DR SABIO-RK; P53041; -. DR SignaLink; P53041; -. DR SIGNOR; P53041; -. DR BioGRID-ORCS; 5536; 22 hits in 1087 CRISPR screens. DR ChiTaRS; PPP5C; human. DR EvolutionaryTrace; P53041; -. DR GeneWiki; PPP5C; -. DR GenomeRNAi; 5536; -. DR Pharos; P53041; Tbio. DR PRO; PR:P53041; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P53041; protein. DR Bgee; ENSG00000011485; Expressed in cortical plate and 125 other tissues. DR ExpressionAtlas; P53041; baseline and differential. DR Genevisible; P53041; HS. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0043531; F:ADP binding; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IDA:MGI. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:CAFA. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC. DR GO; GO:0016791; F:phosphatase activity; IDA:ARUK-UCL. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISS:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; IEA:Ensembl. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0006351; P:DNA-templated transcription; TAS:ProtInc. DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc. DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IDA:UniProtKB. DR GO; GO:0035970; P:peptidyl-threonine dephosphorylation; TAS:ARUK-UCL. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; TAS:ProtInc. DR GO; GO:1904550; P:response to arachidonic acid; ISS:ARUK-UCL. DR GO; GO:0010288; P:response to lead ion; ISS:ARUK-UCL. DR GO; GO:0043278; P:response to morphine; IEA:Ensembl. DR CDD; cd07417; MPP_PP5_C; 1. DR DisProt; DP00365; -. DR Gene3D; 1.25.40.10; -; 1. DR Gene3D; 3.60.21.10; -; 1. DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH. DR InterPro; IPR029052; Metallo-depent_PP-like. DR InterPro; IPR041753; PP5_C. DR InterPro; IPR013235; PPP_dom. DR InterPro; IPR006186; Ser/Thr-sp_prot-phosphatase. DR InterPro; IPR011236; Ser/Thr_PPase_5. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR45668:SF5; SERINE/THREONINE-PROTEIN PHOSPHATASE 5; 1. DR Pfam; PF00149; Metallophos; 1. DR Pfam; PF08321; PPP5; 1. DR Pfam; PF00515; TPR_1; 1. DR PRINTS; PR00114; STPHPHTASE. DR SMART; SM00156; PP2Ac; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF56300; Metallo-dependent phosphatases; 1. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS00125; SER_THR_PHOSPHATASE; 1. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR AGR; HGNC:9322; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alzheimer disease; Amyloid; Amyloidosis; KW Cell membrane; Cytoplasm; DNA damage; DNA repair; Hydrolase; Lipid-binding; KW Magnesium; Manganese; Membrane; Metal-binding; Neurodegeneration; Nucleus; KW Protein phosphatase; Reference proteome; Repeat; TPR repeat. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..499 FT /note="Serine/threonine-protein phosphatase 5" FT /id="PRO_0000058894" FT REPEAT 28..61 FT /note="TPR 1" FT REPEAT 62..95 FT /note="TPR 2" FT REPEAT 96..129 FT /note="TPR 3" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 184..499 FT /note="Catalytic" FT REGION 495..499 FT /note="Required for autoinhibition" FT /evidence="ECO:0000250|UniProtKB:P53042" FT COMPBIAS 9..23 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 304 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000269|PubMed:15155720" FT BINDING 242 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 244 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 244 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15155720" FT BINDING 271 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 271 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 275 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15155720" FT BINDING 303..304 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15155720" FT BINDING 303 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 352 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 400 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15155720" FT BINDING 427 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15155720, FT ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, FT ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, FT ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, FT ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, FT ECO:0007744|PDB:3H64" FT BINDING 427 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:15155720" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MUTAGEN 32 FT /note="K->A: Loss of interaction with HSP90AA1. No effect FT on interaction with S100A1, S100A2 and S100A6." FT /evidence="ECO:0000269|PubMed:22399290" FT MUTAGEN 74 FT /note="R->A: Loss of interaction with HSP90AA1. No effect FT on interaction with S100A1, S100A2 and S100A6." FT /evidence="ECO:0000269|PubMed:22399290" FT MUTAGEN 83 FT /note="G->N: No effect on interaction with HSP90AA1." FT /evidence="ECO:0000269|PubMed:16531226" FT MUTAGEN 93 FT /note="K->E: Decreases interaction with RAC1 and FT translocation to the membrane in presence of active RAC1." FT /evidence="ECO:0000269|PubMed:19948726" FT MUTAGEN 97 FT /note="K->A: Loss of interaction with HSP90AA1. No effect FT on interaction with S100A1, S100A2 and S100A6. Loss of FT interaction with RAF1." FT /evidence="ECO:0000269|PubMed:16892053, FT ECO:0000269|PubMed:22399290" FT MUTAGEN 101 FT /note="R->A: Loss of interaction with HSP90AA1. No effect FT on interaction with S100A1, S100A2 and S100A6." FT /evidence="ECO:0000269|PubMed:22399290" FT MUTAGEN 304 FT /note="H->Q: Catalytically inactive; no effect on FT interaction with CRY2 but increases the stability of the FT interaction with CSNK1E. No effect on RAF1 FT phosphorylation." FT /evidence="ECO:0000269|PubMed:16790549, FT ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:19948726" FT CONFLICT 403 FT /note="S -> T (in Ref. 4; AAB60384)" FT /evidence="ECO:0000305" FT HELIX 22..40 FT /evidence="ECO:0007829|PDB:1A17" FT HELIX 44..57 FT /evidence="ECO:0007829|PDB:1A17" FT HELIX 62..74 FT /evidence="ECO:0007829|PDB:1A17" FT HELIX 78..91 FT /evidence="ECO:0007829|PDB:1A17" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:2BUG" FT HELIX 96..108 FT /evidence="ECO:0007829|PDB:1A17" FT HELIX 112..125 FT /evidence="ECO:0007829|PDB:1A17" FT HELIX 130..164 FT /evidence="ECO:0007829|PDB:1A17" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:5UI1" FT HELIX 188..199 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 206..221 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 247..257 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 262..264 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 266..270 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 273..276 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 279..292 FT /evidence="ECO:0007829|PDB:4ZX2" FT TURN 294..296 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 303..306 FT /evidence="ECO:0007829|PDB:3H66" FT HELIX 307..313 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 315..322 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 325..335 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 340..344 FT /evidence="ECO:0007829|PDB:4ZX2" FT TURN 345..347 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 348..350 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 357..359 FT /evidence="ECO:0007829|PDB:1S95" FT HELIX 363..367 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 372..374 FT /evidence="ECO:0007829|PDB:3H62" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 380..386 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 391..397 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 401..406 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 408..417 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 422..425 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 433..437 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 438..440 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 442..446 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 451..453 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 459..465 FT /evidence="ECO:0007829|PDB:4ZX2" FT STRAND 468..476 FT /evidence="ECO:0007829|PDB:4ZX2" FT TURN 486..489 FT /evidence="ECO:0007829|PDB:4ZX2" FT HELIX 492..495 FT /evidence="ECO:0007829|PDB:1S95" SQ SEQUENCE 499 AA; 56879 MW; DB3B2090D8658BB3 CRC64; MAMAEGERTE CAEPPRDEPP ADGALKRAEE LKTQANDYFK AKDYENAIKF YSQAIELNPS NAIYYGNRSL AYLRTECYGY ALGDATRAIE LDKKYIKGYY RRAASNMALG KFRAALRDYE TVVKVKPHDK DAKMKYQECN KIVKQKAFER AIAGDEHKRS VVDSLDIESM TIEDEYSGPK LEDGKVTISF MKELMQWYKD QKKLHRKCAY QILVQVKEVL SKLSTLVETT LKETEKITVC GDTHGQFYDL LNIFELNGLP SETNPYIFNG DFVDRGSFSV EVILTLFGFK LLYPDHFHLL RGNHETDNMN QIYGFEGEVK AKYTAQMYEL FSEVFEWLPL AQCINGKVLI MHGGLFSEDG VTLDDIRKIE RNRQPPDSGP MCDLLWSDPQ PQNGRSISKR GVSCQFGPDV TKAFLEENNL DYIIRSHEVK AEGYEVAHGG RCVTVFSAPN YCDQMGNKAS YIHLQGSDLR PQFHQFTAVP HPNVKPMAYA NTLLQLGMM // ID TSC2_HUMAN Reviewed; 1807 AA. AC P49815; A7E2E2; B4DIL8; B4DIQ7; B4DRN2; B7Z2B8; C9J378; O75275; Q4LE71; AC Q8TAZ1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 2. DT 14-DEC-2022, entry version 232. DE RecName: Full=Tuberin; DE AltName: Full=Tuberous sclerosis 2 protein; GN Name=TSC2; Synonyms=TSC4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-802. RC TISSUE=Brain; RX PubMed=8269512; DOI=10.1016/0092-8674(93)90618-z; RG The European chromosome 16 tuberous sclerosis consortium; RA Nellist M., Janssen B., Brook-Carter P.T., Hesseling-Janssen A.L.W., RA Maheshwar M.M., Verhoef S., van den Ouweland A.M.W., Lindhout D., RA Eussen B., Cordeiro I., Santos H., Halley D.J.J., Sampson J.R., Ward C.J., RA Peral B., Thomas S., Hughes J., Harris P.C., Roelfsema J.H., Saris J.J., RA Spruit L., Peters D.J.M., Dauwerse J.G., Breuning M.H.; RT "Identification and characterization of the tuberous sclerosis gene on RT chromosome 16."; RL Cell 75:1305-1315(1993). RN [2] RP SEQUENCE REVISION. RA Sampson J.R.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1; 2 RP AND 3). RX PubMed=7558029; DOI=10.1006/geno.1995.1079; RA Xu L., Sterner C., Maheshwar M.M., Wilson P.J., Nellist M., Short M.P., RA Haines J.L., Sampson J.R., Ramesh V.; RT "Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and RT mouse tissues."; RL Genomics 27:475-480(1995). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-94; PHE-320; PHE-619 RP AND ARG-802. RX PubMed=8789450; DOI=10.1093/hmg/5.1.131; RA Maheshwar M.M., Sandford R., Nellist M., Cheadle J.P., Sgotto B., RA Vaudin M., Sampson J.R.; RT "Comparative analysis and genomic structure of the tuberous sclerosis 2 RT (TSC2) gene in human and pufferfish."; RL Hum. Mol. Genet. 5:131-137(1996). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8). RC TISSUE=Brain; RX PubMed=24722188; DOI=10.1038/ncomms4650; RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A., RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.; RT "Protein interaction network of alternatively spliced isoforms from brain RT links genetic risk factors for autism."; RL Nat. Commun. 5:3650-3650(2014). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5; 6; 7 AND 8). RC TISSUE=Amygdala, and Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Aortic endothelium; RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-199. RC TISSUE=Placenta; RX PubMed=9831664; DOI=10.1016/s0378-1119(98)00485-5; RA Imai K., Sarker A.H., Akiyama K., Ikeda S., Yao M., Tsutsui K., RA Shohmori T., Seki S.; RT "Genomic structure and sequence of a human homologue (NTHL1/NTH1) of RT Escherichia coli endonuclease III with those of the adjacent parts of TSC2 RT and SLC9A3R2 genes."; RL Gene 222:287-295(1998). RN [12] RP INTERACTION WITH RABEP1. RX PubMed=9045618; DOI=10.1074/jbc.272.10.6097; RA Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S.; RT "The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase RT activating protein (GAP) in modulating endocytosis."; RL J. Biol. Chem. 272:6097-6100(1997). RN [13] RP INTERACTION WITH TSC1. RX PubMed=9580671; DOI=10.1093/hmg/7.6.1053; RA van Slegtenhorst M.A., Nellist M., Nagelkerken B., Cheadle J.P., RA Snell R.G., van den Ouweland A.M.W., Reuser A., Sampson J.R., RA Halley D.J.J., van der Sluijs P.; RT "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene RT products."; RL Hum. Mol. Genet. 7:1053-1057(1998). RN [14] RP INTERACTION WITH TSC1. RX PubMed=10585443; DOI=10.1074/jbc.274.50.35647; RA Nellist M., van Slegtenhorst M.A., Goedbloed M., van den Ouweland A.M.W., RA Halley D.J.J., van der Sluijs P.; RT "Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a RT cytosolic chaperone for hamartin."; RL J. Biol. Chem. 274:35647-35652(1999). RN [15] RP INVOLVEMENT IN LAM. RX PubMed=11829138; DOI=10.1007/s10038-002-8651-8; RA Sato T., Seyama K., Fujii H., Maruyama H., Setoguchi Y., Iwakami S., RA Fukuchi Y., Hino O.; RT "Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with RT pulmonary lymphangioleiomyomatosis."; RL J. Hum. Genet. 47:20-28(2002). RN [16] RP PHOSPHORYLATION AT SER-939 AND THR-1462. RX PubMed=12150915; DOI=10.1016/s1097-2765(02)00568-3; RA Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C.; RT "Identification of the tuberous sclerosis complex-2 tumor suppressor gene RT product tuberin as a target of the phosphoinositide 3-kinase/akt pathway."; RL Mol. Cell 10:151-162(2002). RN [17] RP FUNCTION, AND CHARACTERIZATION OF VARIANTS TSC2 MET-599 AND SER-1651. RX PubMed=12271141; DOI=10.1073/pnas.202476899; RA Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., RA Blenis J.; RT "Tuberous sclerosis complex-1 and -2 gene products function together to RT inhibit mammalian target of rapamycin (mTOR)-mediated downstream RT signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002). RN [18] RP PHOSPHORYLATION AT THR-1271 AND SER-1387, AND MUTAGENESIS OF THR-1271 AND RP SER-1387. RX PubMed=14651849; DOI=10.1016/s0092-8674(03)00929-2; RA Inoki K., Zhu T., Guan K.L.; RT "TSC2 mediates cellular energy response to control cell growth and RT survival."; RL Cell 115:577-590(2003). RN [19] RP FUNCTION, MUTAGENESIS OF 1637-LYS--ARG-1639; ARG-1745 AND RP 1749-ARG--ARG-1751, AND CHARACTERIZATION OF VARIANTS TSC2 LYS-1643; RP SER-1651; LYS-1681 AND PRO-1743. RX PubMed=15340059; DOI=10.1128/mcb.24.18.7965-7975.2004; RA Li Y., Inoki K., Guan K.-L.; RT "Biochemical and functional characterizations of small GTPase Rheb and TSC2 RT GAP activity."; RL Mol. Cell. Biol. 24:7965-7975(2004). RN [20] RP PHOSPHORYLATION AT SER-1798. RX PubMed=15342917; DOI=10.1073/pnas.0405659101; RA Roux P.P., Ballif B.A., Anjum R., Gygi S.P., Blenis J.; RT "Tumor-promoting phorbol esters and activated Ras inactivate the tuberous RT sclerosis tumor suppressor complex via p90 ribosomal S6 kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 101:13489-13494(2004). RN [21] RP PHOSPHORYLATION AT SER-1387; SER-1418 AND SER-1420, IDENTIFICATION BY MASS RP SPECTROMETRY, INTERACTION WITH HSPA1; HSPA8 AND TSC1, AND CHARACTERIZATION RP OF VARIANTS TSC2 TRP-611 AND GLN-611. RX PubMed=15963462; DOI=10.1016/j.bbrc.2005.05.175; RA Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., RA Luider T.M.; RT "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex."; RL Biochem. Biophys. Res. Commun. 333:818-826(2005). RN [22] RP INTERACTION WITH HERC1 AND TSC1. RX PubMed=16464865; DOI=10.1074/jbc.c500451200; RA Chong-Kopera H., Inoki K., Li Y., Zhu T., Garcia-Gonzalo F.R., Rosa J.L., RA Guan K.-L.; RT "TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the RT HERC1 ubiquitin ligase."; RL J. Biol. Chem. 281:8313-8316(2006). RN [23] RP INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL38. RX PubMed=18407068; DOI=10.1016/j.chom.2008.03.002; RA Moorman N.J., Cristea I.M., Terhune S.S., Rout M.P., Chait B.T., Shenk T.; RT "Human cytomegalovirus protein UL38 inhibits host cell stress responses by RT antagonizing the tuberous sclerosis protein complex."; RL Cell Host Microbe 3:253-262(2008). RN [24] RP UBIQUITINATION BY MYCBP2, PHOSPHORYLATION AT SER-540; SER-664; SER-939; RP THR-1462 AND SER-1798, AND CHARACTERIZATION OF VARIANT GLN-611. RX PubMed=18308511; DOI=10.1016/j.cellsig.2008.01.020; RA Han S., Witt R.M., Santos T.M., Polizzano C., Sabatini B.L., Ramesh V.; RT "Pam (Protein associated with Myc) functions as an E3 ubiquitin ligase and RT regulates TSC/mTOR signaling."; RL Cell. Signal. 20:1084-1091(2008). RN [25] RP UBIQUITINATION, AND INTERACTION WITH FBXW5. RX PubMed=18381890; DOI=10.1101/gad.1624008; RA Hu J., Zacharek S., He Y.J., Lee H., Shumway S., Duronio R.J., Xiong Y.; RT "WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by RT DDB1-CUL4-ROC1 ligase."; RL Genes Dev. 22:866-871(2008). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-927; SER-981; SER-1132; RP SER-1155; SER-1337; SER-1338; SER-1387; SER-1411; SER-1420 AND SER-1452, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [30] RP PHOSPHORYLATION BY DAPK1, AND INTERACTION WITH DAPK1. RX PubMed=18974095; DOI=10.1074/jbc.m805165200; RA Stevens C., Lin Y., Harrison B., Burch L., Ridgway R.A., Sansom O., RA Hupp T.; RT "Peptide combinatorial libraries identify TSC2 as a death-associated RT protein kinase (DAPK) death domain-binding protein and reveal a stimulatory RT role for DAPK in mTORC1 signaling."; RL J. Biol. Chem. 284:334-344(2009). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1155; THR-1462 AND SER-1798, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1346 AND SER-1798, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [33] RP INTERACTION WITH NAA10. RX PubMed=20145209; DOI=10.1126/scisignal.2000590; RA Kuo H.P., Lee D.F., Chen C.T., Liu M., Chou C.K., Lee H.J., Du Y., Xie X., RA Wei Y., Xia W., Weihua Z., Yang J.Y., Yen C.J., Huang T.H., Tan M., RA Xing G., Zhao Y., Lin C.H., Tsai S.F., Fidler I.J., Hung M.C.; RT "ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR RT signaling pathway."; RL Sci. Signal. 3:RA9-RA9(2010). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1132, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-981; SER-1346; SER-1364; RP SER-1411; SER-1420; SER-1452 AND SER-1799, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1411, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [38] RP INTERACTION WITH RRAGA. RX PubMed=25936802; DOI=10.1016/j.molcel.2015.03.033; RA Deng L., Jiang C., Chen L., Jin J., Wei J., Zhao L., Chen M., Pan W., RA Xu Y., Chu H., Wang X., Ge X., Li D., Liao L., Liu M., Li L., Wang P.; RT "The ubiquitination of RagA GTPase by RNF152 negatively regulates mTORC1 RT activation."; RL Mol. Cell 58:804-818(2015). RN [39] RP UBIQUITINATION. RX PubMed=27278822; DOI=10.1038/ncomms11803; RA Bento C.F., Ashkenazi A., Jimenez-Sanchez M., Rubinsztein D.C.; RT "The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate RT autophagy via a common pathway."; RL Nat. Commun. 7:11803-11803(2016). RN [40] RP FUNCTION, INTERACTION WITH TSC1, INVOLVEMENT IN FCORD2, VARIANT FCORD2 RP ILE-1547, AND CHARACTERIZATION OF VARIANT FCORD2 ILE-1547. RX PubMed=28215400; DOI=10.1016/j.ajhg.2017.01.030; RA Lim J.S., Gopalappa R., Kim S.H., Ramakrishna S., Lee M., Kim W.I., Kim J., RA Park S.M., Lee J., Oh J.H., Kim H.D., Park C.H., Lee J.S., Kim S., RA Kim D.S., Han J.M., Kang H.C., Kim H.H., Lee J.H.; RT "Somatic mutations in TSC1 and TSC2 cause focal cortical dysplasia."; RL Am. J. Hum. Genet. 100:454-472(2017). RN [41] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; CDC37; PPP5C; PTGES3; RP TSC1; AKT; CDK4; RAF1 AND NR3C1, AND INTERACTION WITH HSP90AA1 AND TSC1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [42] RP INTERACTION WITH RPAP3 AND URI1. RX PubMed=28561026; DOI=10.1038/ncomms15615; RA Cloutier P., Poitras C., Durand M., Hekmat O., Fiola-Masson E., RA Bouchard A., Faubert D., Chabot B., Coulombe B.; RT "R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 RT to regulate assembly of U5 small nuclear ribonucleoprotein."; RL Nat. Commun. 8:15615-15615(2017). RN [43] RP INTERACTION WITH WDR45B. RX PubMed=28561066; DOI=10.1038/ncomms15637; RA Bakula D., Mueller A.J., Zuleger T., Takacs Z., Franz-Wachtel M., RA Thost A.K., Brigger D., Tschan M.P., Frickey T., Robenek H., Macek B., RA Proikas-Cezanne T.; RT "WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling RT circuits in the control of autophagy."; RL Nat. Commun. 8:15637-15637(2017). RN [44] RP INTERACTION WITH YWHAG. RX PubMed=33473107; DOI=10.1038/s41467-020-20780-2; RA Wang W., Li J., Tan J., Wang M., Yang J., Zhang Z.M., Li C., RA Basnakian A.G., Tang H.W., Perrimon N., Zhou Q.; RT "Endonuclease G promotes autophagy by suppressing mTOR signaling and RT activating the DNA damage response."; RL Nat. Commun. 12:476-476(2021). RN [45] RP FUNCTION. RX PubMed=35772404; DOI=10.1016/j.molcel.2022.06.008; RA Ali E.S., Liponska A., O'Hara B.P., Amici D.R., Torno M.D., Gao P., RA Asara J.M., Yap M.F., Mendillo M.L., Ben-Sahra I.; RT "The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo RT nucleotide synthesis."; RL Mol. Cell 0:0-0(2022). RN [46] RP VARIANTS TSC2 ILE-449; TRP-611; LEU-1227; TRP-1240; PHE-1509 DEL AND RP GLU-1712. RX PubMed=8824881; DOI=10.1093/hmg/5.2.249; RA Wilson P.J., Ramesh V., Kristiansen A., Bove C., Jozwiak S., RA Kwiatkowski D.J., Short M.P., Haines J.L.; RT "Novel mutations detected in the TSC2 gene from both sporadic and familial RT TSC patients."; RL Hum. Mol. Genet. 5:249-256(1996). RN [47] RP VARIANTS TSC2 PHE-1509 DEL; MET-1594; LYS-1643; SER-1651; LEU-1675 AND RP LYS-1681. RX PubMed=9302281; DOI=10.1093/hmg/6.11.1991; RA Maheshwar M.M., Cheadle J.P., Jones A.C., Myring J., Fryer A.E., RA Harris P.C., Sampson J.R.; RT "The GAP-related domain of tuberin, the product of the TSC2 gene, is a RT target for missense mutations in tuberous sclerosis."; RL Hum. Mol. Genet. 6:1991-1996(1997). RN [48] RP VARIANTS TSC2. RX PubMed=9463313; DOI=10.1086/301705; RA Au K.-S., Rodriguez J.A., Finch J.L., Volcik K.A., Roach E.S., RA Delgado M.R., Rodriguez E. Jr., Northrup H.; RT "Germ-line mutational analysis of the TSC2 gene in 90 tuberous-sclerosis RT patients."; RL Am. J. Hum. Genet. 62:286-294(1998). RN [49] RP VARIANTS TSC2. RX PubMed=9829910; RX DOI=10.1002/(sici)1098-1004(1998)12:6<408::aid-humu7>3.0.co;2-p; RA Beauchamp R.L., Banwell A., McNamara P., Jacobsen M., Higgins E., RA Northrup H., Short M.P., Sims K., Ozelius L., Ramesh V.; RT "Exon scanning of the entire TSC2 gene for germline mutations in 40 RT unrelated patients with tuberous sclerosis."; RL Hum. Mutat. 12:408-416(1998). RN [50] RP VARIANTS TSC2. RX PubMed=10732801; DOI=10.1007/s100480050039; RA Gilbert J.R., Guy V., Kumar A., Wolpert C., Kandt R., Aylesworth A., RA Roses A.D., Pericak-Vance M.A.; RT "Mutation and polymorphism analysis in the tuberous sclerosis 2 (TSC2) RT gene."; RL Neurogenetics 1:267-272(1998). RN [51] RP VARIANTS TSC2, AND VARIANTS. RX PubMed=10205261; DOI=10.1086/302381; RA Jones A.C., Shyamsundar M.M., Thomas M.W., Maynard J., Idziaszczyk S.A., RA Tomkins S., Sampson J.R., Cheadle J.P.; RT "Comprehensive mutation analysis of TSC1 and TSC2- and phenotypic RT correlations in 150 families with tuberous sclerosis."; RL Am. J. Hum. Genet. 64:1305-1315(1999). RN [52] RP VARIANT TSC2 ARG-717. RX PubMed=10069705; RX DOI=10.1002/(sici)1096-8628(19990219)82:5<368::aid-ajmg2>3.0.co;2-i; RA Zhang H., Yamamoto T., Nanba E., Kitamura Y., Terada T., Akaboshi S., RA Yuasa I., Ohtani K., Nakamoto S., Takeshita K., Ohno K.; RT "Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis: lack RT of loss of heterozygosity in a lung cyst."; RL Am. J. Med. Genet. 82:368-370(1999). RN [53] RP VARIANTS TSC2, AND VARIANTS. RX PubMed=10735580; DOI=10.1046/j.1469-1809.1999.6350383.x; RA Choy Y.S., Dabora S.L., Hall F., Ramesh V., Niida Y., Franz D., RA Kasprzyk-Obara J., Reeve M.P., Kwiatkowski D.J.; RT "Superiority of denaturing high performance liquid chromatography over RT single-stranded conformation and conformation-sensitive gel electrophoresis RT for mutation detection in TSC2."; RL Ann. Hum. Genet. 63:383-391(1999). RN [54] RP VARIANTS TSC2, AND VARIANTS. RC TISSUE=Blood, and Lymphoblast; RX PubMed=10533067; RX DOI=10.1002/(sici)1098-1004(199911)14:5<412::aid-humu7>3.0.co;2-k; RA Niida Y., Lawrence-Smith N., Banwell A., Hammer E., Lewis J., RA Beauchamp R.L., Sims K., Ramesh V., Ozelius L.; RT "Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated RT patients with tuberous sclerosis."; RL Hum. Mutat. 14:412-422(1999). RN [55] RP VARIANTS TSC2 ARG-137; GLN-611; ASN-647; ARG-717; GLU-769; MET-963 AND RP LEU-1675, VARIANT PHE-320, AND POSSIBLE ASSOCIATION WITH TSC. RX PubMed=10570911; DOI=10.1007/s100380050185; RA Zhang H., Nanba E., Yamamoto T., Ninomiya H., Ohno K., Mizuguchi M., RA Takeshita K.; RT "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with RT tuberous sclerosis complex."; RL J. Hum. Genet. 44:391-396(1999). RN [56] RP VARIANTS TSC2 TRP-611; TRP-905; PRO-1744 AND 1746-HIS--ARG-1751 DEL, AND RP VARIANT PHE-320. RC TISSUE=Peripheral blood leukocyte; RX PubMed=10607950; RX DOI=10.1002/(sici)1096-8628(20000117)90:2<123::aid-ajmg7>3.0.co;2-l; RA Yamashita Y., Ono J., Okada S., Wataya-Kaneda M., Yoshikawa K., RA Nishizawa M., Hirayama Y., Kobayashi E., Seyama K., Hino O.; RT "Analysis of all exons of TSC1 and TSC2 genes for germline mutations in RT Japanese patients with tuberous sclerosis: report of 10 mutations."; RL Am. J. Med. Genet. 90:123-126(2000). RN [57] RP VARIANT LAM GLN-611. RX PubMed=10823953; DOI=10.1073/pnas.97.11.6085; RA Carsillo T., Astrinidis A., Henske E.P.; RT "Mutations in the tuberous sclerosis complex gene TSC2 are a cause of RT sporadic pulmonary lymphangioleiomyomatosis."; RL Proc. Natl. Acad. Sci. U.S.A. 97:6085-6090(2000). RN [58] RP VARIANTS TSC2 SER-1651; PHE-1653; LEU-1675 AND 1746-HIS--ARG-1751 DEL, AND RP VARIANTS THR-607; VAL-862; SER-1429 AND ARG-1450. RX PubMed=15024740; DOI=10.1002/humu.9225; RA Feng J.-H., Yamamoto T., Nanba E., Ninomiya H., Oka A., Ohno K.; RT "Novel TSC2 mutations and decreased expression of tuberin in cultured tumor RT cells with an insertion mutation."; RL Hum. Mutat. 23:397-397(2004). RN [59] RP VARIANTS TSC2 GLN-611; TRP-611 AND PRO-1027, AND VARIANTS GLN-367; RP ARG-1341; ASN-1636 AND LEU-1673. RX PubMed=15595939; DOI=10.1111/j.1600-0404.2004.00366.x; RA Ali M., Girimaji S.C., Markandaya M., Shukla A.K., Sacchidanand S., RA Kumar A.; RT "Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian RT patients with tuberous sclerosis complex."; RL Acta Neurol. Scand. 111:54-63(2005). CC -!- FUNCTION: In complex with TSC1, this tumor suppressor inhibits the CC nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 CC and EIF4EBP1 by negatively regulating mTORC1 signaling CC (PubMed:12271141, PubMed:28215400, PubMed:35772404). Acts as a GTPase- CC activating protein (GAP) for the small GTPase RHEB, a direct activator CC of the protein kinase activity of mTORC1 (PubMed:15340059). May also CC play a role in microtubule-mediated protein transport (By similarity). CC Also stimulates the intrinsic GTPase activity of the Ras-related CC proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, CC ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:15340059, CC ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:35772404}. CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Probably forms a complex CC composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, CC TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex CC does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Forms a complex containing HSP90AA1, TSC1 and TSC2; CC TSC1 is required to recruit TCS2 to the complex thereby stabilizing CC TSC2 (PubMed:29127155). Interacts with TSC1 and HERC1; the interaction CC with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 CC (PubMed:9580671, PubMed:10585443, PubMed:15963462, PubMed:16464865). CC May also interact with the adapter molecule RABEP1 (PubMed:9045618). CC The final complex may contain TSC2 and RABEP1 linked to RAB5 CC (PubMed:9045618). Interacts with HSPA1 and HSPA8 (PubMed:15963462). CC Interacts with DAPK1 (PubMed:18974095). Interacts with FBXW5 CC (PubMed:18381890). Interacts with NAA10 (via C-terminal domain) CC (PubMed:20145209). Interacts with RRAGA (polyubiquitinated) CC (PubMed:25936802). Interacts with WDR45B (PubMed:28561066). Interacts CC with RPAP3 and URI1 (PubMed:28561026). Interacts with YWHAG CC (PubMed:33473107). {ECO:0000269|PubMed:10585443, CC ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:16464865, CC ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:18974095, CC ECO:0000269|PubMed:20145209, ECO:0000269|PubMed:25936802, CC ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:28561026, CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:29127155, CC ECO:0000269|PubMed:33473107, ECO:0000269|PubMed:9045618, CC ECO:0000269|PubMed:9580671}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC protein UL38; this interaction inhibits cellular stress response CC mediated by mTORC1. {ECO:0000269|PubMed:18407068}. CC -!- INTERACTION: CC P49815; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-396587, EBI-79165; CC P49815; P62136: PPP1CA; NbExp=2; IntAct=EBI-396587, EBI-357253; CC P49815; O00141: SGK1; NbExp=4; IntAct=EBI-396587, EBI-1042854; CC P49815; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-396587, EBI-1802965; CC P49815; Q92574: TSC1; NbExp=11; IntAct=EBI-396587, EBI-1047085; CC P49815; P31946: YWHAB; NbExp=4; IntAct=EBI-396587, EBI-359815; CC P49815; P63104: YWHAZ; NbExp=7; IntAct=EBI-396587, EBI-347088; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. CC Note=At steady state found in association with membranes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; CC IsoId=P49815-1; Sequence=Displayed; CC Name=2; CC IsoId=P49815-2; Sequence=VSP_004470; CC Name=3; CC IsoId=P49815-3; Sequence=VSP_004471; CC Name=4; CC IsoId=P49815-4; Sequence=VSP_004472; CC Name=5; CC IsoId=P49815-5; Sequence=VSP_004471, VSP_004472; CC Name=6; CC IsoId=P49815-6; Sequence=VSP_038355, VSP_004470, VSP_004472; CC Name=7; CC IsoId=P49815-7; Sequence=VSP_054163, VSP_004470, VSP_004472; CC Name=8; Synonyms=H, I; CC IsoId=P49815-8; Sequence=VSP_055896, VSP_055897; CC -!- TISSUE SPECIFICITY: Liver, brain, heart, lymphocytes, fibroblasts, CC biliary epithelium, pancreas, skeletal muscle, kidney, lung and CC placenta. CC -!- PTM: Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect CC interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by CC PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by CC AMPK activates it and leads to negative regulation of the mTORC1 CC complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation CC inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by CC DAPK1. {ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:15342917, CC ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:18308511}. CC -!- PTM: Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase CC complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 CC independently of its phosphorylation status leading to subsequent CC degradation; association with TSC1 protects from ubiquitination. CC {ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:18381890, CC ECO:0000269|PubMed:27278822}. CC -!- DISEASE: Tuberous sclerosis 2 (TSC2) [MIM:613254]: An autosomal CC dominant multi-system disorder that affects especially the brain, CC kidneys, heart, and skin. It is characterized by hamartomas (benign CC overgrowths predominantly of a cell or tissue type that occurs normally CC in the organ) and hamartias (developmental abnormalities of tissue CC combination). Clinical manifestations include epilepsy, learning CC difficulties, behavioral problems, and skin lesions. Seizures can be CC intractable and premature death can occur from a variety of disease- CC associated causes. {ECO:0000269|PubMed:10069705, CC ECO:0000269|PubMed:10205261, ECO:0000269|PubMed:10533067, CC ECO:0000269|PubMed:10570911, ECO:0000269|PubMed:10607950, CC ECO:0000269|PubMed:10732801, ECO:0000269|PubMed:10735580, CC ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:15024740, CC ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15595939, CC ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:8824881, CC ECO:0000269|PubMed:9302281, ECO:0000269|PubMed:9463313, CC ECO:0000269|PubMed:9829910}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and CC often fatal lung disease characterized by a diffuse proliferation of CC abnormal smooth muscle cells in the lungs. It affects almost CC exclusively young women and can occur as an isolated disorder or in CC association with tuberous sclerosis complex. CC {ECO:0000269|PubMed:10823953, ECO:0000269|PubMed:11829138}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of CC focal cortical dysplasia, a malformation of cortical development that CC results in medically refractory epilepsy in the pediatric population CC and in adults. FCORD2 is a severe form, with onset usually in CC childhood, characterized by disrupted cortical lamination and specific CC cytological abnormalities. It is classified in 2 subtypes: type IIA CC characterized by dysmorphic neurons and lack of balloon cells; type IIB CC with dysmorphic neurons and balloon cells. CC {ECO:0000269|PubMed:28215400}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 8]: May be due to an intron retention. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE06082.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/TSC2ID184.html"; CC -!- WEB RESOURCE: Name=Tuberous sclerosis database Tuberous sclerosis 2 CC (TSC2); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/TSC2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X75621; CAA53287.1; -; mRNA. DR EMBL; L48546; AAB41564.1; -; Genomic_DNA. DR EMBL; L48517; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48518; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48519; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48521; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48522; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48523; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48524; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48525; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48526; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48527; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48528; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48529; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48530; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48531; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48532; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48533; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48534; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48535; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48536; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48537; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48538; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48539; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48540; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48541; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48542; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48543; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48544; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; L48545; AAB41564.1; JOINED; Genomic_DNA. DR EMBL; KJ535038; AHW56677.1; -; mRNA. DR EMBL; KJ535051; AHW56690.1; -; mRNA. DR EMBL; AK294548; BAH11804.1; -; mRNA. DR EMBL; AK295672; BAG58530.1; -; mRNA. DR EMBL; AK295728; BAG58569.1; -; mRNA. DR EMBL; AK299343; BAG61344.1; -; mRNA. DR EMBL; AB210000; BAE06082.1; ALT_INIT; mRNA. DR EMBL; AC005600; AAC34210.1; -; Genomic_DNA. DR EMBL; AC093513; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85556.1; -; Genomic_DNA. DR EMBL; BC150300; AAI50301.1; -; mRNA. DR EMBL; BC025364; AAH25364.1; -; mRNA. DR EMBL; BC046929; AAH46929.1; -; mRNA. DR EMBL; AB014460; BAA32694.1; -; Genomic_DNA. DR CCDS; CCDS10458.1; -. [P49815-1] DR CCDS; CCDS10459.1; -. [P49815-2] DR CCDS; CCDS45384.1; -. [P49815-4] DR CCDS; CCDS58408.1; -. [P49815-5] DR CCDS; CCDS81933.1; -. [P49815-6] DR CCDS; CCDS81934.1; -. [P49815-7] DR PIR; A49420; A49420. DR RefSeq; NP_000539.2; NM_000548.4. [P49815-1] DR RefSeq; NP_001070651.1; NM_001077183.2. [P49815-5] DR RefSeq; NP_001107854.1; NM_001114382.2. [P49815-4] DR RefSeq; NP_001305756.1; NM_001318827.1. [P49815-6] DR RefSeq; NP_001305758.1; NM_001318829.1. [P49815-7] DR RefSeq; NP_001305760.1; NM_001318831.1. DR RefSeq; NP_001305761.1; NM_001318832.1. DR RefSeq; XP_005255586.2; XM_005255529.4. DR RefSeq; XP_016879105.1; XM_017023616.1. DR PDB; 7DL2; EM; 4.40 A; A/B=50-1807. DR PDBsum; 7DL2; -. DR AlphaFoldDB; P49815; -. DR SMR; P49815; -. DR BioGRID; 113100; 177. DR ComplexPortal; CPX-6142; TSC1-TSC2 complex. DR CORUM; P49815; -. DR IntAct; P49815; 53. DR MINT; P49815; -. DR STRING; 9606.ENSP00000219476; -. DR iPTMnet; P49815; -. DR PhosphoSitePlus; P49815; -. DR SwissPalm; P49815; -. DR BioMuta; TSC2; -. DR DMDM; 269849475; -. DR EPD; P49815; -. DR jPOST; P49815; -. DR MassIVE; P49815; -. DR MaxQB; P49815; -. DR PaxDb; P49815; -. DR PeptideAtlas; P49815; -. DR ProteomicsDB; 4311; -. DR ProteomicsDB; 56142; -. [P49815-1] DR ProteomicsDB; 56143; -. [P49815-2] DR ProteomicsDB; 56144; -. [P49815-3] DR ProteomicsDB; 56145; -. [P49815-4] DR ProteomicsDB; 56146; -. [P49815-5] DR ProteomicsDB; 56147; -. [P49815-6] DR ABCD; P49815; 1 sequenced antibody. DR Antibodypedia; 3702; 2072 antibodies from 44 providers. DR DNASU; 7249; -. DR Ensembl; ENST00000219476.9; ENSP00000219476.3; ENSG00000103197.18. [P49815-1] DR Ensembl; ENST00000350773.9; ENSP00000344383.4; ENSG00000103197.18. [P49815-4] DR Ensembl; ENST00000382538.10; ENSP00000371978.6; ENSG00000103197.18. [P49815-7] DR Ensembl; ENST00000401874.7; ENSP00000384468.2; ENSG00000103197.18. [P49815-5] DR Ensembl; ENST00000439673.6; ENSP00000399232.2; ENSG00000103197.18. [P49815-6] DR Ensembl; ENST00000642936.1; ENSP00000494514.1; ENSG00000103197.18. [P49815-3] DR Ensembl; ENST00000644043.1; ENSP00000496262.1; ENSG00000103197.18. [P49815-2] DR GeneID; 7249; -. DR KEGG; hsa:7249; -. DR MANE-Select; ENST00000219476.9; ENSP00000219476.3; NM_000548.5; NP_000539.2. DR UCSC; uc002con.4; human. [P49815-1] DR CTD; 7249; -. DR DisGeNET; 7249; -. DR GeneCards; TSC2; -. DR GeneReviews; TSC2; -. DR HGNC; HGNC:12363; TSC2. DR HPA; ENSG00000103197; Low tissue specificity. DR MalaCards; TSC2; -. DR MIM; 191092; gene. DR MIM; 606690; phenotype. DR MIM; 607341; phenotype. DR MIM; 613254; phenotype. DR neXtProt; NX_P49815; -. DR OpenTargets; ENSG00000103197; -. DR Orphanet; 210159; Adult hepatocellular carcinoma. DR Orphanet; 88924; Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis. DR Orphanet; 269001; Isolated focal cortical dysplasia type IIa. DR Orphanet; 269008; Isolated focal cortical dysplasia type IIb. DR Orphanet; 538; Lymphangioleiomyomatosis. DR Orphanet; 805; Tuberous sclerosis complex. DR PharmGKB; PA37035; -. DR VEuPathDB; HostDB:ENSG00000103197; -. DR eggNOG; KOG3687; Eukaryota. DR GeneTree; ENSGT00950000183139; -. DR HOGENOM; CLU_001122_0_0_1; -. DR InParanoid; P49815; -. DR OMA; CDIMSAI; -. DR OrthoDB; 341431at2759; -. DR PhylomeDB; P49815; -. DR TreeFam; TF324484; -. DR PathwayCommons; P49815; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-165181; Inhibition of TSC complex formation by PKB. DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-8854214; TBC/RABGAPs. DR SABIO-RK; P49815; -. DR SignaLink; P49815; -. DR SIGNOR; P49815; -. DR BioGRID-ORCS; 7249; 142 hits in 1104 CRISPR screens. DR ChiTaRS; TSC2; human. DR GeneWiki; TSC2; -. DR GenomeRNAi; 7249; -. DR Pharos; P49815; Tbio. DR PRO; PR:P49815; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P49815; protein. DR Bgee; ENSG00000103197; Expressed in right hemisphere of cerebellum and 185 other tissues. DR ExpressionAtlas; P49815; baseline and differential. DR Genevisible; P49815; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO. DR GO; GO:0033596; C:TSC1-TSC2 complex; IDA:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB. DR GO; GO:0043276; P:anoikis; IGI:ParkinsonsUK-UCL. DR GO; GO:0006897; P:endocytosis; TAS:ProtInc. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IBA:GO_Central. DR GO; GO:1901525; P:negative regulation of mitophagy; NAS:ParkinsonsUK-UCL. DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB. DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB. DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; IDA:ComplexPortal. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB. DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:InterPro. DR GO; GO:0016239; P:positive regulation of macroautophagy; IGI:ParkinsonsUK-UCL. DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB. DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB. DR GO; GO:0008104; P:protein localization; ISS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central. DR GO; GO:0030100; P:regulation of endocytosis; ISS:UniProtKB. DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro. DR GO; GO:0016192; P:vesicle-mediated transport; TAS:ProtInc. DR Gene3D; 1.25.10.10; -; 1. DR Gene3D; 3.40.50.11210; -; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR035974; Rap/Ran-GAP_sf. DR InterPro; IPR000331; Rap/Ran_GAP_dom. DR InterPro; IPR003913; Tuberin. DR InterPro; IPR018515; Tuberin-type_domain. DR InterPro; IPR027107; Tuberin/Ral-act_asu. DR InterPro; IPR024584; Tuberin_N. DR PANTHER; PTHR10063; TUBERIN; 3. DR Pfam; PF11864; DUF3384; 1. DR Pfam; PF02145; Rap_GAP; 1. DR Pfam; PF03542; Tuberin; 1. DR PRINTS; PR01431; TUBERIN. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF111347; Rap/Ran-GAP; 1. DR PROSITE; PS50085; RAPGAP; 1. DR AGR; HGNC:12363; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Epilepsy; KW GTPase activation; Host-virus interaction; Membrane; Phosphoprotein; KW Reference proteome; Tumor suppressor; Ubl conjugation. FT CHAIN 1..1807 FT /note="Tuberin" FT /id="PRO_0000065654" FT DOMAIN 1531..1758 FT /note="Rap-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00165" FT REGION 1..400 FT /note="Required for interaction with TSC1" FT REGION 655..676 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 930..964 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1083..1132 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1150..1174 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1331..1352 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1364..1488 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1765..1793 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1083..1102 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1370..1394 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1469..1484 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18308511" FT MOD_RES 664 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18308511" FT MOD_RES 927 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 939 FT /note="Phosphoserine; by PKB/AKT1" FT /evidence="ECO:0000269|PubMed:12150915, FT ECO:0000269|PubMed:18308511" FT MOD_RES 981 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1155 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1271 FT /note="Phosphothreonine; by AMPK" FT /evidence="ECO:0000269|PubMed:14651849" FT MOD_RES 1337 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1338 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1346 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1364 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1387 FT /note="Phosphoserine; by AMPK" FT /evidence="ECO:0000269|PubMed:14651849, FT ECO:0000269|PubMed:15963462, ECO:0007744|PubMed:18669648" FT MOD_RES 1411 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1418 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15963462" FT MOD_RES 1420 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15963462, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 1452 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1462 FT /note="Phosphothreonine; by PKB/AKT1" FT /evidence="ECO:0000269|PubMed:12150915, FT ECO:0000269|PubMed:18308511, ECO:0007744|PubMed:19690332" FT MOD_RES 1764 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q61037" FT MOD_RES 1798 FT /note="Phosphoserine; by RPS6KA1" FT /evidence="ECO:0000269|PubMed:15342917, FT ECO:0000269|PubMed:18308511, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 1799 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..49 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054163" FT VAR_SEQ 76..112 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038355" FT VAR_SEQ 113..239 FT /note="GERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFV FT LQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLD FT AVVCYNCLPAESLPLF -> VRPRATLGWVTSGCPLTVLSLLGRVWTPASVSCWAQGLG FT ADGLWSWMACGVSWCHEVCVTVGTASSPVNRWSLHLPLMGCSGDHMRQFSQSAEIVPGS FT WCGATVLFCPCTLSGPLPCSLHSICAGLG (in isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:24722188" FT /id="VSP_055896" FT VAR_SEQ 240..1807 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:24722188" FT /id="VSP_055897" FT VAR_SEQ 946..989 FT /note="Missing (in isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7" FT /id="VSP_004471" FT VAR_SEQ 946..988 FT /note="Missing (in isoform 2, isoform 6 and isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_004470" FT VAR_SEQ 1272..1294 FT /note="Missing (in isoform 4, isoform 5, isoform 6 and FT isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7" FT /id="VSP_004472" FT VARIANT 94 FT /note="P -> T (in dbSNP:rs1051616)" FT /evidence="ECO:0000269|PubMed:8789450" FT /id="VAR_008019" FT VARIANT 137 FT /note="H -> R (in TSC2; unknown pathological significance; FT dbSNP:rs45517107)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009415" FT VARIANT 160 FT /note="L -> V (in dbSNP:rs45517109)" FT /id="VAR_009416" FT VARIANT 227 FT /note="C -> Y (in TSC2; dbSNP:rs45517122)" FT /id="VAR_008020" FT VARIANT 258 FT /note="K -> N (in TSC2; dbSNP:rs137854875)" FT /id="VAR_009417" FT VARIANT 261 FT /note="R -> P (in TSC2; dbSNP:rs45502703)" FT /id="VAR_009418" FT VARIANT 261 FT /note="R -> W (in dbSNP:rs45517130)" FT /id="VAR_009419" FT VARIANT 286 FT /note="M -> T (in dbSNP:rs45517136)" FT /id="VAR_009420" FT VARIANT 286 FT /note="M -> V (in dbSNP:rs1800748)" FT /id="VAR_009421" FT VARIANT 292 FT /note="L -> P (in TSC2; dbSNP:rs45517138)" FT /id="VAR_005646" FT VARIANT 294 FT /note="G -> E (in TSC2; dbSNP:rs45487497)" FT /id="VAR_009422" FT VARIANT 304 FT /note="W -> WGMALW (in TSC2)" FT /id="VAR_009423" FT VARIANT 309 FT /note="L -> Q (in dbSNP:rs137853986)" FT /id="VAR_009424" FT VARIANT 320 FT /note="L -> F (could be associated with TSC2; FT dbSNP:rs1131825)" FT /evidence="ECO:0000269|PubMed:10570911, FT ECO:0000269|PubMed:10607950, ECO:0000269|PubMed:8789450" FT /id="VAR_009425" FT VARIANT 331 FT /note="N -> K (in TSC2; dbSNP:rs45517153)" FT /id="VAR_008021" FT VARIANT 361 FT /note="L -> P (in TSC2; dbSNP:rs45517147)" FT /id="VAR_009426" FT VARIANT 365 FT /note="Missing (in TSC2; dbSNP:rs137854367)" FT /id="VAR_009427" FT VARIANT 367 FT /note="R -> Q (in dbSNP:rs1800725)" FT /evidence="ECO:0000269|PubMed:15595939" FT /id="VAR_009428" FT VARIANT 378 FT /note="P -> L (in dbSNP:rs45517154)" FT /id="VAR_009429" FT VARIANT 407 FT /note="Y -> D (in TSC2; dbSNP:rs45517156)" FT /id="VAR_005647" FT VARIANT 440 FT /note="G -> S (in dbSNP:rs45484298)" FT /id="VAR_009430" FT VARIANT 449 FT /note="M -> I (in TSC2; dbSNP:rs45443091)" FT /evidence="ECO:0000269|PubMed:8824881" FT /id="VAR_005648" FT VARIANT 463 FT /note="I -> V (in dbSNP:rs45517171)" FT /id="VAR_009431" FT VARIANT 486 FT /note="N -> I (in TSC2; dbSNP:rs45486599)" FT /id="VAR_008022" FT VARIANT 490 FT /note="I -> V (in dbSNP:rs45517175)" FT /id="VAR_008023" FT VARIANT 525 FT /note="N -> S (in TSC2; dbSNP:rs45457694)" FT /id="VAR_009432" FT VARIANT 536 FT /note="A -> V (in dbSNP:rs45517187)" FT /id="VAR_008024" FT VARIANT 583 FT /note="A -> T (in dbSNP:rs1800729)" FT /id="VAR_009433" FT VARIANT 593 FT /note="H -> R (in dbSNP:rs45517198)" FT /id="VAR_009434" FT VARIANT 599 FT /note="K -> M (in TSC2; impairs repression of EIF4EBP1 FT phosphorylation; dbSNP:rs45517202)" FT /evidence="ECO:0000269|PubMed:12271141" FT /id="VAR_009435" FT VARIANT 607 FT /note="A -> T (in dbSNP:rs45517203)" FT /evidence="ECO:0000269|PubMed:15024740" FT /id="VAR_005649" FT VARIANT 611 FT /note="R -> Q (in TSC2 and LAM; impairs phosphorylation at FT S-1387, S-1418 and S-1420; enhances ubiquitination by FT MYCBP2; dbSNP:rs28934872)" FT /evidence="ECO:0000269|PubMed:10570911, FT ECO:0000269|PubMed:10823953, ECO:0000269|PubMed:15595939, FT ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:18308511" FT /id="VAR_005650" FT VARIANT 611 FT /note="R -> W (in TSC2; impairs phosphorylation at S-1387, FT S-1418 and S-1420; dbSNP:rs45469298)" FT /evidence="ECO:0000269|PubMed:10607950, FT ECO:0000269|PubMed:15595939, ECO:0000269|PubMed:15963462, FT ECO:0000269|PubMed:8824881" FT /id="VAR_005651" FT VARIANT 614 FT /note="A -> D (in TSC2; dbSNP:rs45454398)" FT /id="VAR_009436" FT VARIANT 615 FT /note="F -> S (in dbSNP:rs45481105)" FT /id="VAR_008025" FT VARIANT 619 FT /note="L -> F (in dbSNP:rs1131826)" FT /evidence="ECO:0000269|PubMed:8789450" FT /id="VAR_060584" FT VARIANT 647 FT /note="D -> N (in TSC2; unknown pathological significance; FT dbSNP:rs45509392)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009437" FT VARIANT 694 FT /note="Missing (in TSC2)" FT /id="VAR_009438" FT VARIANT 696 FT /note="C -> Y (in TSC2; dbSNP:rs45486196)" FT /id="VAR_009439" FT VARIANT 717 FT /note="L -> R (in TSC2; dbSNP:rs45517214)" FT /evidence="ECO:0000269|PubMed:10069705, FT ECO:0000269|PubMed:10570911" FT /id="VAR_009440" FT VARIANT 769 FT /note="V -> E (in TSC2; unknown pathological significance; FT dbSNP:rs45499191)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009441" FT VARIANT 802 FT /note="S -> R (in dbSNP:rs1051621)" FT /evidence="ECO:0000269|PubMed:8269512, FT ECO:0000269|PubMed:8789450" FT /id="VAR_060585" FT VARIANT 816 FT /note="P -> L (in TSC2; dbSNP:rs45517236)" FT /id="VAR_008026" FT VARIANT 826 FT /note="L -> M (in TSC2; dbSNP:rs45517238)" FT /id="VAR_005652" FT VARIANT 862 FT /note="A -> V (in dbSNP:rs45517249)" FT /evidence="ECO:0000269|PubMed:15024740" FT /id="VAR_018600" FT VARIANT 895 FT /note="M -> V (in TSC2; dbSNP:rs45470695)" FT /id="VAR_009442" FT VARIANT 905 FT /note="R -> Q (in TSC2; dbSNP:rs45517259)" FT /id="VAR_005653" FT VARIANT 905 FT /note="R -> W (in TSC2; dbSNP:rs45517258)" FT /evidence="ECO:0000269|PubMed:10607950" FT /id="VAR_005654" FT VARIANT 963 FT /note="V -> M (in TSC2; unknown pathological significance; FT dbSNP:rs45517275)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009443" FT VARIANT 1027 FT /note="L -> P (in TSC2; dbSNP:rs45438192)" FT /evidence="ECO:0000269|PubMed:15595939" FT /id="VAR_022919" FT VARIANT 1084 FT /note="D -> E (in TSC2; dbSNP:rs45517286)" FT /id="VAR_005655" FT VARIANT 1141 FT /note="A -> V (in dbSNP:rs34870424)" FT /id="VAR_057014" FT VARIANT 1144 FT /note="V -> M (in TSC2; dbSNP:rs45517294)" FT /id="VAR_008027" FT VARIANT 1200 FT /note="R -> W (in TSC2; dbSNP:rs45438205)" FT /id="VAR_005656" FT VARIANT 1227 FT /note="P -> L (in TSC2)" FT /evidence="ECO:0000269|PubMed:8824881" FT /id="VAR_005657" FT VARIANT 1240 FT /note="R -> W (in TSC2)" FT /evidence="ECO:0000269|PubMed:8824881" FT /id="VAR_005658" FT VARIANT 1282 FT /note="S -> G (in dbSNP:rs45446700)" FT /id="VAR_009444" FT VARIANT 1295 FT /note="D -> V (in TSC2)" FT /id="VAR_005659" FT VARIANT 1315 FT /note="P -> S (in TSC2; dbSNP:rs397514916)" FT /id="VAR_008028" FT VARIANT 1329 FT /note="R -> H (in dbSNP:rs45517323)" FT /id="VAR_008029" FT VARIANT 1341 FT /note="S -> R (in dbSNP:rs45462593)" FT /evidence="ECO:0000269|PubMed:15595939" FT /id="VAR_022920" FT VARIANT 1429 FT /note="A -> S (in dbSNP:rs45474795)" FT /evidence="ECO:0000269|PubMed:15024740" FT /id="VAR_018601" FT VARIANT 1450 FT /note="P -> R (in dbSNP:rs45517338)" FT /evidence="ECO:0000269|PubMed:15024740" FT /id="VAR_018602" FT VARIANT 1497 FT /note="P -> R (in TSC2; dbSNP:rs45497997)" FT /id="VAR_009445" FT VARIANT 1498 FT /note="S -> N (in TSC2; dbSNP:rs137854879)" FT /id="VAR_009446" FT VARIANT 1509 FT /note="Missing (in TSC2; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:8824881, FT ECO:0000269|PubMed:9302281" FT /id="VAR_005660" FT VARIANT 1547 FT /note="V -> I (in FCORD2; somatic mutation; decreased FT function in negative regulation of TOR signaling; does not FT affect interaction with TSC1; dbSNP:rs745895675)" FT /evidence="ECO:0000269|PubMed:28215400" FT /id="VAR_078847" FT VARIANT 1549 FT /note="Y -> C (in TSC2; dbSNP:rs45517355)" FT /id="VAR_005661" FT VARIANT 1594 FT /note="L -> M (in TSC2; unknown pathological significance; FT dbSNP:rs45511204)" FT /evidence="ECO:0000269|PubMed:9302281" FT /id="VAR_009447" FT VARIANT 1614 FT /note="Missing (in TSC2)" FT /id="VAR_005662" FT VARIANT 1620 FT /note="H -> Y (in TSC2; dbSNP:rs45446901)" FT /id="VAR_009448" FT VARIANT 1636 FT /note="D -> N (in dbSNP:rs45482398)" FT /evidence="ECO:0000269|PubMed:15595939" FT /id="VAR_022921" FT VARIANT 1643 FT /note="N -> I (in TSC2; dbSNP:rs45517380)" FT /id="VAR_005663" FT VARIANT 1643 FT /note="N -> K (in TSC2; Abolishes GAP activity; FT dbSNP:rs45517381)" FT /evidence="ECO:0000269|PubMed:15340059, FT ECO:0000269|PubMed:9302281" FT /id="VAR_009449" FT VARIANT 1650 FT /note="Y -> C (in TSC2; dbSNP:rs45501091)" FT /id="VAR_005664" FT VARIANT 1651 FT /note="N -> S (in TSC2; greatly reduces the ability to FT enhance the RHEBGTPase activity; dbSNP:rs45517382)" FT /evidence="ECO:0000269|PubMed:12271141, FT ECO:0000269|PubMed:15024740, ECO:0000269|PubMed:15340059, FT ECO:0000269|PubMed:9302281" FT /id="VAR_009450" FT VARIANT 1653 FT /note="S -> F (in TSC2; dbSNP:rs45517383)" FT /evidence="ECO:0000269|PubMed:15024740" FT /id="VAR_018603" FT VARIANT 1673 FT /note="V -> L (in dbSNP:rs45490993)" FT /evidence="ECO:0000269|PubMed:15595939" FT /id="VAR_022922" FT VARIANT 1675 FT /note="P -> L (in TSC2; dbSNP:rs45483392)" FT /evidence="ECO:0000269|PubMed:10570911, FT ECO:0000269|PubMed:15024740, ECO:0000269|PubMed:9302281" FT /id="VAR_009451" FT VARIANT 1681 FT /note="N -> K (in TSC2; Abolishes GAP activity; FT dbSNP:rs45476793)" FT /evidence="ECO:0000269|PubMed:15340059, FT ECO:0000269|PubMed:9302281" FT /id="VAR_009452" FT VARIANT 1690 FT /note="D -> Y (in TSC2; dbSNP:rs137854882)" FT /id="VAR_005665" FT VARIANT 1704 FT /note="S -> T (in TSC2; dbSNP:rs45474691)" FT /id="VAR_009453" FT VARIANT 1709 FT /note="P -> L (in TSC2; dbSNP:rs45517393)" FT /id="VAR_008030" FT VARIANT 1712 FT /note="A -> E (in TSC2)" FT /evidence="ECO:0000269|PubMed:8824881" FT /id="VAR_005666" FT VARIANT 1743 FT /note="R -> P (in TSC2; Abolishes GAP activity; FT dbSNP:rs45507199)" FT /evidence="ECO:0000269|PubMed:15340059" FT /id="VAR_009454" FT VARIANT 1743 FT /note="R -> Q (in TSC2; dbSNP:rs45507199)" FT /id="VAR_008031" FT VARIANT 1744 FT /note="L -> P (in TSC2; dbSNP:rs45517413)" FT /evidence="ECO:0000269|PubMed:10607950" FT /id="VAR_009455" FT VARIANT 1746..1751 FT /note="Missing (in TSC2)" FT /evidence="ECO:0000269|PubMed:10607950, FT ECO:0000269|PubMed:15024740" FT /id="VAR_009456" FT VARIANT 1750 FT /note="L -> F (in TSC2; dbSNP:rs45459299)" FT /id="VAR_005667" FT VARIANT 1773 FT /note="H -> P (in TSC2; dbSNP:rs45517418)" FT /id="VAR_008032" FT VARIANT 1774 FT /note="S -> T (in dbSNP:rs9209)" FT /id="VAR_057015" FT VARIANT 1783 FT /note="E -> Q (in TSC2; dbSNP:rs777166275)" FT /id="VAR_008033" FT VARIANT 1787 FT /note="G -> S (in dbSNP:rs45517419)" FT /id="VAR_009457" FT VARIANT 1791 FT /note="G -> S (in dbSNP:rs45517421)" FT /id="VAR_009458" FT MUTAGEN 939 FT /note="S->A: Inhibits insulin-stimulated phosphorylation FT and activation of S6K1; when associated with A-1462." FT MUTAGEN 1271 FT /note="T->A: Abolishes AMPK-mediated phosphorylation; when FT associated with A-1387." FT /evidence="ECO:0000269|PubMed:14651849" FT MUTAGEN 1387 FT /note="S->A: Abolishes AMPK-mediated phosphorylation; when FT associated with A-1271." FT /evidence="ECO:0000269|PubMed:14651849" FT MUTAGEN 1462 FT /note="T->A: Inhibits insulin-stimulated phosphorylation FT and activation of S6K1; when associated with A-939." FT MUTAGEN 1637..1639 FT /note="KKR->QQQ: Abolishes GAP activity." FT /evidence="ECO:0000269|PubMed:15340059" FT MUTAGEN 1745 FT /note="R->Q: Abolishes GAP activity." FT /evidence="ECO:0000269|PubMed:15340059" FT MUTAGEN 1749..1751 FT /note="RLR->QLQ: No effect." FT /evidence="ECO:0000269|PubMed:15340059" FT CONFLICT 187 FT /note="N -> S (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="A -> V (in Ref. 10; AAI50301)" FT /evidence="ECO:0000305" FT CONFLICT 335 FT /note="S -> P (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" FT CONFLICT 392 FT /note="E -> V (in Ref. 7; BAG58569)" FT /evidence="ECO:0000305" FT CONFLICT 422 FT /note="S -> P (in Ref. 7; BAG58569)" FT /evidence="ECO:0000305" FT CONFLICT 660 FT /note="S -> N (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" FT CONFLICT 704 FT /note="K -> E (in Ref. 10; AAI50301)" FT /evidence="ECO:0000305" FT CONFLICT 706 FT /note="L -> P (in Ref. 7; BAG58569)" FT /evidence="ECO:0000305" FT CONFLICT 1015 FT /note="L -> M (in Ref. 10; AAI50301)" FT /evidence="ECO:0000305" FT CONFLICT 1239 FT /note="E -> V (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" FT CONFLICT 1398 FT /note="L -> V (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" FT CONFLICT 1672 FT /note="I -> M (in Ref. 10; AAI50301)" FT /evidence="ECO:0000305" FT CONFLICT 1807 FT /note="V -> A (in Ref. 7; BAG61344)" FT /evidence="ECO:0000305" SQ SEQUENCE 1807 AA; 200608 MW; 7B915C46970D7D31 CRC64; MAKPTSKDSG LKEKFKILLG LGTPRPNPRS AEGKQTEFII TAEILRELSM ECGLNNRIRM IGQICEVAKT KKFEEHAVEA LWKAVADLLQ PERPLEARHA VLALLKAIVQ GQGERLGVLR ALFFKVIKDY PSNEDLHERL EVFKALTDNG RHITYLEEEL ADFVLQWMDV GLSSEFLLVL VNLVKFNSCY LDEYIARMVQ MICLLCVRTA SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI VTLCRTINVK ELCEPCWKLM RNLLGTHLGH SAIYNMCHLM EDRAYMEDAP LLRGAVFFVG MALWGAHRLY SLRNSPTSVL PSFYQAMACP NEVVSYEIVL SITRLIKKYR KELQVVAWDI LLNIIERLLQ QLQTLDSPEL RTIVHDLLTT VEELCDQNEF HGSQERYFEL VERCADQRPE SSLLNLISYR AQSIHPAKDG WIQNLQALME RFFRSESRGA VRIKVLDVLS FVLLINRQFY EEELINSVVI SQLSHIPEDK DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS PPPELEERDV AAYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYEML VSHIQLHYKH SYTLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCVCDYME PERGSEKKTS GPLSPPTGPP GPAPAGPAVR LGSVPYSLLF RVLLQCLKQE SDWKVLKLVL GRLPESLRYK VLIFTSPCSV DQLCSALCSM LSGPKTLERL RGAPEGFSRT DLHLAVVPVL TALISYHNYL DKTKQREMVY CLEQGLIHRC ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA VPLLEFLSTL ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC RLPFRKDFVP FITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA RPPKQGLNNS PPVKEFKESS AAEAFRCRSI SVSEHVVRSR IQTSLTSASL GSADENSVAQ ADDSLKNLHL ELTETCLDMM ARYVFSNFTA VPKRSPVGEF LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL LGLDSGELQS GPESSSSPGV HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG ALDVPASQFL GSATSPGPRT APAAKPEKAS AGTRVPVQEK TNLAAYVPLL TQGWAEILVR RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHRDTALY KSLSVPAAST AKPPPLPRSN TVASFSSLYQ SSCQGQLHRS VSWADSAVVM EEGSPGEVPV LVEPPGLEDV EAALGMDRRT DAYSRSSSVS SQEEKSLHAE ELVGRGIPIE RVVSSEGGRP SVDLSFQPSQ PLSKSSSSPE LQTLQDILGD PGDKADVGRL SPEVKARSQS GTLDGESAAW SASGEDSRGQ PEGPLPSSSP RSPSGLRPRG YTISDSAPSR RGKRVERDAL KSRATASNAE KVPGINPSFV FLQLYHSPFF GDESNKPILL PNESQSFERS VQLLDQIPSY DTHKIAVLYV GEGQSNSELA ILSNEHGSYR YTEFLTGLGR LIELKDCQPD KVYLGGLDVC GEDGQFTYCW HDDIMQAVFH IATLMPTKDV DKHRCDKKRH LGNDFVSIVY NDSGEDFKLG TIKGQFNFVH VIVTPLDYEC NLVSLQCRKD MEGLVDTSVA KIVSDRNLPF VARQMALHAN MASQVHHSRS NPTDIYPSKW IARLRHIKRL RQRICEEAAY SNPSLPLVHP PSHSKAPAQT PAEPTPGYEV GQRKRLISSV EDFTEFV // ID CDC37_HUMAN Reviewed; 378 AA. AC Q16543; Q53YA2; DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 14-DEC-2022, entry version 202. DE RecName: Full=Hsp90 co-chaperone Cdc37; DE AltName: Full=Hsp90 chaperone protein kinase-targeting subunit; DE AltName: Full=p50Cdc37; DE Contains: DE RecName: Full=Hsp90 co-chaperone Cdc37, N-terminally processed; GN Name=CDC37; Synonyms=CDC37A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=8666233; DOI=10.1101/gad.10.12.1491; RA Stepanova L., Leng X., Parker S.B., Harper J.W.; RT "Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that RT binds and stabilizes Cdk4."; RL Genes Dev. 10:1491-1502(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8703009; DOI=10.1074/jbc.271.36.22030; RA Dai K., Kobayashi R., Beach D.; RT "Physical interaction of mammalian CDC37 with CDK4."; RL J. Biol. Chem. 271:22030-22034(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-360. RG NIEHS SNPs program; RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH CDK4 AND CDK6. RX PubMed=9150368; DOI=10.1038/sj.onc.1201036; RA Lamphere L., Fiore F., Xu X., Brizuela L., Keezer S., Sardet C., RA Draetta G.F., Gyuris J.; RT "Interaction between Cdc37 and Cdk4 in human cells."; RL Oncogene 14:1999-2004(1997). RN [8] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CDK6 AND HSP90AB1. RX PubMed=9482106; DOI=10.1038/sj.onc.1201570; RA Mahony D., Parry D.A., Lees E.; RT "Active cdk6 complexes are predominantly nuclear and represent only a RT minority of the cdk6 in T cells."; RL Oncogene 16:603-611(1998). RN [9] RP INTERACTION WITH KSR1. RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523; RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.; RT "Kinase suppressor of Ras forms a multiprotein signaling complex and RT modulates MEK localization."; RL Mol. Cell. Biol. 19:5523-5534(1999). RN [10] RP CHARACTERIZATION. RX PubMed=10858314; DOI=10.1021/bi000315r; RA Hartson S.D., Irwin A.D., Shao J., Scroggins B.T., Volk L., Huang W., RA Matts R.L.; RT "p50(cdc37) is a nonexclusive Hsp90 cohort which participates intimately in RT Hsp90-mediated folding of immature kinase molecules."; RL Biochemistry 39:7631-7644(2000). RN [11] RP INTERACTION WITH EIF2AK1. RX PubMed=11036079; DOI=10.1074/jbc.m007583200; RA Shao J., Grammatikakis N., Scroggins B.T., Uma S., Huang W., Chen J.-J., RA Hartson S.D., Matts R.L.; RT "Hsp90 regulates p50(cdc37) function during the biogenesis of the active RT conformation of the heme-regulated eIF2 alpha kinase."; RL J. Biol. Chem. 276:206-214(2001). RN [12] RP INTERACTION WITH AR. RX PubMed=11085988; DOI=10.1074/jbc.m007385200; RA Rao J., Lee P., Benzeno S., Cardozo C., Albertus J., Robins D.M., RA Caplan A.J.; RT "Functional interaction of human Cdc37 with the androgen receptor but not RT with the glucocorticoid receptor."; RL J. Biol. Chem. 276:5814-5820(2001). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [14] RP SUMOYLATION. RX PubMed=17709345; DOI=10.1093/nar/gkm617; RA Jakobs A., Himstedt F., Funk M., Korn B., Gaestel M., Niedenthal R.; RT "Ubc9 fusion-directed SUMOylation identifies constitutive and inducible RT SUMOylation."; RL Nucleic Acids Res. 35:E109-E109(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND VAL-2, CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-78 AND LYS-154, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT VAL-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-13, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT VAL-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-13, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [22] RP FUNCTION, AND INTERACTION WITH HSP90AA1. RX PubMed=23569206; DOI=10.1074/jbc.m112.439257; RA Eckl J.M., Rutz D.A., Haslbeck V., Zierer B.K., Reinstein J., Richter K.; RT "Cdc37 (cell division cycle 37) restricts Hsp90 (heat shock protein 90) RT motility by interaction with N-terminal and middle domain binding sites."; RL J. Biol. Chem. 288:16032-16042(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-118 AND SER-120, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [25] RP INTERACTION WITH HSP90AA1; FLCN; FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [26] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; PPP5C; PTGES3; TSC1; RP TSC2; AKT; CDK4; RAF1 AND NR3C1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). CC -!- FUNCTION: Co-chaperone that binds to numerous kinases and promotes CC their interaction with the Hsp90 complex, resulting in stabilization CC and promotion of their activity (PubMed:8666233). Inhibits HSP90AA1 CC ATPase activity (PubMed:23569206). {ECO:0000269|PubMed:23569206, CC ECO:0000269|PubMed:8666233}. CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Probably forms a complex CC composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, CC TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex CC does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Forms a complex with Hsp90/HSP90AB1 and CDK6 CC (PubMed:9482106). Interacts with HSP90AA1 (PubMed:23569206, CC PubMed:27353360). Interacts with AR, CDK4, CDK6 and EIF2AK1 CC (PubMed:11036079, PubMed:11085988, PubMed:9150368, PubMed:9482106). CC Interacts with RB1 (By similarity). Interacts with KSR1 CC (PubMed:10409742). Interacts with FLCN, FNIP1 and FNIP2 CC (PubMed:27353360). {ECO:0000250|UniProtKB:Q63692, CC ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:11036079, CC ECO:0000269|PubMed:11085988, ECO:0000269|PubMed:23569206, CC ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, CC ECO:0000269|PubMed:9150368, ECO:0000269|PubMed:9482106}. CC -!- INTERACTION: CC Q16543; P60709: ACTB; NbExp=3; IntAct=EBI-295634, EBI-353944; CC Q16543; P63261: ACTG1; NbExp=3; IntAct=EBI-295634, EBI-351292; CC Q16543; P31749: AKT1; NbExp=5; IntAct=EBI-295634, EBI-296087; CC Q16543; Q9Y243: AKT3; NbExp=2; IntAct=EBI-295634, EBI-296115; CC Q16543; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-295634, EBI-746752; CC Q16543; P02649: APOE; NbExp=3; IntAct=EBI-295634, EBI-1222467; CC Q16543; Q96GD4: AURKB; NbExp=5; IntAct=EBI-295634, EBI-624291; CC Q16543; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-295634, EBI-10181188; CC Q16543; Q6PI77: BHLHB9; NbExp=3; IntAct=EBI-295634, EBI-11519926; CC Q16543; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-295634, EBI-2548012; CC Q16543; Q9Y2F9: BTBD3; NbExp=3; IntAct=EBI-295634, EBI-311155; CC Q16543; Q9UQM7: CAMK2A; NbExp=5; IntAct=EBI-295634, EBI-1383687; CC Q16543; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-295634, EBI-11523526; CC Q16543; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-295634, EBI-12020154; CC Q16543; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-295634, EBI-3866279; CC Q16543; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-295634, EBI-11530605; CC Q16543; Q6NZI2: CAVIN1; NbExp=3; IntAct=EBI-295634, EBI-2559016; CC Q16543; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-295634, EBI-11524851; CC Q16543; Q96M89-2: CCDC138; NbExp=3; IntAct=EBI-295634, EBI-10972887; CC Q16543; Q4G0S7: CCDC152; NbExp=3; IntAct=EBI-295634, EBI-18398007; CC Q16543; Q7Z6B0-2: CCDC91; NbExp=3; IntAct=EBI-295634, EBI-12012082; CC Q16543; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-295634, EBI-10175300; CC Q16543; Q14004: CDK13; NbExp=2; IntAct=EBI-295634, EBI-968626; CC Q16543; Q96Q40: CDK15; NbExp=2; IntAct=EBI-295634, EBI-1051975; CC Q16543; P11802: CDK4; NbExp=14; IntAct=EBI-295634, EBI-295644; CC Q16543; Q00534: CDK6; NbExp=3; IntAct=EBI-295634, EBI-295663; CC Q16543; P50750: CDK9; NbExp=5; IntAct=EBI-295634, EBI-1383449; CC Q16543; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-295634, EBI-747776; CC Q16543; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-295634, EBI-739624; CC Q16543; Q9UFW8: CGGBP1; NbExp=3; IntAct=EBI-295634, EBI-723153; CC Q16543; O15111: CHUK; NbExp=5; IntAct=EBI-295634, EBI-81249; CC Q16543; Q5HYN5: CT45A1; NbExp=3; IntAct=EBI-295634, EBI-12051833; CC Q16543; P78358: CTAG1B; NbExp=3; IntAct=EBI-295634, EBI-1188472; CC Q16543; Q13620: CUL4B; NbExp=2; IntAct=EBI-295634, EBI-456067; CC Q16543; Q9NTM9: CUTC; NbExp=3; IntAct=EBI-295634, EBI-714918; CC Q16543; Q16832: DDR2; NbExp=3; IntAct=EBI-295634, EBI-1381484; CC Q16543; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-295634, EBI-11988027; CC Q16543; P00533: EGFR; NbExp=13; IntAct=EBI-295634, EBI-297353; CC Q16543; P04626: ERBB2; NbExp=5; IntAct=EBI-295634, EBI-641062; CC Q16543; Q9NWS6: FAM118A; NbExp=3; IntAct=EBI-295634, EBI-8638992; CC Q16543; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-295634, EBI-10175124; CC Q16543; Q969F0: FATE1; NbExp=3; IntAct=EBI-295634, EBI-743099; CC Q16543; Q9UKT8: FBXW2; NbExp=2; IntAct=EBI-295634, EBI-914727; CC Q16543; P16591: FER; NbExp=3; IntAct=EBI-295634, EBI-1380661; CC Q16543; P22607: FGFR3; NbExp=3; IntAct=EBI-295634, EBI-348399; CC Q16543; Q02790: FKBP4; NbExp=3; IntAct=EBI-295634, EBI-1047444; CC Q16543; P06241: FYN; NbExp=4; IntAct=EBI-295634, EBI-515315; CC Q16543; O60861-1: GAS7; NbExp=3; IntAct=EBI-295634, EBI-11745923; CC Q16543; O95995: GAS8; NbExp=3; IntAct=EBI-295634, EBI-1052570; CC Q16543; P14136: GFAP; NbExp=3; IntAct=EBI-295634, EBI-744302; CC Q16543; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-295634, EBI-2548508; CC Q16543; Q08379: GOLGA2; NbExp=3; IntAct=EBI-295634, EBI-618309; CC Q16543; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-295634, EBI-5916454; CC Q16543; Q96HH9: GRAMD2B; NbExp=3; IntAct=EBI-295634, EBI-2832937; CC Q16543; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-295634, EBI-717919; CC Q16543; Q9NSC5: HOMER3; NbExp=3; IntAct=EBI-295634, EBI-748420; CC Q16543; O75031: HSF2BP; NbExp=3; IntAct=EBI-295634, EBI-7116203; CC Q16543; P07900: HSP90AA1; NbExp=14; IntAct=EBI-295634, EBI-296047; CC Q16543; P08238: HSP90AB1; NbExp=11; IntAct=EBI-295634, EBI-352572; CC Q16543; O14879: IFIT3; NbExp=4; IntAct=EBI-295634, EBI-745127; CC Q16543; O14920: IKBKB; NbExp=4; IntAct=EBI-295634, EBI-81266; CC Q16543; Q14164: IKBKE; NbExp=3; IntAct=EBI-295634, EBI-307369; CC Q16543; Q9Y6K9: IKBKG; NbExp=6; IntAct=EBI-295634, EBI-81279; CC Q16543; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-295634, EBI-747204; CC Q16543; O75564-2: JRK; NbExp=3; IntAct=EBI-295634, EBI-17181882; CC Q16543; Q9H079: KATNBL1; NbExp=3; IntAct=EBI-295634, EBI-715394; CC Q16543; Q8WZ19: KCTD13; NbExp=3; IntAct=EBI-295634, EBI-742916; CC Q16543; Q7L273: KCTD9; NbExp=3; IntAct=EBI-295634, EBI-4397613; CC Q16543; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-295634, EBI-14069005; CC Q16543; O95198: KLHL2; NbExp=3; IntAct=EBI-295634, EBI-746999; CC Q16543; O95678: KRT75; NbExp=3; IntAct=EBI-295634, EBI-2949715; CC Q16543; Q01546: KRT76; NbExp=3; IntAct=EBI-295634, EBI-2952745; CC Q16543; Q6VAB6: KSR2; NbExp=7; IntAct=EBI-295634, EBI-6424389; CC Q16543; P53671: LIMK2; NbExp=2; IntAct=EBI-295634, EBI-1384350; CC Q16543; Q03252: LMNB2; NbExp=3; IntAct=EBI-295634, EBI-2830427; CC Q16543; Q5S007: LRRK2; NbExp=7; IntAct=EBI-295634, EBI-5323863; CC Q16543; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-295634, EBI-1216080; CC Q16543; Q9Y6D9: MAD1L1; NbExp=3; IntAct=EBI-295634, EBI-742610; CC Q16543; Q99558: MAP3K14; NbExp=6; IntAct=EBI-295634, EBI-358011; CC Q16543; O43318: MAP3K7; NbExp=2; IntAct=EBI-295634, EBI-358684; CC Q16543; O43318-2: MAP3K7; NbExp=5; IntAct=EBI-295634, EBI-358700; CC Q16543; Q99750: MDFI; NbExp=3; IntAct=EBI-295634, EBI-724076; CC Q16543; O15344: MID1; NbExp=3; IntAct=EBI-295634, EBI-2340316; CC Q16543; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-295634, EBI-2548751; CC Q16543; P00540: MOS; NbExp=2; IntAct=EBI-295634, EBI-1757866; CC Q16543; Q9BYD2: MRPL9; NbExp=3; IntAct=EBI-295634, EBI-726059; CC Q16543; O15146: MUSK; NbExp=3; IntAct=EBI-295634, EBI-6423196; CC Q16543; Q8N987: NECAB1; NbExp=3; IntAct=EBI-295634, EBI-11956853; CC Q16543; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-295634, EBI-10172876; CC Q16543; P29474: NOS3; NbExp=4; IntAct=EBI-295634, EBI-1391623; CC Q16543; Q9NQ35: NRIP3; NbExp=3; IntAct=EBI-295634, EBI-10311735; CC Q16543; Q9BXI3: NT5C1A; NbExp=3; IntAct=EBI-295634, EBI-10441581; CC Q16543; P22234: PAICS; NbExp=3; IntAct=EBI-295634, EBI-712261; CC Q16543; O76083-2: PDE9A; NbExp=3; IntAct=EBI-295634, EBI-11524542; CC Q16543; Q8N165: PDIK1L; NbExp=3; IntAct=EBI-295634, EBI-6423298; CC Q16543; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-295634, EBI-14066006; CC Q16543; Q9UL42: PNMA2; NbExp=3; IntAct=EBI-295634, EBI-302355; CC Q16543; P78424: POU6F2; NbExp=3; IntAct=EBI-295634, EBI-12029004; CC Q16543; P53041: PPP5C; NbExp=5; IntAct=EBI-295634, EBI-716663; CC Q16543; P31321: PRKAR1B; NbExp=3; IntAct=EBI-295634, EBI-2805516; CC Q16543; Q99873-3: PRMT1; NbExp=3; IntAct=EBI-295634, EBI-17165527; CC Q16543; O14744: PRMT5; NbExp=3; IntAct=EBI-295634, EBI-351098; CC Q16543; P41219: PRPH; NbExp=3; IntAct=EBI-295634, EBI-752074; CC Q16543; P86480: PRR20D; NbExp=3; IntAct=EBI-295634, EBI-12754095; CC Q16543; P49768: PSEN1; NbExp=3; IntAct=EBI-295634, EBI-297277; CC Q16543; Q96QS6: PSKH2; NbExp=3; IntAct=EBI-295634, EBI-6424813; CC Q16543; P62333: PSMC6; NbExp=3; IntAct=EBI-295634, EBI-357669; CC Q16543; Q13882: PTK6; NbExp=4; IntAct=EBI-295634, EBI-1383632; CC Q16543; Q9UJ41-4: RABGEF1; NbExp=3; IntAct=EBI-295634, EBI-14093916; CC Q16543; P04049: RAF1; NbExp=7; IntAct=EBI-295634, EBI-365996; CC Q16543; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-295634, EBI-14065960; CC Q16543; Q9HAT0: ROPN1; NbExp=3; IntAct=EBI-295634, EBI-1378139; CC Q16543; Q9UH03: SEPTIN3; NbExp=3; IntAct=EBI-295634, EBI-727037; CC Q16543; Q13501: SQSTM1; NbExp=8; IntAct=EBI-295634, EBI-307104; CC Q16543; P12931: SRC; NbExp=5; IntAct=EBI-295634, EBI-621482; CC Q16543; A7MD48: SRRM4; NbExp=3; IntAct=EBI-295634, EBI-3867173; CC Q16543; O43805: SSNA1; NbExp=3; IntAct=EBI-295634, EBI-2515299; CC Q16543; Q15831: STK11; NbExp=5; IntAct=EBI-295634, EBI-306838; CC Q16543; Q8WU08-2: STK32A; NbExp=3; IntAct=EBI-295634, EBI-13046508; CC Q16543; Q9Y2H1: STK38L; NbExp=6; IntAct=EBI-295634, EBI-991501; CC Q16543; Q16623: STX1A; NbExp=3; IntAct=EBI-295634, EBI-712466; CC Q16543; Q6PIF2: SYCE2; NbExp=3; IntAct=EBI-295634, EBI-11958386; CC Q16543; Q8IZU3: SYCP3; NbExp=3; IntAct=EBI-295634, EBI-7574149; CC Q16543; P15884-3: TCF4; NbExp=3; IntAct=EBI-295634, EBI-13636688; CC Q16543; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-295634, EBI-741515; CC Q16543; Q9BT49: THAP7; NbExp=3; IntAct=EBI-295634, EBI-741350; CC Q16543; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-295634, EBI-2505861; CC Q16543; Q15025: TNIP1; NbExp=3; IntAct=EBI-295634, EBI-357849; CC Q16543; Q12933: TRAF2; NbExp=3; IntAct=EBI-295634, EBI-355744; CC Q16543; Q13114: TRAF3; NbExp=3; IntAct=EBI-295634, EBI-357631; CC Q16543; O00463: TRAF5; NbExp=3; IntAct=EBI-295634, EBI-523498; CC Q16543; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-295634, EBI-2130429; CC Q16543; Q9BXA6: TSSK6; NbExp=2; IntAct=EBI-295634, EBI-851883; CC Q16543; Q6PHR2: ULK3; NbExp=2; IntAct=EBI-295634, EBI-1383475; CC Q16543; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-295634, EBI-739895; CC Q16543; P07947: YES1; NbExp=4; IntAct=EBI-295634, EBI-515331; CC Q16543; O96006: ZBED1; NbExp=3; IntAct=EBI-295634, EBI-740037; CC Q16543; Q9HCK0: ZBTB26; NbExp=3; IntAct=EBI-295634, EBI-3918996; CC Q16543; Q96BR9: ZBTB8A; NbExp=3; IntAct=EBI-295634, EBI-742740; CC Q16543; Q8N554: ZNF276; NbExp=3; IntAct=EBI-295634, EBI-750821; CC Q16543; Q8N720: ZNF655; NbExp=3; IntAct=EBI-295634, EBI-625509; CC Q16543; Q96EG3: ZNF837; NbExp=3; IntAct=EBI-295634, EBI-11962574; CC Q16543; Q8N446: ZNF843; NbExp=2; IntAct=EBI-295634, EBI-6428016; CC Q16543; P33279: EIF2AK1; Xeno; NbExp=3; IntAct=EBI-295634, EBI-640100; CC Q16543; P0DTC9: N; Xeno; NbExp=4; IntAct=EBI-295634, EBI-25475856; CC Q16543; P11500; Xeno; NbExp=3; IntAct=EBI-295634, EBI-640126; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9482106}. CC -!- PTM: Constitutively sumoylated by UBE2I. {ECO:0000269|PubMed:17709345}. CC -!- SIMILARITY: Belongs to the CDC37 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdc37/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U43077; AAB63979.1; -; mRNA. DR EMBL; U63131; AAB04798.1; -; mRNA. DR EMBL; AY864824; AAW34362.1; -; Genomic_DNA. DR EMBL; BT006796; AAP35442.1; -; mRNA. DR EMBL; CH471106; EAW84101.1; -; Genomic_DNA. DR EMBL; BC000083; AAH00083.1; -; mRNA. DR EMBL; BC008793; AAH08793.1; -; mRNA. DR CCDS; CCDS12237.1; -. DR PIR; G02313; G02313. DR RefSeq; NP_008996.1; NM_007065.3. DR PDB; 1US7; X-ray; 2.30 A; B=127-378. DR PDB; 2K5B; NMR; -; B=148-276. DR PDB; 2N5X; NMR; -; A=288-378. DR PDB; 2NCA; NMR; -; A=1-126. DR PDB; 2W0G; X-ray; 1.88 A; A=148-276. DR PDB; 5FWK; EM; 3.90 A; E=1-378. DR PDB; 5FWL; EM; 9.00 A; E=1-378. DR PDB; 5FWM; EM; 8.00 A; E=1-378. DR PDB; 5FWP; EM; 7.20 A; E=1-378. DR PDB; 5HPE; X-ray; 2.27 A; A=5-20. DR PDBsum; 1US7; -. DR PDBsum; 2K5B; -. DR PDBsum; 2N5X; -. DR PDBsum; 2NCA; -. DR PDBsum; 2W0G; -. DR PDBsum; 5FWK; -. DR PDBsum; 5FWL; -. DR PDBsum; 5FWM; -. DR PDBsum; 5FWP; -. DR PDBsum; 5HPE; -. DR AlphaFoldDB; Q16543; -. DR BMRB; Q16543; -. DR SASBDB; Q16543; -. DR SMR; Q16543; -. DR BioGRID; 116312; 559. DR ComplexPortal; CPX-3285; HSP90B-CDC37 chaperone complex. DR ComplexPortal; CPX-3288; HSP90A-CDC37 chaperone complex. DR CORUM; Q16543; -. DR DIP; DIP-27560N; -. DR IntAct; Q16543; 472. DR MINT; Q16543; -. DR STRING; 9606.ENSP00000222005; -. DR BindingDB; Q16543; -. DR ChEMBL; CHEMBL1795123; -. DR MoonDB; Q16543; Predicted. DR TCDB; 8.A.163.1.1; the hsp90/cdc37 (hsp90/cdc37) family. DR GlyGen; Q16543; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q16543; -. DR MetOSite; Q16543; -. DR PhosphoSitePlus; Q16543; -. DR SwissPalm; Q16543; -. DR BioMuta; CDC37; -. DR DMDM; 21542000; -. DR EPD; Q16543; -. DR jPOST; Q16543; -. DR MassIVE; Q16543; -. DR MaxQB; Q16543; -. DR PaxDb; Q16543; -. DR PeptideAtlas; Q16543; -. DR ProteomicsDB; 60906; -. DR TopDownProteomics; Q16543; -. DR Antibodypedia; 1136; 605 antibodies from 38 providers. DR DNASU; 11140; -. DR Ensembl; ENST00000222005.7; ENSP00000222005.1; ENSG00000105401.9. DR GeneID; 11140; -. DR KEGG; hsa:11140; -. DR MANE-Select; ENST00000222005.7; ENSP00000222005.1; NM_007065.4; NP_008996.1. DR UCSC; uc002mof.2; human. DR CTD; 11140; -. DR DisGeNET; 11140; -. DR GeneCards; CDC37; -. DR HGNC; HGNC:1735; CDC37. DR HPA; ENSG00000105401; Low tissue specificity. DR MIM; 605065; gene. DR neXtProt; NX_Q16543; -. DR OpenTargets; ENSG00000105401; -. DR PharmGKB; PA402; -. DR VEuPathDB; HostDB:ENSG00000105401; -. DR eggNOG; KOG2260; Eukaryota. DR GeneTree; ENSGT00390000013443; -. DR InParanoid; Q16543; -. DR OMA; IWCINLE; -. DR OrthoDB; 786744at2759; -. DR PhylomeDB; Q16543; -. DR TreeFam; TF101059; -. DR PathwayCommons; Q16543; -. DR Reactome; R-HSA-1227986; Signaling by ERBB2. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle. DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2. DR Reactome; R-HSA-9652282; Drug-mediated inhibition of ERBB2 signaling. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665233; Resistance of ERBB2 KD mutants to trastuzumab. DR Reactome; R-HSA-9665244; Resistance of ERBB2 KD mutants to sapitinib. DR Reactome; R-HSA-9665245; Resistance of ERBB2 KD mutants to tesevatinib. DR Reactome; R-HSA-9665246; Resistance of ERBB2 KD mutants to neratinib. DR Reactome; R-HSA-9665247; Resistance of ERBB2 KD mutants to osimertinib. DR Reactome; R-HSA-9665249; Resistance of ERBB2 KD mutants to afatinib. DR Reactome; R-HSA-9665250; Resistance of ERBB2 KD mutants to AEE788. DR Reactome; R-HSA-9665251; Resistance of ERBB2 KD mutants to lapatinib. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. DR Reactome; R-HSA-9665737; Drug resistance in ERBB2 TMD/JMD mutants. DR SignaLink; Q16543; -. DR SIGNOR; Q16543; -. DR BioGRID-ORCS; 11140; 747 hits in 1077 CRISPR screens. DR ChiTaRS; CDC37; human. DR EvolutionaryTrace; Q16543; -. DR GeneWiki; CDC37; -. DR GenomeRNAi; 11140; -. DR Pharos; Q16543; Tbio. DR PRO; PR:Q16543; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q16543; protein. DR Bgee; ENSG00000105401; Expressed in sural nerve and 197 other tissues. DR ExpressionAtlas; Q16543; baseline and differential. DR Genevisible; Q16543; HS. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:1990565; C:HSP90-CDC37 chaperone complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central. DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:Ensembl. DR GO; GO:0019900; F:kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0019901; F:protein kinase binding; IEA:InterPro. DR GO; GO:0019887; F:protein kinase regulator activity; IEA:Ensembl. DR GO; GO:0097110; F:scaffold protein binding; IPI:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central. DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IEA:Ensembl. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0050821; P:protein stabilization; IBA:GO_Central. DR GO; GO:0006605; P:protein targeting; TAS:ProtInc. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0060338; P:regulation of type I interferon-mediated signaling pathway; IMP:MGI. DR GO; GO:0060334; P:regulation of type II interferon-mediated signaling pathway; IMP:MGI. DR DisProt; DP01420; -. DR Gene3D; 1.20.58.610; -; 1. DR InterPro; IPR004918; Cdc37. DR InterPro; IPR013873; Cdc37_C. DR InterPro; IPR013874; Cdc37_Hsp90-bd. DR InterPro; IPR038189; Cdc37_Hsp90-bd_sf. DR InterPro; IPR013855; Cdc37_N_dom. DR PANTHER; PTHR12800; CDC37-RELATED; 1. DR Pfam; PF08564; CDC37_C; 1. DR Pfam; PF08565; CDC37_M; 1. DR Pfam; PF03234; CDC37_N; 1. DR SMART; SM01069; CDC37_C; 1. DR SMART; SM01070; CDC37_M; 1. DR SMART; SM01071; CDC37_N; 1. DR AGR; HGNC:1735; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Chaperone; Cytoplasm; Phosphoprotein; KW Reference proteome; Ubl conjugation. FT CHAIN 1..378 FT /note="Hsp90 co-chaperone Cdc37" FT /id="PRO_0000195057" FT INIT_MET 1 FT /note="Removed; alternate" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT CHAIN 2..378 FT /note="Hsp90 co-chaperone Cdc37, N-terminally processed" FT /id="PRO_0000423197" FT REGION 123..145 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 347..378 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 131..145 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 2 FT /note="N-acetylvaline; in Hsp90 co-chaperone Cdc37, N- FT terminally processed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 78 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 118 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 120 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 154 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT VARIANT 360 FT /note="G -> E (in dbSNP:rs280528)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022220" FT TURN 13..15 FT /evidence="ECO:0007829|PDB:2NCA" FT HELIX 27..72 FT /evidence="ECO:0007829|PDB:2NCA" FT HELIX 79..109 FT /evidence="ECO:0007829|PDB:2NCA" FT HELIX 113..116 FT /evidence="ECO:0007829|PDB:2NCA" FT HELIX 149..163 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 168..177 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 179..181 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 184..199 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 203..226 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 230..241 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 247..272 FT /evidence="ECO:0007829|PDB:2W0G" FT HELIX 294..300 FT /evidence="ECO:0007829|PDB:1US7" FT HELIX 303..310 FT /evidence="ECO:0007829|PDB:2N5X" FT HELIX 317..321 FT /evidence="ECO:0007829|PDB:1US7" FT STRAND 325..327 FT /evidence="ECO:0007829|PDB:1US7" FT HELIX 328..338 FT /evidence="ECO:0007829|PDB:1US7" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:2N5X" FT STRAND 365..367 FT /evidence="ECO:0007829|PDB:2N5X" SQ SEQUENCE 378 AA; 44468 MW; 55BFEFFF3C2A5442 CRC64; MVDYSVWDHI EVSDDEDETH PNIDTASLFR WRHQARVERM EQFQKEKEEL DRGCRECKRK VAECQRKLKE LEVAEGGKAE LERLQAEAQQ LRKEERSWEQ KLEEMRKKEK SMPWNVDTLS KDGFSKSMVN TKPEKTEEDS EEVREQKHKT FVEKYEKQIK HFGMLRRWDD SQKYLSDNVH LVCEETANYL VIWCIDLEVE EKCALMEQVA HQTIVMQFIL ELAKSLKVDP RACFRQFFTK IKTADRQYME GFNDELEAFK ERVRGRAKLR IEKAMKEYEE EERKKRLGPG GLDPVEVYES LPEELQKCFD VKDVQMLQDA ISKMDPTDAK YHMQRCIDSG LWVPNSKASE AKEGEEAGPG DPLLEAVPKT GDEKDVSV // ID TSC1_HUMAN Reviewed; 1164 AA. AC Q92574; B7Z897; Q5VVN5; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 2. DT 14-DEC-2022, entry version 210. DE RecName: Full=Hamartin; DE AltName: Full=Tuberous sclerosis 1 protein; GN Name=TSC1; Synonyms=KIAA0243, TSC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-587. RX PubMed=9242607; DOI=10.1126/science.277.5327.805; RA van Slegtenhorst M.A., de Hoogt R., Hermans C., Nellist M., Janssen B., RA Verhoef S., Lindhout D., van den Ouweland A.M.W., Halley D.J.J., Young J., RA Burley M., Jeremiah S., Woodward K., Nahmias J., Fox M., Ekong R., RA Osborne J., Wolfe J., Povey S., Snell R.G., Cheadle J.P., Jones A.C., RA Tachataki M., Ravine D., Sampson J.R., Reeve M.P., Richardson P., RA Wilmer F., Munro C., Hawkins T.L., Sepp T., Ali J.B.M., Ward S., RA Green A.J., Yates J.R.W., Kwiatkowska J., Henske E.P., Short M.P., RA Haines J.H., Jozwiak S., Kwiatkowski D.J.; RT "Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34."; RL Science 277:805-808(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-1164 (ISOFORM 1/2). RC TISSUE=Bone marrow; RX PubMed=9039502; DOI=10.1093/dnares/3.5.321; RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., RA Tanaka A., Kotani H., Miyajima N., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. VI. The RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of RT cDNA clones from cell line KG-1 and brain."; RL DNA Res. 3:321-329(1996). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 568-586. RA Fang L., Wang N., Murong S.X., Wu Z.Y., Lin M.T.; RT "A silent mutation 1947 T-->C in exon 15 of TSC1 in Chinese."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TSC2. RX PubMed=9809973; RA Plank T.L., Yeung R.S., Henske E.P.; RT "Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts RT with tuberin and appears to be localized to cytoplasmic vesicles."; RL Cancer Res. 58:4766-4770(1998). RN [8] RP INTERACTION WITH TSC2. RX PubMed=9580671; DOI=10.1093/hmg/7.6.1053; RA van Slegtenhorst M.A., Nellist M., Nagelkerken B., Cheadle J.P., RA Snell R.G., van den Ouweland A.M.W., Reuser A., Sampson J.R., RA Halley D.J.J., van der Sluijs P.; RT "Interaction between hamartin and tuberin, the TSC1 and TSC2 gene RT products."; RL Hum. Mol. Genet. 7:1053-1057(1998). RN [9] RP INTERACTION WITH TSC2. RX PubMed=10585443; DOI=10.1074/jbc.274.50.35647; RA Nellist M., van Slegtenhorst M.A., Goedbloed M., van den Ouweland A.M.W., RA Halley D.J.J., van der Sluijs P.; RT "Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a RT cytosolic chaperone for hamartin."; RL J. Biol. Chem. 274:35647-35652(1999). RN [10] RP INVOLVEMENT IN LAM, AND VARIANT TSC1 165-CYS--SER-1164 DEL. RX PubMed=11829138; DOI=10.1007/s10038-002-8651-8; RA Sato T., Seyama K., Fujii H., Maruyama H., Setoguchi Y., Iwakami S., RA Fukuchi Y., Hino O.; RT "Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with RT pulmonary lymphangioleiomyomatosis."; RL J. Hum. Genet. 47:20-28(2002). RN [11] RP FUNCTION. RX PubMed=12271141; DOI=10.1073/pnas.202476899; RA Tee A.R., Fingar D.C., Manning B.D., Kwiatkowski D.J., Cantley L.C., RA Blenis J.; RT "Tuberous sclerosis complex-1 and -2 gene products function together to RT inhibit mammalian target of rapamycin (mTOR)-mediated downstream RT signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13571-13576(2002). RN [12] RP FUNCTION. RX PubMed=15340059; DOI=10.1128/mcb.24.18.7965-7975.2004; RA Li Y., Inoki K., Guan K.-L.; RT "Biochemical and functional characterizations of small GTPase Rheb and TSC2 RT GAP activity."; RL Mol. Cell. Biol. 24:7965-7975(2004). RN [13] RP PHOSPHORYLATION AT SER-505, IDENTIFICATION BY MASS SPECTROMETRY, AND RP INTERACTION WITH DOCK7 AND TSC2. RX PubMed=15963462; DOI=10.1016/j.bbrc.2005.05.175; RA Nellist M., Burgers P.C., van den Ouweland A.M.W., Halley D.J.J., RA Luider T.M.; RT "Phosphorylation and binding partner analysis of the TSC1-TSC2 complex."; RL Biochem. Biophys. Res. Commun. 333:818-826(2005). RN [14] RP FUNCTION, AND INTERACTION WITH TSC2. RX PubMed=16464865; DOI=10.1074/jbc.c500451200; RA Chong-Kopera H., Inoki K., Li Y., Zhu T., Garcia-Gonzalo F.R., Rosa J.L., RA Guan K.-L.; RT "TSC1 stabilizes TSC2 by inhibiting the interaction between TSC2 and the RT HERC1 ubiquitin ligase."; RL J. Biol. Chem. 281:8313-8316(2006). RN [15] RP INTERACTION WITH TBC1D7. RX PubMed=17658474; DOI=10.1016/j.bbrc.2007.07.011; RA Nakashima A., Yoshino K., Miyamoto T., Eguchi S., Oshiro N., Kikkawa U., RA Yonezawa K.; RT "Identification of TBC7 having TBC domain as a novel binding protein to RT TSC1-TSC2 complex."; RL Biochem. Biophys. Res. Commun. 361:218-223(2007). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] RP INTERACTION WITH FBXW5. RX PubMed=18381890; DOI=10.1101/gad.1624008; RA Hu J., Zacharek S., He Y.J., Lee H., Shumway S., Duronio R.J., Xiong Y.; RT "WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by RT DDB1-CUL4-ROC1 ligase."; RL Genes Dev. 22:866-871(2008). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505; SER-511 AND SER-598, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487; SER-505 AND SER-521, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1100, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [25] RP FUNCTION, INTERACTION WITH TSC2, INVOLVEMENT IN FCORD2, VARIANTS FCORD2 RP TRP-22 AND CYS-204, AND CHARACTERIZATION OF VARIANTS FCORD2 TRP-22 AND RP CYS-204. RX PubMed=28215400; DOI=10.1016/j.ajhg.2017.01.030; RA Lim J.S., Gopalappa R., Kim S.H., Ramakrishna S., Lee M., Kim W.I., Kim J., RA Park S.M., Lee J., Oh J.H., Kim H.D., Park C.H., Lee J.S., Kim S., RA Kim D.S., Han J.M., Kang H.C., Kim H.H., Lee J.H.; RT "Somatic mutations in TSC1 and TSC2 cause focal cortical dysplasia."; RL Am. J. Hum. Genet. 100:454-472(2017). RN [26] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; STIP1; CDC37; RP PPP5C; PTGES3; TSC2; AKT; CDK4; RAF1 AND NR3C1, INTERACTION WITH HSP90AA1 RP AND TSC2, AND VARIANT PRO-117. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [27] RP INTERACTION WITH RPAP3 AND URI1. RX PubMed=28561026; DOI=10.1038/ncomms15615; RA Cloutier P., Poitras C., Durand M., Hekmat O., Fiola-Masson E., RA Bouchard A., Faubert D., Chabot B., Coulombe B.; RT "R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 RT to regulate assembly of U5 small nuclear ribonucleoprotein."; RL Nat. Commun. 8:15615-15615(2017). RN [28] RP INTERACTION WITH WDR45B, AND REGION. RX PubMed=28561066; DOI=10.1038/ncomms15637; RA Bakula D., Mueller A.J., Zuleger T., Takacs Z., Franz-Wachtel M., RA Thost A.K., Brigger D., Tschan M.P., Frickey T., Robenek H., Macek B., RA Proikas-Cezanne T.; RT "WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling RT circuits in the control of autophagy."; RL Nat. Commun. 8:15637-15637(2017). RN [29] RP VARIANT TSC1 GLU-726, AND VARIANTS THR-322; TYR-732 AND SER-1035. RC TISSUE=Peripheral blood; RX PubMed=9328481; DOI=10.1093/hmg/6.12.2155; RA Jones A.C., Daniells C.E., Snell R.G., Tachataki M., Idziaszczyk S.A., RA Krawczak M., Sampson J.R., Cheadle J.P.; RT "Molecular genetic and phenotypic analysis reveals differences between TSC1 RT and TSC2 associated familial and sporadic tuberous sclerosis."; RL Hum. Mol. Genet. 6:2155-2161(1997). RN [30] RP VARIANTS THR-322; ARG-587; TYR-732; SER-1035 AND SER-1108. RC TISSUE=Blood; RX PubMed=9924605; DOI=10.1046/j.1469-1809.1998.6240277.x; RA Kwiatkowska J., Jozwiak S., Hall F., Henske E.P., Haines J.L., McNamara P., RA Braiser J., Wigowska-Sowinska J., Kasprzyk-Obara J., Short M.P., RA Kwiatkowski D.J.; RT "Comprehensive mutational analysis of the TSC1 gene: observations on RT frequency of mutation, associated features, and nonpenetrance."; RL Ann. Hum. Genet. 62:277-285(1998). RN [31] RP VARIANT TSC1 PRO-72. RX PubMed=10533069; RX DOI=10.1002/(sici)1098-1004(199911)14:5<428::aid-humu9>3.0.co;2-5; RA Benit P., Kara-Mostefa A., Hadj-Rabia S., Munnich A., Bonnefont J.-P.; RT "Protein truncation test for screening hamartin gene mutations and report RT of new disease-causing mutations."; RL Hum. Mutat. 14:428-432(1999). RN [32] RP VARIANTS THR-322; TYR-732 AND GLN-809. RC TISSUE=Blood, and Lymphoblast; RX PubMed=10533067; RX DOI=10.1002/(sici)1098-1004(199911)14:5<412::aid-humu7>3.0.co;2-k; RA Niida Y., Lawrence-Smith N., Banwell A., Hammer E., Lewis J., RA Beauchamp R.L., Sims K., Ramesh V., Ozelius L.; RT "Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated RT patients with tuberous sclerosis."; RL Hum. Mutat. 14:412-422(1999). RN [33] RP VARIANTS TSC1 ILE-417; GLU-654 AND SER-899, AND VARIANT THR-322. RC TISSUE=Blood; RX PubMed=10570911; DOI=10.1007/s100380050185; RA Zhang H., Nanba E., Yamamoto T., Ninomiya H., Ohno K., Mizuguchi M., RA Takeshita K.; RT "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with RT tuberous sclerosis complex."; RL J. Hum. Genet. 44:391-396(1999). RN [34] RP VARIANTS TSC1, AND VARIANTS. RC TISSUE=Peripheral blood; RX PubMed=10227394; RA Van Slegtenhorst M.A., Verhoef S., Tempelaars A., Bakker L., Wang Q., RA Wessels M., Bakker R., Nellist M., Lindhout D., Halley D.J.J., RA van den Ouweland A.M.W.; RT "Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis RT complex patients: no evidence for genotype-phenotype correlation."; RL J. Med. Genet. 36:285-289(1999). RN [35] RP VARIANTS THR-322; ILE-417; ASP-577 AND ARG-829. RC TISSUE=Peripheral blood leukocyte; RX PubMed=10607950; RX DOI=10.1002/(sici)1096-8628(20000117)90:2<123::aid-ajmg7>3.0.co;2-l; RA Yamashita Y., Ono J., Okada S., Wataya-Kaneda M., Yoshikawa K., RA Nishizawa M., Hirayama Y., Kobayashi E., Seyama K., Hino O.; RT "Analysis of all exons of TSC1 and TSC2 genes for germline mutations in RT Japanese patients with tuberous sclerosis: report of 10 mutations."; RL Am. J. Med. Genet. 90:123-126(2000). RN [36] RP VARIANT TSC1 GLN-500. RX PubMed=10874311; RX DOI=10.1002/1098-1004(200007)16:1<88::aid-humu15>3.0.co;2-j; RA Hass J., Mayer K., Rott H.-D.; RT "Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a RT combination of HDA and TGGE."; RL Hum. Mutat. 16:88-88(2000). RN [37] RP VARIANT TYR-732. RX PubMed=12112044; DOI=10.1002/ana.10251; RA Becker A.J., Urbach H., Scheffler B., Baden T., Normann S., Lahl R., RA Pannek H.W., Tuxhorn I., Elger C.E., Schramm J., Wiestler O.D., RA Bluemcke I.; RT "Focal cortical dysplasia of Taylor's balloon cell type: mutational RT analysis of the TSC1 gene indicates a pathogenic relationship to tuberous RT sclerosis."; RL Ann. Neurol. 52:29-37(2002). RN [38] RP VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417, AND RP CHARACTERIZATION OF VARIANTS ARG-68; CYS-158; ASP-206; LEU-216 AND ILE-417. RX PubMed=18397877; DOI=10.1093/hmg/ddn098; RA Pymar L.S., Platt F.M., Askham J.M., Morrison E.E., Knowles M.A.; RT "Bladder tumour-derived somatic TSC1 missense mutations cause loss of RT function via distinct mechanisms."; RL Hum. Mol. Genet. 17:2006-2017(2008). RN [39] RP VARIANTS TSC1 PRO-117; VAL-128 DEL; PRO-180; HIS-191; 198-ASN-PHE-199 RP DELINS ILE; ARG-224; LYS-246; ARG-305 AND TRP-305, VARIANTS GLN-509; RP SER-1035 AND HIS-1097, CHARACTERIZATION OF VARIANTS TSC1 PRO-117; VAL-128 RP DEL; PRO-180; HIS-191; 198-ASN-PHE-199 DELINS ILE; ARG-224; LYS-246; RP ARG-305 AND TRP-305, AND CHARACTERIZATION OF VARIANTS GLN-509; SER-1035 AND RP HIS-1097. RX PubMed=18830229; DOI=10.1038/ejhg.2008.170; RA Nellist M., van den Heuvel D., Schluep D., Exalto C., Goedbloed M., RA Maat-Kievit A., van Essen T., van Spaendonck-Zwarts K., Jansen F., RA Helderman P., Bartalini G., Vierimaa O., Penttinen M., van den Ende J., RA van den Ouweland A., Halley D.; RT "Missense mutations to the TSC1 gene cause tuberous sclerosis complex."; RL Eur. J. Hum. Genet. 17:319-328(2009). RN [40] RP VARIANTS TSC1 ARG-61; ILE-126; ASP-132; ILE-133; GLN-336; SER-362; ILE-411; RP PRO-523; HIS-693; ARG-698; HIS-701; SER-762; GLY-811; THR-883; VAL-978; RP SER-1043 DEL AND TYR-1146, VARIANTS SER-158; PRO-204; SER-448 AND VAL-567, RP CHARACTERIZATION OF VARIANTS TSC1 ARG-61; PRO-117; ILE-126; ASP-132; RP ILE-133; GLN-336; SER-362; ILE-411; PRO-523; HIS-693; ARG-698; HIS-701; RP SER-762; GLY-811; THR-883; VAL-978; SER-1043 DEL AND TYR-1146, AND RP CHARACTERIZATION OF VARIANTS SER-158; PRO-204; SER-448 AND VAL-567. RX PubMed=22161988; DOI=10.1002/humu.22007; RA Hoogeveen-Westerveld M., Ekong R., Povey S., Karbassi I., Batish S.D., RA den Dunnen J.T., van Eeghen A., Thiele E., Mayer K., Dies K., Wen L., RA Thompson C., Sparagana S.P., Davies P., Aalfs C., van den Ouweland A., RA Halley D., Nellist M.; RT "Functional assessment of TSC1 missense variants identified in individuals RT with tuberous sclerosis complex."; RL Hum. Mutat. 33:476-479(2012). CC -!- FUNCTION: In complex with TSC2, inhibits the nutrient-mediated or CC growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by CC negatively regulating mTORC1 signaling (PubMed:12271141, CC PubMed:28215400). Seems not to be required for TSC2 GAP activity CC towards RHEB (PubMed:15340059). Implicated as a tumor suppressor. CC Involved in microtubule-mediated protein transport, but this seems to CC be due to unregulated mTOR signaling (By similarity). Acts as a co- CC chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein CC clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 CC (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits CC HSP90AA1 ATPase activity (PubMed:29127155). Competes with the CC activating co-chaperone AHSA1 for binding to HSP90AA1, thereby CC providing a reciprocal regulatory mechanism for chaperoning of client CC proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes CC TSC2 by preventing the interaction between TSC2 and ubiquitin ligase CC HERC1 (PubMed:16464865, PubMed:29127155). CC {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:12271141, CC ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, CC ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155}. CC -!- SUBUNIT: Probably forms a complex composed of chaperones HSP90 and CC HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and CC client protein TSC2 (PubMed:29127155). Forms a complex composed of CC chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client CC protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain CC co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Forms a CC complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit CC TCS2 to the complex (PubMed:29127155). Interacts (via C-terminus) with CC the closed form of HSP90AA1 (via the middle domain and TPR repeat- CC binding motif) (PubMed:29127155). Interacts with TSC2; the interaction CC stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, CC PubMed:15963462, PubMed:16464865, PubMed:9580671, PubMed:9809973, CC PubMed:29127155, PubMed:28215400). Interacts with DOCK7 CC (PubMed:15963462). Interacts with FBXW5 (PubMed:18381890). Interacts CC with TBC1D7 (PubMed:17658474). Interacts with WDR45B (PubMed:28561066). CC Interacts with RPAP3 and URI1 (PubMed:28561026). CC {ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:15963462, CC ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:17658474, CC ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:28215400, CC ECO:0000269|PubMed:28561026, ECO:0000269|PubMed:28561066, CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:9580671, CC ECO:0000269|PubMed:9809973}. CC -!- INTERACTION: CC Q92574; Q00994: BEX3; NbExp=5; IntAct=EBI-1047085, EBI-741753; CC Q92574; P02794: FTH1; NbExp=3; IntAct=EBI-1047085, EBI-713259; CC Q92574; O14920: IKBKB; NbExp=3; IntAct=EBI-1047085, EBI-81266; CC Q92574; Q674X7: KAZN; NbExp=2; IntAct=EBI-1047085, EBI-949239; CC Q92574; Q16539: MAPK14; NbExp=2; IntAct=EBI-1047085, EBI-73946; CC Q92574; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-1047085, EBI-79165; CC Q92574; Q92844: TANK; NbExp=3; IntAct=EBI-1047085, EBI-356349; CC Q92574; P49815: TSC2; NbExp=11; IntAct=EBI-1047085, EBI-396587; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9809973}. Membrane CC {ECO:0000269|PubMed:9809973}; Peripheral membrane protein CC {ECO:0000269|PubMed:9809973}. Note=At steady state found in association CC with membranes. {ECO:0000269|PubMed:9809973}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92574-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92574-2; Sequence=VSP_042890; CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, followed by CC heart, brain, placenta, pancreas, lung, liver and kidney. Also CC expressed in embryonic kidney cells. CC -!- DOMAIN: The C-terminal putative coiled-coil domain is necessary for CC interaction with TSC2. {ECO:0000269|PubMed:9580671}. CC -!- PTM: Phosphorylation at Ser-505 does not affect interaction with TSC2. CC {ECO:0000269|PubMed:15963462}. CC -!- DISEASE: Tuberous sclerosis 1 (TSC1) [MIM:191100]: An autosomal CC dominant multi-system disorder that affects especially the brain, CC kidneys, heart, and skin. It is characterized by hamartomas (benign CC overgrowths predominantly of a cell or tissue type that occurs normally CC in the organ) and hamartias (developmental abnormalities of tissue CC combination). Clinical manifestations include epilepsy, learning CC difficulties, behavioral problems, and skin lesions. Seizures can be CC intractable and premature death can occur from a variety of disease- CC associated causes. {ECO:0000269|PubMed:10227394, CC ECO:0000269|PubMed:10533069, ECO:0000269|PubMed:10570911, CC ECO:0000269|PubMed:10874311, ECO:0000269|PubMed:11829138, CC ECO:0000269|PubMed:18830229, ECO:0000269|PubMed:22161988, CC ECO:0000269|PubMed:9328481}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and CC often fatal lung disease characterized by a diffuse proliferation of CC abnormal smooth muscle cells in the lungs. It affects almost CC exclusively young women and can occur as an isolated disorder or in CC association with tuberous sclerosis complex. CC {ECO:0000269|PubMed:11829138}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of CC focal cortical dysplasia, a malformation of cortical development that CC results in medically refractory epilepsy in the pediatric population CC and in adults. FCORD2 is a severe form, with onset usually in CC childhood, characterized by disrupted cortical lamination and specific CC cytological abnormalities. It is classified in 2 subtypes: type IIA CC characterized by dysmorphic neurons and lack of balloon cells; type IIB CC with dysmorphic neurons and balloon cells. CC {ECO:0000269|PubMed:28215400}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/TSC1ID183.html"; CC -!- WEB RESOURCE: Name=Tuberous sclerosis database Tuberous sclerosis 1 CC (TSC1); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/TSC1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF013168; AAC51674.1; -; mRNA. DR EMBL; AK303030; BAH13883.1; -; mRNA. DR EMBL; AL445645; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW88021.1; -; Genomic_DNA. DR EMBL; AC002096; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; D87683; BAA13436.1; -; mRNA. DR EMBL; AF234185; AAF61948.1; -; Genomic_DNA. DR CCDS; CCDS55350.1; -. [Q92574-2] DR CCDS; CCDS6956.1; -. [Q92574-1] DR PIR; T03814; T03814. DR RefSeq; NP_000359.1; NM_000368.4. [Q92574-1] DR RefSeq; NP_001155898.1; NM_001162426.1. DR RefSeq; NP_001155899.1; NM_001162427.1. [Q92574-2] DR RefSeq; XP_005272268.1; XM_005272211.1. [Q92574-1] DR RefSeq; XP_006717334.1; XM_006717271.1. [Q92574-1] DR RefSeq; XP_011517281.1; XM_011518979.2. [Q92574-1] DR RefSeq; XP_016870585.1; XM_017015096.1. [Q92574-1] DR RefSeq; XP_016870586.1; XM_017015097.1. [Q92574-1] DR PDB; 4Z6Y; X-ray; 2.81 A; C/D/F/H=938-993. DR PDB; 5EJC; X-ray; 3.10 A; C/D/E/F=939-992. DR PDB; 7DL2; EM; 4.40 A; C/D=1-1164. DR PDBsum; 4Z6Y; -. DR PDBsum; 5EJC; -. DR PDBsum; 7DL2; -. DR AlphaFoldDB; Q92574; -. DR SMR; Q92574; -. DR BioGRID; 113099; 270. DR ComplexPortal; CPX-6142; TSC1-TSC2 complex. DR CORUM; Q92574; -. DR IntAct; Q92574; 126. DR MINT; Q92574; -. DR STRING; 9606.ENSP00000298552; -. DR CarbonylDB; Q92574; -. DR GlyGen; Q92574; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q92574; -. DR PhosphoSitePlus; Q92574; -. DR BioMuta; TSC1; -. DR DMDM; 9297077; -. DR EPD; Q92574; -. DR jPOST; Q92574; -. DR MassIVE; Q92574; -. DR MaxQB; Q92574; -. DR PaxDb; Q92574; -. DR PeptideAtlas; Q92574; -. DR ProteomicsDB; 75334; -. [Q92574-1] DR ProteomicsDB; 75335; -. [Q92574-2] DR Antibodypedia; 3164; 1880 antibodies from 45 providers. DR DNASU; 7248; -. DR Ensembl; ENST00000298552.9; ENSP00000298552.3; ENSG00000165699.15. [Q92574-1] DR Ensembl; ENST00000440111.6; ENSP00000394524.2; ENSG00000165699.15. [Q92574-1] DR Ensembl; ENST00000545250.5; ENSP00000444017.1; ENSG00000165699.15. [Q92574-2] DR Ensembl; ENST00000643072.1; ENSP00000496691.1; ENSG00000165699.15. [Q92574-2] DR Ensembl; ENST00000643875.1; ENSP00000495158.1; ENSG00000165699.15. [Q92574-1] DR Ensembl; ENST00000646625.1; ENSP00000496263.1; ENSG00000165699.15. [Q92574-1] DR GeneID; 7248; -. DR KEGG; hsa:7248; -. DR MANE-Select; ENST00000298552.9; ENSP00000298552.3; NM_000368.5; NP_000359.1. DR UCSC; uc064wss.1; human. [Q92574-1] DR CTD; 7248; -. DR DisGeNET; 7248; -. DR GeneCards; TSC1; -. DR GeneReviews; TSC1; -. DR HGNC; HGNC:12362; TSC1. DR HPA; ENSG00000165699; Low tissue specificity. DR MalaCards; TSC1; -. DR MIM; 191100; phenotype. DR MIM; 605284; gene. DR MIM; 606690; phenotype. DR MIM; 607341; phenotype. DR neXtProt; NX_Q92574; -. DR OpenTargets; ENSG00000165699; -. DR Orphanet; 210159; Adult hepatocellular carcinoma. DR Orphanet; 269008; Isolated focal cortical dysplasia type IIb. DR Orphanet; 538; Lymphangioleiomyomatosis. DR Orphanet; 805; Tuberous sclerosis complex. DR PharmGKB; PA37034; -. DR VEuPathDB; HostDB:ENSG00000165699; -. DR eggNOG; ENOG502QQPT; Eukaryota. DR GeneTree; ENSGT00390000014148; -. DR HOGENOM; CLU_011546_0_0_1; -. DR InParanoid; Q92574; -. DR OMA; NRMASYS; -. DR PhylomeDB; Q92574; -. DR TreeFam; TF325466; -. DR PathwayCommons; Q92574; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-165181; Inhibition of TSC complex formation by PKB. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-8854214; TBC/RABGAPs. DR SABIO-RK; Q92574; -. DR SignaLink; Q92574; -. DR SIGNOR; Q92574; -. DR BioGRID-ORCS; 7248; 84 hits in 1100 CRISPR screens. DR ChiTaRS; TSC1; human. DR GeneWiki; TSC1; -. DR GenomeRNAi; 7248; -. DR Pharos; Q92574; Tbio. DR PRO; PR:Q92574; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q92574; protein. DR Bgee; ENSG00000165699; Expressed in substantia nigra pars compacta and 212 other tissues. DR ExpressionAtlas; Q92574; baseline and differential. DR Genevisible; Q92574; HS. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:ParkinsonsUK-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ParkinsonsUK-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0033596; C:TSC1-TSC2 complex; IDA:UniProtKB. DR GO; GO:0042030; F:ATPase inhibitor activity; IDA:UniProtKB. DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB. DR GO; GO:0032794; F:GTPase activating protein binding; IEA:Ensembl. DR GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:Ensembl. DR GO; GO:0008344; P:adult locomotory behavior; ISS:ParkinsonsUK-UCL. DR GO; GO:0008306; P:associative learning; IEA:Ensembl. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0030030; P:cell projection organization; IEA:Ensembl. DR GO; GO:0007160; P:cell-matrix adhesion; IMP:UniProtKB. DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; ISS:ParkinsonsUK-UCL. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0046323; P:glucose import; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0043379; P:memory T cell differentiation; IEA:Ensembl. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0045792; P:negative regulation of cell size; IEA:Ensembl. DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl. DR GO; GO:0016242; P:negative regulation of macroautophagy; ISS:ParkinsonsUK-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl. DR GO; GO:1903204; P:negative regulation of oxidative stress-induced neuron death; IEA:Ensembl. DR GO; GO:0032007; P:negative regulation of TOR signaling; IDA:ComplexPortal. DR GO; GO:0017148; P:negative regulation of translation; IMP:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0016239; P:positive regulation of macroautophagy; IEA:Ensembl. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl. DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central. DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IMP:UniProtKB. DR GO; GO:1901214; P:regulation of neuron death; ISS:ParkinsonsUK-UCL. DR GO; GO:0043666; P:regulation of phosphoprotein phosphatase activity; IMP:UniProtKB. DR GO; GO:0045859; P:regulation of protein kinase activity; IEA:Ensembl. DR GO; GO:0051492; P:regulation of stress fiber assembly; IDA:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IDA:UniProtKB. DR GO; GO:0032868; P:response to insulin; IDA:UniProtKB. DR GO; GO:0006407; P:rRNA export from nucleus; IMP:UniProtKB. DR GO; GO:0050808; P:synapse organization; IEA:Ensembl. DR DisProt; DP02744; -. DR InterPro; IPR007483; Hamartin. DR PANTHER; PTHR15154; HAMARTIN; 1. DR Pfam; PF04388; Hamartin; 1. DR AGR; HGNC:12362; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chaperone; Coiled coil; Cytoplasm; KW Disease variant; Epilepsy; Membrane; Phosphoprotein; Reference proteome; KW Tumor suppressor. FT CHAIN 1..1164 FT /note="Hamartin" FT /id="PRO_0000065651" FT REGION 403..787 FT /note="Mediates interaction with WDR45B" FT /evidence="ECO:0000269|PubMed:28561066" FT REGION 439..571 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1006..1085 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1131..1164 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 721..997 FT /evidence="ECO:0000255" FT COMPBIAS 468..484 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 512..534 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1017..1049 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1059..1084 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 487 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 505 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15963462, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 511 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 521 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 598 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1100 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 70..120 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042890" FT VARIANT 22 FT /note="R -> W (in FCORD2; somatic mutation; decreased FT interaction with TSC2; decreased function in negative FT regulation of TOR signaling; dbSNP:rs749030456)" FT /evidence="ECO:0000269|PubMed:28215400" FT /id="VAR_078844" FT VARIANT 51 FT /note="E -> D (in TSC1; unknown pathological significance; FT dbSNP:rs118203342)" FT /id="VAR_009397" FT VARIANT 61 FT /note="L -> R (in TSC1; unknown pathological significance; FT reduced expression; altered subcellular localization; FT reduced inhibition of TORC1 signaling; dbSNP:rs118203345)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070636" FT VARIANT 68 FT /note="H -> R (in a bladder tumor; somatic mutation; FT reduced stability; does not affect interaction with TSC2; FT dbSNP:rs118203347)" FT /evidence="ECO:0000269|PubMed:18397877" FT /id="VAR_054386" FT VARIANT 72 FT /note="L -> P (in TSC1; dbSNP:rs118203354)" FT /evidence="ECO:0000269|PubMed:10533069" FT /id="VAR_054387" FT VARIANT 117 FT /note="L -> P (in TSC1; reduced expression; altered FT subcellular localization; reduced interaction with TSC2; FT reduced inhibition of TORC1 signaling; dbSNP:rs118203368)" FT /evidence="ECO:0000269|PubMed:18830229, FT ECO:0000269|PubMed:22161988, ECO:0000269|PubMed:29127155" FT /id="VAR_070637" FT VARIANT 126 FT /note="V -> I (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514843)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070638" FT VARIANT 128 FT /note="Missing (in TSC1; reduced expression; reduced FT inhibition of TORC1 signaling)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070639" FT VARIANT 132 FT /note="G -> D (in TSC1; unknown pathological significance; FT reduced expression; altered subcellular localization; FT reduced inhibition of TORC1 signaling; dbSNP:rs397514784)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070640" FT VARIANT 133 FT /note="V -> I (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs118203381)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070641" FT VARIANT 158 FT /note="F -> C (in a bladder tumor; somatic mutation; FT reduced stability; does not affect interaction with TSC2; FT dbSNP:rs118203385)" FT /evidence="ECO:0000269|PubMed:18397877" FT /id="VAR_054388" FT VARIANT 158 FT /note="F -> S (found in a patient suspected of having FT tuberous sclerosis; unknown pathological significance; FT reduced expression; altered subcellular localization; FT reduced inhibition of TORC1 signaling; dbSNP:rs118203385)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070642" FT VARIANT 165..1164 FT /note="Missing (in TSC1)" FT /evidence="ECO:0000269|PubMed:11829138" FT /id="VAR_078845" FT VARIANT 180 FT /note="L -> P (in TSC1; reduced expression; reduced FT inhibition of TORC1 signaling; dbSNP:rs118203396)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070643" FT VARIANT 190 FT /note="R -> S" FT /id="VAR_009398" FT VARIANT 191 FT /note="L -> H (in TSC1; reduced expression; reduced FT inhibition of TORC1 signaling; dbSNP:rs118203403)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_009399" FT VARIANT 198..199 FT /note="NF -> I (in TSC1; reduced expression; altered FT subcellular localization; reduced interaction with TSC2; FT reduced inhibition of TORC1 signaling)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_009400" FT VARIANT 204 FT /note="R -> C (in FCORD2; somatic mutation; decreased FT interaction with TSC2; decreased function in negative FT regulation of TOR signaling; dbSNP:rs1060505021)" FT /evidence="ECO:0000269|PubMed:28215400" FT /id="VAR_078846" FT VARIANT 204 FT /note="R -> P (found in a patient suspected of having FT tuberous sclerosis; reduced expression; altered subcellular FT localization; reduced inhibition of TORC1 signaling; FT dbSNP:rs397514834)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070644" FT VARIANT 206 FT /note="H -> D (in a bladder tumor; somatic mutation; FT reduced stability; does not affect interaction with TSC2)" FT /evidence="ECO:0000269|PubMed:18397877" FT /id="VAR_054389" FT VARIANT 216 FT /note="F -> L (in a bladder tumor; diffuse punctate FT cytoplasmic distribution in aminoacid-starved conditions; FT does not affect interaction with TSC2; dbSNP:rs1323541164)" FT /evidence="ECO:0000269|PubMed:18397877" FT /id="VAR_054390" FT VARIANT 224 FT /note="M -> R (in TSC1; reduced expression; reduced FT inhibition of TORC1 signaling; dbSNP:rs118203426)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_009401" FT VARIANT 246 FT /note="R -> K (in TSC1; unknown pathological significance; FT no effect on expression; no effect on inhibition of TORC1 FT signaling; dbSNP:rs118203436)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070645" FT VARIANT 305 FT /note="G -> R (in TSC1; unknown pathological significance; FT no effect on expression; no effect on inhibition of TORC1 FT signaling; dbSNP:rs118203468)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070646" FT VARIANT 305 FT /note="G -> W (in TSC1; unknown pathological significance; FT no effect on expression; no effect on inhibition of TORC1 FT signaling; dbSNP:rs118203468)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070647" FT VARIANT 322 FT /note="M -> T (in dbSNP:rs1073123)" FT /evidence="ECO:0000269|PubMed:10533067, FT ECO:0000269|PubMed:10570911, ECO:0000269|PubMed:10607950, FT ECO:0000269|PubMed:9328481, ECO:0000269|PubMed:9924605" FT /id="VAR_009402" FT VARIANT 336 FT /note="R -> Q (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514808)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070648" FT VARIANT 362 FT /note="P -> S (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514864)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070649" FT VARIANT 411 FT /note="L -> I (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514840)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070650" FT VARIANT 417 FT /note="T -> I (in TSC1; unknown pathological significance; FT does not affect interaction with TSC2; dbSNP:rs77464996)" FT /evidence="ECO:0000269|PubMed:10570911, FT ECO:0000269|PubMed:10607950, ECO:0000269|PubMed:18397877" FT /id="VAR_009403" FT VARIANT 448 FT /note="P -> S (no effect on expression; no effect on FT subcellular localization; no effect on inhibition of TORC1 FT signaling; dbSNP:rs118203518)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070651" FT VARIANT 500 FT /note="R -> Q (in TSC1; dbSNP:rs118203538)" FT /evidence="ECO:0000269|PubMed:10874311" FT /id="VAR_054391" FT VARIANT 509 FT /note="R -> Q (no effect on expression; no effect on FT inhibition of TORC1 signaling; dbSNP:rs118203543)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070652" FT VARIANT 523 FT /note="A -> P (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs118203548)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070653" FT VARIANT 567 FT /note="A -> V (no effect on expression; no effect on FT subcellular localization; no effect on inhibition of TORC1 FT signaling; dbSNP:rs397514880)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070654" FT VARIANT 577 FT /note="E -> D (in dbSNP:rs118203571)" FT /evidence="ECO:0000269|PubMed:10607950" FT /id="VAR_009404" FT VARIANT 586..589 FT /note="CKIP -> S (in TSC1)" FT /id="VAR_009405" FT VARIANT 587 FT /note="K -> R (in dbSNP:rs118203576)" FT /evidence="ECO:0000269|PubMed:9242607, FT ECO:0000269|PubMed:9924605" FT /id="VAR_009406" FT VARIANT 654 FT /note="Q -> E (in TSC1; dbSNP:rs75820036)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009407" FT VARIANT 693 FT /note="D -> H (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514800)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070655" FT VARIANT 698 FT /note="L -> R (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514802)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070656" FT VARIANT 701 FT /note="Q -> H (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs118203639)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070657" FT VARIANT 726 FT /note="A -> E (in TSC1; dbSNP:rs118203655)" FT /evidence="ECO:0000269|PubMed:9328481" FT /id="VAR_009408" FT VARIANT 732 FT /note="H -> Y (might be associated with susceptibility to FT focal cortical dysplasia of the Taylor balloon cell type; FT dbSNP:rs118203657)" FT /evidence="ECO:0000269|PubMed:10533067, FT ECO:0000269|PubMed:12112044, ECO:0000269|PubMed:9328481, FT ECO:0000269|PubMed:9924605" FT /id="VAR_009409" FT VARIANT 762 FT /note="N -> S (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs118203670)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070658" FT VARIANT 809 FT /note="E -> Q (in dbSNP:rs118203692)" FT /evidence="ECO:0000269|PubMed:10533067" FT /id="VAR_009410" FT VARIANT 811 FT /note="R -> G (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514814)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070659" FT VARIANT 829 FT /note="S -> R (in dbSNP:rs118203699)" FT /evidence="ECO:0000269|PubMed:10607950" FT /id="VAR_009411" FT VARIANT 883 FT /note="A -> T (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs118203721)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070660" FT VARIANT 899 FT /note="T -> S (in TSC1; dbSNP:rs76801599)" FT /evidence="ECO:0000269|PubMed:10570911" FT /id="VAR_009412" FT VARIANT 978 FT /note="L -> V (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514859)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070661" FT VARIANT 1035 FT /note="G -> S (no effect on expression; no effect on FT inhibition of TORC1 signaling; dbSNP:rs118203742)" FT /evidence="ECO:0000269|PubMed:18830229, FT ECO:0000269|PubMed:9328481, ECO:0000269|PubMed:9924605" FT /id="VAR_009413" FT VARIANT 1043 FT /note="Missing (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070662" FT VARIANT 1097 FT /note="R -> H (no effect on expression; no effect on FT inhibition of TORC1 signaling; dbSNP:rs118203750)" FT /evidence="ECO:0000269|PubMed:18830229" FT /id="VAR_070663" FT VARIANT 1108 FT /note="G -> S (in dbSNP:rs118203753)" FT /evidence="ECO:0000269|PubMed:9924605" FT /id="VAR_009414" FT VARIANT 1146 FT /note="D -> Y (in TSC1; unknown pathological significance; FT no effect on expression; no effect on subcellular FT localization; no effect on inhibition of TORC1 signaling; FT dbSNP:rs397514806)" FT /evidence="ECO:0000269|PubMed:22161988" FT /id="VAR_070664" FT HELIX 941..971 FT /evidence="ECO:0007829|PDB:4Z6Y" FT HELIX 975..991 FT /evidence="ECO:0007829|PDB:4Z6Y" SQ SEQUENCE 1164 AA; 129767 MW; EF15509385C7AACC CRC64; MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL ETSSQPALHI LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ PSWKHKLSQA PLLPSLLKCL KMDTDVVVLT TGVLVLITML PMIPQSGKQH LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL HASVYALFHR LYGMYPCNFV SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH ELDPRRWKRL ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS MVCGMTTPPT SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL CHSDDYVHIS LPQATVTPPR KEERMDSARP CLHRQHHLLN DRGSEEPPGS KGSVTLSDLP GFLGDLASEE DSIEKDKEEA AISRELSEIT TAEAEPVVPR GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL DKLGPDTPKQ AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD RLIQQGADAH SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN QLLYERFKRQ QHALRNRRLL RKVIKAAALE EHNAAMKDQL KLQEKDIQMW KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR QLQHDREEFY NQSQELQTKL EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES VQQQMEFLNR QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA QKRITQVFEL EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC SDSMVGHNEE ASGHNGETKT PRPSSARGSS GSRGGGGSSS SSSELSTPEK PPHQRAGPFS SRWETTMGEA SASIPTTVGS LPSSKSFLGM KARELFRNKS ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP SPPTPDSVGQ LHIMDYNETH HEHS // ID CDK4_HUMAN Reviewed; 303 AA. AC P11802; B2R9A0; B4DNF9; O00576; Q6FG61; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 14-DEC-2022, entry version 250. DE RecName: Full=Cyclin-dependent kinase 4; DE EC=2.7.11.22; DE AltName: Full=Cell division protein kinase 4; DE AltName: Full=PSK-J3; GN Name=CDK4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Hanks S.K.; RL Submitted (FEB-1987) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9192850; DOI=10.1006/geno.1997.4727; RA Elkahloun A.G., Krizman D.B., Wang Z., Hofmann T.A., Roe B.A., RA Meltzer P.S.; RT "Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 RT amplification in human cancers."; RL Genomics 42:295-301(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CMM3 CYS-24, AND RP CHARACTERIZATION OF VARIANT CYS-24. RX PubMed=7652577; DOI=10.1126/science.7652577; RA Wolfel T., Hauer M., Schneider J., Serrano M., Wolfel C., Klehmann-Hieb E., RA De Plaen E., Hankeln T., Meyer Zum Bueschenfelde K.-H., Beach D.; RT "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in RT a human melanoma."; RL Science 269:1281-1284(1995). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CMM3 CYS-24, AND RP CHARACTERIZATION OF VARIANT CYS-24. RX PubMed=8528263; DOI=10.1038/ng0196-97; RA Zuo L., Weger J., Yang Q., Goldstein A.M., Tucker M.A., Walker G.J., RA Hayward N., Dracopoli N.C.; RT "Germline mutations in the p16INK4a binding domain of CDK4 in familial RT melanoma."; RL Nat. Genet. 12:97-99(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-82. RG NIEHS SNPs program; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Embryo; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 88-188 (ISOFORM 1). RX PubMed=2948189; DOI=10.1073/pnas.84.2.388; RA Hanks S.K.; RT "Homology probing: identification of cDNA clones encoding members of the RT protein-serine kinase family."; RL Proc. Natl. Acad. Sci. U.S.A. 84:388-392(1987). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182. RX PubMed=8221695; RA Khatib Z.A., Matsushime H., Valentine M., Shapiro D.N., Sherr C.J., RA Look A.T.; RT "Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas."; RL Cancer Res. 53:5535-5541(1993). RN [13] RP FUNCTION. RX PubMed=9003781; DOI=10.1002/j.1460-2075.1996.tb01097.x; RA Kitagawa M., Higashi H., Jung H.K., Suzuki-Takahashi I., Ikeda M., RA Tamai K., Kato J., Segawa K., Yoshida E., Nishimura S., Taya Y.; RT "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different RT from that for phosphorylation by cyclin A/E-Cdk2."; RL EMBO J. 15:7060-7069(1996). RN [14] RP INTERACTION WITH CDKN1A; CCND1 AND CCND3, SUBCELLULAR LOCATION, AND RP CATALYTIC ACTIVITY. RX PubMed=9106657; DOI=10.1101/gad.11.7.847; RA LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., RA Chou H.S., Fattaey A., Harlow E.; RT "New functional activities for the p21 family of CDK inhibitors."; RL Genes Dev. 11:847-862(1997). RN [15] RP INTERACTION WITH SEI1. RX PubMed=10580009; DOI=10.1101/gad.13.22.3027; RA Sugimoto M., Nakamura T., Ohtani N., Hampson L., Hampson I.N., RA Shimamoto A., Furuichi Y., Okumura K., Niwa S., Taya Y., Hara E.; RT "Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)."; RL Genes Dev. 13:3027-3033(1999). RN [16] RP INTERACTION WITH CEBPA. RX PubMed=15107404; DOI=10.1101/gad.1183304; RA Wang G.L., Iakova P., Wilde M., Awad S., Timchenko N.A.; RT "Liver tumors escape negative control of proliferation via PI3K/Akt- RT mediated block of C/EBP alpha growth inhibitory activity."; RL Genes Dev. 18:912-925(2004). RN [17] RP FUNCTION. RX PubMed=15241418; DOI=10.1038/nature02650; RA Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.; RT "Cyclin-dependent kinases regulate the antiproliferative function of RT Smads."; RL Nature 430:226-231(2004). RN [18] RP INTERACTION WITH ZNF655. RX PubMed=15558030; DOI=10.1038/sj.onc.1208043; RA Houlard M., Romero-Portillo F., Germani A., Depaux A., Regnier-Ricard F., RA Gisselbrecht S., Varin-Blank N.; RT "Characterization of VIK-1: a new Vav-interacting Kruppel-like protein."; RL Oncogene 24:28-38(2005). RN [19] RP PHOSPHORYLATION AT THR-172, INTERACTION WITH CCND1; CCND3; CDKN2A AND RP CDKN1B, AND MUTAGENESIS OF THR-172. RX PubMed=16782892; DOI=10.1128/mcb.02006-05; RA Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., RA de Launoit Y., Roger P.P., Coulonval K.; RT "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase RT 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."; RL Mol. Cell. Biol. 26:5070-5085(2006). RN [20] RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH CCND2. RX PubMed=18827403; DOI=10.1247/csf.08019; RA Wang Z., Xie Y., Zhang L., Zhang H., An X., Wang T., Meng A.; RT "Migratory localization of cyclin D2-Cdk4 complex suggests a spatial RT regulation of the G1-S transition."; RL Cell Struct. Funct. 33:171-183(2008). RN [21] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [22] RP INTERACTION WITH CCND1. RX PubMed=19124461; DOI=10.1074/jbc.m808843200; RA Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.; RT "Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 RT binding and induces cell cycle arrest."; RL J. Biol. Chem. 284:5574-5581(2009). RN [23] RP INTERACTION WITH CDKN1B, PHOSPHORYLATION, AND CATALYTIC ACTIVITY. RX PubMed=19075005; DOI=10.1128/mcb.00898-08; RA Ray A., James M.K., Larochelle S., Fisher R.P., Blain S.W.; RT "p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent RT modes."; RL Mol. Cell. Biol. 29:986-999(2009). RN [24] RP PHOSPHORYLATION AT THR-172, ACTIVITY REGULATION, AND MUTAGENESIS OF RP PRO-173. RX PubMed=19487459; DOI=10.1128/mcb.01823-08; RA Bockstaele L., Bisteau X., Paternot S., Roger P.P.; RT "Differential regulation of cyclin-dependent kinase 4 (CDK4) and CDK6, RT evidence that CDK4 might not be activated by CDK7, and design of a CDK6 RT activating mutation."; RL Mol. Cell. Biol. 29:4188-4200(2009). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [26] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CCND1. RX PubMed=20399237; DOI=10.1016/j.bbamcr.2010.04.001; RA Kim H., Kang M., Lee S.A., Kwak T.K., Jung O., Lee H.J., Kim S.H., RA Lee J.W.; RT "TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression RT and RhoA activity."; RL Biochim. Biophys. Acta 1803:975-982(2010). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP INTERACTION WITH FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [29] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; CDC37; PPP5C; TSC1; TSC2; RP AKT; RAF1 AND NR3C1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF THR-172-PHOSPHORYLATED WILD TYPE RP AND MUTANTS ALA-172; PHE-172 AND ASP-172 IN COMPLEX WITH CCND1, RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-172, AND RP CATALYTIC ACTIVITY. RX PubMed=19237565; DOI=10.1073/pnas.0809645106; RA Day P.J., Cleasby A., Tickle I.J., O'Reilly M., Coyle J.E., Holding F.P., RA McMenamin R.L., Yon J., Chopra R., Lengauer C., Jhoti H.; RT "Crystal structure of human CDK4 in complex with a D-type cyclin."; RL Proc. Natl. Acad. Sci. U.S.A. 106:4166-4170(2009). RN [31] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF NONPHOSPHORYLATED FORM IN COMPLEX RP WITH CCND3, PHOSPHORYLATION AT THR-172, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=19237555; DOI=10.1073/pnas.0809674106; RA Takaki T., Echalier A., Brown N.R., Hunt T., Endicott J.A., Noble M.E.; RT "The structure of CDK4/cyclin D3 has implications for models of CDK RT activation."; RL Proc. Natl. Acad. Sci. U.S.A. 106:4171-4176(2009). RN [32] RP VARIANT CMM3 SER-41. RX PubMed=9311594; RX DOI=10.1002/(sici)1097-0215(19970904)72:5<780::aid-ijc13>3.0.co;2-d; RA Guldberg P., Kirkin A.F., Gronbaek K., thor Straten P., Ahrenkiel V., RA Zeuthen J.; RT "Complete scanning of the CDK4 gene by denaturing gradient gel RT electrophoresis: a novel missense mutation but low overall frequency of RT mutations in sporadic metastatic malignant melanoma."; RL Int. J. Cancer 72:780-783(1997). RN [33] RP VARIANT CMM3 HIS-24. RX PubMed=9425228; DOI=10.1093/hmg/7.2.209; RA Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., RA Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.; RT "Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone RT families in France."; RL Hum. Mol. Genet. 7:209-216(1998). RN [34] RP ERRATUM OF PUBMED:9425228. RA Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., RA Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.; RL Hum. Mol. Genet. 7:941-941(1998). RN [35] RP VARIANT [LARGE SCALE ANALYSIS] HIS-122. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that CC phosphorylate and inhibit members of the retinoblastoma (RB) protein CC family including RB1 and regulate the cell-cycle during G(1)/S CC transition. Phosphorylation of RB1 allows dissociation of the CC transcription factor E2F from the RB/E2F complexes and the subsequent CC transcription of E2F target genes which are responsible for the CC progression through the G(1) phase. Hypophosphorylates RB1 in early CC G(1) phase. Cyclin D-CDK4 complexes are major integrators of various CC mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a CC cell-cycle-dependent manner and represses its transcriptional activity. CC Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for CC nuclear translocation and activity of the cyclin D-CDK4 complex. CC {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, CC ECO:0000269|PubMed:9003781}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19237565, CC ECO:0000269|PubMed:9106657}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.22; Evidence={ECO:0000269|PubMed:19075005, CC ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:9106657}; CC -!- ACTIVITY REGULATION: Both phosphorylation at Thr-172 and binding of a CC D-type cyclin are necessary for enzymatic activity. Full activation of CC the cyclin-D-CDK4 complex appears to require other factors such as CC recruitment of the substrate via a substrate recruitment motif, and/or CC formation of the CDKN1B ternary complex. Inhibited by INK4 family CC members. In resting cells, the non-tyrosine-phosphorylated form of CC CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in CC proliferating cells, tyrosine phosphorylation of CDKN1B allows CC phosphorylation of Thr-172 of CDK4 and subsequent activation. CC {ECO:0000269|PubMed:19487459}. CC -!- SUBUNIT: Component of the D-CDK4 complex, composed of CDK4 and some D- CC type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the CC complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. CC Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CC CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated CC on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the CC cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation CC and enhances the cyclin D-CDK4 complex activity. CDK4 activity is CC either inhibited or enhanced depending on stoichiometry of complex. The CC non-tyrosine-phosphorylated form of CDKN1B prevents T-loop CC phosphorylation of CDK4 producing inactive CDK4. Interacts CC (unphosphorylated form) with CDK2. Also forms ternary complexes with CC CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); CC the interaction promotes the assembly of the cyclin D-CDK4 complex, its CC nuclear translocation and promotes the cyclin D-dependent enzyme CC activity of CDK4. Interacts with CCND1; the interaction is prevented CC with the binding of CCND1 to INSM1 during cell cycle progression. CC Probably forms a complex composed of chaperones HSP90 and HSP70, co- CC chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 CC and NR3C1; this complex does not contain co-chaperones STIP1/HOP and CC PTGES3/p23 (PubMed:29127155). Interacts with CEBPA (when CC phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 CC (PubMed:27353360). {ECO:0000250|UniProtKB:P30285, CC ECO:0000269|PubMed:10580009, ECO:0000269|PubMed:15107404, CC ECO:0000269|PubMed:15558030, ECO:0000269|PubMed:16782892, CC ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:19075005, CC ECO:0000269|PubMed:19124461, ECO:0000269|PubMed:19237555, CC ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:20399237, CC ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, CC ECO:0000269|PubMed:9106657}. CC -!- INTERACTION: CC P11802; Q9UH17: APOBEC3B; NbExp=9; IntAct=EBI-295644, EBI-2967317; CC P11802; P24385: CCND1; NbExp=42; IntAct=EBI-295644, EBI-375001; CC P11802; P30279: CCND2; NbExp=15; IntAct=EBI-295644, EBI-748789; CC P11802; P30281: CCND3; NbExp=38; IntAct=EBI-295644, EBI-375013; CC P11802; Q16543: CDC37; NbExp=14; IntAct=EBI-295644, EBI-295634; CC P11802; P50613: CDK7; NbExp=2; IntAct=EBI-295644, EBI-1245958; CC P11802; P38936: CDKN1A; NbExp=8; IntAct=EBI-295644, EBI-375077; CC P11802; P46527: CDKN1B; NbExp=11; IntAct=EBI-295644, EBI-519280; CC P11802; P42771: CDKN2A; NbExp=16; IntAct=EBI-295644, EBI-375053; CC P11802; P42772: CDKN2B; NbExp=20; IntAct=EBI-295644, EBI-711280; CC P11802; P42773: CDKN2C; NbExp=23; IntAct=EBI-295644, EBI-711290; CC P11802; P55273: CDKN2D; NbExp=25; IntAct=EBI-295644, EBI-745859; CC P11802; Q9UJC3: HOOK1; NbExp=14; IntAct=EBI-295644, EBI-746704; CC P11802; P08238: HSP90AB1; NbExp=5; IntAct=EBI-295644, EBI-352572; CC P11802; Q9UKT9: IKZF3; NbExp=6; IntAct=EBI-295644, EBI-747204; CC P11802; Q0VD86: INCA1; NbExp=3; IntAct=EBI-295644, EBI-6509505; CC P11802; P01106: MYC; NbExp=2; IntAct=EBI-295644, EBI-447544; CC P11802; Q9ULD0: OGDHL; NbExp=3; IntAct=EBI-295644, EBI-3940481; CC P11802; P28749: RBL1; NbExp=2; IntAct=EBI-295644, EBI-971402; CC P11802; P09936: UCHL1; NbExp=4; IntAct=EBI-295644, EBI-714860; CC P11802; Q8N720: ZNF655; NbExp=6; IntAct=EBI-295644, EBI-625509; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18827403}. Nucleus CC {ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:20399237, CC ECO:0000269|PubMed:9106657}. Nucleus membrane CC {ECO:0000269|PubMed:18827403}. Note=Cytoplasmic when non-complexed. CC Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress CC through G(1) phase. The complex accumulates on the nuclear membrane and CC enters the nucleus on transition from G(1) to S phase. Also present in CC nucleoli and heterochromatin lumps. Colocalizes with RB1 after release CC into the nucleus. {ECO:0000269|PubMed:18827403}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11802-1; Sequence=Displayed; CC Name=2; CC IsoId=P11802-2; Sequence=VSP_056487; CC -!- PTM: Phosphorylation at Thr-172 is required for enzymatic activity. CC Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, CC appears to be phosphorylated by a proline-directed kinase. In the CC cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 CC enzyme activity, is dependent on the tyrosine phosphorylation state of CC CDKN1B. Thus, in proliferating cells, CDK4 within the complex is CC phosphorylated on Thr-172 in the T-loop. In resting cells, CC phosphorylation on Thr-172 is prevented by the non-tyrosine- CC phosphorylated form of CDKN1B. {ECO:0000269|PubMed:16782892, CC ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19237555, CC ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:19487459}. CC -!- DISEASE: Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A CC malignant neoplasm of melanocytes, arising de novo or from a pre- CC existing benign nevus, which occurs most often in the skin but may also CC involve other sites. {ECO:0000269|PubMed:7652577, CC ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, CC ECO:0000269|PubMed:9425228}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CDK4ID238ch12q14.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdk4/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14505; AAA35673.1; -; mRNA. DR EMBL; U81031; AAC39521.2; -; Genomic_DNA. DR EMBL; Z48970; CAA88834.1; -; mRNA. DR EMBL; U37022; AAC50506.1; -; Genomic_DNA. DR EMBL; AF507942; AAM23014.1; -; Genomic_DNA. DR EMBL; AK297901; BAG60221.1; -; mRNA. DR EMBL; AK313701; BAG36447.1; -; mRNA. DR EMBL; CR407668; CAG28596.1; -; mRNA. DR EMBL; CR542247; CAG47043.1; -; mRNA. DR EMBL; AC025165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471054; EAW97058.1; -; Genomic_DNA. DR EMBL; BC003644; AAH03644.1; -; mRNA. DR EMBL; BC005864; AAH05864.1; -; mRNA. DR EMBL; BC010153; AAH10153.1; -; mRNA. DR EMBL; S67448; AAD13991.1; -; Genomic_DNA. DR CCDS; CCDS8953.1; -. [P11802-1] DR PIR; I52695; I52695. DR PIR; S52841; S52841. DR RefSeq; NP_000066.1; NM_000075.3. [P11802-1] DR PDB; 2W96; X-ray; 2.30 A; B=1-303. DR PDB; 2W99; X-ray; 2.80 A; B=1-303. DR PDB; 2W9F; X-ray; 2.85 A; B=1-303. DR PDB; 2W9Z; X-ray; 2.45 A; B=1-303. DR PDB; 3G33; X-ray; 3.00 A; A/C=1-303. DR PDB; 5FWK; EM; 3.90 A; K=1-303. DR PDB; 5FWL; EM; 9.00 A; K=1-303. DR PDB; 5FWM; EM; 8.00 A; K=1-303. DR PDB; 5FWP; EM; 7.20 A; K=1-303. DR PDB; 6P8E; X-ray; 2.30 A; B=2-303. DR PDB; 6P8F; X-ray; 2.89 A; B=2-303. DR PDB; 6P8G; X-ray; 2.80 A; B=2-303. DR PDB; 6P8H; X-ray; 3.19 A; B=2-303. DR PDBsum; 2W96; -. DR PDBsum; 2W99; -. DR PDBsum; 2W9F; -. DR PDBsum; 2W9Z; -. DR PDBsum; 3G33; -. DR PDBsum; 5FWK; -. DR PDBsum; 5FWL; -. DR PDBsum; 5FWM; -. DR PDBsum; 5FWP; -. DR PDBsum; 6P8E; -. DR PDBsum; 6P8F; -. DR PDBsum; 6P8G; -. DR PDBsum; 6P8H; -. DR AlphaFoldDB; P11802; -. DR SMR; P11802; -. DR BioGRID; 107454; 282. DR ComplexPortal; CPX-2010; Cyclin D1-CDK4 complex. DR ComplexPortal; CPX-2011; Cyclin D2-CDK4 complex. DR ComplexPortal; CPX-2012; Cyclin D3-CDK4 complex. DR CORUM; P11802; -. DR DIP; DIP-875N; -. DR ELM; P11802; -. DR IntAct; P11802; 129. DR MINT; P11802; -. DR STRING; 9606.ENSP00000257904; -. DR BindingDB; P11802; -. DR ChEMBL; CHEMBL331; -. DR DrugBank; DB12001; Abemaciclib. DR DrugBank; DB03496; Alvocidib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB09073; Palbociclib. DR DrugBank; DB02733; Purvalanol. DR DrugBank; DB11730; Ribociclib. DR DrugBank; DB15442; Trilaciclib. DR DrugCentral; P11802; -. DR GuidetoPHARMACOLOGY; 1976; -. DR GlyGen; P11802; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11802; -. DR MetOSite; P11802; -. DR PhosphoSitePlus; P11802; -. DR SwissPalm; P11802; -. DR BioMuta; CDK4; -. DR DMDM; 1168867; -. DR EPD; P11802; -. DR jPOST; P11802; -. DR MassIVE; P11802; -. DR MaxQB; P11802; -. DR PaxDb; P11802; -. DR PeptideAtlas; P11802; -. DR ProteomicsDB; 4694; -. DR ProteomicsDB; 52805; -. [P11802-1] DR ABCD; P11802; 1 sequenced antibody. DR Antibodypedia; 4190; 1125 antibodies from 46 providers. DR DNASU; 1019; -. DR Ensembl; ENST00000257904.11; ENSP00000257904.5; ENSG00000135446.17. [P11802-1] DR GeneID; 1019; -. DR KEGG; hsa:1019; -. DR MANE-Select; ENST00000257904.11; ENSP00000257904.5; NM_000075.4; NP_000066.1. DR UCSC; uc001spv.4; human. [P11802-1] DR CTD; 1019; -. DR DisGeNET; 1019; -. DR GeneCards; CDK4; -. DR HGNC; HGNC:1773; CDK4. DR HPA; ENSG00000135446; Low tissue specificity. DR MalaCards; CDK4; -. DR MIM; 123829; gene. DR MIM; 609048; phenotype. DR neXtProt; NX_P11802; -. DR OpenTargets; ENSG00000135446; -. DR Orphanet; 99970; Dedifferentiated liposarcoma. DR Orphanet; 618; Familial melanoma. DR Orphanet; 99971; Well-differentiated liposarcoma. DR PharmGKB; PA102; -. DR VEuPathDB; HostDB:ENSG00000135446; -. DR eggNOG; KOG0594; Eukaryota. DR GeneTree; ENSGT00940000154770; -. DR InParanoid; P11802; -. DR OMA; THTHCWH; -. DR PhylomeDB; P11802; -. DR TreeFam; TF101022; -. DR BRENDA; 2.7.11.22; 2681. DR PathwayCommons; P11802; -. DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2559585; Oncogene Induced Senescence. DR Reactome; R-HSA-3214858; RMTs methylate histone arginines. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D. DR Reactome; R-HSA-8849470; PTK6 Regulates Cell Cycle. DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9630791; Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4. DR Reactome; R-HSA-9630794; Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6. DR Reactome; R-HSA-9632697; Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4. DR Reactome; R-HSA-9632700; Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6. DR Reactome; R-HSA-9661069; Defective binding of RB1 mutants to E2F1,(E2F2, E2F3). DR Reactome; R-HSA-9754119; Drug-mediated inhibition of CDK4/CDK6 activity. DR SignaLink; P11802; -. DR SIGNOR; P11802; -. DR BioGRID-ORCS; 1019; 291 hits in 1124 CRISPR screens. DR ChiTaRS; CDK4; human. DR EvolutionaryTrace; P11802; -. DR GeneWiki; Cyclin-dependent_kinase_4; -. DR GenomeRNAi; 1019; -. DR Pharos; P11802; Tclin. DR PRO; PR:P11802; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P11802; protein. DR Bgee; ENSG00000135446; Expressed in ganglionic eminence and 99 other tissues. DR ExpressionAtlas; P11802; baseline and differential. DR Genevisible; P11802; HS. DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0097128; C:cyclin D1-CDK4 complex; IPI:ComplexPortal. DR GO; GO:0097129; C:cyclin D2-CDK4 complex; IPI:ComplexPortal. DR GO; GO:0097130; C:cyclin D3-CDK4 complex; IPI:ComplexPortal. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; TAS:Reactome. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IBA:GO_Central. DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl. DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl. DR GO; GO:1904637; P:cellular response to ionomycin; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; IEA:Ensembl. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0046890; P:regulation of lipid biosynthetic process; IEA:Ensembl. DR GO; GO:0050994; P:regulation of lipid catabolic process; IEA:Ensembl. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0060260; P:regulation of transcription initiation by RNA polymerase II; TAS:Reactome. DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:UniProtKB. DR GO; GO:0007165; P:signal transduction; IEA:Ensembl. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR AGR; HGNC:1773; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle; KW Cell division; Cytoplasm; Disease variant; Kinase; Membrane; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..303 FT /note="Cyclin-dependent kinase 4" FT /id="PRO_0000085778" FT DOMAIN 6..295 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 50..56 FT /note="Required for binding D-type cyclins" FT ACT_SITE 140 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 12..20 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 35 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 172 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:16782892, FT ECO:0000269|PubMed:19237555, ECO:0000269|PubMed:19237565, FT ECO:0000269|PubMed:19487459, ECO:0007744|PubMed:19369195" FT VAR_SEQ 1..120 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056487" FT VARIANT 24 FT /note="R -> C (in CMM3; somatic and familial; generates a FT dominant oncogene resistant to inhibition by p16(INK4a); FT dbSNP:rs11547328)" FT /evidence="ECO:0000269|PubMed:7652577, FT ECO:0000269|PubMed:8528263" FT /id="VAR_006200" FT VARIANT 24 FT /note="R -> H (in CMM3; dbSNP:rs104894340)" FT /evidence="ECO:0000269|PubMed:9425228" FT /id="VAR_006201" FT VARIANT 41 FT /note="N -> S (in CMM3; sporadic; dbSNP:rs144890720)" FT /evidence="ECO:0000269|PubMed:9311594" FT /id="VAR_021152" FT VARIANT 82 FT /note="R -> Q (in dbSNP:rs3211612)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_029153" FT VARIANT 122 FT /note="R -> H (in dbSNP:rs34386532)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041976" FT MUTAGEN 172 FT /note="T->A: Weak enzyme activity towards RB1, but no FT effect on binding of CCDN1 nor CCDN3." FT /evidence="ECO:0000269|PubMed:16782892" FT MUTAGEN 172 FT /note="T->E: Retains moderate enzyme activity." FT /evidence="ECO:0000269|PubMed:16782892" FT MUTAGEN 173 FT /note="P->S: No effect on in vitro phosphorylation by CDK7. FT Greatly reduced T-172 phosphorylation and enzyme activity." FT /evidence="ECO:0000269|PubMed:19487459" FT CONFLICT 117 FT /note="I -> L (in Ref. 6; BAG36447)" FT /evidence="ECO:0000305" FT STRAND 7..13 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:3G33" FT STRAND 20..24 FT /evidence="ECO:0007829|PDB:2W96" FT TURN 26..28 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 31..40 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:6P8G" FT HELIX 51..63 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 74..82 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 84..94 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:2W9Z" FT HELIX 100..105 FT /evidence="ECO:0007829|PDB:2W96" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:2W9F" FT HELIX 114..133 FT /evidence="ECO:0007829|PDB:2W96" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 146..148 FT /evidence="ECO:0007829|PDB:2W96" FT TURN 150..152 FT /evidence="ECO:0007829|PDB:2W9Z" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 162..169 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 172..175 FT /evidence="ECO:0007829|PDB:3G33" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 195..208 FT /evidence="ECO:0007829|PDB:2W96" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 219..230 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:6P8E" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:2W99" FT HELIX 246..248 FT /evidence="ECO:0007829|PDB:6P8E" FT HELIX 257..259 FT /evidence="ECO:0007829|PDB:6P8E" FT HELIX 266..275 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 280..282 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 286..290 FT /evidence="ECO:0007829|PDB:2W96" FT HELIX 293..295 FT /evidence="ECO:0007829|PDB:6P8E" SQ SEQUENCE 303 AA; 33730 MW; 0916A0C07403A33A CRC64; MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGGGGGLP ISTVREVALL RRLEAFEHPN VVRLMDVCAT SRTDREIKVT LVFEHVDQDL RTYLDKAPPP GLPAETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFP PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKDEG NPE // ID HS90A_HUMAN Reviewed; 732 AA. AC P07900; A8K500; B3KPJ9; Q2PP14; Q5CAQ6; Q5CAQ7; Q9BVQ5; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 5. DT 14-DEC-2022, entry version 268. DE RecName: Full=Heat shock protein HSP 90-alpha {ECO:0000305}; DE EC=3.6.4.10 {ECO:0000269|PubMed:12526792}; DE AltName: Full=Heat shock 86 kDa; DE Short=HSP 86; DE Short=HSP86; DE AltName: Full=Lipopolysaccharide-associated protein 2; DE Short=LAP-2; DE Short=LPS-associated protein 2; DE AltName: Full=Renal carcinoma antigen NY-REN-38; GN Name=HSP90AA1 {ECO:0000312|HGNC:HGNC:5253}; GN Synonyms=HSP90A, HSPC1, HSPCA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Peripheral blood lymphocyte; RX PubMed=2780322; DOI=10.1093/nar/17.17.7108; RA Soeda E., Yokoyama K., Yamazaki M., Akaogi K., Miwa T., Imai T.; RT "Nucleotide sequence of a full-length cDNA for 90 kDa heat-shock protein RT from human peripheral blood lymphocytes."; RL Nucleic Acids Res. 17:7108-7108(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1368637; DOI=10.1271/bbb1961.54.3163; RA Yamazaki M., Tashiro H., Yokoyama K., Soeda E.; RT "Molecular cloning of cDNA encoding a human heat-shock protein whose RT expression is induced by adenovirus type 12 E1A in HeLa cells."; RL Agric. Biol. Chem. 54:3163-3170(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=2527334; DOI=10.1128/mcb.9.6.2615-2626.1989; RA Hickey E., Brandon S.E., Smale G., Lloyd D., Weber L.A.; RT "Sequence and regulation of a gene encoding a human 89-kilodalton heat RT shock protein."; RL Mol. Cell. Biol. 9:2615-2626(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND NOMENCLATURE. RX PubMed=16269234; DOI=10.1016/j.ygeno.2005.08.012; RA Chen B., Piel W.H., Gui L., Bruford E., Monteiro A.; RT "The HSP90 family of genes in the human genome: insights into their RT divergence and evolution."; RL Genomics 86:627-637(2005). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Placenta, and Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-312. RX PubMed=2469626; DOI=10.1016/0378-1119(88)90182-5; RA Hoffmann T., Hovemann B.; RT "Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes RT encode formerly identified tumour-specific transplantation antigens."; RL Gene 74:491-501(1988). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-312. RX PubMed=2591742; DOI=10.1016/0378-1119(89)90408-3; RA Walter T., Drabent B., Krebs H., Tomalak M., Heiss S., Benecke B.J.J.; RT "Cloning and analysis of a human 86-kDa heat-shock-protein-encoding gene."; RL Gene 83:105-115(1989). RN [11] RP PROTEIN SEQUENCE OF 101-112; 210-224; 300-314; 328-338; 346-355; 387-400; RP 465-478 AND 633-647, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 185-732. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 539-732. RC TISSUE=Heart; RA Tanaka M., Tanaka T., Mitsui Y., Yamamoto M., Wood J.N.; RT "The analysis of the genes reactive to monoclonal antibody, CE5."; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [14] RP PROTEIN SEQUENCE OF 2-21, AND PHOSPHORYLATION AT SER-231 AND SER-263. RX PubMed=2492519; DOI=10.1016/s0021-9258(19)81631-9; RA Lees-Miller S.P., Anderson C.W.; RT "Two human 90-kDa heat shock proteins are phosphorylated in vivo at RT conserved serines that are phosphorylated in vitro by casein kinase II."; RL J. Biol. Chem. 264:2431-2437(1989). RN [15] RP PROTEIN SEQUENCE OF 154-163 AND 186-191, AND INTERACTION WITH KSR1. RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523; RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.; RT "Kinase suppressor of Ras forms a multiprotein signaling complex and RT modulates MEK localization."; RL Mol. Cell. Biol. 19:5523-5534(1999). RN [16] RP PROTEIN SEQUENCE OF 592-612, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF RP CYS-598, AND S-NITROSYLATION AT CYS-598. RX PubMed=15937123; DOI=10.1073/pnas.0407294102; RA Martinez-Ruiz A., Villanueva L., Gonzalez de Orduna C., Lopez-Ferrer D., RA Higueras M.A., Tarin C., Rodriguez-Crespo I., Vazquez J., Lamas S.; RT "S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and RT endothelial nitric oxide synthase regulatory activities."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8525-8530(2005). RN [17] RP PHOSPHORYLATION AT THR-5 AND THR-7. RX PubMed=2507541; DOI=10.1016/s0021-9258(18)71488-9; RA Lees-Miller S.P., Anderson C.W.; RT "The human double-stranded DNA-activated protein kinase phosphorylates the RT 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine RT residues."; RL J. Biol. Chem. 264:17275-17280(1989). RN [18] RP HOMODIMERIZATION. RX PubMed=8289821; DOI=10.1128/mcb.14.2.1459-1464.1994; RA Minami Y., Kimura Y., Kawasaki H., Suzuki K., Yahara I.; RT "The carboxy-terminal region of mammalian HSP90 is required for its RT dimerization and function in vivo."; RL Mol. Cell. Biol. 14:1459-1464(1994). RN [19] RP SUBUNIT. RX PubMed=7588731; DOI=10.1111/j.1432-1033.1995.001_1.x; RA Nemoto T., Ohara-Nemoto Y., Ota M., Takagi T., Yokoyama K.; RT "Mechanism of dimer formation of the 90-kDa heat-shock protein."; RL Eur. J. Biochem. 233:1-8(1995). RN [20] RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4; PPID; PPP5C OR STIP1. RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224; RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K., RA Chinkers M., Pratt W.B.; RT "Protein phosphatase 5 is a major component of glucocorticoid RT receptor.hsp90 complexes with properties of an FK506-binding RT immunophilin."; RL J. Biol. Chem. 272:16224-16230(1997). RN [21] RP INTERACTION WITH TOM34. RX PubMed=9660753; DOI=10.1074/jbc.273.29.18007; RA Young J.C., Obermann W.M., Hartl F.U.; RT "Specific binding of tetratricopeptide repeat proteins to the C-terminal RT 12-kDa domain of hsp90."; RL J. Biol. Chem. 273:18007-18010(1998). RN [22] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [23] RP INTERACTION WITH TERT, AND FUNCTION AS A CO-CHAPERONE IN TELOMERASE RP HOLOENZYME ASSEMBLY. RX PubMed=11274138; DOI=10.1074/jbc.c100055200; RA Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.; RT "Stable association of hsp90 and p23, but Not hsp70, with active human RT telomerase."; RL J. Biol. Chem. 276:15571-15574(2001). RN [24] RP INTERACTION WITH HSF1. RX PubMed=11583998; DOI=10.1074/jbc.m105931200; RA Guo Y., Guettouche T., Fenna M., Boellmann F., Pratt W.B., Toft D.O., RA Smith D.F., Voellmy R.; RT "Evidence for a mechanism of repression of heat shock factor 1 RT transcriptional activity by a multichaperone complex."; RL J. Biol. Chem. 276:45791-45799(2001). RN [25] RP FUNCTION, IDENTIFICATION AS LPS RECEPTOR, INTERACTION WITH CXCR4; GDF5 AND RP HSPA8, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11276205; DOI=10.1038/86342; RA Triantafilou K., Triantafilou M., Dedrick R.L.; RT "A CD14-independent LPS receptor cluster."; RL Nat. Immunol. 2:338-345(2001). RN [26] RP FUNCTION, INTERACTION WITH TOMM70, AND CATALYTIC ACTIVITY. RX PubMed=12526792; DOI=10.1016/s0092-8674(02)01250-3; RA Young J.C., Hoogenraad N.J., Hartl F.U.; RT "Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the RT mitochondrial import receptor Tom70."; RL Cell 112:41-50(2003). RN [27] RP INTERACTION WITH DNAJC7. RX PubMed=12853476; DOI=10.1093/emboj/cdg362; RA Brychzy A., Rein T., Winklhofer K.F., Hartl F.U., Young J.C., RA Obermann W.M.; RT "Cofactor Tpr2 combines two TPR domains and a J domain to regulate the RT Hsp70/Hsp90 chaperone system."; RL EMBO J. 22:3613-3623(2003). RN [28] RP INTERACTION WITH AHSA1. RX PubMed=12604615; DOI=10.1074/jbc.m212761200; RA Lotz G.P., Lin H., Harst A., Obermann W.M.J.; RT "Aha1 binds to the middle domain of Hsp90, contributes to client protein RT activation, and stimulates the ATPase activity of the molecular RT chaperone."; RL J. Biol. Chem. 278:17228-17235(2003). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [30] RP INTERACTION WITH SMYD3. RX PubMed=15235609; DOI=10.1038/ncb1151; RA Hamamoto R., Furukawa Y., Morita M., Iimura Y., Silva F.P., Li M., RA Yagyu R., Nakamura Y.; RT "SMYD3 encodes a histone methyltransferase involved in the proliferation of RT cancer cells."; RL Nat. Cell Biol. 6:731-740(2004). RN [31] RP INTERACTION WITH SGTA AND TTC1. RX PubMed=15708368; DOI=10.1016/j.abb.2004.12.020; RA Liou S.T., Wang C.; RT "Small glutamine-rich tetratricopeptide repeat-containing protein is RT composed of three structural units with distinct functions."; RL Arch. Biochem. Biophys. 435:253-263(2005). RN [32] RP INTERACTION WITH PPP5C, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15383005; DOI=10.1042/bj20040690; RA Zeke T., Morrice N., Vazquez-Martin C., Cohen P.T.; RT "Human protein phosphatase 5 dissociates from heat-shock proteins and is RT proteolytically activated in response to arachidonic acid and the RT microtubule-depolymerizing drug nocodazole."; RL Biochem. J. 385:45-56(2005). RN [33] RP FUNCTION, AND INTERACTION WITH PPP5C. RX PubMed=15577939; DOI=10.1038/sj.emboj.7600496; RA Yang J., Roe S.M., Cliff M.J., Williams M.A., Ladbury J.E., Cohen P.T., RA Barford D.; RT "Molecular basis for TPR domain-mediated regulation of protein phosphatase RT 5."; RL EMBO J. 24:1-10(2005). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-263, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Pituitary; RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x; RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.; RT "Phosphoproteomic analysis of the human pituitary."; RL Pituitary 9:109-120(2006). RN [36] RP INTERACTION WITH PPP5C. RX PubMed=16531226; DOI=10.1016/j.str.2005.12.009; RA Cliff M.J., Harris R., Barford D., Ladbury J.E., Williams M.A.; RT "Conformational diversity in the TPR domain-mediated interaction of protein RT phosphatase 5 with Hsp90."; RL Structure 14:415-426(2006). RN [37] RP INTERACTION WITH NLRP12. RX PubMed=17947705; DOI=10.4049/jimmunol.179.9.6291; RA Arthur J.C., Lich J.D., Aziz R.K., Kotb M., Ting J.P.; RT "Heat shock protein 90 associates with monarch-1 and regulates its ability RT to promote degradation of NF-kappaB-inducing kinase."; RL J. Immunol. 179:6291-6296(2007). RN [38] RP SUBUNIT, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=18400751; DOI=10.1074/jbc.m800540200; RA Richter K., Soroka J., Skalniak L., Leskovar A., Hessling M., Reinstein J., RA Buchner J.; RT "Conserved conformational changes in the ATPase cycle of human Hsp90."; RL J. Biol. Chem. 283:17757-17765(2008). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252 AND SER-263, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231 AND SER-263, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [44] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [46] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-443; LYS-458; LYS-489 AND RP LYS-585, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [47] RP INTERACTION WITH CHORDC1. RX PubMed=19875381; DOI=10.1074/mcp.m900261-mcp200; RA Gano J.J., Simon J.A.; RT "A proteomic investigation of ligand-dependent HSP90 complexes reveals RT CHORDC1 as a novel ADP-dependent HSP90-interacting protein."; RL Mol. Cell. Proteomics 9:255-270(2010). RN [48] RP ISGYLATION. RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132; RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.; RT "Proteomic identification of proteins conjugated to ISG15 in mouse and RT human cells."; RL Biochem. Biophys. Res. Commun. 336:496-506(2005). RN [49] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [50] RP INTERACTION WITH FNIP1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=17028174; DOI=10.1073/pnas.0603781103; RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A., RA Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M., RA Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B.; RT "Folliculin encoded by the BHD gene interacts with a binding protein, RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006). RN [51] RP MUTAGENESIS OF GLY-97. RX PubMed=18256191; DOI=10.1242/dev.018150; RA Hawkins T.A., Haramis A.P., Etard C., Prodromou C., Vaughan C.K., RA Ashworth R., Ray S., Behra M., Holder N., Talbot W.S., Pearl L.H., RA Strahle U., Wilson S.W.; RT "The ATPase-dependent chaperoning activity of Hsp90a regulates thick RT filament formation and integration during skeletal muscle RT myofibrillogenesis."; RL Development 135:1147-1156(2008). RN [52] RP MUTAGENESIS OF CYS-598. RX PubMed=19696785; DOI=10.1038/embor.2009.153; RA Retzlaff M., Stahl M., Eberl H.C., Lagleder S., Beck J., Kessler H., RA Buchner J.; RT "Hsp90 is regulated by a switch point in the C-terminal domain."; RL EMBO Rep. 10:1147-1153(2009). RN [53] RP FUNCTION, INTERACTION WITH TOMM70; IRF3 AND TBK1, AND MUTAGENESIS OF RP 729-GLU--ASP-732. RX PubMed=20628368; DOI=10.1038/cr.2010.103; RA Liu X.Y., Wei B., Shi H.X., Shan Y.F., Wang C.; RT "Tom70 mediates activation of interferon regulatory factor 3 on RT mitochondria."; RL Cell Res. 20:994-1011(2010). RN [54] RP INTERACTION WITH HSP90AB1. RX PubMed=20353823; DOI=10.1016/j.cellsig.2010.03.012; RA Cheng M.B., Zhang Y., Zhong X., Sutter B., Cao C.Y., Chen X.S., Cheng X.K., RA Zhang Y., Xiao L., Shen Y.F.; RT "Stat1 mediates an auto-regulation of hsp90beta gene in heat shock RT response."; RL Cell. Signal. 22:1206-1213(2010). RN [55] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [56] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [57] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [58] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH N.MENINGITIDIS ADHESIN RP A (MICROBIAL INFECTION). RX PubMed=22066472; DOI=10.1111/j.1462-5822.2011.01722.x; RA Montanari P., Bozza G., Capecchi B., Caproni E., Barrile R., Norais N., RA Capitani M., Sallese M., Cecchini P., Ciucchi L., Gao Z., Rappuoli R., RA Pizza M., Arico B., Merola M.; RT "Human heat shock protein (Hsp) 90 interferes with Neisseria meningitidis RT adhesin A (NadA)-mediated adhesion and invasion."; RL Cell. Microbiol. 14:368-385(2012). RN [59] RP INTERACTION WITH CDC37. RX PubMed=23569206; DOI=10.1074/jbc.m112.439257; RA Eckl J.M., Rutz D.A., Haslbeck V., Zierer B.K., Reinstein J., Richter K.; RT "Cdc37 (cell division cycle 37) restricts Hsp90 (heat shock protein 90) RT motility by interaction with N-terminal and middle domain binding sites."; RL J. Biol. Chem. 288:16032-16042(2013). RN [60] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; SER-252; SER-263; RP SER-476 AND SER-641, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [61] RP FUNCTION, AND INTERACTION WITH STUB1 AND SMAD3. RX PubMed=24613385; DOI=10.1016/j.bbrc.2014.02.124; RA Shang Y., Xu X., Duan X., Guo J., Wang Y., Ren F., He D., Chang Z.; RT "Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through RT CHIP/Stub1."; RL Biochem. Biophys. Res. Commun. 446:387-392(2014). RN [62] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [63] RP INTERACTION WITH NWD1. RX PubMed=24681825; DOI=10.18632/oncotarget.1850; RA Correa R.G., Krajewska M., Ware C.F., Gerlic M., Reed J.C.; RT "The NLR-related protein NWD1 is associated with prostate cancer and RT modulates androgen receptor signaling."; RL Oncotarget 5:1666-1682(2014). RN [64] RP REVIEW. RX PubMed=25973397; DOI=10.3389/fonc.2015.00100; RA Khurana N., Bhattacharyya S.; RT "Hsp90, the concertmaster: tuning transcription."; RL Front. Oncol. 5:100-100(2015). RN [65] RP FUNCTION, INTERACTION WITH TOMM70 AND IRF3, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 728-MET--ASP-732. RX PubMed=25609812; DOI=10.1128/jvi.02959-14; RA Wei B., Cui Y., Huang Y., Liu H., Li L., Li M., Ruan K.C., Zhou Q., RA Wang C.; RT "Tom70 mediates Sendai virus-induced apoptosis on mitochondria."; RL J. Virol. 89:3804-3818(2015). RN [66] RP INTERACTION WITH SMYD3. RX PubMed=25738358; DOI=10.18632/oncotarget.2970; RA Brown M.A., Foreman K., Harriss J., Das C., Zhu L., Edwards M., Shaaban S., RA Tucker H.; RT "C-terminal domain of SMYD3 serves as a unique HSP90-regulated motif in RT oncogenesis."; RL Oncotarget 6:4005-4019(2015). RN [67] RP INTERACTION WITH HSF1; HIF1A; ERBB2; MET; KEAP1 AND RHOBTB2, AND RP MUTAGENESIS OF GLU-47 AND ASP-93. RX PubMed=26517842; DOI=10.1371/journal.pone.0141786; RA Prince T.L., Kijima T., Tatokoro M., Lee S., Tsutsumi S., Yim K., Rivas C., RA Alarcon S., Schwartz H., Khamit-Kush K., Scroggins B.T., Beebe K., RA Trepel J.B., Neckers L.; RT "Client proteins and small molecule inhibitors display distinct binding RT preferences for constitutive and stress-induced HSP90 isoforms and their RT conformationally restricted mutants."; RL PLoS ONE 10:E0141786-E0141786(2015). RN [68] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [69] RP REVIEW. RX PubMed=27295069; DOI=10.1016/j.biochi.2016.05.018; RA Verma S., Goyal S., Jamal S., Singh A., Grover A.; RT "Hsp90: Friends, clients and natural foes."; RL Biochimie 127:227-240(2016). RN [70] RP REVIEW. RX PubMed=26991466; DOI=10.1002/bip.22835; RA Pearl L.H.; RT "Review: The HSP90 molecular chaperone-an enigmatic ATPase."; RL Biopolymers 105:594-607(2016). RN [71] RP FUNCTION, AND INTERACTION WITH FLCN; AHSA1; HSP70; CDC37; FNIP1; FNIP2; RP STUB1; STIP1; PTGES3 AND PPP5C. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [72] RP INTERACTION WITH HSF1. RX PubMed=26754925; DOI=10.1038/srep19174; RA Asano Y., Kawase T., Okabe A., Tsutsumi S., Ichikawa H., Tatebe S., RA Kitabayashi I., Tashiro F., Namiki H., Kondo T., Semba K., Aburatani H., RA Taya Y., Nakagama H., Ohki R.; RT "IER5 generates a novel hypo-phosphorylated active form of HSF1 and RT contributes to tumorigenesis."; RL Sci. Rep. 6:19174-19174(2016). RN [73] RP FUNCTION, ACTIVITY REGULATION, IDENTIFICATION IN A COMPLEX WITH TSC1 AND RP TSC2, INTERACTION WITH TSC1 AND AHSA1, SUBUNIT, AND MUTAGENESIS OF GLU-47; RP ASP-93; TYR-313 AND 728-MET--ASP-732. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [74] RP INTERACTION WITH NLRP12. RX PubMed=30559449; DOI=10.1038/s41467-018-07750-5; RA Normand S., Waldschmitt N., Neerincx A., Martinez-Torres R.J., Chauvin C., RA Couturier-Maillard A., Boulard O., Cobret L., Awad F., Huot L., RA Ribeiro-Ribeiro A., Lautz K., Ruez R., Delacre M., Bondu C., Guilliams M., RA Scott C., Segal A., Amselem S., Hot D., Karabina S., Bohn E., Ryffel B., RA Poulin L.F., Kufer T.A., Chamaillard M.; RT "Proteasomal degradation of NOD2 by NLRP12 in monocytes promotes bacterial RT tolerance and colonization by enteropathogens."; RL Nat. Commun. 9:5338-5338(2018). RN [75] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN US11 (MICROBIAL INFECTION). RX PubMed=29743370; DOI=10.1128/jvi.00402-18; RA Liu X., Main D., Ma Y., He B.; RT "Herpes Simplex Virus 1 Inhibits TANK-Binding Kinase 1 through Formation of RT the Us11-Hsp90 Complex."; RL J. Virol. 92:0-0(2018). RN [76] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 11-223 IN COMPLEX WITH RP GELDANAMYCIN. RX PubMed=9108479; DOI=10.1016/s0092-8674(00)80203-2; RA Stebbins C.E., Russo A.A., Schneider C., Rosen N., Hartl F.U., RA Pavletich N.P.; RT "Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein RT chaperone by an antitumor agent."; RL Cell 89:239-250(1997). RN [77] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 11-223 IN COMPLEX WITH ADP, RP CATALYTIC ACTIVITY, AND INTERACTION WITH PTGES3. RX PubMed=9817749; DOI=10.1083/jcb.143.4.901; RA Obermann W.M., Sondermann H., Russo A.A., Pavletich N.P., Hartl F.U.; RT "In vivo function of Hsp90 is dependent on ATP binding and ATP RT hydrolysis."; RL J. Cell Biol. 143:901-910(1998). RN [78] RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 724-732 IN COMPLEX WITH STUB1, RP INTERACTION WITH STUB1 AND UBE2N, AND MOTIF TPR REPEAT-BINDING. RX PubMed=16307917; DOI=10.1016/j.molcel.2005.09.023; RA Zhang M., Windheim M., Roe S.M., Peggie M., Cohen P., Prodromou C., RA Pearl L.H.; RT "Chaperoned ubiquitylation -- crystal structures of the CHIP U box E3 RT ubiquitin ligase and a CHIP-Ubc13-Uev1a complex."; RL Mol. Cell 20:525-538(2005). CC -!- FUNCTION: Molecular chaperone that promotes the maturation, structural CC maintenance and proper regulation of specific target proteins involved CC for instance in cell cycle control and signal transduction. Undergoes a CC functional cycle that is linked to its ATPase activity which is CC essential for its chaperone activity. This cycle probably induces CC conformational changes in the client proteins, thereby causing their CC activation. Interacts dynamically with various co-chaperones that CC modulate its substrate recognition, ATPase cycle and chaperone function CC (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, CC PubMed:29127155, PubMed:12526792). Engages with a range of client CC protein classes via its interaction with various co-chaperone proteins CC or complexes, that act as adapters, simultaneously able to interact CC with the specific client and the central chaperone itself CC (PubMed:29127155). Recruitment of ATP and co-chaperone followed by CC client protein forms a functional chaperone. After the completion of CC the chaperoning process, properly folded client protein and co- CC chaperone leave HSP90 in an ADP-bound partially open conformation and CC finally, ADP is released from HSP90 which acquires an open conformation CC for the next cycle (PubMed:27295069, PubMed:26991466). Plays a critical CC role in mitochondrial import, delivers preproteins to the mitochondrial CC import receptor TOMM70 (PubMed:12526792). Apart from its chaperone CC activity, it also plays a role in the regulation of the transcription CC machinery. HSP90 and its co-chaperones modulate transcription at least CC at three different levels (PubMed:25973397). In the first place, they CC alter the steady-state levels of certain transcription factors in CC response to various physiological cues(PubMed:25973397). Second, they CC modulate the activity of certain epigenetic modifiers, such as histone CC deacetylases or DNA methyl transferases, and thereby respond to the CC change in the environment (PubMed:25973397). Third, they participate in CC the eviction of histones from the promoter region of certain genes and CC thereby turn on gene expression (PubMed:25973397). Binds bacterial CC lipopolysaccharide (LPS) and mediates LPS-induced inflammatory CC response, including TNF secretion by monocytes (PubMed:11276205). CC Antagonizes STUB1-mediated inhibition of TGF-beta signaling via CC inhibition of STUB1-mediated SMAD3 ubiquitination and degradation CC (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 CC in mitochondrial outer membrane which promotes host antiviral response CC (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, CC ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, CC ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, CC ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, CC ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, CC ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}. CC -!- FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis CC NadA-mediated invasion of human cells. Decreasing HSP90 levels CC increases adhesion and entry of E.coli expressing NadA into human Chang CC cells; increasing its levels leads to decreased adhesion and invasion. CC {ECO:0000305|PubMed:22066472}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.10; CC Evidence={ECO:0000269|PubMed:12526792}; CC -!- ACTIVITY REGULATION: In the resting state, through the dimerization of CC its C-terminal domain, HSP90 forms a homodimer which is defined as the CC open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal CC domain undergoes significant conformational changes and comes in CC contact to form an active closed conformation (PubMed:18400751). After CC HSP90 finishes its chaperoning tasks of assisting the proper folding, CC stabilization and activation of client proteins under the active state, CC ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and CC directs the protein back to the resting state (PubMed:18400751). Co- CC chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase CC activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes CC HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, CC Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155, PubMed:12526792). CC {ECO:0000269|PubMed:18400751, ECO:0000269|PubMed:29127155}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=300 uM for ATP {ECO:0000269|PubMed:18400751}; CC -!- SUBUNIT: Homodimer (PubMed:7588731, PubMed:8289821, PubMed:18400751, CC PubMed:29127155). Identified in NR3C1/GCR steroid receptor-chaperone CC complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins CC containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 CC (PubMed:15383005, PubMed:9195923). Forms a complex containing HSP90AA1, CC TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex CC (PubMed:29127155). The closed form interacts (via the middle domain and CC TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) CC (PubMed:29127155). Interacts with TOM34 (PubMed:9660753). Interacts CC with TERT; the interaction, together with PTGES3, is required for CC correct assembly and stabilization of the TERT holoenzyme complex CC (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 CC (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may CC couple the chaperone and ubiquitination systems (PubMed:16307917, CC PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C CC (via TPR repeats); the interaction is direct and activates PPP5C CC phosphatase activity (PubMed:15383005, PubMed:15577939, CC PubMed:16531226, PubMed:27353360). Following LPS binding, may form a CC complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with CC KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C- CC terminus); the interaction inhibits HSP90AA1 ATPase activity CC (PubMed:23569206, PubMed:27353360). May interact with NWD1 CC (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction CC inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). CC Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the CC interaction activates HSP90AA1 ATPase activity and results in the CC dissociation of TSC1 from HSP90AA1 (PubMed:12604615, PubMed:27353360, CC PubMed:29127155). Interacts with FLCN in the presence of FNIP1 CC (PubMed:27353360). Interacts with HSP70, STIP1 and PTGES3 CC (PubMed:27353360). Interacts with SMYD3; this interaction enhances CC SMYD3 histone-lysine N-methyltransferase (PubMed:15235609, CC PubMed:25738358). Interacts with SGTA (via TPR repeats) CC (PubMed:15708368). Interacts with TTC1 (via TPR repeats) CC (PubMed:15708368). Interacts with HSF1 in an ATP-dependent manner CC (PubMed:11583998. PubMed:26517842). Interacts with MET; the interaction CC suppresses MET kinase activity (PubMed:26517842). Interacts with ERBB2 CC in an ATP-dependent manner; the interaction suppresses ERBB2 kinase CC activity (PubMed:26517842). Interacts with HIF1A, KEAP1 and RHOBTB2 CC (PubMed:26517842). Interacts with HSF1; this interaction is decreased CC in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, CC homotrimerization and DNA-binding activities (PubMed:26754925). CC Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with CC HSP90AB1; interaction is constitutive (PubMed:20353823). Interacts with CC HECTD1 (via N-terminus) (By similarity). Interacts with NR3C1 (via CC domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts CC with NLPR12 (PubMed:30559449, PubMed:17947705). Interacts with PDCL3 CC (By similarity). Interacts with TOMM70; the interaction is required for CC preprotein mitochondrial import (PubMed:12526792). Interacts with CC TOMM70, IRF3 and TBK1; the interactions are direct and mediate the CC association of TOMM70 with IRF3 and TBK1 (PubMed:20628368). Forms a CC complex with ASL, ASS1 and NOS2; the complex regulates cell-autonomous CC L-arginine synthesis and citrulline recycling while channeling CC extracellular L-arginine to nitric oxide synthesis pathway. CC {ECO:0000250|UniProtKB:P07901, ECO:0000250|UniProtKB:P82995, CC ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:11274138, CC ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11583998, CC ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:12604615, CC ECO:0000269|PubMed:12853476, ECO:0000269|PubMed:15235609, CC ECO:0000269|PubMed:15383005, ECO:0000269|PubMed:15577939, CC ECO:0000269|PubMed:15708368, ECO:0000269|PubMed:16307917, CC ECO:0000269|PubMed:16531226, ECO:0000269|PubMed:17028174, CC ECO:0000269|PubMed:17947705, ECO:0000269|PubMed:18400751, CC ECO:0000269|PubMed:19875381, ECO:0000269|PubMed:20353823, CC ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:23569206, CC ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:24681825, CC ECO:0000269|PubMed:25738358, ECO:0000269|PubMed:26517842, CC ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:30559449, CC ECO:0000269|PubMed:7588731, ECO:0000269|PubMed:8289821, CC ECO:0000269|PubMed:9195923, ECO:0000269|PubMed:9660753, CC ECO:0000269|PubMed:9817749}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC protein US11; this interaction inhibits TBK1-induced interferon CC production. {ECO:0000269|PubMed:29743370}. CC -!- SUBUNIT: (Microbial infection) Interacts with N.meningitidis serogroup CC B adhesin A (nadA). Interaction is stabilized by ADP and 17-AAG (17-N- CC allylamino-17-demethoxygeldanamycin) and inhibited by ATP. Decreasing CC HSP90 levels increases adhesion and entry of bacterial into human Chang CC cells; increasing its levels leads to decreased adhseion and invasion. CC {ECO:0000269|PubMed:22066472}. CC -!- INTERACTION: CC P07900; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-296047, EBI-10173507; CC P07900; O95433: AHSA1; NbExp=4; IntAct=EBI-296047, EBI-448610; CC P07900; P05067: APP; NbExp=5; IntAct=EBI-296047, EBI-77613; CC P07900; Q9H0C5: BTBD1; NbExp=4; IntAct=EBI-296047, EBI-935503; CC P07900; Q9UQM7: CAMK2A; NbExp=5; IntAct=EBI-296047, EBI-1383687; CC P07900; Q8IWD4: CCDC117; NbExp=5; IntAct=EBI-296047, EBI-3387963; CC P07900; Q9BV29: CCDC32; NbExp=3; IntAct=EBI-296047, EBI-2874058; CC P07900; Q16543: CDC37; NbExp=14; IntAct=EBI-296047, EBI-295634; CC P07900; Q7L3B6: CDC37L1; NbExp=2; IntAct=EBI-296047, EBI-2841876; CC P07900; P50750: CDK9; NbExp=3; IntAct=EBI-296047, EBI-1383449; CC P07900; Q96G23: CERS2; NbExp=2; IntAct=EBI-296047, EBI-1057080; CC P07900; Q9UHD1: CHORDC1; NbExp=8; IntAct=EBI-296047, EBI-2550959; CC P07900; O15111: CHUK; NbExp=3; IntAct=EBI-296047, EBI-81249; CC P07900; Q6QEF8-4: CORO6; NbExp=3; IntAct=EBI-296047, EBI-10699285; CC P07900; Q14194: CRMP1; NbExp=3; IntAct=EBI-296047, EBI-473101; CC P07900; P35222: CTNNB1; NbExp=3; IntAct=EBI-296047, EBI-491549; CC P07900; Q15438: CYTH1; NbExp=3; IntAct=EBI-296047, EBI-997830; CC P07900; Q9NR20: DYRK4; NbExp=2; IntAct=EBI-296047, EBI-3914009; CC P07900; P00533: EGFR; NbExp=7; IntAct=EBI-296047, EBI-297353; CC P07900; P04626: ERBB2; NbExp=6; IntAct=EBI-296047, EBI-641062; CC P07900; Q02790: FKBP4; NbExp=8; IntAct=EBI-296047, EBI-1047444; CC P07900; Q13451: FKBP5; NbExp=8; IntAct=EBI-296047, EBI-306914; CC P07900; Q14318: FKBP8; NbExp=7; IntAct=EBI-296047, EBI-724839; CC P07900; P06241: FYN; NbExp=6; IntAct=EBI-296047, EBI-515315; CC P07900; Q96LI6-3: HSFY2; NbExp=3; IntAct=EBI-296047, EBI-25830912; CC P07900; P07900: HSP90AA1; NbExp=6; IntAct=EBI-296047, EBI-296047; CC P07900; Q6PK50: HSP90AB1; NbExp=2; IntAct=EBI-296047, EBI-9356629; CC P07900; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-296047, EBI-81279; CC P07900; Q9UHH9: IP6K2; NbExp=2; IntAct=EBI-296047, EBI-747509; CC P07900; P05412: JUN; NbExp=4; IntAct=EBI-296047, EBI-852823; CC P07900; Q92993-2: KAT5; NbExp=3; IntAct=EBI-296047, EBI-20795332; CC P07900; Q6VAB6: KSR2; NbExp=6; IntAct=EBI-296047, EBI-6424389; CC P07900; P06239: LCK; NbExp=3; IntAct=EBI-296047, EBI-1348; CC P07900; Q99558: MAP3K14; NbExp=5; IntAct=EBI-296047, EBI-358011; CC P07900; O43318-2: MAP3K7; NbExp=5; IntAct=EBI-296047, EBI-358700; CC P07900; P00540: MOS; NbExp=2; IntAct=EBI-296047, EBI-1757866; CC P07900; P04150: NR3C1; NbExp=8; IntAct=EBI-296047, EBI-493507; CC P07900; Q8WVJ2: NUDCD2; NbExp=4; IntAct=EBI-296047, EBI-1052153; CC P07900; P43034: PAFAH1B1; NbExp=5; IntAct=EBI-296047, EBI-720620; CC P07900; P53041: PPP5C; NbExp=12; IntAct=EBI-296047, EBI-716663; CC P07900; P17612: PRKACA; NbExp=4; IntAct=EBI-296047, EBI-476586; CC P07900; Q8WUY3: PRUNE2; NbExp=3; IntAct=EBI-296047, EBI-743880; CC P07900; Q96QS6: PSKH2; NbExp=2; IntAct=EBI-296047, EBI-6424813; CC P07900; Q15185: PTGES3; NbExp=6; IntAct=EBI-296047, EBI-1049387; CC P07900; P04049: RAF1; NbExp=4; IntAct=EBI-296047, EBI-365996; CC P07900; Q13127: REST; NbExp=4; IntAct=EBI-296047, EBI-926706; CC P07900; Q9H6T3: RPAP3; NbExp=6; IntAct=EBI-296047, EBI-356928; CC P07900; P61247: RPS3A; NbExp=3; IntAct=EBI-296047, EBI-352378; CC P07900; P12931: SRC; NbExp=3; IntAct=EBI-296047, EBI-621482; CC P07900; Q15831: STK11; NbExp=3; IntAct=EBI-296047, EBI-306838; CC P07900; Q9UNE7: STUB1; NbExp=9; IntAct=EBI-296047, EBI-357085; CC P07900; O94826: TOMM70; NbExp=4; IntAct=EBI-296047, EBI-2800236; CC P07900; Q9BXA6: TSSK6; NbExp=2; IntAct=EBI-296047, EBI-851883; CC P07900; P10599: TXN; NbExp=3; IntAct=EBI-296047, EBI-594644; CC P07900; Q9H6R7-2: WDCP; NbExp=3; IntAct=EBI-296047, EBI-25833271; CC P07900; P26882: PPID; Xeno; NbExp=4; IntAct=EBI-296047, EBI-6477155; CC P07900; P35467: S100a1; Xeno; NbExp=4; IntAct=EBI-296047, EBI-6477109; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P07901}. Cytoplasm CC {ECO:0000250|UniProtKB:P07901}. Melanosome CC {ECO:0000269|PubMed:17081065}. Cell membrane CC {ECO:0000269|PubMed:11276205}. Mitochondrion CC {ECO:0000269|PubMed:25609812}. Note=Identified by mass spectrometry in CC melanosome fractions from stage I to stage IV. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=HSP90AA1-1, HSP90-alpha 2; CC IsoId=P07900-1; Sequence=Displayed; CC Name=2; Synonyms=HSP90AA1-2; CC IsoId=P07900-2; Sequence=VSP_026604; CC -!- DOMAIN: The TPR repeat-binding motif mediates interaction with TPR CC repeat-containing proteins like the co-chaperone STUB1. CC {ECO:0000269|PubMed:16307917}. CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}. CC -!- PTM: S-nitrosylated; negatively regulates the ATPase activity and the CC activation of eNOS by HSP90AA1. {ECO:0000269|PubMed:15937123}. CC -!- PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. CC Ubiquitination promotes translocation into the cytoplasm away from the CC membrane and secretory pathways. {ECO:0000250|UniProtKB:P07901}. CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X15183; CAA33259.1; -; mRNA. DR EMBL; M27024; AAA63194.1; -; Genomic_DNA. DR EMBL; AJ890082; CAI64495.1; -; mRNA. DR EMBL; AJ890083; CAI64496.1; -; mRNA. DR EMBL; DQ314871; ABC40730.1; -; Genomic_DNA. DR EMBL; AK056446; BAG51711.1; -; mRNA. DR EMBL; AK291115; BAF83804.1; -; mRNA. DR EMBL; AK291607; BAF84296.1; -; mRNA. DR EMBL; AL133223; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471061; EAW81765.1; -; Genomic_DNA. DR EMBL; X07270; CAA30255.1; -; mRNA. DR EMBL; M30626; AAA36023.1; -; Genomic_DNA. DR EMBL; BC000987; AAH00987.1; -; mRNA. DR EMBL; BC121062; AAI21063.1; -; mRNA. DR EMBL; D87666; BAA13430.1; -; mRNA. DR EMBL; D87666; BAA13431.1; -; mRNA. DR CCDS; CCDS32160.1; -. [P07900-2] DR CCDS; CCDS9967.1; -. [P07900-1] DR PIR; A32319; HHHU86. DR RefSeq; NP_001017963.2; NM_001017963.2. [P07900-2] DR RefSeq; NP_005339.3; NM_005348.3. [P07900-1] DR PDB; 1BYQ; X-ray; 1.50 A; A=9-236. DR PDB; 1OSF; X-ray; 1.75 A; A=9-223. DR PDB; 1UY6; X-ray; 1.90 A; A=2-236. DR PDB; 1UY7; X-ray; 1.90 A; A=2-236. DR PDB; 1UY8; X-ray; 1.98 A; A=2-236. DR PDB; 1UY9; X-ray; 2.00 A; A=2-236. DR PDB; 1UYC; X-ray; 2.00 A; A=2-236. DR PDB; 1UYD; X-ray; 2.20 A; A=2-236. DR PDB; 1UYE; X-ray; 2.00 A; A=2-236. DR PDB; 1UYF; X-ray; 2.00 A; A=2-236. DR PDB; 1UYG; X-ray; 2.00 A; A=2-236. DR PDB; 1UYH; X-ray; 2.20 A; A=2-236. DR PDB; 1UYI; X-ray; 2.20 A; A=2-236. DR PDB; 1UYK; X-ray; 2.20 A; A=2-236. DR PDB; 1UYL; X-ray; 1.40 A; A=2-236. DR PDB; 1YC1; X-ray; 1.70 A; A=9-236. DR PDB; 1YC3; X-ray; 2.12 A; A=9-236. DR PDB; 1YC4; X-ray; 1.81 A; A=9-236. DR PDB; 1YER; X-ray; 1.65 A; A=9-236. DR PDB; 1YES; X-ray; 2.20 A; A=9-236. DR PDB; 1YET; X-ray; 1.90 A; A=9-236. DR PDB; 2BSM; X-ray; 2.05 A; A=2-236. DR PDB; 2BT0; X-ray; 1.90 A; A/B=2-236. DR PDB; 2BUG; NMR; -; B=728-732. DR PDB; 2BYH; X-ray; 1.90 A; A=11-236. DR PDB; 2BYI; X-ray; 1.60 A; A=11-236. DR PDB; 2BZ5; X-ray; 1.90 A; A/B=2-236. DR PDB; 2C2L; X-ray; 3.30 A; E/F/G/H=724-732. DR PDB; 2CCS; X-ray; 1.79 A; A=1-236. DR PDB; 2CCT; X-ray; 2.30 A; A=1-236. DR PDB; 2CCU; X-ray; 2.70 A; A=1-236. DR PDB; 2FWY; X-ray; 2.10 A; A=1-236. DR PDB; 2FWZ; X-ray; 2.10 A; A=1-236. DR PDB; 2H55; X-ray; 2.00 A; A=1-236. DR PDB; 2JJC; X-ray; 1.95 A; A=9-223. DR PDB; 2K5B; NMR; -; A=14-223. DR PDB; 2QF6; X-ray; 3.10 A; A/B/C/D=17-223. DR PDB; 2QFO; X-ray; 1.68 A; A/B=17-223. DR PDB; 2QG0; X-ray; 1.85 A; A/B=17-223. DR PDB; 2QG2; X-ray; 1.80 A; A=17-223. DR PDB; 2UWD; X-ray; 1.90 A; A=2-236. DR PDB; 2VCI; X-ray; 2.00 A; A=1-236. DR PDB; 2VCJ; X-ray; 2.50 A; A=1-236. DR PDB; 2WI1; X-ray; 2.30 A; A=1-236. DR PDB; 2WI2; X-ray; 2.09 A; A/B=1-236. DR PDB; 2WI3; X-ray; 1.90 A; A=1-236. DR PDB; 2WI4; X-ray; 2.40 A; A=1-236. DR PDB; 2WI5; X-ray; 2.10 A; A=1-236. DR PDB; 2WI6; X-ray; 2.18 A; A=1-236. DR PDB; 2WI7; X-ray; 2.50 A; A=1-236. DR PDB; 2XAB; X-ray; 1.90 A; A/B=9-236. DR PDB; 2XDK; X-ray; 1.97 A; A=9-236. DR PDB; 2XDL; X-ray; 1.98 A; A=9-236. DR PDB; 2XDS; X-ray; 1.97 A; A=9-236. DR PDB; 2XDU; X-ray; 1.74 A; A=14-224. DR PDB; 2XDX; X-ray; 2.42 A; A=9-236. DR PDB; 2XHR; X-ray; 2.20 A; A=9-236. DR PDB; 2XHT; X-ray; 2.27 A; A=9-236. DR PDB; 2XHX; X-ray; 2.80 A; A=9-236. DR PDB; 2XJG; X-ray; 2.25 A; A=9-236. DR PDB; 2XJJ; X-ray; 1.90 A; A/B=9-236. DR PDB; 2XJX; X-ray; 1.66 A; A=9-236. DR PDB; 2XK2; X-ray; 1.95 A; A=9-236. DR PDB; 2YE2; X-ray; 1.90 A; A=9-236. DR PDB; 2YE3; X-ray; 1.95 A; A=9-236. DR PDB; 2YE4; X-ray; 2.30 A; A=9-236. DR PDB; 2YE5; X-ray; 1.73 A; A=9-236. DR PDB; 2YE6; X-ray; 2.56 A; A=9-236. DR PDB; 2YE7; X-ray; 2.20 A; A=9-236. DR PDB; 2YE8; X-ray; 2.30 A; A=9-236. DR PDB; 2YE9; X-ray; 2.20 A; A=9-236. DR PDB; 2YEA; X-ray; 1.73 A; A=9-236. DR PDB; 2YEB; X-ray; 2.40 A; A=9-236. DR PDB; 2YEC; X-ray; 2.10 A; A=9-236. DR PDB; 2YED; X-ray; 2.10 A; A=9-236. DR PDB; 2YEE; X-ray; 2.30 A; A=9-236. DR PDB; 2YEF; X-ray; 1.55 A; A=9-236. DR PDB; 2YEG; X-ray; 2.50 A; A/B=9-236. DR PDB; 2YEH; X-ray; 2.10 A; A=9-236. DR PDB; 2YEI; X-ray; 2.20 A; A=9-236. DR PDB; 2YEJ; X-ray; 2.20 A; A=9-236. DR PDB; 2YI0; X-ray; 1.60 A; A=1-229. DR PDB; 2YI5; X-ray; 2.50 A; A=1-229. DR PDB; 2YI6; X-ray; 1.80 A; A=1-229. DR PDB; 2YI7; X-ray; 1.40 A; A=1-229. DR PDB; 2YJW; X-ray; 1.61 A; A=18-223. DR PDB; 2YJX; X-ray; 1.83 A; A=18-223. DR PDB; 2YK2; X-ray; 1.74 A; A=18-223. DR PDB; 2YK9; X-ray; 1.32 A; A=18-223. DR PDB; 2YKB; X-ray; 1.93 A; A=18-223. DR PDB; 2YKC; X-ray; 1.67 A; A=18-223. DR PDB; 2YKE; X-ray; 1.43 A; A=18-223. DR PDB; 2YKI; X-ray; 1.67 A; A=18-223. DR PDB; 2YKJ; X-ray; 1.46 A; A=18-223. DR PDB; 3B24; X-ray; 1.70 A; A/B=9-236. DR PDB; 3B25; X-ray; 1.75 A; A=9-236. DR PDB; 3B26; X-ray; 2.10 A; A/B=9-236. DR PDB; 3B27; X-ray; 1.50 A; A=9-236. DR PDB; 3B28; X-ray; 1.35 A; A/B=9-236. DR PDB; 3BM9; X-ray; 1.60 A; A=14-236. DR PDB; 3BMY; X-ray; 1.60 A; A=14-236. DR PDB; 3D0B; X-ray; 1.74 A; A=1-232. DR PDB; 3EKO; X-ray; 1.55 A; A/B=9-225. DR PDB; 3EKR; X-ray; 2.00 A; A/B=9-225. DR PDB; 3FT5; X-ray; 1.90 A; A=9-236. DR PDB; 3FT8; X-ray; 2.00 A; A=9-236. DR PDB; 3HEK; X-ray; 1.95 A; A/B=9-225. DR PDB; 3HHU; X-ray; 1.59 A; A/B=1-224. DR PDB; 3HYY; X-ray; 1.90 A; A=9-236. DR PDB; 3HYZ; X-ray; 2.30 A; A/B=9-236. DR PDB; 3HZ1; X-ray; 2.30 A; A=9-236. DR PDB; 3HZ5; X-ray; 1.90 A; A=9-236. DR PDB; 3INW; X-ray; 1.95 A; A=10-236. DR PDB; 3INX; X-ray; 1.75 A; A=10-236. DR PDB; 3K97; X-ray; 1.95 A; A=9-236. DR PDB; 3K98; X-ray; 2.40 A; A/B=9-225. DR PDB; 3K99; X-ray; 2.10 A; A/B/C/D=9-225. DR PDB; 3MNR; X-ray; 1.90 A; P=1-232. DR PDB; 3O0I; X-ray; 1.47 A; A=1-236. DR PDB; 3OW6; X-ray; 1.80 A; A=17-223. DR PDB; 3OWB; X-ray; 2.05 A; A=17-223. DR PDB; 3OWD; X-ray; 1.63 A; A=17-223. DR PDB; 3Q6M; X-ray; 3.00 A; A/B/C=293-732. DR PDB; 3Q6N; X-ray; 3.05 A; A/B/C/D/E/F=293-732. DR PDB; 3QDD; X-ray; 1.79 A; A=1-236. DR PDB; 3QTF; X-ray; 1.57 A; A=14-236. DR PDB; 3R4M; X-ray; 1.70 A; A=9-236. DR PDB; 3R4N; X-ray; 2.00 A; A/B=9-225. DR PDB; 3R4O; X-ray; 2.65 A; A/B=9-225. DR PDB; 3R4P; X-ray; 1.70 A; A/B=9-225. DR PDB; 3R91; X-ray; 1.58 A; A=14-236. DR PDB; 3R92; X-ray; 1.58 A; A=14-236. DR PDB; 3RKZ; X-ray; 1.57 A; A=14-236. DR PDB; 3RLP; X-ray; 1.70 A; A/B=9-225. DR PDB; 3RLQ; X-ray; 1.90 A; A/B=9-225. DR PDB; 3RLR; X-ray; 1.70 A; A/B=9-225. DR PDB; 3T0H; X-ray; 1.20 A; A=9-236. DR PDB; 3T0Z; X-ray; 2.19 A; A=9-236. DR PDB; 3T10; X-ray; 1.24 A; A=9-236. DR PDB; 3T1K; X-ray; 1.50 A; A/B=9-236. DR PDB; 3T2S; X-ray; 1.50 A; A/B=9-236. DR PDB; 3TUH; X-ray; 1.80 A; A/B=16-224. DR PDB; 3VHA; X-ray; 1.39 A; A=9-236. DR PDB; 3VHC; X-ray; 1.41 A; A=9-236. DR PDB; 3VHD; X-ray; 1.52 A; A/B=9-236. DR PDB; 3WHA; X-ray; 1.30 A; A/B=9-236. DR PDB; 3WQ9; X-ray; 1.80 A; A=1-236. DR PDB; 4AIF; X-ray; 2.01 A; D/E=726-732. DR PDB; 4AWO; X-ray; 1.70 A; A/B=9-236. DR PDB; 4AWP; X-ray; 1.82 A; A/B=9-236. DR PDB; 4AWQ; X-ray; 1.60 A; A/B=9-236. DR PDB; 4B7P; X-ray; 1.70 A; A=9-236. DR PDB; 4BQG; X-ray; 1.90 A; A=9-236. DR PDB; 4BQJ; X-ray; 2.00 A; A=9-236. DR PDB; 4CGQ; X-ray; 2.00 A; Q=726-732. DR PDB; 4CGU; X-ray; 2.11 A; C=726-732. DR PDB; 4CGV; X-ray; 2.54 A; E/F=726-732. DR PDB; 4CGW; X-ray; 3.00 A; C/D=726-732. DR PDB; 4CWF; X-ray; 2.00 A; A=9-236. DR PDB; 4CWN; X-ray; 1.80 A; A=9-236. DR PDB; 4CWO; X-ray; 2.31 A; A=9-236. DR PDB; 4CWP; X-ray; 1.95 A; A=9-236. DR PDB; 4CWQ; X-ray; 2.00 A; A=9-236. DR PDB; 4CWR; X-ray; 2.00 A; A=9-236. DR PDB; 4CWS; X-ray; 2.30 A; A=9-236. DR PDB; 4CWT; X-ray; 1.90 A; A=9-236. DR PDB; 4EEH; X-ray; 1.60 A; A=9-236. DR PDB; 4EFT; X-ray; 2.12 A; A=9-236. DR PDB; 4EFU; X-ray; 2.00 A; A=9-236. DR PDB; 4EGH; X-ray; 1.60 A; A=9-236. DR PDB; 4EGI; X-ray; 1.79 A; A=9-236. DR PDB; 4EGK; X-ray; 1.69 A; A=9-236. DR PDB; 4FCP; X-ray; 2.00 A; A/B=1-236. DR PDB; 4FCQ; X-ray; 2.15 A; A=1-236. DR PDB; 4FCR; X-ray; 1.70 A; A=1-236. DR PDB; 4HY6; X-ray; 1.65 A; A=9-236. DR PDB; 4JQL; X-ray; 1.72 A; A=9-236. DR PDB; 4L8Z; X-ray; 1.70 A; A=9-236. DR PDB; 4L90; X-ray; 2.00 A; A=9-236. DR PDB; 4L91; X-ray; 1.75 A; A=9-236. DR PDB; 4L93; X-ray; 1.84 A; A/B=9-236. DR PDB; 4L94; X-ray; 1.65 A; A=9-236. DR PDB; 4LWE; X-ray; 1.50 A; A=17-224. DR PDB; 4LWF; X-ray; 1.75 A; A=17-224. DR PDB; 4LWG; X-ray; 1.60 A; A=17-224. DR PDB; 4LWH; X-ray; 1.70 A; A=16-224. DR PDB; 4LWI; X-ray; 1.70 A; A=17-224. DR PDB; 4NH7; X-ray; 2.00 A; A/B=9-236. DR PDB; 4NH8; X-ray; 1.65 A; A=9-236. DR PDB; 4O04; X-ray; 1.82 A; A=9-236. DR PDB; 4O05; X-ray; 1.79 A; A=9-236. DR PDB; 4O07; X-ray; 1.86 A; A=9-236. DR PDB; 4O09; X-ray; 1.96 A; A=9-236. DR PDB; 4O0B; X-ray; 1.93 A; A=9-236. DR PDB; 4R3M; X-ray; 1.80 A; A=16-224. DR PDB; 4U93; X-ray; 1.55 A; A=1-236. DR PDB; 4W7T; X-ray; 1.80 A; A=1-236. DR PDB; 4XIP; X-ray; 1.70 A; A=9-236. DR PDB; 4XIQ; X-ray; 1.84 A; A=9-236. DR PDB; 4XIR; X-ray; 1.70 A; A=9-236. DR PDB; 4XIT; X-ray; 1.86 A; A=9-236. DR PDB; 4YKQ; X-ray; 1.91 A; A=2-236. DR PDB; 4YKR; X-ray; 1.61 A; A=2-236. DR PDB; 4YKT; X-ray; 1.85 A; A=2-236. DR PDB; 4YKU; X-ray; 1.70 A; A=2-236. DR PDB; 4YKW; X-ray; 1.85 A; A/B=2-236. DR PDB; 4YKX; X-ray; 1.80 A; A=2-236. DR PDB; 4YKY; X-ray; 1.78 A; A=2-236. DR PDB; 4YKZ; X-ray; 1.85 A; A=2-236. DR PDB; 5CF0; X-ray; 1.80 A; A=9-236. DR PDB; 5FNC; X-ray; 2.20 A; A=1-236. DR PDB; 5FND; X-ray; 2.00 A; A=1-236. DR PDB; 5FNF; X-ray; 2.10 A; A=1-236. DR PDB; 5GGZ; X-ray; 2.02 A; A/B/C/D=16-225. DR PDB; 5J20; X-ray; 1.76 A; A=17-223. DR PDB; 5J27; X-ray; 1.70 A; A=16-224. DR PDB; 5J2V; X-ray; 1.59 A; A=17-223. DR PDB; 5J2X; X-ray; 1.22 A; A=17-224. DR PDB; 5J64; X-ray; 1.38 A; A=9-236. DR PDB; 5J6L; X-ray; 1.75 A; A=9-236. DR PDB; 5J6M; X-ray; 1.64 A; A=9-234. DR PDB; 5J6N; X-ray; 1.90 A; A=9-234. DR PDB; 5J80; X-ray; 1.17 A; A=9-233. DR PDB; 5J82; X-ray; 2.17 A; A=9-233. DR PDB; 5J86; X-ray; 1.87 A; A=9-233. DR PDB; 5J8M; X-ray; 1.90 A; A/B=9-233. DR PDB; 5J8U; X-ray; 1.75 A; A/B=9-233. DR PDB; 5J9X; X-ray; 1.80 A; A=9-233. DR PDB; 5LNY; X-ray; 1.88 A; A=9-236. DR PDB; 5LNZ; X-ray; 1.54 A; A=9-236. DR PDB; 5LO0; X-ray; 2.30 A; A=9-236. DR PDB; 5LO1; X-ray; 2.70 A; A=9-236. DR PDB; 5LO5; X-ray; 1.44 A; A=9-236. DR PDB; 5LO6; X-ray; 2.40 A; A=9-236. DR PDB; 5LQ9; X-ray; 1.90 A; A=17-223. DR PDB; 5LR1; X-ray; 1.44 A; A=18-223. DR PDB; 5LR7; X-ray; 1.86 A; A=18-223. DR PDB; 5LRL; X-ray; 1.33 A; A=18-223. DR PDB; 5LRZ; X-ray; 2.00 A; A=18-223. DR PDB; 5LS1; X-ray; 1.85 A; A=17-223. DR PDB; 5M4E; X-ray; 1.90 A; A=9-236. DR PDB; 5M4H; X-ray; 2.00 A; A=9-236. DR PDB; 5NYH; X-ray; 1.65 A; A=9-236. DR PDB; 5NYI; X-ray; 1.44 A; A=9-235. DR PDB; 5OCI; X-ray; 1.62 A; A=9-236. DR PDB; 5OD7; X-ray; 2.00 A; A=9-236. DR PDB; 5ODX; X-ray; 1.82 A; A=9-236. DR PDB; 5T21; X-ray; 2.10 A; A=18-223. DR PDB; 5VYY; X-ray; 1.79 A; A=1-236. DR PDB; 5XQD; X-ray; 1.60 A; A=9-236. DR PDB; 5XQE; X-ray; 1.70 A; A=9-236. DR PDB; 5XR5; X-ray; 1.60 A; A=9-236. DR PDB; 5XR9; X-ray; 1.50 A; A=9-236. DR PDB; 5XRB; X-ray; 1.65 A; A=9-236. DR PDB; 5XRD; X-ray; 1.30 A; A=9-236. DR PDB; 5XRE; X-ray; 1.50 A; A=9-236. DR PDB; 5ZR3; X-ray; 2.50 A; A/C/E/G=1-236. DR PDB; 6B99; X-ray; 1.60 A; A=1-236. DR PDB; 6B9A; X-ray; 1.65 A; A/B=1-236. DR PDB; 6CEO; X-ray; 1.90 A; A=1-236. DR PDB; 6CYG; X-ray; 1.50 A; A/B=1-236. DR PDB; 6CYH; X-ray; 1.49 A; A/B=1-236. DR PDB; 6EI5; X-ray; 2.20 A; A=15-223. DR PDB; 6EL5; X-ray; 1.67 A; A=1-236. DR PDB; 6ELN; X-ray; 1.60 A; A=17-223. DR PDB; 6ELO; X-ray; 1.80 A; A=1-236. DR PDB; 6ELP; X-ray; 1.85 A; A=1-236. DR PDB; 6EY8; X-ray; 2.16 A; A=1-236. DR PDB; 6EY9; X-ray; 2.00 A; A=1-236. DR PDB; 6EYA; X-ray; 2.10 A; A=1-236. DR PDB; 6EYB; X-ray; 1.90 A; A=1-236. DR PDB; 6F1N; X-ray; 2.09 A; A=1-236. DR PDB; 6FCJ; X-ray; 2.49 A; A=9-236. DR PDB; 6FDP; NMR; -; B=724-732. DR PDB; 6GP4; X-ray; 1.70 A; A=1-236. DR PDB; 6GP8; X-ray; 1.75 A; A=1-236. DR PDB; 6GPF; X-ray; 1.55 A; A=1-236. DR PDB; 6GPH; X-ray; 1.56 A; A=1-236. DR PDB; 6GPO; X-ray; 1.48 A; A=1-236. DR PDB; 6GPP; X-ray; 1.51 A; A=1-236. DR PDB; 6GPR; X-ray; 2.35 A; A=1-236. DR PDB; 6GPT; X-ray; 2.00 A; A=1-236. DR PDB; 6GPW; X-ray; 1.60 A; A=1-236. DR PDB; 6GPY; X-ray; 2.25 A; A=1-236. DR PDB; 6GQ6; X-ray; 2.25 A; A=1-236. DR PDB; 6GQR; X-ray; 2.05 A; A=1-236. DR PDB; 6GQS; X-ray; 1.43 A; A=1-236. DR PDB; 6GQU; X-ray; 1.72 A; A=1-236. DR PDB; 6GR1; X-ray; 2.05 A; A=1-236. DR PDB; 6GR3; X-ray; 1.88 A; A=1-236. DR PDB; 6GR4; X-ray; 1.50 A; A=1-236. DR PDB; 6GR5; X-ray; 1.34 A; A=1-236. DR PDB; 6HHR; X-ray; 2.00 A; A=17-224. DR PDB; 6KSQ; X-ray; 2.20 A; A=293-554. DR PDB; 6LR9; X-ray; 2.20 A; A=9-236. DR PDB; 6LSZ; X-ray; 1.99 A; A=9-236. DR PDB; 6LT8; X-ray; 1.59 A; A=9-236. DR PDB; 6LTI; X-ray; 1.59 A; A=9-236. DR PDB; 6LTK; X-ray; 2.14 A; A=9-236. DR PDB; 6N8X; X-ray; 1.49 A; A=1-236. DR PDB; 6OLX; X-ray; 1.44 A; A=1-236. DR PDB; 6TN4; X-ray; 1.27 A; AAA=9-236. DR PDB; 6TN5; X-ray; 1.17 A; AAA=9-236. DR PDB; 6U98; X-ray; 1.50 A; A=2-236. DR PDB; 6U99; X-ray; 1.60 A; A=2-236. DR PDB; 6U9A; X-ray; 1.65 A; A=2-236. DR PDB; 6U9B; X-ray; 1.75 A; A=2-236. DR PDB; 7DMC; X-ray; 2.34 A; A=16-224. DR PDB; 7KRJ; EM; 2.56 A; A/B=1-732. DR PDB; 7KW7; EM; 3.57 A; A/B=1-732. DR PDB; 7L7I; EM; 3.30 A; A/B=1-732. DR PDB; 7L7J; EM; 3.10 A; A/B=1-732. DR PDB; 7LSZ; X-ray; 1.70 A; A=1-293. DR PDB; 7LT0; X-ray; 1.70 A; A=1-293. DR PDB; 7RY1; X-ray; 3.52 A; A/B/C=293-714. DR PDB; 7S8Y; X-ray; 1.59 A; A=1-236. DR PDB; 7S8Z; X-ray; 1.64 A; A=1-236. DR PDB; 7S90; X-ray; 1.79 A; A=1-236. DR PDB; 7S95; X-ray; 1.71 A; A=1-236. DR PDB; 7S98; X-ray; 1.90 A; A=1-236. DR PDB; 7S99; X-ray; 1.52 A; A=1-236. DR PDB; 7S9F; X-ray; 2.30 A; A=1-236. DR PDB; 7S9G; X-ray; 1.79 A; A=1-236. DR PDB; 7S9H; X-ray; 1.45 A; A=1-236. DR PDB; 7S9I; X-ray; 1.75 A; A=1-236. DR PDB; 8AGI; X-ray; 2.10 A; A/B=1-236. DR PDB; 8AGJ; X-ray; 2.32 A; A/B=1-236. DR PDB; 8AGL; X-ray; 2.20 A; A/B=1-236. DR PDBsum; 1BYQ; -. DR PDBsum; 1OSF; -. DR PDBsum; 1UY6; -. DR PDBsum; 1UY7; -. DR PDBsum; 1UY8; -. DR PDBsum; 1UY9; -. DR PDBsum; 1UYC; -. DR PDBsum; 1UYD; -. DR PDBsum; 1UYE; -. DR PDBsum; 1UYF; -. DR PDBsum; 1UYG; -. DR PDBsum; 1UYH; -. DR PDBsum; 1UYI; -. DR PDBsum; 1UYK; -. DR PDBsum; 1UYL; -. DR PDBsum; 1YC1; -. DR PDBsum; 1YC3; -. DR PDBsum; 1YC4; -. DR PDBsum; 1YER; -. DR PDBsum; 1YES; -. DR PDBsum; 1YET; -. DR PDBsum; 2BSM; -. DR PDBsum; 2BT0; -. DR PDBsum; 2BUG; -. DR PDBsum; 2BYH; -. DR PDBsum; 2BYI; -. DR PDBsum; 2BZ5; -. DR PDBsum; 2C2L; -. DR PDBsum; 2CCS; -. DR PDBsum; 2CCT; -. DR PDBsum; 2CCU; -. DR PDBsum; 2FWY; -. DR PDBsum; 2FWZ; -. DR PDBsum; 2H55; -. DR PDBsum; 2JJC; -. DR PDBsum; 2K5B; -. DR PDBsum; 2QF6; -. DR PDBsum; 2QFO; -. DR PDBsum; 2QG0; -. DR PDBsum; 2QG2; -. DR PDBsum; 2UWD; -. DR PDBsum; 2VCI; -. DR PDBsum; 2VCJ; -. DR PDBsum; 2WI1; -. DR PDBsum; 2WI2; -. DR PDBsum; 2WI3; -. DR PDBsum; 2WI4; -. DR PDBsum; 2WI5; -. DR PDBsum; 2WI6; -. DR PDBsum; 2WI7; -. DR PDBsum; 2XAB; -. DR PDBsum; 2XDK; -. DR PDBsum; 2XDL; -. DR PDBsum; 2XDS; -. DR PDBsum; 2XDU; -. DR PDBsum; 2XDX; -. DR PDBsum; 2XHR; -. DR PDBsum; 2XHT; -. DR PDBsum; 2XHX; -. DR PDBsum; 2XJG; -. DR PDBsum; 2XJJ; -. DR PDBsum; 2XJX; -. DR PDBsum; 2XK2; -. DR PDBsum; 2YE2; -. DR PDBsum; 2YE3; -. DR PDBsum; 2YE4; -. DR PDBsum; 2YE5; -. DR PDBsum; 2YE6; -. DR PDBsum; 2YE7; -. DR PDBsum; 2YE8; -. DR PDBsum; 2YE9; -. DR PDBsum; 2YEA; -. DR PDBsum; 2YEB; -. DR PDBsum; 2YEC; -. DR PDBsum; 2YED; -. DR PDBsum; 2YEE; -. DR PDBsum; 2YEF; -. DR PDBsum; 2YEG; -. DR PDBsum; 2YEH; -. DR PDBsum; 2YEI; -. DR PDBsum; 2YEJ; -. DR PDBsum; 2YI0; -. DR PDBsum; 2YI5; -. DR PDBsum; 2YI6; -. DR PDBsum; 2YI7; -. DR PDBsum; 2YJW; -. DR PDBsum; 2YJX; -. DR PDBsum; 2YK2; -. DR PDBsum; 2YK9; -. DR PDBsum; 2YKB; -. DR PDBsum; 2YKC; -. DR PDBsum; 2YKE; -. DR PDBsum; 2YKI; -. DR PDBsum; 2YKJ; -. DR PDBsum; 3B24; -. DR PDBsum; 3B25; -. DR PDBsum; 3B26; -. DR PDBsum; 3B27; -. DR PDBsum; 3B28; -. DR PDBsum; 3BM9; -. DR PDBsum; 3BMY; -. DR PDBsum; 3D0B; -. DR PDBsum; 3EKO; -. DR PDBsum; 3EKR; -. DR PDBsum; 3FT5; -. DR PDBsum; 3FT8; -. DR PDBsum; 3HEK; -. DR PDBsum; 3HHU; -. DR PDBsum; 3HYY; -. DR PDBsum; 3HYZ; -. DR PDBsum; 3HZ1; -. DR PDBsum; 3HZ5; -. DR PDBsum; 3INW; -. DR PDBsum; 3INX; -. DR PDBsum; 3K97; -. DR PDBsum; 3K98; -. DR PDBsum; 3K99; -. DR PDBsum; 3MNR; -. DR PDBsum; 3O0I; -. DR PDBsum; 3OW6; -. DR PDBsum; 3OWB; -. DR PDBsum; 3OWD; -. DR PDBsum; 3Q6M; -. DR PDBsum; 3Q6N; -. DR PDBsum; 3QDD; -. DR PDBsum; 3QTF; -. DR PDBsum; 3R4M; -. DR PDBsum; 3R4N; -. DR PDBsum; 3R4O; -. DR PDBsum; 3R4P; -. DR PDBsum; 3R91; -. DR PDBsum; 3R92; -. DR PDBsum; 3RKZ; -. DR PDBsum; 3RLP; -. DR PDBsum; 3RLQ; -. DR PDBsum; 3RLR; -. DR PDBsum; 3T0H; -. DR PDBsum; 3T0Z; -. DR PDBsum; 3T10; -. DR PDBsum; 3T1K; -. DR PDBsum; 3T2S; -. DR PDBsum; 3TUH; -. DR PDBsum; 3VHA; -. DR PDBsum; 3VHC; -. DR PDBsum; 3VHD; -. DR PDBsum; 3WHA; -. DR PDBsum; 3WQ9; -. DR PDBsum; 4AIF; -. DR PDBsum; 4AWO; -. DR PDBsum; 4AWP; -. DR PDBsum; 4AWQ; -. DR PDBsum; 4B7P; -. DR PDBsum; 4BQG; -. DR PDBsum; 4BQJ; -. DR PDBsum; 4CGQ; -. DR PDBsum; 4CGU; -. DR PDBsum; 4CGV; -. DR PDBsum; 4CGW; -. DR PDBsum; 4CWF; -. DR PDBsum; 4CWN; -. DR PDBsum; 4CWO; -. DR PDBsum; 4CWP; -. DR PDBsum; 4CWQ; -. DR PDBsum; 4CWR; -. DR PDBsum; 4CWS; -. DR PDBsum; 4CWT; -. DR PDBsum; 4EEH; -. DR PDBsum; 4EFT; -. DR PDBsum; 4EFU; -. DR PDBsum; 4EGH; -. DR PDBsum; 4EGI; -. DR PDBsum; 4EGK; -. DR PDBsum; 4FCP; -. DR PDBsum; 4FCQ; -. DR PDBsum; 4FCR; -. DR PDBsum; 4HY6; -. DR PDBsum; 4JQL; -. DR PDBsum; 4L8Z; -. DR PDBsum; 4L90; -. DR PDBsum; 4L91; -. DR PDBsum; 4L93; -. DR PDBsum; 4L94; -. DR PDBsum; 4LWE; -. DR PDBsum; 4LWF; -. DR PDBsum; 4LWG; -. DR PDBsum; 4LWH; -. DR PDBsum; 4LWI; -. DR PDBsum; 4NH7; -. DR PDBsum; 4NH8; -. DR PDBsum; 4O04; -. DR PDBsum; 4O05; -. DR PDBsum; 4O07; -. DR PDBsum; 4O09; -. DR PDBsum; 4O0B; -. DR PDBsum; 4R3M; -. DR PDBsum; 4U93; -. DR PDBsum; 4W7T; -. DR PDBsum; 4XIP; -. DR PDBsum; 4XIQ; -. DR PDBsum; 4XIR; -. DR PDBsum; 4XIT; -. DR PDBsum; 4YKQ; -. DR PDBsum; 4YKR; -. DR PDBsum; 4YKT; -. DR PDBsum; 4YKU; -. DR PDBsum; 4YKW; -. DR PDBsum; 4YKX; -. DR PDBsum; 4YKY; -. DR PDBsum; 4YKZ; -. DR PDBsum; 5CF0; -. DR PDBsum; 5FNC; -. DR PDBsum; 5FND; -. DR PDBsum; 5FNF; -. DR PDBsum; 5GGZ; -. DR PDBsum; 5J20; -. DR PDBsum; 5J27; -. DR PDBsum; 5J2V; -. DR PDBsum; 5J2X; -. DR PDBsum; 5J64; -. DR PDBsum; 5J6L; -. DR PDBsum; 5J6M; -. DR PDBsum; 5J6N; -. DR PDBsum; 5J80; -. DR PDBsum; 5J82; -. DR PDBsum; 5J86; -. DR PDBsum; 5J8M; -. DR PDBsum; 5J8U; -. DR PDBsum; 5J9X; -. DR PDBsum; 5LNY; -. DR PDBsum; 5LNZ; -. DR PDBsum; 5LO0; -. DR PDBsum; 5LO1; -. DR PDBsum; 5LO5; -. DR PDBsum; 5LO6; -. DR PDBsum; 5LQ9; -. DR PDBsum; 5LR1; -. DR PDBsum; 5LR7; -. DR PDBsum; 5LRL; -. DR PDBsum; 5LRZ; -. DR PDBsum; 5LS1; -. DR PDBsum; 5M4E; -. DR PDBsum; 5M4H; -. DR PDBsum; 5NYH; -. DR PDBsum; 5NYI; -. DR PDBsum; 5OCI; -. DR PDBsum; 5OD7; -. DR PDBsum; 5ODX; -. DR PDBsum; 5T21; -. DR PDBsum; 5VYY; -. DR PDBsum; 5XQD; -. DR PDBsum; 5XQE; -. DR PDBsum; 5XR5; -. DR PDBsum; 5XR9; -. DR PDBsum; 5XRB; -. DR PDBsum; 5XRD; -. DR PDBsum; 5XRE; -. DR PDBsum; 5ZR3; -. DR PDBsum; 6B99; -. DR PDBsum; 6B9A; -. DR PDBsum; 6CEO; -. DR PDBsum; 6CYG; -. DR PDBsum; 6CYH; -. DR PDBsum; 6EI5; -. DR PDBsum; 6EL5; -. DR PDBsum; 6ELN; -. DR PDBsum; 6ELO; -. DR PDBsum; 6ELP; -. DR PDBsum; 6EY8; -. DR PDBsum; 6EY9; -. DR PDBsum; 6EYA; -. DR PDBsum; 6EYB; -. DR PDBsum; 6F1N; -. DR PDBsum; 6FCJ; -. DR PDBsum; 6FDP; -. DR PDBsum; 6GP4; -. DR PDBsum; 6GP8; -. DR PDBsum; 6GPF; -. DR PDBsum; 6GPH; -. DR PDBsum; 6GPO; -. DR PDBsum; 6GPP; -. DR PDBsum; 6GPR; -. DR PDBsum; 6GPT; -. DR PDBsum; 6GPW; -. DR PDBsum; 6GPY; -. DR PDBsum; 6GQ6; -. DR PDBsum; 6GQR; -. DR PDBsum; 6GQS; -. DR PDBsum; 6GQU; -. DR PDBsum; 6GR1; -. DR PDBsum; 6GR3; -. DR PDBsum; 6GR4; -. DR PDBsum; 6GR5; -. DR PDBsum; 6HHR; -. DR PDBsum; 6KSQ; -. DR PDBsum; 6LR9; -. DR PDBsum; 6LSZ; -. DR PDBsum; 6LT8; -. DR PDBsum; 6LTI; -. DR PDBsum; 6LTK; -. DR PDBsum; 6N8X; -. DR PDBsum; 6OLX; -. DR PDBsum; 6TN4; -. DR PDBsum; 6TN5; -. DR PDBsum; 6U98; -. DR PDBsum; 6U99; -. DR PDBsum; 6U9A; -. DR PDBsum; 6U9B; -. DR PDBsum; 7DMC; -. DR PDBsum; 7KRJ; -. DR PDBsum; 7KW7; -. DR PDBsum; 7L7I; -. DR PDBsum; 7L7J; -. DR PDBsum; 7LSZ; -. DR PDBsum; 7LT0; -. DR PDBsum; 7RY1; -. DR PDBsum; 7S8Y; -. DR PDBsum; 7S8Z; -. DR PDBsum; 7S90; -. DR PDBsum; 7S95; -. DR PDBsum; 7S98; -. DR PDBsum; 7S99; -. DR PDBsum; 7S9F; -. DR PDBsum; 7S9G; -. DR PDBsum; 7S9H; -. DR PDBsum; 7S9I; -. DR PDBsum; 8AGI; -. DR PDBsum; 8AGJ; -. DR PDBsum; 8AGL; -. DR AlphaFoldDB; P07900; -. DR BMRB; P07900; -. DR SMR; P07900; -. DR BioGRID; 109552; 1120. DR ComplexPortal; CPX-3288; HSP90A-CDC37 chaperone complex. DR CORUM; P07900; -. DR DIP; DIP-27595N; -. DR IntAct; P07900; 399. DR MINT; P07900; -. DR STRING; 9606.ENSP00000335153; -. DR BindingDB; P07900; -. DR ChEMBL; CHEMBL3880; -. DR DrugBank; DB07317; (3E)-3-[(phenylamino)methylidene]dihydrofuran-2(3H)-one. DR DrugBank; DB08197; (5E,7S)-2-amino-7-(4-fluoro-2-pyridin-3-ylphenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one oxime. DR DrugBank; DB08443; 2-(1H-pyrrol-1-ylcarbonyl)benzene-1,3,5-triol. DR DrugBank; DB08557; 2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamide. DR DrugBank; DB08789; 2-AMINO-4-(2,4-DICHLOROPHENYL)-N-ETHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXAMIDE. DR DrugBank; DB06969; 2-amino-4-[2,4-dichloro-5-(2-pyrrolidin-1-ylethoxy)phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamide. DR DrugBank; DB08788; 3,6-DIAMINO-5-CYANO-4-(4-ETHOXYPHENYL)THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE. DR DrugBank; DB07324; 3-({2-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)ETHYNYL]BENZYL}AMINO)-1,3-OXAZOL-2(3H)-ONE. DR DrugBank; DB02840; 4-(1,3-Benzodioxol-5-Yl)-5-(5-Ethyl-2,4-Dihydroxyphenyl)-2h-Pyrazole-3-Carboxylic Acid. DR DrugBank; DB03749; 4-(1h-Imidazol-4-Yl)-3-(5-Ethyl-2,4-Dihydroxy-Phenyl)-1h-Pyrazole. DR DrugBank; DB08787; 4-(2,4-dichlorophenyl)-5-phenyldiazenyl-pyrimidin-2-amine. DR DrugBank; DB08786; 4-(2-methoxyethoxy)-6-methylpyrimidin-2-amine. DR DrugBank; DB07502; 4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diol. DR DrugBank; DB07100; 4-CHLORO-6-(4-PIPERAZIN-1-YL-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL. DR DrugBank; DB06957; 4-CHLORO-6-(4-{4-[4-(METHYLSULFONYL)BENZYL]PIPERAZIN-1-YL}-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL. DR DrugBank; DB07601; 4-chloro-6-{5-[(2-morpholin-4-ylethyl)amino]-1,2-benzisoxazol-3-yl}benzene-1,3-diol. DR DrugBank; DB08194; 4-methyl-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amine. DR DrugBank; DB08442; 4-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diol. DR DrugBank; DB07495; 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)-1H-PYRAZOLE-3-CARBOXAMIDE. DR DrugBank; DB06964; 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)ISOXAZOLE-3-CARBOXAMIDE. DR DrugBank; DB06961; 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]isoxazole-3-carboxamide. DR DrugBank; DB06958; 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-PIPERAZIN-1-YL-1H-PYRAZOLE-3-CARBOXAMIDE. DR DrugBank; DB07319; 6-(3-BROMO-2-NAPHTHYL)-1,3,5-TRIAZINE-2,4-DIAMINE. DR DrugBank; DB03137; 8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9-Pent-9h-Purin-6-Ylamine. DR DrugBank; DB03093; 8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-Ylamine. DR DrugBank; DB02550; 8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-2-Fluoro-9-Pent-4-Ylnyl-9h-Purin-6-Ylamine. DR DrugBank; DB04505; 8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9-Pent-4-Ylnyl-9h-Purin-6-Ylamine. DR DrugBank; DB07877; 8-(6-BROMO-BENZO[1,3]DIOXOL-5-YLSULFANYL)-9-(3-ISOPROPYLAMINO-PROPYL)-ADENINE. DR DrugBank; DB04254; 8-Benzo[1,3]Dioxol-,5-Ylmethyl-9-Butyl-2-Fluoro-9h-Purin-6-Ylamine. DR DrugBank; DB08436; 8-BENZO[1,3]DIOXOL-,5-YLMETHYL-9-BUTYL-9H. DR DrugBank; DB04054; 9-Butyl-8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-Ylamine. DR DrugBank; DB02359; 9-Butyl-8-(2,5-Dimethoxy-Benzyl)-9h-Purin-6-Ylamine. DR DrugBank; DB03504; 9-Butyl-8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9h-Purin-6-Ylamine. DR DrugBank; DB02754; 9-Butyl-8-(3,4,5-Trimethoxybenzyl)-9h-Purin-6-Amine. DR DrugBank; DB03809; 9-Butyl-8-(3-Methoxybenzyl)-9h-Purin-6-Amine. DR DrugBank; DB03899; 9-Butyl-8-(4-Methoxybenzyl)-9h-Purin-6-Amine. DR DrugBank; DB12442; Alvespimycin. DR DrugBank; DB07594; CCT-018159. DR DrugBank; DB09130; Copper. DR DrugBank; DB02424; Geldanamycin. DR DrugBank; DB06956; N-(4-ACETYLPHENYL)-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE. DR DrugBank; DB07325; N-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)METHYL]-3-{[(E)-(2-OXODIHYDROFURAN-3(2H)-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDE. DR DrugBank; DB04588; N-[4-(AMINOSULFONYL)BENZYL]-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE. DR DrugBank; DB00716; Nedocromil. DR DrugBank; DB09221; Polaprezinc. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB00615; Rifabutin. DR DrugBank; DB06070; SNX-5422. DR DrugBank; DB05134; Tanespimycin. DR DrugCentral; P07900; -. DR GuidetoPHARMACOLOGY; 2905; -. DR MoonDB; P07900; Predicted. DR CarbonylDB; P07900; -. DR GlyConnect; 1301; 1 N-Linked glycan (1 site). DR GlyGen; P07900; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P07900; -. DR MetOSite; P07900; -. DR PhosphoSitePlus; P07900; -. DR SwissPalm; P07900; -. DR BioMuta; HSP90AA1; -. DR DMDM; 92090606; -. DR OGP; P07900; -. DR REPRODUCTION-2DPAGE; IPI00784295; -. DR EPD; P07900; -. DR jPOST; P07900; -. DR MassIVE; P07900; -. DR MaxQB; P07900; -. DR PaxDb; P07900; -. DR PeptideAtlas; P07900; -. DR PRIDE; P07900; -. DR ProteomicsDB; 52031; -. [P07900-1] DR ProteomicsDB; 52032; -. [P07900-2] DR TopDownProteomics; P07900-1; -. [P07900-1] DR Antibodypedia; 3676; 1854 antibodies from 44 providers. DR DNASU; 3320; -. DR Ensembl; ENST00000216281.13; ENSP00000216281.8; ENSG00000080824.19. [P07900-1] DR Ensembl; ENST00000334701.11; ENSP00000335153.7; ENSG00000080824.19. [P07900-2] DR GeneID; 3320; -. DR KEGG; hsa:3320; -. DR MANE-Select; ENST00000216281.13; ENSP00000216281.8; NM_005348.4; NP_005339.3. DR UCSC; uc001yku.5; human. [P07900-1] DR CTD; 3320; -. DR DisGeNET; 3320; -. DR GeneCards; HSP90AA1; -. DR HGNC; HGNC:5253; HSP90AA1. DR HPA; ENSG00000080824; Tissue enhanced (brain). DR MIM; 140571; gene. DR neXtProt; NX_P07900; -. DR OpenTargets; ENSG00000080824; -. DR PharmGKB; PA29519; -. DR VEuPathDB; HostDB:ENSG00000080824; -. DR eggNOG; KOG0019; Eukaryota. DR GeneTree; ENSGT01020000230401; -. DR HOGENOM; CLU_006684_1_3_1; -. DR InParanoid; P07900; -. DR OMA; AHDQPME; -. DR OrthoDB; 188544at2759; -. DR PhylomeDB; P07900; -. DR TreeFam; TF300686; -. DR BRENDA; 3.6.4.10; 2681. DR PathwayCommons; P07900; -. DR Reactome; R-HSA-1227986; Signaling by ERBB2. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation. DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta. DR Reactome; R-HSA-192905; vRNP Assembly. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-203615; eNOS activation. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-3000484; Scavenging by Class F Receptors. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-3371511; HSF1 activation. DR Reactome; R-HSA-3371568; Attenuation phase. DR Reactome; R-HSA-3371571; HSF1-dependent transactivation. DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-HSA-399954; Sema3A PAK dependent Axon repulsion. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-HSA-5336415; Uptake and function of diphtheria toxin. DR Reactome; R-HSA-5601884; PIWI-interacting RNA (piRNA) biogenesis. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5675482; Regulation of necroptotic cell death. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint. DR Reactome; R-HSA-8854518; AURKA Activation by TPX2. DR Reactome; R-HSA-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-HSA-8939211; ESR-mediated signaling. DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling. DR Reactome; R-HSA-9013418; RHOBTB2 GTPase cycle. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-9613829; Chaperone Mediated Autophagy. DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2. DR Reactome; R-HSA-9646399; Aggrephagy. DR Reactome; R-HSA-9652282; Drug-mediated inhibition of ERBB2 signaling. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665233; Resistance of ERBB2 KD mutants to trastuzumab. DR Reactome; R-HSA-9665244; Resistance of ERBB2 KD mutants to sapitinib. DR Reactome; R-HSA-9665245; Resistance of ERBB2 KD mutants to tesevatinib. DR Reactome; R-HSA-9665246; Resistance of ERBB2 KD mutants to neratinib. DR Reactome; R-HSA-9665247; Resistance of ERBB2 KD mutants to osimertinib. DR Reactome; R-HSA-9665249; Resistance of ERBB2 KD mutants to afatinib. DR Reactome; R-HSA-9665250; Resistance of ERBB2 KD mutants to AEE788. DR Reactome; R-HSA-9665251; Resistance of ERBB2 KD mutants to lapatinib. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. DR Reactome; R-HSA-9665737; Drug resistance in ERBB2 TMD/JMD mutants. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; P07900; -. DR SIGNOR; P07900; -. DR BioGRID-ORCS; 3320; 37 hits in 1091 CRISPR screens. DR ChiTaRS; HSP90AA1; human. DR EvolutionaryTrace; P07900; -. DR GenomeRNAi; 3320; -. DR Pharos; P07900; Tchem. DR PRO; PR:P07900; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P07900; protein. DR Bgee; ENSG00000080824; Expressed in Brodmann (1909) area 23 and 216 other tissues. DR ExpressionAtlas; P07900; baseline and differential. DR Genevisible; P07900; HS. DR GO; GO:0044295; C:axonal growth cone; ISS:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:CAFA. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0044294; C:dendritic growth cone; ISS:ARUK-UCL. DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0043202; C:lysosomal lumen; TAS:ParkinsonsUK-UCL. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0043209; C:myelin sheath; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro. DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA. DR GO; GO:0070182; F:DNA polymerase binding; IPI:BHF-UCL. DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0023026; F:MHC class II protein complex binding; HDA:UniProtKB. DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:1990782; F:protein tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0097110; F:scaffold protein binding; IPI:UniProtKB. DR GO; GO:0048156; F:tau protein binding; IPI:ARUK-UCL. DR GO; GO:0030911; F:TPR domain binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ARUK-UCL. DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central. DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB. DR GO; GO:0048675; P:axon extension; ISS:ARUK-UCL. DR GO; GO:0034605; P:cellular response to heat; IBA:GO_Central. DR GO; GO:0098586; P:cellular response to virus; IDA:UniProtKB. DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISS:ARUK-UCL. DR GO; GO:0061684; P:chaperone-mediated autophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:BHF-UCL. DR GO; GO:0030010; P:establishment of cell polarity; ISS:ARUK-UCL. DR GO; GO:0006839; P:mitochondrial transport; TAS:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:ARUK-UCL. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:ARUK-UCL. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:ARUK-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:ARUK-UCL. DR GO; GO:0032273; P:positive regulation of protein polymerization; IDA:ARUK-UCL. DR GO; GO:1902949; P:positive regulation of tau-protein kinase activity; IDA:ARUK-UCL. DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0045040; P:protein insertion into mitochondrial outer membrane; IDA:BHF-UCL. DR GO; GO:0042026; P:protein refolding; TAS:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB. DR GO; GO:0043335; P:protein unfolding; NAS:ParkinsonsUK-UCL. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0032880; P:regulation of protein localization; ISS:ARUK-UCL. DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:BHF-UCL. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; NAS:ParkinsonsUK-UCL. DR GO; GO:0046677; P:response to antibiotic; ISS:AgBase. DR GO; GO:0009409; P:response to cold; ISS:AgBase. DR GO; GO:0009408; P:response to heat; ISS:AgBase. DR GO; GO:0006986; P:response to unfolded protein; NAS:UniProtKB. DR GO; GO:1905323; P:telomerase holoenzyme complex assembly; IDA:BHF-UCL. DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:BHF-UCL. DR Gene3D; 1.20.120.790; -; 1. DR Gene3D; 3.30.565.10; -; 1. DR HAMAP; MF_00505; HSP90; 1. DR InterPro; IPR003594; HATPase_C. DR InterPro; IPR036890; HATPase_C_sf. DR InterPro; IPR019805; Heat_shock_protein_90_CS. DR InterPro; IPR037196; HSP90_C. DR InterPro; IPR001404; Hsp90_fam. DR InterPro; IPR020575; Hsp90_N. DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold. DR PANTHER; PTHR11528; HEAT SHOCK PROTEIN 90 FAMILY MEMBER; 1. DR Pfam; PF02518; HATPase_c; 1. DR Pfam; PF00183; HSP90; 1. DR PIRSF; PIRSF002583; Hsp90; 1. DR PRINTS; PR00775; HEATSHOCK90. DR SMART; SM00387; HATPase_c; 1. DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1. DR SUPFAM; SSF110942; HSP90 C-terminal domain; 1. DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1. DR PROSITE; PS00298; HSP90; 1. DR AGR; HGNC:5253; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell membrane; Chaperone; Cytoplasm; Direct protein sequencing; KW Host-virus interaction; Hydrolase; Membrane; Mitochondrion; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW S-nitrosylation; Stress response; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:2492519" FT CHAIN 2..732 FT /note="Heat shock protein HSP 90-alpha" FT /id="PRO_0000062911" FT REGION 9..236 FT /note="Interaction with NR3C1" FT /evidence="ECO:0000250|UniProtKB:P07901" FT REGION 225..278 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 271..616 FT /note="Interaction with NR3C1" FT /evidence="ECO:0000250|UniProtKB:P07901" FT REGION 284..732 FT /note="Interaction with FLCN and FNIP1" FT /evidence="ECO:0000269|PubMed:27353360" FT REGION 284..620 FT /note="Interaction with FNIP2 and TSC1" FT /evidence="ECO:0000269|PubMed:27353360, FT ECO:0000269|PubMed:29127155" FT REGION 628..731 FT /note="Interaction with NR1D1" FT /evidence="ECO:0000250|UniProtKB:P07901" FT REGION 682..732 FT /note="Required for homodimerization" FT /evidence="ECO:0000269|PubMed:8289821" FT REGION 700..732 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 728..732 FT /note="Essential for interaction with SMYD3, TSC1 and FT STIP1/HOP" FT /evidence="ECO:0000269|PubMed:25738358, FT ECO:0000269|PubMed:29127155" FT REGION 729..732 FT /note="Essential for interaction with SGTA and TTC1" FT /evidence="ECO:0000269|PubMed:15708368" FT MOTIF 723..732 FT /note="TPR repeat-binding" FT /evidence="ECO:0000269|PubMed:16307917" FT COMPBIAS 243..257 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 51 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 93 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 112 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 138 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 400 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 5 FT /note="Phosphothreonine; by PRKDC" FT /evidence="ECO:0000269|PubMed:2507541" FT MOD_RES 7 FT /note="Phosphothreonine; by PRKDC" FT /evidence="ECO:0000269|PubMed:2507541" FT MOD_RES 58 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P07901" FT MOD_RES 84 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P07901" FT MOD_RES 231 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2492519, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 252 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 263 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2492519, FT ECO:0007744|PubMed:16807684, ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19367720, ECO:0007744|PubMed:23186163" FT MOD_RES 313 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P07901" FT MOD_RES 443 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P82995" FT MOD_RES 458 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 476 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 489 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 492 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P07901" FT MOD_RES 585 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 598 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:15937123" FT MOD_RES 641 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1 FT /note="M -> MPPCSGGDGSTPPGPSLRDRDCPAQSAEYPRDRLDPRPGSPSEASSP FT PFLRSRAPVNWYQEKAQVFLWHLMVSGSTTLLCLWKQPFHVSAFPVTASLAFRQSQGAG FT QHLYKDLQPFILLRLLM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:16269234" FT /id="VSP_026604" FT MUTAGEN 47 FT /note="E->A: Strong ATP-binding. Strong interaction with FT HSF1, HIF1A, ERBB2, MET, KEAP1 and RHOBTB2. No effect on FT interaction with TSC1." FT /evidence="ECO:0000269|PubMed:26517842, FT ECO:0000269|PubMed:29127155" FT MUTAGEN 93 FT /note="D->A: Impaired ATP-binding. Strong interaction with FT HIF1A, MET, KEAP1 and RHOBTB2. Loss of interaction with FT HSF1 and ERBB2. Los of interaction with TSC1." FT /evidence="ECO:0000269|PubMed:26517842, FT ECO:0000269|PubMed:29127155" FT MUTAGEN 97 FT /note="G->D: Abolishes ATPase activity." FT /evidence="ECO:0000269|PubMed:18256191" FT MUTAGEN 313 FT /note="Y->E: Loss of interaction with TSC1 and increases FT interacrion with AHSA1." FT /evidence="ECO:0000269|PubMed:29127155" FT MUTAGEN 313 FT /note="Y->F: No deffect on the interaction with TSC1." FT /evidence="ECO:0000269|PubMed:29127155" FT MUTAGEN 598 FT /note="C->A,N,D: Reduces ATPase activity and client protein FT activation." FT /evidence="ECO:0000269|PubMed:15937123, FT ECO:0000269|PubMed:19696785" FT MUTAGEN 598 FT /note="C->S: Loss of S-nitrosylation." FT /evidence="ECO:0000269|PubMed:15937123, FT ECO:0000269|PubMed:19696785" FT MUTAGEN 728..732 FT /note="MEEVD->AAAA: Loss of interaction with TOMM70. No FT effect on interaction with IRF3." FT /evidence="ECO:0000269|PubMed:25609812" FT MUTAGEN 728..732 FT /note="Missing: Loss of interaction with TSC1." FT /evidence="ECO:0000269|PubMed:29127155" FT MUTAGEN 729..732 FT /note="Missing: Loss of interaction with TOMM70." FT /evidence="ECO:0000269|PubMed:20628368" FT MUTAGEN 731..732 FT /note="VD->AA: Loss of interaction with TOMM70. No effect FT on interaction with IRF3." FT /evidence="ECO:0000269|PubMed:20628368, FT ECO:0000269|PubMed:25609812" FT CONFLICT 63 FT /note="S -> T (in Ref. 1; CAA33259)" FT /evidence="ECO:0000305" FT CONFLICT 74 FT /note="K -> R (in Ref. 4; CAI64495 and 6; BAG51711)" FT /evidence="ECO:0000305" FT CONFLICT 86 FT /note="D -> G (in Ref. 4; CAI64495 and 6; BAG51711)" FT /evidence="ECO:0000305" FT CONFLICT 162 FT /note="W -> D (in Ref. 15; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 2..5 FT /evidence="ECO:0007829|PDB:6GQS" FT STRAND 18..21 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 24..35 FT /evidence="ECO:0007829|PDB:5J80" FT TURN 39..42 FT /evidence="ECO:0007829|PDB:6GPF" FT HELIX 43..65 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 67..70 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 78..83 FT /evidence="ECO:0007829|PDB:5J80" FT TURN 84..87 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 88..93 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 100..104 FT /evidence="ECO:0007829|PDB:5J80" FT TURN 105..108 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 111..123 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 128..134 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 145..153 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:2WI6" FT STRAND 160..164 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 169..174 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 181..190 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 192..198 FT /evidence="ECO:0007829|PDB:5J80" FT HELIX 200..210 FT /evidence="ECO:0007829|PDB:5J80" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:3VHC" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:5J80" FT TURN 221..224 FT /evidence="ECO:0007829|PDB:3T1K" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:3T1K" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:2XJX" FT STRAND 284..289 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 301..303 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 306..317 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 324..331 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 337..343 FT /evidence="ECO:0007829|PDB:6KSQ" FT TURN 351..353 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 362..365 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 368..372 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 375..377 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 380..382 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 386..394 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 400..405 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 407..428 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 431..451 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 453..455 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 456..460 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 465..467 FT /evidence="ECO:0007829|PDB:7KRJ" FT TURN 468..472 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 477..482 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 490..495 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 499..504 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 506..513 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 518..521 FT /evidence="ECO:0007829|PDB:6KSQ" FT HELIX 525..532 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 539..543 FT /evidence="ECO:0007829|PDB:6KSQ" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:7L7I" FT HELIX 555..567 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 569..578 FT /evidence="ECO:0007829|PDB:7KRJ" FT TURN 579..582 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 586..588 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 593..595 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 598..601 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 603..605 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 608..614 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 622..624 FT /evidence="ECO:0007829|PDB:7KRJ" FT TURN 625..629 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 632..636 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 641..652 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 657..673 FT /evidence="ECO:0007829|PDB:7KRJ" FT HELIX 681..695 FT /evidence="ECO:0007829|PDB:7KRJ" FT STRAND 728..730 FT /evidence="ECO:0007829|PDB:4CGW" FT VARIANT P07900-2:71 FT /note="M -> L (in dbSNP:rs8005905)" FT /evidence="ECO:0000305" FT /id="VAR_082835" SQ SEQUENCE 732 AA; 84660 MW; 969F65FCC0BC86FD CRC64; MPEETQTQDQ PMEEEEVETF AFQAEIAQLM SLIINTFYSN KEIFLRELIS NSSDALDKIR YESLTDPSKL DSGKELHINL IPNKQDRTLT IVDTGIGMTK ADLINNLGTI AKSGTKAFME ALQAGADISM IGQFGVGFYS AYLVAEKVTV ITKHNDDEQY AWESSAGGSF TVRTDTGEPM GRGTKVILHL KEDQTEYLEE RRIKEIVKKH SQFIGYPITL FVEKERDKEV SDDEAEEKED KEEEKEKEEK ESEDKPEIED VGSDEEEEKK DGDKKKKKKI KEKYIDQEEL NKTKPIWTRN PDDITNEEYG EFYKSLTNDW EDHLAVKHFS VEGQLEFRAL LFVPRRAPFD LFENRKKKNN IKLYVRRVFI MDNCEELIPE YLNFIRGVVD SEDLPLNISR EMLQQSKILK VIRKNLVKKC LELFTELAED KENYKKFYEQ FSKNIKLGIH EDSQNRKKLS ELLRYYTSAS GDEMVSLKDY CTRMKENQKH IYYITGETKD QVANSAFVER LRKHGLEVIY MIEPIDEYCV QQLKEFEGKT LVSVTKEGLE LPEDEEEKKK QEEKKTKFEN LCKIMKDILE KKVEKVVVSN RLVTSPCCIV TSTYGWTANM ERIMKAQALR DNSTMGYMAA KKHLEINPDH SIIETLRQKA EADKNDKSVK DLVILLYETA LLSSGFSLED PQTHANRIYR MIKLGLGIDE DDPTADDTSA AVTEEMPPLE GDDDTSRMEE VD // ID RAF1_HUMAN Reviewed; 648 AA. AC P04049; B0LPH8; B2R5N3; Q15278; Q9UC20; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 14-DEC-2022, entry version 254. DE RecName: Full=RAF proto-oncogene serine/threonine-protein kinase {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:17603483}; DE AltName: Full=Proto-oncogene c-RAF; DE Short=cRaf; DE AltName: Full=Raf-1; GN Name=RAF1 {ECO:0000312|HGNC:HGNC:9829}; Synonyms=RAF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3003687; DOI=10.1093/nar/14.2.1009; RA Bonner T.I., Oppermann H., Seeburg P., Kerby S.B., Gunnell M.A., RA Young A.C., Rapp U.R.; RT "The complete coding sequence of the human raf oncogene and the RT corresponding structure of the c-raf-1 gene."; RL Nucleic Acids Res. 14:1009-1015(1986). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-308. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-308. RG NIEHS SNPs program; RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-648. RX PubMed=2993863; DOI=10.1128/mcb.5.6.1400-1407.1985; RA Bonner T.I., Kerby S.B., Sutrave P., Gunnell M.A., Mark G., Rapp U.R.; RT "Structure and biological activity of human homologs of the raf/mil RT oncogene."; RL Mol. Cell. Biol. 5:1400-1407(1985). RN [7] RP PROTEIN SEQUENCE OF 42-53; 60-65; 310-316 AND 564-572, INTERACTION WITH RP PRMT5, METHYLATION AT ARG-563, PHOSPHORYLATION AT SER-289; SER-296; RP SER-301; SER-338 AND SER-621, AND MUTAGENESIS OF ARG-563. RX PubMed=21917714; DOI=10.1126/scisignal.2001936; RA Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M., RA Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G., RA Avila M.A., Recio J.A.; RT "Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction RT amplitude and cell fate through CRAF."; RL Sci. Signal. 4:RA58-RA58(2011). RN [8] RP PROTEIN SEQUENCE OF 254-278, AND PHOSPHORYLATION AT THR-269. RX PubMed=7477354; DOI=10.1038/378307a0; RA Yao B., Zhang Y., Delikat S., Mathias S., Basu S., Kolesnick R.; RT "Phosphorylation of Raf by ceramide-activated protein kinase."; RL Nature 378:307-310(1995). RN [9] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; RX PubMed=1886707; RA Dozier C., Ansieau S., Ferreira E., Coll J., Stehelin D.; RT "An alternatively spliced c-mil/raf mRNA is predominantly expressed in RT chicken muscular tissues and conserved among vertebrate species."; RL Oncogene 6:1307-1311(1991). RN [10] RP PHOSPHORYLATION AT SER-43; SER-259; THR-268; SER-499 AND SER-621. RX PubMed=8349614; DOI=10.1016/s0021-9258(19)85336-x; RA Morrison D.K., Heidecker G., Rapp U.R., Copeland T.D.; RT "Identification of the major phosphorylation sites of the Raf-1 kinase."; RL J. Biol. Chem. 268:17309-17316(1993). RN [11] RP INTERACTION WITH YWHAZ, AND FUNCTION. RX PubMed=9360956; DOI=10.1074/jbc.272.46.28882; RA Dubois T., Rommel C., Howell S., Steinhussen U., Soneji Y., Morrice N., RA Moelling K., Aitken A.; RT "14-3-3 is phosphorylated by casein kinase I on residue 233. RT Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction."; RL J. Biol. Chem. 272:28882-28888(1997). RN [12] RP PHOSPHORYLATION. RX PubMed=9823899; DOI=10.1038/24184; RA King A.J., Sun H., Diaz B., Barnard D., Miao W., Bagrodia S., RA Marshall M.S.; RT "The protein kinase Pak3 positively regulates Raf-1 activity through RT phosphorylation of serine 338."; RL Nature 396:180-183(1998). RN [13] RP ERRATUM OF PUBMED:9823899. RA King A.J., Sun H., Diaz B., Barnard D., Miao W., Bagrodia S., RA Marshall M.S.; RL Nature 406:439-439(2000). RN [14] RP PHOSPHORYLATION AT SER-259 BY PKB/AKT1, ACTIVITY REGULATION, AND RP INTERACTION WITH PKB/AKT1. RX PubMed=10576742; DOI=10.1126/science.286.5445.1741; RA Zimmermann S., Moelling K.; RT "Phosphorylation and regulation of Raf by Akt (protein kinase B)."; RL Science 286:1741-1744(1999). RN [15] RP PHOSPHORYLATION AT SER-259 AND SER-621, DEPHOSPHORYLATION AT SER-43; RP SER-259 AND SER-621, ACTIVITY REGULATION, AND INTERACTION WITH PPP2CA AND RP PPP2R1B. RX PubMed=10801873; DOI=10.1074/jbc.m003259200; RA Abraham D., Podar K., Pacher M., Kubicek M., Welzel N., Hemmings B.A., RA Dilworth S.M., Mischak H., Kolch W., Baccarini M.; RT "Raf-1-associated protein phosphatase 2A as a positive regulator of kinase RT activation."; RL J. Biol. Chem. 275:22300-22304(2000). RN [16] RP ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-491 AND SER-494. RX PubMed=11447113; DOI=10.1093/emboj/20.14.3716; RA Chong H., Lee J., Guan K.L.; RT "Positive and negative regulation of Raf kinase activity and function by RT phosphorylation."; RL EMBO J. 20:3716-3727(2001). RN [17] RP FUNCTION, AND INTERACTION WITH MAP3K5/ASK1. RX PubMed=11427728; DOI=10.1073/pnas.141224398; RA Chen J., Fujii K., Zhang L., Roberts T., Fu H.; RT "Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating RT kinase 1 through a MEK-ERK independent mechanism."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7783-7788(2001). RN [18] RP FUNCTION IN PHOSPHORYLATION OF PPP1R12A, AND INTERACTION WITH PPP1R12A. RX PubMed=11719507; DOI=10.1074/jbc.m106343200; RA Broustas C.G., Grammatikakis N., Eto M., Dent P., Brautigan D.L., Kasid U.; RT "Phosphorylation of the myosin-binding subunit of myosin phosphatase by RT Raf-1 and inhibition of phosphatase activity."; RL J. Biol. Chem. 277:3053-3059(2002). RN [19] RP PHOSPHORYLATION AT SER-338 BY PAK1, ACTIVITY REGULATION, AND INTERACTION RP WITH PAK1. RX PubMed=11733498; DOI=10.1074/jbc.m110000200; RA Zang M., Hayne C., Luo Z.; RT "Interaction between active Pak1 and Raf-1 is necessary for phosphorylation RT and activation of Raf-1."; RL J. Biol. Chem. 277:4395-4405(2002). RN [20] RP PHOSPHORYLATION AT SER-259, DEPHOSPHORYLATION AT SER-259, AND SUBCELLULAR RP LOCATION. RX PubMed=11756411; DOI=10.1074/jbc.m108733200; RA Kubicek M., Pacher M., Abraham D., Podar K., Eulitz M., Baccarini M.; RT "Dephosphorylation of Ser-259 regulates Raf-1 membrane association."; RL J. Biol. Chem. 277:7913-7919(2002). RN [21] RP COMPETITION WITH RIN1. RX PubMed=11784866; DOI=10.1128/mcb.22.3.916-926.2001; RA Wang Y., Waldron R.T., Dhaka A., Patel A., Riley M.M., Rozengurt E., RA Colicelli J.; RT "The RAS effector RIN1 directly competes with RAF and is regulated by 14-3- RT 3 proteins."; RL Mol. Cell. Biol. 22:916-926(2002). RN [22] RP ACTIVITY REGULATION, AND INTERACTION WITH SPRY2 AND SPRY4. RX PubMed=12717443; DOI=10.1038/ncb978; RA Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., RA Kuriyama M., Saito N., Shibuya M., Yoshimura A.; RT "Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to RT Raf1."; RL Nat. Cell Biol. 5:427-432(2003). RN [23] RP PHOSPHORYLATION AT SER-259. RX PubMed=15047712; DOI=10.1074/jbc.m314192200; RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.; RT "LGI1, a putative tumor metastasis suppressor gene, controls in vitro RT invasiveness and expression of matrix metalloproteinases in glioma cells RT through the ERK1/2 pathway."; RL J. Biol. Chem. 279:23151-23157(2004). RN [24] RP ERRATUM OF PUBMED:15047712. RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.; RL J. Biol. Chem. 282:2752-2752(2007). RN [25] RP FUNCTION IN PHOSPHORYLATION OF ADCY2; ADCY5 AND ADCY6, AND INTERACTION WITH RP ADCY2; ADCY5 AND ADCY6. RX PubMed=15385642; DOI=10.1124/mol.66.4.921; RA Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.; RT "Raf kinase activation of adenylyl cyclases: isoform-selective RT regulation."; RL Mol. Pharmacol. 66:921-928(2004). RN [26] RP INTERACTION WITH STK3/MST2, AND FUNCTION. RX PubMed=15618521; DOI=10.1126/science.1103233; RA O'Neill E., Rushworth L., Baccarini M., Kolch W.; RT "Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene RT product Raf-1."; RL Science 306:2267-2270(2004). RN [27] RP INTERACTION WITH RCAN1/DSCR1. RX PubMed=15935327; DOI=10.1016/j.abb.2005.05.002; RA Cho Y.J., Abe M., Kim S.Y., Sato Y.; RT "Raf-1 is a binding partner of DSCR1."; RL Arch. Biochem. Biophys. 439:121-128(2005). RN [28] RP REVIEW ON FUNCTION. RX PubMed=15943972; DOI=10.1016/j.febslet.2005.03.024; RA Baccarini M.; RT "Second nature: biological functions of the Raf-1 'kinase'."; RL FEBS Lett. 579:3271-3277(2005). RN [29] RP FUNCTION IN PHOSPHORYLATION OF BAD, PHOSPHORYLATION AT SER-338 AND SER-339 RP BY PAK1, SUBCELLULAR LOCATION, AND INTERACTION WITH BCL2. RX PubMed=15849194; DOI=10.1074/jbc.m413374200; RA Jin S., Zhuo Y., Guo W., Field J.; RT "p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates RT its mitochondrial localization, phosphorylation of BAD, and Bcl-2 RT association."; RL J. Biol. Chem. 280:24698-24705(2005). RN [30] RP PHOSPHORYLATION AT SER-471. RX PubMed=16093354; DOI=10.1091/mbc.e05-02-0090; RA Zhu J., Balan V., Bronisz A., Balan K., Sun H., Leicht D.T., Luo Z., RA Qin J., Avruch J., Tzivion G.; RT "Identification of Raf-1 S471 as a novel phosphorylation site critical for RT Raf-1 and B-Raf kinase activities and for MEK binding."; RL Mol. Biol. Cell 16:4733-4744(2005). RN [31] RP IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; SHOC2 AND MRAS, RP PHOSPHORYLATION AT SER-259, AND CHARACTERIZATION OF VARIANT ALA-259. RX PubMed=16630891; DOI=10.1016/j.molcel.2006.03.027; RA Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M., RA McCormick F.; RT "A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit RT of PP1 functions as an M-Ras effector to modulate Raf activity."; RL Mol. Cell 22:217-230(2006). RN [32] RP SUBUNIT. RX PubMed=16508002; DOI=10.1128/mcb.26.6.2262-2272.2006; RA Rushworth L.K., Hindley A.D., O'Neill E., Kolch W.; RT "Regulation and role of Raf-1/B-Raf heterodimerization."; RL Mol. Cell. Biol. 26:2262-2272(2006). RN [33] RP FUNCTION AS KINASE, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-259; RP SER-338; TYR-340; TYR-341 AND SER-621, DEPHOSPHORYLATION AT SER-338 BY RP PPP5C, AND MUTAGENESIS OF 338-SER-SER-339; 340-TYR-TYR-341; THR-491 AND RP SER-494. RX PubMed=16892053; DOI=10.1038/ncb1465; RA von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.; RT "Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5."; RL Nat. Cell Biol. 8:1011-1016(2006). RN [34] RP REVIEW ON REGULATION. RX PubMed=17218791; DOI=10.4161/cc.6.1.3593; RA Dhillon A.S., von Kriegsheim A., Grindlay J., Kolch W.; RT "Phosphatase and feedback regulation of Raf-1 signaling."; RL Cell Cycle 6:3-7(2007). RN [35] RP FUNCTION. RX PubMed=16924233; DOI=10.1038/sj.onc.1209902; RA Wang Z., Wade P., Mandell K.J., Akyildiz A., Parkos C.A., Mrsny R.J., RA Nusrat A.; RT "Raf 1 represses expression of the tight junction protein occludin via RT activation of the zinc-finger transcription factor slug."; RL Oncogene 26:1222-1230(2007). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [37] RP ACTIVITY REGULATION, AND INTERACTION WITH PEBP1/RKIP. RX PubMed=18294816; DOI=10.1016/j.cellsig.2008.01.012; RA Rath O., Park S., Tang H.H., Banfield M.J., Brady R.L., Lee Y.C., RA Dignam J.D., Sedivy J.M., Kolch W., Yeung K.C.; RT "The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the RT phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated RT phosphorylation of MEK."; RL Cell. Signal. 20:935-941(2008). RN [38] RP PHOSPHORYLATION AT SER-338 BY PAK5. RX PubMed=18465753; DOI=10.1002/jcb.21809; RA Wu X., Carr H.S., Dan I., Ruvolo P.P., Frost J.A.; RT "p21 activated kinase 5 activates Raf-1 and targets it to mitochondria."; RL J. Cell. Biochem. 105:167-175(2008). RN [39] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [40] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [42] RP SUBCELLULAR LOCATION. RX PubMed=19298812; DOI=10.1016/j.yexcr.2009.03.004; RA Smith J., Bunaciu R.P., Reiterer G., Coder D., George T., Asaly M., Yen A.; RT "Retinoic acid induces nuclear accumulation of Raf1 during differentiation RT of HL-60 cells."; RL Exp. Cell Res. 315:2241-2248(2009). RN [43] RP ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND INTERACTION WITH RP DGKH. RX PubMed=19710016; DOI=10.1074/jbc.m109.043604; RA Yasuda S., Kai M., Imai S., Takeishi K., Taketomi A., Toyota M., Kanoh H., RA Sakane F.; RT "Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf RT heterodimerization."; RL J. Biol. Chem. 284:29559-29570(2009). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289 AND SER-301, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [45] RP REVIEW. RX PubMed=20674547; DOI=10.1016/j.bbrc.2010.07.092; RA Roskoski R. Jr.; RT "RAF protein-serine/threonine kinases: structure and regulation."; RL Biochem. Biophys. Res. Commun. 399:313-317(2010). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [47] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [48] RP REVIEW. RX PubMed=21779496; DOI=10.1177/1947601911407323; RA Matallanas D., Birtwistle M., Romano D., Zebisch A., Rauch J., RA von Kriegsheim A., Kolch W.; RT "Raf family kinases: old dogs have learned new tricks."; RL Genes Cancer 2:232-260(2011). RN [49] RP MUTAGENESIS OF LYS-375, AND INTERACTION WITH NEK10 AND MAP2K1. RX PubMed=20956560; DOI=10.1128/mcb.00648-10; RA Moniz L.S., Stambolic V.; RT "Nek10 mediates G2/M cell cycle arrest and MEK autoactivation in response RT to UV irradiation."; RL Mol. Cell. Biol. 31:30-42(2011). RN [50] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [51] RP INTERACTION WITH FAM83B. RX PubMed=22886302; DOI=10.1172/jci60517; RA Cipriano R., Graham J., Miskimen K.L., Bryson B.L., Bruntz R.C., RA Scott S.A., Brown H.A., Stark G.R., Jackson M.W.; RT "FAM83B mediates EGFR- and RAS-driven oncogenic transformation."; RL J. Clin. Invest. 122:3197-3210(2012). RN [52] RP INTERACTION WITH GLS. RX PubMed=22538822; DOI=10.1073/pnas.1116573109; RA Thangavelu K., Pan C.Q., Karlberg T., Balaji G., Uttamchandani M., RA Suresh V., Schuler H., Low B.C., Sivaraman J.; RT "Structural basis for the allosteric inhibitory mechanism of human kidney- RT type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in RT cancer cell metabolism."; RL Proc. Natl. Acad. Sci. U.S.A. 109:7705-7710(2012). RN [53] RP INTERACTION WITH MFHAS1. RX PubMed=23327923; DOI=10.1182/blood-2011-10-385252; RA Kumkhaek C., Aerbajinai W., Liu W., Zhu J., Uchida N., Kurlander R., RA Hsieh M.M., Tisdale J.F., Rodgers G.P.; RT "MASL1 induces erythroid differentiation in human erythropoietin-dependent RT CD34+ cells through the Raf/MEK/ERK pathway."; RL Blood 121:3216-3227(2013). RN [54] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296; SER-301 AND SER-642, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [55] RP INTERACTION WITH PDE8A. RX PubMed=23509299; DOI=10.1073/pnas.1303004110; RA Brown K.M., Day J.P., Huston E., Zimmermann B., Hampel K., Christian F., RA Romano D., Terhzaz S., Lee L.C., Willis M.J., Morton D.B., Beavo J.A., RA Shimizu-Albergine M., Davies S.A., Kolch W., Houslay M.D., Baillie G.S.; RT "Phosphodiesterase-8A binds to and regulates Raf-1 kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 110:E1533-E1542(2013). RN [56] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [57] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; CDC37; PPP5C; TSC1; TSC2; RP AKT; CDK4 AND NR3C1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [58] RP INTERACTION WITH LZTR1. RX PubMed=30368668; DOI=10.1007/s00439-018-1951-7; RA Umeki I., Niihori T., Abe T., Kanno S.I., Okamoto N., Mizuno S., RA Kurosawa K., Nagasaki K., Yoshida M., Ohashi H., Inoue S.I., Matsubara Y., RA Fujiwara I., Kure S., Aoki Y.; RT "Delineation of LZTR1 mutation-positive patients with Noonan syndrome and RT identification of LZTR1 binding to RAF1-PPP1CB complexes."; RL Hum. Genet. 138:21-35(2019). RN [59] RP INTERACTION WITH YWHAZ. RX PubMed=31024343; DOI=10.3389/fphys.2019.00388; RA Popov I.K., Hiatt S.M., Whalen S., Keren B., Ruivenkamp C., RA van Haeringen A., Chen M.J., Cooper G.M., Korf B.R., Chang C.; RT "A YWHAZ variant associated with cardiofaciocutaneous syndrome activates RT the RAF-ERK pathway."; RL Front. Physiol. 10:388-388(2019). RN [60] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 51-131. RX PubMed=7791872; DOI=10.1038/375554a0; RA Nassar N., Horn G., Herrmann C., Scherer A., McCormick F., Wittinghofer A.; RT "The 2.2 A crystal structure of the Ras-binding domain of the RT serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue."; RL Nature 375:554-560(1995). RN [61] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-131. RX PubMed=8756332; DOI=10.1038/nsb0896-723; RA Nassar N., Horn G., Herrmann C., Block C., Janknecht R., Wittinghofer A.; RT "Ras/Rap effector specificity determined by charge reversal."; RL Nat. Struct. Biol. 3:723-729(1996). RN [62] RP STRUCTURE BY NMR OF 55-132. RX PubMed=7766599; DOI=10.1021/bi00021a001; RA Emerson S.D., Madison V.S., Palermo R.E., Waugh D.S., Scheffler J.E., RA Tsao K.L., Kiefer S.E., Liu S.P., Fry D.C.; RT "Solution structure of the Ras-binding domain of c-Raf-1 and identification RT of its Ras interaction surface."; RL Biochemistry 34:6911-6918(1995). RN [63] RP STRUCTURE BY NMR OF 136-187. RX PubMed=8710867; DOI=10.1073/pnas.93.16.8312; RA Mott H.R., Carpenter J.W., Zhong S., Ghosh S., Bell R.M., Campbell S.L.; RT "The solution structure of the Raf-1 cysteine-rich domain: a novel ras and RT phospholipid binding site."; RL Proc. Natl. Acad. Sci. U.S.A. 93:8312-8317(1996). RN [64] RP VARIANTS NS5 SER-256; PHE-259; ARG-260; LEU-261; SER-261; ASN-486; GLY-486; RP ILE-491; ARG-491 AND THR-612, VARIANT HYPERTROPHIC CARDIOMYOPATHY ILE-260, RP VARIANTS LPRD2 LEU-257 AND VAL-613, VARIANT NS5 LEU-257, CHARACTERIZATION RP OF VARIANTS NS5 SER-261; ASN-486 AND ILE-491, CHARACTERIZATION OF VARIANT RP LPRD2 VAL-613, AND CATALYTIC ACTIVITY. RX PubMed=17603483; DOI=10.1038/ng2073; RA Pandit B., Sarkozy A., Pennacchio L.A., Carta C., Oishi K., Martinelli S., RA Pogna E.A., Schackwitz W., Ustaszewska A., Landstrom A., Bos J.M., RA Ommen S.R., Esposito G., Lepri F., Faul C., Mundel P., Lopez Siguero J.P., RA Tenconi R., Selicorni A., Rossi C., Mazzanti L., Torrente I., Marino B., RA Digilio M.C., Zampino G., Ackerman M.J., Dallapiccola B., Tartaglia M., RA Gelb B.D.; RT "Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with RT hypertrophic cardiomyopathy."; RL Nat. Genet. 39:1007-1012(2007). RN [65] RP VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613, AND RP CHARACTERIZATION OF VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND RP VAL-613. RX PubMed=17603482; DOI=10.1038/ng2078; RA Razzaque M.A., Nishizawa T., Komoike Y., Yagi H., Furutani M., Amo R., RA Kamisago M., Momma K., Katayama H., Nakagawa M., Fujiwara Y., RA Matsushima M., Mizuno K., Tokuyama M., Hirota H., Muneuchi J., RA Higashinakagawa T., Matsuoka R.; RT "Germline gain-of-function mutations in RAF1 cause Noonan syndrome."; RL Nat. Genet. 39:1013-1017(2007). RN [66] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-259 AND HIS-335. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [67] RP VARIANT NS5 SER-261. RX PubMed=20683980; DOI=10.1002/ajmg.a.33564; RA Longoni M., Moncini S., Cisternino M., Morella I.M., Ferraiuolo S., RA Russo S., Mannarino S., Brazzelli V., Coi P., Zippel R., Venturin M., RA Riva P.; RT "Noonan syndrome associated with both a new Jnk-activating familial SOS1 RT and a de novo RAF1 mutations."; RL Am. J. Med. Genet. A 152:2176-2184(2010). RN [68] RP INVOLVEMENT IN CMD1NN, VARIANTS CMD1NN THR-237; ALA-310; ALA-332; PRO-603; RP ARG-626 AND MET-641, AND CHARACTERIZATION OF VARIANTS CMD1NN THR-237; RP ALA-310; ALA-332; PRO-603; ARG-626 AND MET-641. RX PubMed=24777450; DOI=10.1038/ng.2963; RA Dhandapany P.S., Razzaque M.A., Muthusami U., Kunnoth S., Edwards J.J., RA Mulero-Navarro S., Riess I., Pardo S., Sheng J., Rani D.S., Rani B., RA Govindaraj P., Flex E., Yokota T., Furutani M., Nishizawa T., Nakanishi T., RA Robbins J., Limongelli G., Hajjar R.J., Lebeche D., Bahl A., Khullar M., RA Rathinavel A., Sadler K.C., Tartaglia M., Matsuoka R., Thangaraj K., RA Gelb B.D.; RT "RAF1 mutations in childhood-onset dilated cardiomyopathy."; RL Nat. Genet. 46:635-639(2014). CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a regulatory CC link between the membrane-associated Ras GTPases and the MAPK/ERK CC cascade, and this critical regulatory link functions as a switch CC determining cell fate decisions including proliferation, CC differentiation, apoptosis, survival and oncogenic transformation. RAF1 CC activation initiates a mitogen-activated protein kinase (MAPK) cascade CC that comprises a sequential phosphorylation of the dual-specific MAPK CC kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal- CC regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form CC of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates CC BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl CC cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. CC Phosphorylates PPP1R12A resulting in inhibition of the phosphatase CC activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote CC NF-kB activation and inhibit signal transducers involved in motility CC (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and CC angiogenesis (RB1). Can protect cells from apoptosis also by CC translocating to the mitochondria where it binds BCL2 and displaces CC BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and CC migration, and is required for normal wound healing. Plays a role in CC the oncogenic transformation of epithelial cells via repression of the CC TJ protein, occludin (OCLN) by inducing the up-regulation of a CC transcriptional repressor SNAI2/SLUG, which induces down-regulation of CC OCLN. Restricts caspase activation in response to selected stimuli, CC notably Fas stimulation, pathogen-mediated macrophage apoptosis, and CC erythroid differentiation. {ECO:0000269|PubMed:11427728, CC ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, CC ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, CC ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, CC ECO:0000269|PubMed:9360956}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:17603483}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:17603483}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:17603483}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:17603483}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Note=Binds 2 Zn(2+) ions per subunit.; CC -!- ACTIVITY REGULATION: Regulation is a highly complex process involving CC membrane recruitment, protein-protein interactions, dimerization, and CC phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the CC membrane, thereby promoting its activation. The inactive conformation CC of RAF1 is maintained by autoinhibitory interactions occurring between CC the N-terminal regulatory and the C-terminal catalytic domains and by CC the binding of a 14-3-3 protein that contacts two phosphorylation CC sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A CC cooperate to release autoinhibition and the subsequent phosphorylation CC of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a CC fully active kinase. Through a negative feedback mechanism involving CC MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, CC Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, CC desensitized kinase. The signaling-competent conformation of RAF1 is CC finally re-established by the coordinated action of PIN1, a prolyl CC isomerase that converts pSer and pThr residues from the cis to the CC trans conformation, which is preferentially recognized and CC dephosphorylated by PPP2R1A. Activated by homodimerization and CC heterodimerization (with BRAF). Also regulated through association with CC other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin CC and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates CC MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the CC displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting CC cell membrane localization and phosphorylation of RAF1 at the CC activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras- CC dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 CC activation. {ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10801873, CC ECO:0000269|PubMed:11447113, ECO:0000269|PubMed:11733498, CC ECO:0000269|PubMed:12717443, ECO:0000269|PubMed:16892053, CC ECO:0000269|PubMed:18294816, ECO:0000269|PubMed:19710016}. CC -!- SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this CC heterodimer possesses a highly increased kinase activity compared to CC the respective homodimers or monomers (PubMed:16508002). CC Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins CC (PubMed:16508002). MAPK1/ERK2 activation can induce a negative feedback CC that promotes the dissociation of the heterodimer (PubMed:16508002). CC Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein CC phosphatase 1 (PPP1CA, PPP1CB and PPP1CC) (PubMed:16630891). Interacts CC with LZTR1 (PubMed:30368668). Interacts with Ras proteins; the CC interaction is antagonized by RIN1 (PubMed:11784866). Weakly interacts CC with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the CC interaction mediates the formation of a ternary complex with BRAF, a CC ternary complex inhibited by GNAI1 (By similarity). Probably forms a CC complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, CC PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this CC complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Interacts with STK3/MST2; the interaction inhibits CC its pro-apoptotic activity (PubMed:15618521). Interacts (when CC phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232') CC (PubMed:9360956, PubMed:31024343). Interacts with MAP2K1/MEK1 and CC MAP2K2/MEK2 (By similarity). Interacts with MAP3K5/ASF1 (via N- CC terminus) and this interaction inhibits the proapoptotic function of CC MAP3K5/ASK1 (PubMed:11427728). Interacts with PAK1 (via kinase domain) CC (PubMed:11733498). The phosphorylated form interacts with PIN1 (By CC similarity). The Ser-338 and Ser-339 phosphorylated form (by PAK1) CC interacts with BCL2 (PubMed:15849194). Interacts with PEBP1/RKIP and CC this interaction is enhanced if RAF1 is phosphorylated on residues Ser- CC 338, Ser-339, Tyr-340 and Tyr-341 (PubMed:18294816). Interacts with CC ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, PPP1R12A, PKB/AKT1, PPP2CA, CC PPP2R1B, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin CC (PubMed:10801873, PubMed:11719507, PubMed:12717443, PubMed:15385642, CC PubMed:15935327, PubMed:19710016, PubMed:10576742). Interacts with CC ROCK2 (By similarity). In its active form, interacts with PRMT5 CC (PubMed:21917714). Interacts with FAM83B; displaces 14-3-3 proteins CC from RAF1 and activates RAF1 (PubMed:22886302). Interacts with PDE8A; CC the interaction promotes RAF1 activity (PubMed:23509299). Interacts CC with MFHAS1 (PubMed:23327923). Interacts with GLS (PubMed:22538822). CC Interacts with NEK10 and MAP2K1; the interaction is direct with NEK10 CC and required for ERK1/2-signaling pathway activation in response to UV CC irradiation (PubMed:20956560). {ECO:0000250|UniProtKB:P11345, CC ECO:0000250|UniProtKB:Q99N57, ECO:0000269|PubMed:10576742, CC ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:11427728, CC ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:11733498, CC ECO:0000269|PubMed:11784866, ECO:0000269|PubMed:12717443, CC ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, CC ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:15935327, CC ECO:0000269|PubMed:16508002, ECO:0000269|PubMed:16630891, CC ECO:0000269|PubMed:18294816, ECO:0000269|PubMed:19710016, CC ECO:0000269|PubMed:20956560, ECO:0000269|PubMed:21917714, CC ECO:0000269|PubMed:22538822, ECO:0000269|PubMed:22886302, CC ECO:0000269|PubMed:23327923, ECO:0000269|PubMed:23509299, CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:30368668, CC ECO:0000269|PubMed:9360956}. CC -!- INTERACTION: CC P04049; P05067: APP; NbExp=3; IntAct=EBI-365996, EBI-77613; CC P04049; O95816: BAG2; NbExp=3; IntAct=EBI-365996, EBI-355275; CC P04049; P15056: BRAF; NbExp=57; IntAct=EBI-365996, EBI-365980; CC P04049; Q14790: CASP8; NbExp=3; IntAct=EBI-365996, EBI-78060; CC P04049; P49368: CCT3; NbExp=5; IntAct=EBI-365996, EBI-356673; CC P04049; P30304: CDC25A; NbExp=4; IntAct=EBI-365996, EBI-747671; CC P04049; Q16543: CDC37; NbExp=7; IntAct=EBI-365996, EBI-295634; CC P04049; P31327: CPS1; NbExp=4; IntAct=EBI-365996, EBI-536811; CC P04049; P01112: HRAS; NbExp=25; IntAct=EBI-365996, EBI-350145; CC P04049; P07900: HSP90AA1; NbExp=4; IntAct=EBI-365996, EBI-296047; CC P04049; P08238: HSP90AB1; NbExp=6; IntAct=EBI-365996, EBI-352572; CC P04049; P11021: HSPA5; NbExp=5; IntAct=EBI-365996, EBI-354921; CC P04049; P01116: KRAS; NbExp=6; IntAct=EBI-365996, EBI-367415; CC P04049; P01116-2: KRAS; NbExp=3; IntAct=EBI-365996, EBI-367427; CC P04049; Q02750: MAP2K1; NbExp=38; IntAct=EBI-365996, EBI-492564; CC P04049; P36507: MAP2K2; NbExp=6; IntAct=EBI-365996, EBI-1056930; CC P04049; Q12968: NFATC3; NbExp=2; IntAct=EBI-365996, EBI-5278441; CC P04049; P01111: NRAS; NbExp=9; IntAct=EBI-365996, EBI-721993; CC P04049; O43482: OIP5; NbExp=4; IntAct=EBI-365996, EBI-536879; CC P04049; Q13177: PAK2; NbExp=2; IntAct=EBI-365996, EBI-1045887; CC P04049; Q6TCH7: PAQR3; NbExp=3; IntAct=EBI-365996, EBI-15654365; CC P04049; P30086: PEBP1; NbExp=10; IntAct=EBI-365996, EBI-716384; CC P04049; Q96S96: PEBP4; NbExp=4; IntAct=EBI-365996, EBI-8563667; CC P04049; Q13526: PIN1; NbExp=2; IntAct=EBI-365996, EBI-714158; CC P04049; P14618: PKM; NbExp=3; IntAct=EBI-365996, EBI-353408; CC P04049; P67775: PPP2CA; NbExp=2; IntAct=EBI-365996, EBI-712311; CC P04049; Q13362: PPP2R5C; NbExp=2; IntAct=EBI-365996, EBI-1266156; CC P04049; P04049: RAF1; NbExp=6; IntAct=EBI-365996, EBI-365996; CC P04049; P62834: RAP1A; NbExp=2; IntAct=EBI-365996, EBI-491414; CC P04049; P06400: RB1; NbExp=3; IntAct=EBI-365996, EBI-491274; CC P04049; P53805-2: RCAN1; NbExp=4; IntAct=EBI-365996, EBI-1541912; CC P04049; P31947: SFN; NbExp=6; IntAct=EBI-365996, EBI-476295; CC P04049; Q13188: STK3; NbExp=6; IntAct=EBI-365996, EBI-992580; CC P04049; Q3ZCQ8: TIMM50; NbExp=6; IntAct=EBI-365996, EBI-355175; CC P04049; P31946: YWHAB; NbExp=21; IntAct=EBI-365996, EBI-359815; CC P04049; P62258: YWHAE; NbExp=6; IntAct=EBI-365996, EBI-356498; CC P04049; P61981: YWHAG; NbExp=6; IntAct=EBI-365996, EBI-359832; CC P04049; Q04917: YWHAH; NbExp=10; IntAct=EBI-365996, EBI-306940; CC P04049; P27348: YWHAQ; NbExp=7; IntAct=EBI-365996, EBI-359854; CC P04049; P63104: YWHAZ; NbExp=16; IntAct=EBI-365996, EBI-347088; CC P04049; P32883: Kras; Xeno; NbExp=2; IntAct=EBI-365996, EBI-644267; CC P04049; P28301: Lox; Xeno; NbExp=2; IntAct=EBI-365996, EBI-642911; CC P04049; Q9ESN9-2: Mapk8ip3; Xeno; NbExp=2; IntAct=EBI-365996, EBI-9549291; CC P04049; P03495: NS; Xeno; NbExp=2; IntAct=EBI-365996, EBI-2548993; CC P04049; O39474: NS5A; Xeno; NbExp=4; IntAct=EBI-365996, EBI-7016711; CC P04049; P01120: RAS2; Xeno; NbExp=2; IntAct=EBI-365996, EBI-14838; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Mitochondrion. Nucleus. CC Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and CC membranes. Phosphorylation at Ser-259 impairs its membrane CC accumulation. Recruited to the cell membrane by the active Ras protein. CC Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its CC mitochondrial localization. Retinoic acid-induced Ser-621 CC phosphorylated form of RAF1 is predominantly localized at the nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=6C; CC IsoId=P04049-1; Sequence=Displayed; CC Name=2; Synonyms=1A; CC IsoId=P04049-2; Sequence=VSP_034649; CC -!- TISSUE SPECIFICITY: In skeletal muscle, isoform 1 is more abundant than CC isoform 2. {ECO:0000269|PubMed:1886707}. CC -!- PTM: Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 CC results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, CC Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. CC Phosphorylation at Ser-259 induces the interaction with YWHAZ and CC inactivates kinase activity. Dephosphorylation of Ser-259 by the CC complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves CC inactivation, leading to stimulate RAF1 activity. Phosphorylation at CC Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its CC mitochondrial localization. Phosphorylation at Ser-621 in response to CC growth factor treatment stabilizes the protein, possibly by preventing CC proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, CC Ser-338 and Ser-621 are somehow linked to the methylation potential of CC cells. Treatment of cells with HGF in the presence of the methylation CC inhibitor 5'-methylthioadenosine (MTA) results in increased CC phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at CC Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C CC results in an activity decrease. {ECO:0000269|PubMed:10576742, CC ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:11447113, CC ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11756411, CC ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:15849194, CC ECO:0000269|PubMed:16093354, ECO:0000269|PubMed:16630891, CC ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:18465753, CC ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:7477354, CC ECO:0000269|PubMed:8349614, ECO:0000269|PubMed:9823899}. CC -!- PTM: Methylated at Arg-563 in response to EGF treatment. This CC modification leads to destabilization of the protein, possibly through CC proteasomal degradation. {ECO:0000269|PubMed:21917714}. CC -!- DISEASE: Noonan syndrome 5 (NS5) [MIM:611553]: A form of Noonan CC syndrome, a disease characterized by short stature, facial dysmorphic CC features such as hypertelorism, a downward eyeslant and low-set CC posteriorly rotated ears, and a high incidence of congenital heart CC defects and hypertrophic cardiomyopathy. Other features can include a CC short neck with webbing or redundancy of skin, deafness, motor delay, CC variable intellectual deficits, multiple skeletal defects, CC cryptorchidism, and bleeding diathesis. Individuals with Noonan CC syndrome are at risk of juvenile myelomonocytic leukemia, a CC myeloproliferative disorder characterized by excessive production of CC myelomonocytic cells. {ECO:0000269|PubMed:17603482, CC ECO:0000269|PubMed:17603483, ECO:0000269|PubMed:20683980}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: LEOPARD syndrome 2 (LPRD2) [MIM:611554]: A disorder CC characterized by lentigines, electrocardiographic conduction CC abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities CC of genitalia, retardation of growth, and sensorineural deafness. CC {ECO:0000269|PubMed:17603483}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cardiomyopathy, dilated 1NN (CMD1NN) [MIM:615916]: A disorder CC characterized by ventricular dilation and impaired systolic function, CC resulting in congestive heart failure and arrhythmia. Patients are at CC risk of premature death. {ECO:0000269|PubMed:24777450}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. RAF subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/raf1/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RAF1ID42032ch3p25.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03484; CAA27204.1; -; mRNA. DR EMBL; AY271661; AAP03432.1; -; Genomic_DNA. DR EMBL; AK312248; BAG35180.1; -; mRNA. DR EMBL; EU332868; ABY87557.1; -; Genomic_DNA. DR EMBL; CH471055; EAW64134.1; -; Genomic_DNA. DR EMBL; BC018119; AAH18119.1; -; mRNA. DR EMBL; L00212; AAA60247.1; -; Genomic_DNA. DR EMBL; L00206; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00207; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00208; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00209; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00210; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00211; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; L00213; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; M11376; AAA60247.1; JOINED; Genomic_DNA. DR EMBL; X54851; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS2612.1; -. [P04049-1] DR CCDS; CCDS87047.1; -. [P04049-2] DR PIR; A00637; TVHUF6. DR PIR; S60341; S60341. DR RefSeq; NP_002871.1; NM_002880.3. [P04049-1] DR RefSeq; XP_005265412.1; XM_005265355.2. DR RefSeq; XP_011532276.1; XM_011533974.2. [P04049-1] DR PDB; 1C1Y; X-ray; 1.90 A; B=55-131. DR PDB; 1FAQ; NMR; -; A=136-187. DR PDB; 1FAR; NMR; -; A=136-187. DR PDB; 1GUA; X-ray; 2.00 A; B=51-131. DR PDB; 1RFA; NMR; -; A=55-132. DR PDB; 3CU8; X-ray; 2.40 A; P/Q=256-264. DR PDB; 3IQJ; X-ray; 1.15 A; P=255-264. DR PDB; 3IQU; X-ray; 1.05 A; P=255-260. DR PDB; 3IQV; X-ray; 1.20 A; P=255-260. DR PDB; 3KUC; X-ray; 1.92 A; B=51-131. DR PDB; 3KUD; X-ray; 2.15 A; B=51-131. DR PDB; 3NKX; X-ray; 2.40 A; P/Q=255-264. DR PDB; 3O8I; X-ray; 2.00 A; B=255-264. DR PDB; 3OMV; X-ray; 4.00 A; A/B=323-618. DR PDB; 4FJ3; X-ray; 1.95 A; P=229-264. DR PDB; 4G0N; X-ray; 2.45 A; B=54-131. DR PDB; 4G3X; X-ray; 3.25 A; B=55-131. DR PDB; 4IEA; X-ray; 1.70 A; P=618-625. DR PDB; 4IHL; X-ray; 2.20 A; P=229-264. DR PDB; 6NTC; X-ray; 2.90 A; B=55-131. DR PDB; 6NTD; X-ray; 3.15 A; B=55-131. DR PDB; 6PTS; NMR; -; D=56-187. DR PDB; 6PTW; NMR; -; D=56-187. DR PDB; 6VJJ; X-ray; 1.40 A; B=52-131. DR PDB; 6XGU; X-ray; 2.70 A; B=52-188. DR PDB; 6XGV; X-ray; 2.11 A; B=52-188. DR PDB; 6XHA; X-ray; 2.87 A; B=52-188. DR PDB; 6XHB; X-ray; 2.50 A; B=52-188. DR PDB; 6XI7; X-ray; 1.95 A; B=52-188. DR PDB; 7JHP; X-ray; 2.77 A; C=55-187. DR PDBsum; 1C1Y; -. DR PDBsum; 1FAQ; -. DR PDBsum; 1FAR; -. DR PDBsum; 1GUA; -. DR PDBsum; 1RFA; -. DR PDBsum; 3CU8; -. DR PDBsum; 3IQJ; -. DR PDBsum; 3IQU; -. DR PDBsum; 3IQV; -. DR PDBsum; 3KUC; -. DR PDBsum; 3KUD; -. DR PDBsum; 3NKX; -. DR PDBsum; 3O8I; -. DR PDBsum; 3OMV; -. DR PDBsum; 4FJ3; -. DR PDBsum; 4G0N; -. DR PDBsum; 4G3X; -. DR PDBsum; 4IEA; -. DR PDBsum; 4IHL; -. DR PDBsum; 6NTC; -. DR PDBsum; 6NTD; -. DR PDBsum; 6PTS; -. DR PDBsum; 6PTW; -. DR PDBsum; 6VJJ; -. DR PDBsum; 6XGU; -. DR PDBsum; 6XGV; -. DR PDBsum; 6XHA; -. DR PDBsum; 6XHB; -. DR PDBsum; 6XI7; -. DR PDBsum; 7JHP; -. DR AlphaFoldDB; P04049; -. DR BMRB; P04049; -. DR SMR; P04049; -. DR BioGRID; 111831; 325. DR CORUM; P04049; -. DR DIP; DIP-1048N; -. DR IntAct; P04049; 208. DR MINT; P04049; -. DR STRING; 9606.ENSP00000251849; -. DR BindingDB; P04049; -. DR ChEMBL; CHEMBL1906; -. DR DrugBank; DB08862; Cholecystokinin. DR DrugBank; DB08912; Dabrafenib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB05268; iCo-007. DR DrugBank; DB04973; LErafAON. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB05190; XL281. DR DrugCentral; P04049; -. DR GuidetoPHARMACOLOGY; 2184; -. DR MoonDB; P04049; Predicted. DR GlyGen; P04049; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P04049; -. DR PhosphoSitePlus; P04049; -. DR BioMuta; RAF1; -. DR DMDM; 125651; -. DR CPTAC; CPTAC-1335; -. DR CPTAC; CPTAC-1336; -. DR CPTAC; CPTAC-1546; -. DR CPTAC; CPTAC-1762; -. DR EPD; P04049; -. DR jPOST; P04049; -. DR MassIVE; P04049; -. DR MaxQB; P04049; -. DR PaxDb; P04049; -. DR PeptideAtlas; P04049; -. DR ProteomicsDB; 51637; -. [P04049-1] DR ProteomicsDB; 51638; -. [P04049-2] DR Antibodypedia; 1131; 3156 antibodies from 49 providers. DR CPTC; P04049; 8 antibodies. DR DNASU; 5894; -. DR Ensembl; ENST00000251849.9; ENSP00000251849.4; ENSG00000132155.14. [P04049-1] DR Ensembl; ENST00000442415.7; ENSP00000401888.2; ENSG00000132155.14. [P04049-2] DR Ensembl; ENST00000685653.1; ENSP00000509968.1; ENSG00000132155.14. [P04049-1] DR Ensembl; ENST00000691899.1; ENSP00000508763.1; ENSG00000132155.14. [P04049-1] DR GeneID; 5894; -. DR KEGG; hsa:5894; -. DR MANE-Select; ENST00000251849.9; ENSP00000251849.4; NM_002880.4; NP_002871.1. DR UCSC; uc003bxf.5; human. [P04049-1] DR CTD; 5894; -. DR DisGeNET; 5894; -. DR GeneCards; RAF1; -. DR GeneReviews; RAF1; -. DR HGNC; HGNC:9829; RAF1. DR HPA; ENSG00000132155; Low tissue specificity. DR MalaCards; RAF1; -. DR MIM; 164760; gene. DR MIM; 611553; phenotype. DR MIM; 611554; phenotype. DR MIM; 615916; phenotype. DR neXtProt; NX_P04049; -. DR OpenTargets; ENSG00000132155; -. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 648; Noonan syndrome. DR Orphanet; 500; Noonan syndrome with multiple lentigines. DR Orphanet; 251615; Pilomyxoid astrocytoma. DR PharmGKB; PA34183; -. DR VEuPathDB; HostDB:ENSG00000132155; -. DR eggNOG; KOG0193; Eukaryota. DR GeneTree; ENSGT00940000156084; -. DR InParanoid; P04049; -. DR OMA; SWCHRFW; -. DR OrthoDB; 243095at2759; -. DR PhylomeDB; P04049; -. DR TreeFam; TF317006; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P04049; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR Reactome; R-HSA-392517; Rap1 signalling. DR Reactome; R-HSA-430116; GP1b-IX-V activation signalling. DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling. DR Reactome; R-HSA-5673000; RAF activation. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR Reactome; R-HSA-5674499; Negative feedback regulation of MAPK pathway. DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway. DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants. DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF. DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants. DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR Reactome; R-HSA-9726840; SHOC2 M1731 mutant abolishes MRAS complex function. DR Reactome; R-HSA-9726842; Gain-of-function MRAS complexes activate RAF signaling. DR SignaLink; P04049; -. DR SIGNOR; P04049; -. DR BioGRID-ORCS; 5894; 93 hits in 1120 CRISPR screens. DR ChiTaRS; RAF1; human. DR EvolutionaryTrace; P04049; -. DR GeneWiki; C-Raf; -. DR GenomeRNAi; 5894; -. DR Pharos; P04049; Tclin. DR PRO; PR:P04049; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P04049; protein. DR Bgee; ENSG00000132155; Expressed in gastrocnemius and 212 other tissues. DR ExpressionAtlas; P04049; baseline and differential. DR Genevisible; P04049; HS. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IPI:MGI. DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:ProtInc. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0007190; P:activation of adenylate cyclase activity; IDA:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; TAS:GO_Central. DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl. DR GO; GO:0071550; P:death-inducing signaling complex assembly; IEA:Ensembl. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0060324; P:face development; IEA:Ensembl. DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:UniProtKB. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:GO_Central. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; TAS:UniProtKB. DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; TAS:UniProtKB. DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl. DR GO; GO:0044342; P:type B pancreatic cell proliferation; IEA:Ensembl. DR GO; GO:0042060; P:wound healing; TAS:UniProtKB. DR CDD; cd00029; C1; 1. DR IDEAL; IID00292; -. DR InterPro; IPR046349; C1-like_sf. DR InterPro; IPR020454; DAG/PE-bd. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR002219; PE/DAG-bd. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR003116; RBD_dom. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. DR AGR; HGNC:9829; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cardiomyopathy; KW Cell membrane; Cytoplasm; Deafness; Direct protein sequencing; KW Disease variant; Kinase; Membrane; Metal-binding; Methylation; KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc; KW Zinc-finger. FT CHAIN 1..648 FT /note="RAF proto-oncogene serine/threonine-protein kinase" FT /id="PRO_0000086596" FT DOMAIN 56..131 FT /note="RBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262" FT DOMAIN 349..609 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ZN_FING 138..184 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 220..334 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 331..349 FT /note="Interaction with PEBP1/RKIP" FT COMPBIAS 222..269 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 284..310 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 468 FT /note="Proton acceptor" FT BINDING 139 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 152 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 165 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 168 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 173 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 176 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 184 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 355..363 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 375 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 29 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000250|UniProtKB:Q99N57" FT MOD_RES 43 FT /note="Phosphoserine; by PKA and MAPK1" FT /evidence="ECO:0000269|PubMed:8349614" FT MOD_RES 252 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 259 FT /note="Phosphoserine; by PKA, PKC and PKB/AKT1" FT /evidence="ECO:0000269|PubMed:10576742, FT ECO:0000269|PubMed:10801873, ECO:0000269|PubMed:11756411, FT ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:16630891, FT ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:8349614" FT MOD_RES 268 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8349614" FT MOD_RES 269 FT /note="Phosphothreonine; by PKA" FT /evidence="ECO:0000269|PubMed:7477354" FT MOD_RES 289 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:21917714, FT ECO:0007744|PubMed:19690332" FT MOD_RES 296 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 301 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:21917714, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 338 FT /note="Phosphoserine; by PAK1, PAK2, PAK3 and PAK5" FT /evidence="ECO:0000269|PubMed:11733498, FT ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, FT ECO:0000269|PubMed:18465753, ECO:0000269|PubMed:21917714" FT MOD_RES 339 FT /note="Phosphoserine; by PAK1, PAK2 and PAK3" FT /evidence="ECO:0000269|PubMed:15849194" FT MOD_RES 340 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:16892053" FT MOD_RES 341 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:16892053" FT MOD_RES 471 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16093354" FT MOD_RES 491 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:11447113" FT MOD_RES 494 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11447113" FT MOD_RES 499 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000269|PubMed:8349614" FT MOD_RES 563 FT /note="Symmetric dimethylarginine; by PRMT5" FT /evidence="ECO:0000269|PubMed:21917714" FT MOD_RES 621 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10801873, FT ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:21917714, FT ECO:0000269|PubMed:8349614" FT MOD_RES 642 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 278 FT /note="E -> ENNNLSASPRAWSRRFCLRGR (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_034649" FT VARIANT 237 FT /note="A -> T (in CMD1NN; shows a mild increase in kinase FT activity; dbSNP:rs587777588)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071844" FT VARIANT 256 FT /note="R -> S (in NS5; dbSNP:rs397516826)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037807" FT VARIANT 257 FT /note="S -> L (in NS5 and LPRD2; shows in vitro greater FT kinase activity and enhanced ERK activation than wild-type; FT dbSNP:rs80338796)" FT /evidence="ECO:0000269|PubMed:17603482, FT ECO:0000269|PubMed:17603483" FT /id="VAR_037808" FT VARIANT 259 FT /note="S -> A (in an ovarian serous carcinoma sample; FT somatic mutation; increased ERK activation; FT dbSNP:rs3730271)" FT /evidence="ECO:0000269|PubMed:16630891, FT ECO:0000269|PubMed:17344846" FT /id="VAR_041037" FT VARIANT 259 FT /note="S -> F (in NS5; dbSNP:rs397516827)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037809" FT VARIANT 260 FT /note="T -> I (in hypertrophic cardiomyopathy; unknown FT pathological significance; dbSNP:rs869025501)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037810" FT VARIANT 260 FT /note="T -> R (in NS5)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037811" FT VARIANT 261 FT /note="P -> A (in NS5; shows in vitro greater kinase FT activity and enhanced MAPK1 activation than wild-type; FT dbSNP:rs121434594)" FT /evidence="ECO:0000269|PubMed:17603482" FT /id="VAR_037812" FT VARIANT 261 FT /note="P -> L (in NS5; shows greater kinase activity and FT enhanced MAPK1 activation than wild-type; FT dbSNP:rs397516828)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037813" FT VARIANT 261 FT /note="P -> S (in NS5; shows in vitro greater kinase FT activity and enhanced MAPK1 activation than wild-type; FT dbSNP:rs121434594)" FT /evidence="ECO:0000269|PubMed:17603482, FT ECO:0000269|PubMed:17603483, ECO:0000269|PubMed:20683980" FT /id="VAR_037814" FT VARIANT 263 FT /note="V -> A (in NS5; shows in vitro greater kinase FT activity and enhanced MAPK1 activation than wild-type; FT dbSNP:rs397516830)" FT /evidence="ECO:0000269|PubMed:17603482" FT /id="VAR_037815" FT VARIANT 308 FT /note="P -> L (in dbSNP:rs5746220)" FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3" FT /id="VAR_018840" FT VARIANT 310 FT /note="T -> A (in CMD1NN; shows a mild increase in kinase FT activity; dbSNP:rs778155315)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071845" FT VARIANT 332 FT /note="P -> A (in CMD1NN; shows a mild increase in kinase FT activity; dbSNP:rs1057403865)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071846" FT VARIANT 335 FT /note="Q -> H (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041038" FT VARIANT 486 FT /note="D -> G (in NS5; dbSNP:rs397516815)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037816" FT VARIANT 486 FT /note="D -> N (in NS5; has reduced or absent kinase FT activity; dbSNP:rs80338798)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037817" FT VARIANT 491 FT /note="T -> I (in NS5; has reduced or absent kinase FT activity; dbSNP:rs80338799)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037818" FT VARIANT 491 FT /note="T -> R (in NS5; dbSNP:rs80338799)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037819" FT VARIANT 603 FT /note="L -> P (in CMD1NN; shows impaired kinase activity FT and reduced MAPK3 activation with this mutation; FT dbSNP:rs587777586)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071847" FT VARIANT 612 FT /note="S -> T (in NS5; dbSNP:rs1448392469)" FT /evidence="ECO:0000269|PubMed:17603483" FT /id="VAR_037820" FT VARIANT 613 FT /note="L -> V (in NS5 and LPRD2; shows in vitro greater FT kinase activity and enhanced MAPK1 activation than FT wild-type; dbSNP:rs80338797)" FT /evidence="ECO:0000269|PubMed:17603482, FT ECO:0000269|PubMed:17603483" FT /id="VAR_037821" FT VARIANT 626 FT /note="H -> R (in CMD1NN; shows a mild increase in kinase FT activity; dbSNP:rs1553609795)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071848" FT VARIANT 641 FT /note="T -> M (in CMD1NN; shows a mild increase in kinase FT activity; dbSNP:rs587777587)" FT /evidence="ECO:0000269|PubMed:24777450" FT /id="VAR_071849" FT MUTAGEN 338..339 FT /note="SS->AA: Reduced kinase activity; when associated FT with 340-D-D-341." FT /evidence="ECO:0000269|PubMed:16892053" FT MUTAGEN 338..339 FT /note="SS->DE: Non-inhibited by PPP5C. Constitutively FT active and non-inhibited by PPP5C; when associated with FT 340-D-D-341." FT /evidence="ECO:0000269|PubMed:16892053" FT MUTAGEN 340..341 FT /note="YY->DD: Constitutively active and highly FT phosphorylated on S-338, inhibited by PPP5C. Reduced kinase FT activity; when associated with 338-A-A-339. Constitutively FT active and non-inhibited by PPP5C; when associated with FT 338-D-E-339." FT /evidence="ECO:0000269|PubMed:16892053" FT MUTAGEN 375 FT /note="K->W: Catalytically inactive." FT /evidence="ECO:0000269|PubMed:20956560" FT MUTAGEN 491 FT /note="T->D: Increased kinase activity but can still be FT inhibited by PPP5C; when associated with D-494." FT /evidence="ECO:0000269|PubMed:16892053" FT MUTAGEN 494 FT /note="S->D: Increased kinase activity but can still be FT inhibited by PPP5C; when associated with D-491." FT /evidence="ECO:0000269|PubMed:16892053" FT MUTAGEN 563 FT /note="R->K: Loss of methylation. Increased stability and FT catalytic activity in response to EGF treatment." FT /evidence="ECO:0000269|PubMed:21917714" FT CONFLICT 240 FT /note="F -> L (in Ref. 6; AAA60247)" FT /evidence="ECO:0000305" FT CONFLICT 542 FT /note="M -> I (in Ref. 6; AAA60247)" FT /evidence="ECO:0000305" FT STRAND 57..61 FT /evidence="ECO:0007829|PDB:6VJJ" FT TURN 63..65 FT /evidence="ECO:0007829|PDB:1C1Y" FT STRAND 67..71 FT /evidence="ECO:0007829|PDB:6VJJ" FT HELIX 78..88 FT /evidence="ECO:0007829|PDB:6VJJ" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:6VJJ" FT STRAND 96..100 FT /evidence="ECO:0007829|PDB:6VJJ" FT STRAND 103..107 FT /evidence="ECO:0007829|PDB:6VJJ" FT STRAND 109..112 FT /evidence="ECO:0007829|PDB:3KUC" FT HELIX 118..121 FT /evidence="ECO:0007829|PDB:6VJJ" FT STRAND 125..130 FT /evidence="ECO:0007829|PDB:6VJJ" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:6PTW" FT STRAND 135..137 FT /evidence="ECO:0007829|PDB:6XGV" FT STRAND 141..145 FT /evidence="ECO:0007829|PDB:6XI7" FT TURN 153..155 FT /evidence="ECO:0007829|PDB:6XI7" FT STRAND 160..165 FT /evidence="ECO:0007829|PDB:6XI7" FT TURN 166..168 FT /evidence="ECO:0007829|PDB:6XI7" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:7JHP" FT HELIX 174..179 FT /evidence="ECO:0007829|PDB:6XI7" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:6XGV" SQ SEQUENCE 648 AA; 73052 MW; EF821B5349711BC3 CRC64; MEHIQGAWKT ISNGFGFKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV PTMCVDWSNI RQLLLFPNST IGDSGVPALP SLTMRRMRES VSRMPVSSQH RYSTPHAFTF NTSSPSSEGS LSQRQRSTST PNVHMVSTTL PVDSRMIEDA IRSHSESASP SALSSSPNNL SPTGWSQPKT PVPAQRERAP VSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF // ID GCR_HUMAN Reviewed; 777 AA. AC P04150; A0ZXF9; B0LPG8; D3DQF4; F5ATB7; P04151; Q53EP5; Q6N0A4; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 14-DEC-2022, entry version 278. DE RecName: Full=Glucocorticoid receptor; DE Short=GR; DE AltName: Full=Nuclear receptor subfamily 3 group C member 1; GN Name=NR3C1; Synonyms=GRL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). RC TISSUE=Fibroblast; RX PubMed=2867473; DOI=10.1038/318635a0; RA Hollenberg S.M., Weinberger C., Ong E.S., Cerelli G., Oro A., Lebo R., RA Thompson E.B., Rosenfeld M.G., Evans R.M.; RT "Primary structure and expression of a functional human glucocorticoid RT receptor cDNA."; RL Nature 318:635-641(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA AND BETA). RX PubMed=1707881; DOI=10.1016/s0021-9258(20)89627-6; RA Encio I.J., Detera-Wadleigh S.D.; RT "The genomic structure of the human glucocorticoid receptor."; RL J. Biol. Chem. 266:7182-7188(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=20843780; DOI=10.1093/nar/gkq750; RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., RA Speed T.P., Scharfe C.; RT "Identification of rare DNA variants in mitochondrial disorders with RT improved array-based sequencing."; RL Nucleic Acids Res. 39:44-58(2011). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10). RX PubMed=17404046; DOI=10.1196/annals.1397.037; RA Turner J.D., Schote A.B., Keipes M., Muller C.P.; RT "A new transcript splice variant of the human glucocorticoid receptor: RT identification and tissue distribution of hGR Delta 313-338, an alternative RT exon 2 transactivation domain isoform."; RL Ann. N. Y. Acad. Sci. 1095:334-341(2007). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), VARIANTS ASP-72; ALA-321 AND RP SER-766, AND CHARACTERIZATION OF VARIANTS ASP-72; ALA-321 AND SER-766. RX PubMed=21701417; DOI=10.1097/shk.0b013e318228eca7; RA Tung K., Baker A.C., Amini A., Green T.L., Chew V.W., Lim D., Nguyen S.T., RA Yee K.S., Cho K., Greenhalgh D.G.; RT "Novel hyperactive glucocorticoid receptor isoform identified within a RT human population."; RL Shock 36:339-344(2011). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2). RC TISSUE=Osteosarcoma; RA Munroe D.G., Pang J., Taylor G.R., Lau C., Plante R.K., Zhou L.; RT "Alternative splicing within the DNA binding domain creates a novel isoform RT of the human glucocorticoid receptor."; RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Kidney; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Uterine endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-23 AND VAL-65. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX PubMed=2026589; DOI=10.1016/s0021-9258(18)31504-7; RA Leclerc S., Xie B.X., Roy R., Govindan M.V.; RT "Purification of a human glucocorticoid receptor gene promoter-binding RT protein. Production of polyclonal antibodies against the purified factor."; RL J. Biol. Chem. 266:8711-8719(1991). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX PubMed=1958537; DOI=10.1016/0960-0760(91)90197-d; RA Govindan M.V., Pothier F., Leclerc S., Palaniswami R., Xie B.; RT "Human glucocorticoid receptor gene promotor-homologous down regulation."; RL J. Steroid Biochem. Mol. Biol. 40:317-323(1991). RN [16] RP DOMAINS. RX PubMed=3841189; DOI=10.1038/318670a0; RA Weinberger C., Hollenberg S.M., Rosenfeld M.G., Evans R.M.; RT "Domain structure of human glucocorticoid receptor and its relationship to RT the v-erb-A oncogene product."; RL Nature 318:670-672(1985). RN [17] RP ALTERNATIVE SPLICING (ISOFORMS GR-P; GR-A ALPHA AND GR-A BETA). RX PubMed=8358712; RA Moalli P.A., Pillay S., Krett N.L., Rosen S.T.; RT "Alternatively spliced glucocorticoid receptor messenger RNAs in RT glucocorticoid-resistant human multiple myeloma cells."; RL Cancer Res. 53:3877-3879(1993). RN [18] RP FUNCTION (ISOFORM BETA), AND TISSUE SPECIFICITY (ISOFORM BETA). RX PubMed=7769088; DOI=10.1172/jci117943; RA Bamberger C.M., Bamberger A.M., de Castro M., Chrousos G.P.; RT "Glucocorticoid receptor beta, a potential endogenous inhibitor of RT glucocorticoid action in humans."; RL J. Clin. Invest. 95:2435-2441(1995). RN [19] RP FUNCTION (ISOFORM BETA), SUBCELLULAR LOCATION (ISOFORMS ALPHA AND BETA), RP AND TISSUE SPECIFICITY (ISOFORM BETA). RX PubMed=8621628; DOI=10.1074/jbc.271.16.9550; RA Oakley R.H., Sar M., Cidlowski J.A.; RT "The human glucocorticoid receptor beta isoform. Expression, biochemical RT properties, and putative function."; RL J. Biol. Chem. 271:9550-9559(1996). RN [20] RP INTERACTION WITH HNRNPU. RX PubMed=9353307; DOI=10.1074/jbc.272.45.28471; RA Eggert M., Michel J., Schneider S., Bornfleth H., Baniahmad A., RA Fackelmayer F.O., Schmidt S., Renkawitz R.; RT "The glucocorticoid receptor is associated with the RNA-binding nuclear RT matrix protein hnRNP U."; RL J. Biol. Chem. 272:28471-28478(1997). RN [21] RP INTERACTION WITH TADA2L AND THE ADA COMPLEX, AND MUTAGENESIS OF PHE-191; RP ILE-193; LEU-194; LEU-197; TRP-213; LEU-224; LEU-225; PHE-235 AND LEU-236. RX PubMed=9154805; DOI=10.1128/mcb.17.6.3065; RA Henriksson A., Almloef T., Ford J., McEwan I.J., Gustafsson J.-A., RA Wright A.P.H.; RT "Role of the Ada adaptor complex in gene activation by the glucocorticoid RT receptor."; RL Mol. Cell. Biol. 17:3065-3073(1997). RN [22] RP FUNCTION, AND INTERACTION WITH THE SMARCA4 COMPLEX; NCOA1; NCOA2 AND THE RP CREBBP/EP300 COMPLEX. RX PubMed=9590696; DOI=10.1038/30032; RA Fryer C.J., Archer T.K.; RT "Chromatin remodelling by the glucocorticoid receptor requires the BRG1 RT complex."; RL Nature 393:88-91(1998). RN [23] RP INTERACTION WITH BAG1. RX PubMed=10477749; DOI=10.1083/jcb.146.5.929; RA Schneikert J., Huebner S., Martin E., Cato A.B.C.; RT "A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of RT glucocorticoid receptor activity."; RL J. Cell Biol. 146:929-940(1999). RN [24] RP ALTERNATIVE SPLICING (ISOFORMS ALPHA-2 AND BETA-2), AND TISSUE SPECIFICITY RP (ISOFORM ALPHA-2). RX PubMed=10566686; DOI=10.1210/jcem.84.11.6235; RA Rivers C., Levy A., Hancock J., Lightman S., Norman M.; RT "Insertion of an amino acid in the DNA-binding domain of the glucocorticoid RT receptor as a result of alternative splicing."; RL J. Clin. Endocrinol. Metab. 84:4283-4286(1999). RN [25] RP TISSUE SPECIFICITY. RX PubMed=10902803; DOI=10.1210/jcem.85.7.6663; RA Kayes-Wandover K.M., White P.C.; RT "Steroidogenic enzyme gene expression in the human heart."; RL J. Clin. Endocrinol. Metab. 85:2519-2525(2000). RN [26] RP INTERACTION WITH NCOA6. RX PubMed=10866662; DOI=10.1128/mcb.20.14.5048-5063.2000; RA Mahajan M.A., Samuels H.H.; RT "A new family of nuclear receptor coregulators that integrates nuclear RT receptor signaling through CBP."; RL Mol. Cell. Biol. 20:5048-5063(2000). RN [27] RP EFFECT ON EXPANDED POLYGLUTAMINE PROTEIN. RX PubMed=10639135; DOI=10.1073/pnas.97.2.657; RA Diamond M.I., Robinson M.R., Yamamoto K.R.; RT "Regulation of expanded polyglutamine protein aggregation and nuclear RT localization by the glucocorticoid receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 97:657-661(2000). RN [28] RP FUNCTION (ISOFORM GR-P). RX PubMed=11358809; RA de Lange P., Segeren C.M., Koper J.W., Wiemer E., Sonneveld P., RA Brinkmann A.O., White A., Brogan I.J., de Jong F.H., Lamberts S.W.; RT "Expression in hematological malignancies of a glucocorticoid receptor RT splice variant that augments glucocorticoid receptor-mediated effects in RT transfected cells."; RL Cancer Res. 61:3937-3941(2001). RN [29] RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION. RX PubMed=11555652; DOI=10.1074/jbc.m106033200; RA Wallace A.D., Cidlowski J.A.; RT "Proteasome-mediated glucocorticoid receptor degradation restricts RT transcriptional signaling by glucocorticoids."; RL J. Biol. Chem. 276:42714-42721(2001). RN [30] RP REDUCTION OF CELL DEATH IN RESPONSE TO CORTICOSTEROIDS. RX PubMed=11238589; DOI=10.1084/jem.193.5.585; RA Strickland I., Kisich K., Hauk P.J., Vottero A., Chrousos G.P., Klemm D.J., RA Leung D.Y.M.; RT "High constitutive glucocorticoid receptor beta in human neutrophils RT enables them to reduce their spontaneous rate of cell death in response to RT corticosteroids."; RL J. Exp. Med. 193:585-593(2001). RN [31] RP FUNCTION (ISOFORMS ALPHA AND ALPHA-B), ALTERNATIVE INITIATION, AND RP MUTAGENESIS OF MET-1 AND MET-27. RX PubMed=11435610; DOI=10.1210/mend.15.7.0667; RA Yudt M.R., Cidlowski J.A.; RT "Molecular identification and characterization of A and B forms of the RT glucocorticoid receptor."; RL Mol. Endocrinol. 15:1093-1103(2001). RN [32] RP INDUCTION (ISOFORMS ALPHA AND BETA). RX PubMed=11381138; DOI=10.1073/pnas.121455098; RA Webster J.C., Oakley R.H., Jewell C.M., Cidlowski J.A.; RT "Proinflammatory cytokines regulate human glucocorticoid receptor gene RT expression and lead to the accumulation of the dominant negative beta RT isoform: a mechanism for the generation of glucocorticoid resistance."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6865-6870(2001). RN [33] RP SUMOYLATION, AND MUTAGENESIS OF LYS-277; LYS-293 AND LYS-703. RX PubMed=12144530; DOI=10.1042/bj20021085; RA Tian S., Poukka H., Palvimo J.J., Jaenne O.A.; RT "Small ubiquitin-related modifier-1 (SUMO-1) modification of the RT glucocorticoid receptor."; RL Biochem. J. 367:907-911(2002). RN [34] RP PHOSPHORYLATION AT SER-203 AND SER-211. RX PubMed=12000743; DOI=10.1074/jbc.m110530200; RA Wang Z., Frederick J., Garabedian M.J.; RT "Deciphering the phosphorylation 'code' of the glucocorticoid receptor in RT vivo."; RL J. Biol. Chem. 277:26573-26580(2002). RN [35] RP RETRACTED PAPER. RX PubMed=12415108; DOI=10.1073/pnas.192569699; RA Wong C.-W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.; RT "Estrogen receptor-interacting protein that modulates its nongenomic RT activity-crosstalk with Src/Erk phosphorylation cascade."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002). RN [36] RP RETRACTION NOTICE OF PUBMED:12415108. RX PubMed=19666546; DOI=10.1073/pnas.0908685106; RA Wong C.W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.; RL Proc. Natl. Acad. Sci. U.S.A. 106:14180-14180(2009). RN [37] RP REVIEW ON ALTERNATIVE SPLICING, AND ALTERNATIVE INITIATION. RX PubMed=15265776; DOI=10.1196/annals.1321.008; RA Lu N.Z., Cidlowski J.A.; RT "The origin and functions of multiple human glucocorticoid receptor RT isoforms."; RL Ann. N. Y. Acad. Sci. 1024:102-123(2004). RN [38] RP INTERACTION WITH TGFB1I1. RX PubMed=15211577; DOI=10.1002/jcb.20109; RA Guerrero-Santoro J., Yang L., Stallcup M.R., DeFranco D.B.; RT "Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix RT targeting and glucocorticoid receptor binding and coactivation."; RL J. Cell. Biochem. 92:810-819(2004). RN [39] RP FUNCTION (ISOFORMS ALPHA; ALPHA-B; ALPHA-C1; ALPHA-C2; ALPHA-C3; ALPHA-D1; RP ALPHA-D2 AND ALPHA-D3), SUBCELLULAR LOCATION (ISOFORM ALPHA-B), ALTERNATIVE RP INITIATION (ISOFORMS ALPHA; ALPHA-B; ALPHA-C1; ALPHA-C2; ALPHA-C3; RP ALPHA-D1; ALPHA-D2 AND ALPHA-D3), AND MUTAGENESIS OF MET-1; MET-27; MET-86; RP MET-90; MET-98; MET-316; MET-331 AND MET-336. RX PubMed=15866175; DOI=10.1016/j.molcel.2005.03.025; RA Lu N.Z., Cidlowski J.A.; RT "Translational regulatory mechanisms generate N-terminal glucocorticoid RT receptor isoforms with unique transcriptional target genes."; RL Mol. Cell 18:331-342(2005). RN [40] RP INTERACTION WITH NR4A3. RX PubMed=15591535; DOI=10.1210/me.2004-0333; RA Martens C., Bilodeau S., Maira M., Gauthier Y., Drouin J.; RT "Protein-protein interactions and transcriptional antagonism between the RT subfamily of NGFI-B/Nur77 orphan nuclear receptors and glucocorticoid RT receptor."; RL Mol. Endocrinol. 19:885-897(2005). RN [41] RP INTERACTION WITH HEXIM1. RX PubMed=15941832; DOI=10.1073/pnas.0409863102; RA Shimizu N., Ouchida R., Yoshikawa N., Hisada T., Watanabe H., Okamoto K., RA Kusuhara M., Handa H., Morimoto C., Tanaka H.; RT "HEXIM1 forms a transcriptionally abortive complex with glucocorticoid RT receptor without involving 7SK RNA and positive transcription elongation RT factor b."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8555-8560(2005). RN [42] RP INTERACTION WITH MCM3AP. RX PubMed=16914116; DOI=10.1016/j.bbrc.2006.07.182; RA Osman W., Laine S., Zilliacus J.; RT "Functional interaction between the glucocorticoid receptor and RT GANP/MCM3AP."; RL Biochem. Biophys. Res. Commun. 348:1239-1244(2006). RN [43] RP INTERACTION WITH UNC45A. RX PubMed=16478993; DOI=10.1128/mcb.26.5.1722-1730.2006; RA Chadli A., Graham J.D., Abel M.G., Jackson T.A., Gordon D.F., Wood W.M., RA Felts S.J., Horwitz K.B., Toft D.; RT "GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 RT chaperoning pathway."; RL Mol. Cell. Biol. 26:1722-1730(2006). RN [44] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [46] RP INTERACTION WITH GSK3B, SUBCELLULAR LOCATION (ISOFORM ALPHA), RP PHOSPHORYLATION AT SER-404, MUTAGENESIS OF SER-404, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=18838540; DOI=10.1128/mcb.00808-08; RA Galliher-Beckley A.J., Williams J.G., Collins J.B., Cidlowski J.A.; RT "Glycogen synthase kinase 3beta-mediated serine phosphorylation of the RT human glucocorticoid receptor redirects gene expression profiles."; RL Mol. Cell. Biol. 28:7309-7322(2008). RN [47] RP PHOSPHORYLATION AT SER-203; SER-211 AND SER-226, AND MUTAGENESIS OF SER-211 RP AND SER-226. RX PubMed=18483179; DOI=10.1210/me.2007-0219; RA Chen W., Dang T., Blind R.D., Wang Z., Cavasotto C.N., Hittelman A.B., RA Rogatsky I., Logan S.K., Garabedian M.J.; RT "Glucocorticoid receptor phosphorylation differentially affects target gene RT expression."; RL Mol. Endocrinol. 22:1754-1766(2008). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134; SER-226 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [49] RP FUNCTION (ISOFORMS ALPHA AND BETA), AND SUBCELLULAR LOCATION (ISOFORM RP BETA). RX PubMed=19248771; DOI=10.1016/j.bbrc.2009.02.110; RA Kino T., Manoli I., Kelkar S., Wang Y., Su Y.A., Chrousos G.P.; RT "Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent RT transcriptional activity."; RL Biochem. Biophys. Res. Commun. 381:671-675(2009). RN [50] RP FUNCTION (ISOFORM ALPHA), ACETYLATION AT LYS-480; LYS-492; LYS-494 AND RP LYS-495, MUTAGENESIS OF LYS-480; LYS-492; LYS-494 AND LYS-495, AND RP INTERACTION WITH CLOCK. RX PubMed=19141540; DOI=10.1096/fj.08-117697; RA Nader N., Chrousos G.P., Kino T.; RT "Circadian rhythm transcription factor CLOCK regulates the transcriptional RT activity of the glucocorticoid receptor by acetylating its hinge region RT lysine cluster: potential physiological implications."; RL FASEB J. 23:1572-1583(2009). RN [51] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [52] RP INTERACTION WITH TACC1. RX PubMed=20078863; DOI=10.1186/1471-2199-11-3; RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.; RT "The transforming acidic coiled coil (TACC1) protein modulates the RT transcriptional activity of the nuclear receptors TR and RAR."; RL BMC Mol. Biol. 11:3-3(2010). RN [53] RP FUNCTION (ISOFORMS ALPHA; BETA; ALPHA-2 AND 10). RX PubMed=20484466; DOI=10.1210/en.2009-1254; RA Taniguchi Y., Iwasaki Y., Tsugita M., Nishiyama M., Taguchi T., Okazaki M., RA Nakayama S., Kambayashi M., Hashimoto K., Terada Y.; RT "Glucocorticoid receptor-beta and receptor-gamma exert dominant negative RT effect on gene repression but not on gene induction."; RL Endocrinology 151:3204-3213(2010). RN [54] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [55] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [56] RP FUNCTION (ISOFORM ALPHA), AND SUBCELLULAR LOCATION (ISOFORM ALPHA). RX PubMed=21664385; DOI=10.1016/j.bbamcr.2011.05.014; RA Psarra A.M., Sekeris C.E.; RT "Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: RT role of the mitochondrial glucocorticoid receptor."; RL Biochim. Biophys. Acta 1813:1814-1821(2011). RN [57] RP SUBUNIT. RX PubMed=21730050; DOI=10.1074/jbc.m111.256610; RA Gallo L.I., Lagadari M., Piwien-Pilipuk G., Galigniana M.D.; RT "The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a RT mitochondrial protein that translocates to the nucleus to protect cells RT against oxidative stress."; RL J. Biol. Chem. 286:30152-30160(2011). RN [58] RP INTERACTION WITH CRY1 AND CRY2. RX PubMed=22170608; DOI=10.1038/nature10700; RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W., RA Downes M., Evans R.M.; RT "Cryptochromes mediate rhythmic repression of the glucocorticoid RT receptor."; RL Nature 480:552-556(2011). RN [59] RP ACETYLATION, AND INTERACTION WITH CLOCK. RX PubMed=21980503; DOI=10.1371/journal.pone.0025612; RA Charmandari E., Chrousos G.P., Lambrou G.I., Pavlaki A., Koide H., Ng S.S., RA Kino T.; RT "Peripheral CLOCK regulates target-tissue glucocorticoid receptor RT transcriptional activity in a circadian fashion in man."; RL PLoS ONE 6:E25612-E25612(2011). RN [60] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS ALPHA-B AND BETA-B), RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [61] RP FUNCTION (ISOFORMS ALPHA; ALPHA-C3 AND ALPHA-D3). RX PubMed=23303127; DOI=10.1038/cddis.2012.193; RA Wu I., Shin S.C., Cao Y., Bender I.K., Jafari N., Feng G., Lin S., RA Cidlowski J.A., Schleimer R.P., Lu N.Z.; RT "Selective glucocorticoid receptor translational isoforms reveal RT glucocorticoid-induced apoptotic transcriptomes."; RL Cell Death Dis. 4:E453-E453(2013). RN [62] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8; SER-45 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [63] RP MUTAGENESIS OF LYS-703. RX PubMed=23508108; DOI=10.1128/mcb.01470-12; RA Druker J., Liberman A.C., Antunica-Noguerol M., Gerez J., Paez-Pereda M., RA Rein T., Iniguez-Lluhi J.A., Holsboer F., Arzt E.; RT "RSUME enhances glucocorticoid receptor SUMOylation and transcriptional RT activity."; RL Mol. Cell. Biol. 33:2116-2127(2013). RN [64] RP FUNCTION (ISOFORMS ALPHA; ALPHA-C3 AND ALPHA-D3), AND MUTAGENESIS OF RP ASP-101; 106-GLN-GLN-107 AND 113-SER-SER-114. RX PubMed=23820903; DOI=10.1210/me.2013-1009; RA Bender I.K., Cao Y., Lu N.Z.; RT "Determinants of the heightened activity of glucocorticoid receptor RT translational isoforms."; RL Mol. Endocrinol. 27:1577-1587(2013). RN [65] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [66] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-293, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [67] RP FUNCTION (ISOFORM BETA), AND SUBCELLULAR LOCATION (ISOFORM BETA). RX PubMed=26711253; DOI=10.1128/mcb.00908-15; RA He B., Cruz-Topete D., Oakley R.H., Xiao X., Cidlowski J.A.; RT "Human Glucocorticoid Receptor beta (hGRbeta) Regulates Gluconeogenesis and RT Inflammation in Mouse Liver."; RL Mol. Cell. Biol. 36:714-730(2015). RN [68] RP FUNCTION, AND INTERACTION WITH PNRC2. RX PubMed=25775514; DOI=10.1073/pnas.1409612112; RA Cho H., Park O.H., Park J., Ryu I., Kim J., Ko J., Kim Y.K.; RT "Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner RT to recruit UPF1 for rapid mRNA degradation."; RL Proc. Natl. Acad. Sci. U.S.A. 112:E1540-E1549(2015). RN [69] RP FUNCTION (ISOFORM ALPHA), SUBCELLULAR LOCATION (ISOFORM ALPHA), TISSUE RP SPECIFICITY, DOMAIN, AND PHOSPHORYLATION AT SER-203 AND SER-211. RX PubMed=25847991; DOI=10.1073/pnas.1411356112; RA Matthews L.C., Berry A.A., Morgan D.J., Poolman T.M., Bauer K., Kramer F., RA Spiller D.G., Richardson R.V., Chapman K.E., Farrow S.N., Norman M.R., RA Williamson A.J., Whetton A.D., Taylor S.S., Tuckermann J.P., White M.R., RA Ray D.W.; RT "Glucocorticoid receptor regulates accurate chromosome segregation and is RT associated with malignancy."; RL Proc. Natl. Acad. Sci. U.S.A. 112:5479-5484(2015). RN [70] RP INTERACTION WITH FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [71] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; CDC37; PPP5C; TSC1; TSC2; RP AKT; CDK4 AND RAF1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [72] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-258 AND LYS-277, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [73] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 521-777 OF MUTANT SER-602 IN RP COMPLEX WITH NCOA2; DEXAMETHASONE AND RU-486, AND MUTAGENESIS OF ARG-585; RP ASP-590; PHE-602; PRO-625 AND ILE-628. RX PubMed=12151000; DOI=10.1016/s0092-8674(02)00817-6; RA Bledsoe R.K., Montana V.G., Stanley T.B., Delves C.J., Apolito C.J., RA McKee D.D., Consler T.G., Parks D.J., Stewart E.L., Willson T.M., RA Lambert M.H., Moore J.T., Pearce K.H., Xu H.E.; RT "Crystal structure of the glucocorticoid receptor ligand binding domain RT reveals a novel mode of receptor dimerization and coactivator RT recognition."; RL Cell 110:93-105(2002). RN [74] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 500-777 OF MUTANT SER-602 IN RP COMPLEX WITH COACTIVATOR PEPTIDE; DEXAMETHASONE AND WITH RU-486. RX PubMed=12686538; DOI=10.1074/jbc.m212711200; RA Kauppi B., Jakob C., Faernegaardh M., Yang J., Ahola H., Alarcon M., RA Calles K., Engstrom O., Harlan J., Muchmore S., Ramqvist A.-K., Thorell S., RA Oehman L., Greer J., Gustafsson J.-A., Carlstedt-Duke J., Carlquist M.; RT "The three-dimensional structures of antagonistic and agonistic forms of RT the glucocorticoid receptor ligand-binding domain: RU-486 induces a RT transconformation that leads to active antagonism."; RL J. Biol. Chem. 278:22748-22754(2003). RN [75] RP CHARACTERIZATION OF VARIANT GCCR VAL-641. RX PubMed=1704018; DOI=10.1172/jci115046; RA Hurley D.M., Accili D., Stratakis C.A., Karl M., Vamvakopoulos N., RA Rorer E., Constantine K., Taylor S.I., Chrousos G.P.; RT "Point mutation causing a single amino acid substitution in the hormone RT binding domain of the glucocorticoid receptor in familial glucocorticoid RT resistance."; RL J. Clin. Invest. 87:680-686(1991). RN [76] RP VARIANTS TYR-421 AND PHE-753. RX PubMed=8358735; RA Powers J.H., Hillmann A.G., Tang D.C., Harmon J.M.; RT "Cloning and expression of mutant glucocorticoid receptors from RT glucocorticoid-sensitive and -resistant human leukemic cells."; RL Cancer Res. 53:4059-4065(1993). RN [77] RP VARIANT SER-363. RX PubMed=8445027; DOI=10.1210/jcem.76.3.8445027; RA Karl M., Lamberts S.W.J., Detera-Wadleigh S.D., Encio I.J., Stratakis C.A., RA Hurley D.M., Accili D., Chrousos G.P.; RT "Familial glucocorticoid resistance caused by a splice site deletion in the RT human glucocorticoid receptor gene."; RL J. Clin. Endocrinol. Metab. 76:683-689(1993). RN [78] RP VARIANT GCCR ILE-729. RX PubMed=7683692; DOI=10.1172/jci116410; RA Malchoff D.M., Brufsky A., Reardon G., McDermott P., Javier E.C., RA Bergh C.H., Rowe D., Malchoff C.D.; RT "A mutation of the glucocorticoid receptor in primary cortisol RT resistance."; RL J. Clin. Invest. 91:1918-1925(1993). RN [79] RP VARIANT PHE-753. RX PubMed=8316249; DOI=10.1210/mend.7.5.8316249; RA Ashraf J., Thompson E.B.; RT "Identification of the activation-labile gene: a single point mutation in RT the human glucocorticoid receptor presents as two distinct receptor RT phenotypes."; RL Mol. Endocrinol. 7:631-642(1993). RN [80] RP VARIANTS LYS-23 AND SER-363. RX PubMed=9150737; DOI=10.1007/s004390050425; RA Koper J.W., Stolk R.P., de Lange P., Huizenga N.A.T.M., Molijn G.-J., RA Pols H.A.P., Grobbee D.E., Karl M., de Jong F.H., Brinkmann A.O., RA Lamberts S.W.J.; RT "Lack of association between five polymorphisms in the human glucocorticoid RT receptor gene and glucocorticoid resistance."; RL Hum. Genet. 99:663-668(1997). RN [81] RP VARIANTS LYS-23; VAL-65 AND SER-363. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [82] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [83] RP VARIANTS LYS-23; LEU-29; PHE-112; ASN-233 AND SER-363. RX PubMed=10898924; RX DOI=10.1002/1096-8628(20000612)96:3<412::aid-ajmg33>3.0.co;2-c; RA Feng J., Zheng J., Bennett W.P., Heston L.L., Jones I.R., Craddock N., RA Sommer S.S.; RT "Five missense variants in the amino-terminal domain of the glucocorticoid RT receptor: no association with puerperal psychosis or schizophrenia."; RL Am. J. Med. Genet. 96:412-417(2000). RN [84] RP VARIANTS GCCR HIS-477 AND SER-679. RX PubMed=11589680; DOI=10.1046/j.1365-2265.2001.01323.x; RA Ruiz M., Lind U., Gaafvels M., Eggertsen G., Carlstedt-Duke J., Nilsson L., RA Holtmann M., Stierna P., Wikstroem A.-C., Werner S.; RT "Characterization of two novel mutations in the glucocorticoid receptor RT gene in patients with primary cortisol resistance."; RL Clin. Endocrinol. (Oxf.) 55:363-371(2001). RN [85] RP VARIANT SER-363. RX PubMed=11344238; DOI=10.1210/jcem.86.5.7465; RA Dobson M.G., Redfern C.P.F., Unwin N., Weaver J.U.; RT "The N363S polymorphism of the glucocorticoid receptor: potential RT contribution to central obesity in men and lack of association with other RT risk factors for coronary heart disease and diabetes mellitus."; RL J. Clin. Endocrinol. Metab. 86:2270-2274(2001). RN [86] RP CHARACTERIZATION OF VARIANT GCCR ASN-559. RX PubMed=11701741; DOI=10.1210/jcem.86.11.8017; RA Kino T., Stauber R.H., Resau J.H., Pavlakis G.N., Chrousos G.P.; RT "Pathologic human GR mutant has a transdominant negative effect on the RT wild-type GR by inhibiting its translocation into the nucleus: importance RT of the ligand-binding domain for intracellular GR trafficking."; RL J. Clin. Endocrinol. Metab. 86:5600-5608(2001). RN [87] RP VARIANT LYS-23. RX PubMed=12351458; DOI=10.2337/diabetes.51.10.3128; RA van Rossum E.F.C., Koper J.W., Huizenga N.A.T.M., Uitterlinden A.G., RA Janssen J.A.M.J.L., Brinkmann A.O., Grobbee D.E., de Jong F.H., RA van Duyn C.M., Pols H.A.P., Lamberts S.W.J.; RT "A polymorphism in the glucocorticoid receptor gene, which decreases RT sensitivity to glucocorticoids in vivo, is associated with low insulin and RT cholesterol levels."; RL Diabetes 51:3128-3134(2002). RN [88] RP VARIANT PSEUDOHERMAPHRODITISM ALA-571. RX PubMed=11932321; DOI=10.1210/jcem.87.4.8379; RA Mendonca B.B., Leite M.V., de Castro M., Kino T., Elias L.L.K., RA Bachega T.A.S., Arnhold I.J.P., Chrousos G.P., Latronico A.C.; RT "Female pseudohermaphroditism caused by a novel homozygous missense RT mutation of the GR gene."; RL J. Clin. Endocrinol. Metab. 87:1805-1809(2002). RN [89] RP VARIANT GCCR MET-747, AND ALTERED INTERACTION WITH THE COACTIVATOR NCOA2. RX PubMed=12050230; DOI=10.1210/jcem.87.6.8520; RA Vottero A., Kino T., Combe H., Lecomte P., Chrousos G.P.; RT "A novel, C-terminal dominant negative mutation of the GR causes familial RT glucocorticoid resistance through abnormal interactions with p160 steroid RT receptor coactivators."; RL J. Clin. Endocrinol. Metab. 87:2658-2667(2002). RN [90] RP VARIANT LYS-23. RX PubMed=15276593; DOI=10.1016/j.amjmed.2004.01.027; RA van Rossum E.F.C., Feelders R.A., van den Beld A.W., Uitterlinden A.G., RA Janssen J.A.M.J.L., Ester W., Brinkmann A.O., Grobbee D.E., de Jong F.H., RA Pols H.A.P., Koper J.W., Lamberts S.W.J.; RT "Association of the ER22/23EK polymorphism in the glucocorticoid receptor RT gene with survival and C-reactive protein levels in elderly men."; RL Am. J. Med. 117:158-162(2004). RN [91] RP VARIANT LYS-23. RX PubMed=15292341; DOI=10.1210/jc.2003-031422; RA van Rossum E.F.C., Voorhoeve P.G., te Velde S.J., Koper J.W., RA Delemarre-van de Waal H.A., Kemper H.C.G., Lamberts S.W.J.; RT "The ER22/23EK polymorphism in the glucocorticoid receptor gene is RT associated with a beneficial body composition and muscle strength in young RT adults."; RL J. Clin. Endocrinol. Metab. 89:4004-4009(2004). RN [92] RP VARIANT GCCR PRO-773, CHARACTERIZATION OF VARIANT GCCR PRO-773, INVOLVEMENT RP IN GCCR, FUNCTION (ISOFORM ALPHA), INTERACTION WITH GRIP1, AND SUBCELLULAR RP LOCATION (ISOFORM ALPHA). RX PubMed=15769988; DOI=10.1210/jc.2004-1920; RA Charmandari E., Raji A., Kino T., Ichijo T., Tiulpakov A., Zachman K., RA Chrousos G.P.; RT "A novel point mutation in the ligand-binding domain (LBD) of the human RT glucocorticoid receptor (hGR) causing generalized glucocorticoid RT resistance: the importance of the C terminus of hGR LBD in conferring RT transactivational activity."; RL J. Clin. Endocrinol. Metab. 90:3696-3705(2005). RN [93] RP VARIANTS LYS-23 AND SER-363, AND CHARACTERIZATION OF VARIANTS LYS-23 AND RP SER-363. RX PubMed=16030164; DOI=10.1210/jc.2005-0646; RA Russcher H., Smit P., van den Akker E.L., van Rossum E.F., Brinkmann A.O., RA de Jong F.H., Lamberts S.W., Koper J.W.; RT "Two polymorphisms in the glucocorticoid receptor gene directly affect RT glucocorticoid-regulated gene expression."; RL J. Clin. Endocrinol. Metab. 90:5804-5810(2005). RN [94] RP VARIANT GCCR LEU-737, CHARACTERIZATION OF VARIANT GCCR LEU-737, FUNCTION RP (ISOFORM ALPHA), INTERACTION WITH GRIP1, AND SUBCELLULAR LOCATION (ISOFORM RP ALPHA). RX PubMed=17635946; DOI=10.1210/jc.2006-2830; RA Charmandari E., Kino T., Ichijo T., Jubiz W., Mejia L., Zachman K., RA Chrousos G.P.; RT "A novel point mutation in helix 11 of the ligand-binding domain of the RT human glucocorticoid receptor gene causing generalized glucocorticoid RT resistance."; RL J. Clin. Endocrinol. Metab. 92:3986-3990(2007). RN [95] RP VARIANT GCCR GLN-714, AND CHARACTERIZATION OF VARIANT GCCR GLN-714. RX PubMed=20335448; DOI=10.1210/jc.2009-2463; RA Nader N., Bachrach B.E., Hurt D.E., Gajula S., Pittman A., Lescher R., RA Kino T.; RT "A novel point mutation in helix 10 of the human glucocorticoid receptor RT causes generalized glucocorticoid resistance by disrupting the structure of RT the ligand-binding domain."; RL J. Clin. Endocrinol. Metab. 95:2281-2285(2010). RN [96] RP VARIANT GCCR ILE-556. RX PubMed=21362280; RA Zhu H.J., Dai Y.F., Wang O., Li M., Lu L., Zhao W.G., Xing X.P., Pan H., RA Li N.S., Gong F.Y.; RT "Generalized glucocorticoid resistance accompanied with an adrenocortical RT adenoma and caused by a novel point mutation of human glucocorticoid RT receptor gene."; RL Chin. Med. J. 124:551-555(2011). RN [97] RP CHARACTERIZATION OF VARIANT GCCR ALA-423. RX PubMed=23426617; DOI=10.1210/jc.2012-3549; RA Roberts M.L., Kino T., Nicolaides N.C., Hurt D.E., Katsantoni E., RA Sertedaki A., Komianou F., Kassiou K., Chrousos G.P., Charmandari E.; RT "A novel point mutation in the DNA-binding domain (DBD) of the human RT glucocorticoid receptor causes primary generalized glucocorticoid RT resistance by disrupting the hydrophobic structure of its DBD."; RL J. Clin. Endocrinol. Metab. 98:E790-E795(2013). RN [98] RP VARIANT GCCR GLY-575, AND CHARACTERIZATION OF VARIANT GCCR GLY-575. RX PubMed=24483153; DOI=10.1210/jc.2013-3005; RA Nicolaides N.C., Roberts M.L., Kino T., Braatvedt G., Hurt D.E., RA Katsantoni E., Sertedaki A., Chrousos G.P., Charmandari E.; RT "A novel point mutation of the human glucocorticoid receptor gene causes RT primary generalized glucocorticoid resistance through impaired interaction RT with the LXXLL motif of the p160 coactivators: dissociation of the RT transactivating and transreppressive activities."; RL J. Clin. Endocrinol. Metab. 99:E902-E907(2014). RN [99] RP VARIANT GCCR ARG-726, AND CHARACTERIZATION OF VARIANT GCCR ARG-726. RX PubMed=26031419; DOI=10.1111/eci.12470; RA Nicolaides N.C., Geer E.B., Vlachakis D., Roberts M.L., Psarra A.M., RA Moutsatsou P., Sertedaki A., Kossida S., Charmandari E.; RT "A novel mutation of the hGR gene causing Chrousos syndrome."; RL Eur. J. Clin. Invest. 45:782-791(2015). RN [100] RP CHARACTERIZATION OF VARIANT GCCR ILE-556. RX PubMed=26541474; DOI=10.1111/eci.12563; RA Nicolaides N.C., Skyrla E., Vlachakis D., Psarra A.M., Moutsatsou P., RA Sertedaki A., Kossida S., Charmandari E.; RT "Functional characterization of the hGRalphaT556I causing Chrousos RT syndrome."; RL Eur. J. Clin. Invest. 46:42-49(2016). RN [101] RP VARIANTS GCCR SER-477; CYS-478 AND PRO-672, CHARACTERIZATION OF VARIANTS RP GCCR SER-477; CYS-478 AND CYS-478, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27120390; DOI=10.1002/humu.23008; RA Vitellius G., Fagart J., Delemer B., Amazit L., Ramos N., Bouligand J., RA Le Billan F., Castinetti F., Guiochon-Mantel A., Trabado S., Lombes M.; RT "Three novel heterozygous point mutations of NR3C1 causing glucocorticoid RT resistance."; RL Hum. Mutat. 37:794-803(2016). CC -!- FUNCTION: Receptor for glucocorticoids (GC) (PubMed:27120390). Has a CC dual mode of action: as a transcription factor that binds to CC glucocorticoid response elements (GRE), both for nuclear and CC mitochondrial DNA, and as a modulator of other transcription factors. CC Affects inflammatory responses, cellular proliferation and CC differentiation in target tissues. Involved in chromatin remodeling CC (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to CC the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand- CC dependent manner which recruits the RNA helicase UPF1 and the mRNA- CC decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could CC act as a coactivator for STAT5-dependent transcription upon growth CC hormone (GH) stimulation and could reveal an essential role of hepatic CC GR in the control of body growth (By similarity). CC {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:25775514, CC ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:9590696}. CC -!- FUNCTION: [Isoform Alpha]: Has transcriptional activation and CC repression activity (PubMed:15866175, PubMed:19248771, PubMed:20484466, CC PubMed:23820903, PubMed:11435610, PubMed:15769988, PubMed:17635946, CC PubMed:19141540, PubMed:21664385). Mediates glucocorticoid-induced CC apoptosis (PubMed:23303127). Promotes accurate chromosome segregation CC during mitosis (PubMed:25847991). May act as a tumor suppressor CC (PubMed:25847991). May play a negative role in adipogenesis through the CC regulation of lipolytic and antilipogenic gene expression (By CC similarity). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771, CC ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903, CC ECO:0000269|PubMed:25847991}. CC -!- FUNCTION: [Isoform Beta]: Acts as a dominant negative inhibitor of CC isoform Alpha (PubMed:7769088, PubMed:8621628, PubMed:20484466). Has CC intrinsic transcriptional activity independent of isoform Alpha when CC both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses CC this transcription modulator function on its own (PubMed:20484466). Has CC no hormone-binding activity (PubMed:8621628). May play a role in CC controlling glucose metabolism by maintaining insulin sensitivity (By CC similarity). Reduces hepatic gluconeogenesis through down-regulation of CC PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly CC regulates STAT1 expression in isoform Alpha-independent manner CC (PubMed:26711253). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, CC ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088, CC ECO:0000269|PubMed:8621628}. CC -!- FUNCTION: [Isoform Alpha-2]: Has lower transcriptional activation CC activity than isoform Alpha. Exerts a dominant negative effect on CC isoform Alpha trans-repression mechanism (PubMed:20484466). CC -!- FUNCTION: [Isoform GR-P]: Increases activity of isoform Alpha. CC {ECO:0000269|PubMed:11358809}. CC -!- FUNCTION: [Isoform Alpha-B]: More effective than isoform Alpha in CC transcriptional activation, but not repression activity. CC {ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform 10]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:20484466}. CC -!- FUNCTION: [Isoform Alpha-C1]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-C2]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-C3]: Has highest transcriptional activation CC activity of all isoforms created by alternative initiation CC (PubMed:15866175, PubMed:23820903). Has transcriptional repression CC activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis CC (PubMed:23303127, PubMed:23820903). {ECO:0000269|PubMed:15866175, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. CC -!- FUNCTION: [Isoform Alpha-D1]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-D2]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-D3]: Has lowest transcriptional activation CC activity of all isoforms created by alternative initiation CC (PubMed:15866175, PubMed:23820903). Has transcriptional repression CC activity (PubMed:23303127). {ECO:0000269|PubMed:15866175, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90AA1, CC HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, CC or the immunophilin homolog PPP5C (PubMed:21730050). Upon ligand CC binding FKBP5 dissociates from the complex and FKBP4 takes its place, CC thereby linking the complex to dynein and mediating transport to the CC nucleus, where the complex dissociates (By similarity). Probably forms CC a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, CC PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this CC complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Directly interacts with UNC45A (PubMed:16478993). CC Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the CC retinoid X receptor. Binds STAT5A and STAT5B homodimers and CC heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and CC TRIM28 (By similarity). Interacts with several coactivator complexes, CC including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and CC p160 coactivators such as NCOA2 and NCOA6 (PubMed:10866662, CC PubMed:12151000, PubMed:12686538, PubMed:9154805, PubMed:9590696). CC Interaction with BAG1 inhibits transactivation (PubMed:10477749). CC Interacts with HEXIM1 and TGFB1I1 (PubMed:12415108, PubMed:15211577, CC PubMed:15941832). Interacts with NCOA1 (PubMed:9590696). Interacts with CC NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). CC Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion CC (PubMed:19141540, PubMed:21980503, PubMed:22170608). Interacts with CC CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts CC with UBE2I/UBC9 and this interaction is enhanced in the presence of CC RWDD3 (By similarity). Interacts with GRIP1 (PubMed:15769988, CC PubMed:17635946). Interacts with NR4A3 (via nuclear receptor DNA- CC binding domain), represses transcription activity of NR4A3 on the POMC CC promoter Nur response element (NurRE) (PubMed:15591535). Directly CC interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; CC the interaction leads to rapid mRNA degradation (PubMed:25775514). CC Interacts with GSK3B (PubMed:18838540). Interacts with FNIP1 and FNIP2 CC (PubMed:27353360). Interacts (via C-terminus) with HNRNPU (via C- CC terminus) (PubMed:9353307). Interacts with MCM3AP (PubMed:16914116). CC Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By CC similarity). In the absence of hormonal ligand, interacts with TACC1 CC (PubMed:20078863). {ECO:0000250|UniProtKB:P06536, CC ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:10477749, CC ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:12151000, CC ECO:0000269|PubMed:12686538, ECO:0000269|PubMed:15211577, CC ECO:0000269|PubMed:15591535, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:16478993, CC ECO:0000269|PubMed:16914116, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:19141540, CC ECO:0000269|PubMed:20078863, ECO:0000269|PubMed:21730050, CC ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22170608, CC ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:9154805, CC ECO:0000269|PubMed:9353307, ECO:0000269|PubMed:9590696}. CC -!- INTERACTION: CC P04150; P31749: AKT1; NbExp=5; IntAct=EBI-493507, EBI-296087; CC P04150; P01730: CD4; NbExp=2; IntAct=EBI-493507, EBI-353826; CC P04150; P00533: EGFR; NbExp=3; IntAct=EBI-493507, EBI-297353; CC P04150; P41235: HNF4A; NbExp=2; IntAct=EBI-493507, EBI-1049011; CC P04150; P07900: HSP90AA1; NbExp=8; IntAct=EBI-493507, EBI-296047; CC P04150; Q6ZU52: KIAA0408; NbExp=2; IntAct=EBI-493507, EBI-739493; CC P04150; P06239: LCK; NbExp=3; IntAct=EBI-493507, EBI-1348; CC P04150; P28702: RXRB; NbExp=4; IntAct=EBI-493507, EBI-748576; CC P04150; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-493507, EBI-745901; CC P04150; O95416: SOX14; NbExp=3; IntAct=EBI-493507, EBI-9087806; CC P04150; P82094: TMF1; NbExp=3; IntAct=EBI-493507, EBI-949763; CC P04150; P59598: Asxl1; Xeno; NbExp=2; IntAct=EBI-493507, EBI-5743705; CC P04150; Q62667: Mvp; Xeno; NbExp=2; IntAct=EBI-493507, EBI-918333; CC P04150-1; Q61026: Ncoa2; Xeno; NbExp=3; IntAct=EBI-15750116, EBI-688662; CC -!- SUBCELLULAR LOCATION: [Isoform Alpha]: Cytoplasm CC {ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:27120390, CC ECO:0000269|PubMed:8621628}. Nucleus {ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:18838540, CC ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:8621628}. Mitochondrion CC {ECO:0000269|PubMed:21664385}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000269|PubMed:25847991}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:25847991}. Note=After CC ligand activation, translocates from the cytoplasm to the nucleus. In CC the presence of NR1D1 shows a time-dependent subcellular localization, CC localizing to the cytoplasm at ZT8 and to the nucleus at ZT20 (By CC similarity). Lacks this diurnal pattern of localization in the absence CC of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 CC (By similarity). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:27120390, CC ECO:0000269|PubMed:8621628}. CC -!- SUBCELLULAR LOCATION: [Isoform Beta]: Nucleus CC {ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:26711253, CC ECO:0000269|PubMed:8621628}. Cytoplasm {ECO:0000269|PubMed:19248771, CC ECO:0000269|PubMed:26711253}. Note=Expressed predominantly in the CC nucleus with some expression also detected in the cytoplasm. CC {ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:26711253}. CC -!- SUBCELLULAR LOCATION: [Isoform Alpha-B]: Nucleus CC {ECO:0000269|PubMed:15866175}. Cytoplasm {ECO:0000269|PubMed:15866175}. CC Note=After ligand activation, translocates from the cytoplasm to the CC nucleus. {ECO:0000269|PubMed:15866175}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=16; CC Name=Alpha; Synonyms=Alpha-A, GR-alphaA; CC IsoId=P04150-1; Sequence=Displayed; CC Name=Beta; Synonyms=Beta-A; CC IsoId=P04150-2; Sequence=VSP_003703; CC Name=Alpha-2; Synonyms=Gamma; CC IsoId=P04150-3; Sequence=VSP_007363; CC Name=Beta-2; CC IsoId=P04150-6; Sequence=VSP_007363, VSP_003703; CC Name=GR-A alpha; CC IsoId=P04150-5; Sequence=VSP_013340; CC Name=GR-A beta; CC IsoId=P04150-7; Sequence=VSP_013340, VSP_003703; CC Name=GR-P; CC IsoId=P04150-4; Sequence=Not described; CC Name=Alpha-B; Synonyms=GR-alphaB; CC IsoId=P04150-8; Sequence=VSP_018773; CC Name=Beta-B; CC IsoId=P04150-9; Sequence=VSP_018773, VSP_003703; CC Name=10; Synonyms=hGRDelta313-338; CC IsoId=P04150-10; Sequence=VSP_043908; CC Name=Alpha-C1; Synonyms=GR-alphaC1; CC IsoId=P04150-11; Sequence=VSP_058317; CC Name=Alpha-C2; Synonyms=GR-alphaC2; CC IsoId=P04150-12; Sequence=VSP_058316; CC Name=Alpha-C3; Synonyms=GR-alphaC3; CC IsoId=P04150-13; Sequence=VSP_058315; CC Name=Alpha-D1; Synonyms=GR-alphaD1; CC IsoId=P04150-14; Sequence=VSP_058314; CC Name=Alpha-D2; Synonyms=GR-alphaD2; CC IsoId=P04150-15; Sequence=VSP_058313; CC Name=Alpha-D3; Synonyms=GR-alphaD3; CC IsoId=P04150-16; Sequence=VSP_058312; CC -!- TISSUE SPECIFICITY: Widely expressed including bone, stomach, lung, CC liver, colon, breast, ovary, pancreas and kidney (PubMed:25847991). In CC the heart, detected in left and right atria, left and right ventricles, CC aorta, apex, intraventricular septum, and atrioventricular node as well CC as whole adult and fetal heart (PubMed:10902803). CC {ECO:0000269|PubMed:10902803, ECO:0000269|PubMed:25847991}. CC -!- TISSUE SPECIFICITY: [Isoform Beta]: Widely expressed including brain, CC bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, CC skeletal muscle, heart, placenta and blood leukocytes. CC {ECO:0000269|PubMed:7769088, ECO:0000269|PubMed:8621628}. CC -!- TISSUE SPECIFICITY: [Isoform Alpha-2]: Widely expressed. CC {ECO:0000269|PubMed:10566686}. CC -!- INDUCTION: [Isoform Alpha]: Induced by TNF (at protein level). CC {ECO:0000269|PubMed:11381138}. CC -!- INDUCTION: [Isoform Beta]: Induced by TNF and becomes the predominant CC isoform which may lead to glucocorticoid resistance (at protein level). CC {ECO:0000269|PubMed:11381138}. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain CC (PubMed:3841189). The ligand-binding domain is required for correct CC chromosome segregation during mitosis although ligand binding is not CC required (PubMed:25847991). {ECO:0000269|PubMed:25847991, CC ECO:0000269|PubMed:3841189}. CC -!- PTM: Acetylation by CLOCK reduces its binding to glucocorticoid CC response elements and its transcriptional activity. CC {ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:21980503}. CC -!- PTM: Increased proteasome-mediated degradation in response to CC glucocorticoids (PubMed:11555652). Isoform Alpha-B appears to be more CC susceptible to proteolytic degradation than isoform Alpha CC (PubMed:11435610). {ECO:0000269|PubMed:11435610, CC ECO:0000269|PubMed:11555652}. CC -!- PTM: Phosphorylated in the absence of hormone; becomes CC hyperphosphorylated in the presence of glucocorticoid. The Ser-203, CC Ser-226 and Ser-404-phosphorylated forms are mainly cytoplasmic, and CC the Ser-211-phosphorylated form is nuclear (PubMed:12000743, CC PubMed:18838540). Phosphorylation at Ser-211 increases transcriptional CC activity (PubMed:12000743, PubMed:18483179). Phosphorylation at Ser- CC 203, Ser-226 and Ser-404 decreases signaling capacity (PubMed:12000743, CC PubMed:18483179, PubMed:18838540). Phosphorylation at Ser-404 may CC protect from glucocorticoid-induced apoptosis (PubMed:18838540). CC Phosphorylation at Ser-203 and Ser-211 is not required in regulation of CC chromosome segregation (PubMed:25847991). May be dephosphorylated by CC PPP5C, attenuates NR3C1 action (By similarity). CC {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:12000743, CC ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:18838540, CC ECO:0000269|PubMed:25847991}. CC -!- PTM: Sumoylation at Lys-277 and Lys-293 negatively regulates its CC transcriptional activity (PubMed:12144530). Sumoylation at Lys-703 CC positively regulates its transcriptional activity in the presence of CC RWDD3 (By similarity). Sumoylation at Lys-277 and Lys-293 is CC dispensable whereas sumoylation at Lys-703 is critical for the CC stimulatory effect of RWDD3 on its transcriptional activity (By CC similarity). Heat shock increases sumoylation in a RWDD3-dependent CC manner (By similarity). {ECO:0000250|UniProtKB:P06536, CC ECO:0000269|PubMed:12144530}. CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated transcriptional CC signaling. {ECO:0000250|UniProtKB:P06537}. CC -!- POLYMORPHISM: Carriers of the 22-Glu-Lys-23 allele are relatively more CC resistant to the effects of GCs with respect to the sensitivity of the CC adrenal feedback mechanism than non-carriers, resulting in a better CC metabolic health profile. Carriers have a better survival than non- CC carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 CC polymorphism is associated with a sex-specific, beneficial body CC composition at young-adult age, as well as greater muscle strength in CC males. CC -!- DISEASE: Glucocorticoid resistance, generalized (GCCR) [MIM:615962]: An CC autosomal dominant disease characterized by increased plasma cortisol CC concentration and high urinary free cortisol, resistance to adrenal CC suppression by dexamethasone, and the absence of Cushing syndrome CC typical signs. Clinical features include hypoglycemia, hypertension, CC metabolic alkalosis, chronic fatigue and profound anxiety. CC {ECO:0000269|PubMed:11589680, ECO:0000269|PubMed:11701741, CC ECO:0000269|PubMed:12050230, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:1704018, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:20335448, ECO:0000269|PubMed:21362280, CC ECO:0000269|PubMed:23426617, ECO:0000269|PubMed:24483153, CC ECO:0000269|PubMed:26031419, ECO:0000269|PubMed:26541474, CC ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:7683692}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform Beta]: High constitutive expression by CC neutrophils may provide a mechanism by which these cells escape CC glucocorticoid-induced cell death and up-regulation by pro-inflammatory CC cytokines such as IL8 further enhances their survival in the presence CC of glucocorticoids during inflammation. {ECO:0000269|PubMed:11238589}. CC -!- MISCELLANEOUS: Can up- or down-modulate aggregation and nuclear CC localization of expanded polyglutamine polypeptides derived from AR and CC HD through specific regulation of gene expression. Aggregation and CC nuclear localization of expanded polyglutamine proteins are regulated CC cellular processes that can be modulated by this receptor, a well- CC characterized transcriptional regulator. {ECO:0000269|PubMed:10639135}. CC -!- MISCELLANEOUS: [Isoform Alpha]: Predominant physiological form. CC {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-2]: Due to a partial intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Beta-2]: Due to a partial intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform GR-A alpha]: Lacks exons 5, 6 and 7. Found in CC glucocorticoid-resistant myeloma patients. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform GR-A beta]: Lacks exons 5, 6 and 7. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform GR-P]: Encoded by exons 2-7 plus several CC basepairs from the subsequent intron region. Lacks the ligand binding CC domain. Accounts for up to 10-20% of mRNAs. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform Alpha-B]: Produced by alternative initiation at CC Met-27 of isoform Alpha. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Beta-B]: Produced by alternative initiation at CC Met-27 of isoform Beta. {ECO:0000269|PubMed:15866175, ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Alpha-C1]: Produced by alternative initiation CC at Met-86 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-C2]: Produced by alternative initiation CC at Met-90 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-C3]: Produced by alternative initiation CC at Met-98 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D1]: Produced by alternative initiation CC at Met-316 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D2]: Produced by alternative initiation CC at Met-331 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D3]: Produced by alternative initiation CC at Met-336 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. {ECO:0000305}. CC -!- CAUTION: Had previously been shown to interact with PELP1. However this CC paper was retracted as cell-based data was viewed as unreliable. CC {ECO:0000305|PubMed:12415108, ECO:0000305|PubMed:19666546}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/nr3c1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glucocorticoid receptor entry; CC URL="https://en.wikipedia.org/wiki/Glucocorticoid_receptor"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03225; CAA26976.1; -; mRNA. DR EMBL; X03348; CAA27054.1; -; mRNA. DR EMBL; AH005496; AAB64353.1; -; Genomic_DNA. DR EMBL; AH005496; AAB64354.1; -; Genomic_DNA. DR EMBL; HQ205546; ADP91135.1; -; Genomic_DNA. DR EMBL; HQ205547; ADP91138.1; -; Genomic_DNA. DR EMBL; HQ205548; ADP91141.1; -; Genomic_DNA. DR EMBL; HQ205549; ADP91144.1; -; Genomic_DNA. DR EMBL; HQ205550; ADP91147.1; -; Genomic_DNA. DR EMBL; HQ205551; ADP91150.1; -; Genomic_DNA. DR EMBL; HQ205552; ADP91153.1; -; Genomic_DNA. DR EMBL; HQ205553; ADP91156.1; -; Genomic_DNA. DR EMBL; HQ205554; ADP91159.1; -; Genomic_DNA. DR EMBL; HQ205555; ADP91162.1; -; Genomic_DNA. DR EMBL; HQ205556; ADP91165.1; -; Genomic_DNA. DR EMBL; HQ205557; ADP91168.1; -; Genomic_DNA. DR EMBL; HQ205558; ADP91171.1; -; Genomic_DNA. DR EMBL; HQ205559; ADP91174.1; -; Genomic_DNA. DR EMBL; HQ205560; ADP91177.1; -; Genomic_DNA. DR EMBL; HQ205561; ADP91180.1; -; Genomic_DNA. DR EMBL; HQ205562; ADP91183.1; -; Genomic_DNA. DR EMBL; HQ205563; ADP91186.1; -; Genomic_DNA. DR EMBL; HQ205564; ADP91189.1; -; Genomic_DNA. DR EMBL; HQ205565; ADP91192.1; -; Genomic_DNA. DR EMBL; HQ205566; ADP91195.1; -; Genomic_DNA. DR EMBL; HQ205567; ADP91198.1; -; Genomic_DNA. DR EMBL; HQ205568; ADP91201.1; -; Genomic_DNA. DR EMBL; HQ205569; ADP91204.1; -; Genomic_DNA. DR EMBL; HQ205570; ADP91207.1; -; Genomic_DNA. DR EMBL; HQ205571; ADP91210.1; -; Genomic_DNA. DR EMBL; HQ205572; ADP91213.1; -; Genomic_DNA. DR EMBL; HQ205573; ADP91216.1; -; Genomic_DNA. DR EMBL; HQ205574; ADP91219.1; -; Genomic_DNA. DR EMBL; HQ205575; ADP91222.1; -; Genomic_DNA. DR EMBL; HQ205576; ADP91225.1; -; Genomic_DNA. DR EMBL; HQ205577; ADP91228.1; -; Genomic_DNA. DR EMBL; HQ205578; ADP91231.1; -; Genomic_DNA. DR EMBL; HQ205579; ADP91234.1; -; Genomic_DNA. DR EMBL; HQ205580; ADP91237.1; -; Genomic_DNA. DR EMBL; HQ205581; ADP91240.1; -; Genomic_DNA. DR EMBL; HQ205582; ADP91243.1; -; Genomic_DNA. DR EMBL; HQ205583; ADP91246.1; -; Genomic_DNA. DR EMBL; HQ205584; ADP91249.1; -; Genomic_DNA. DR EMBL; HQ205585; ADP91252.1; -; Genomic_DNA. DR EMBL; AM183262; CAJ65924.1; -; mRNA. DR EMBL; HQ450643; AED99114.1; -; mRNA. DR EMBL; U01351; AAA16603.1; -; mRNA. DR EMBL; AK223594; BAD97314.1; -; mRNA. DR EMBL; BX640610; CAE45716.1; -; mRNA. DR EMBL; AY436590; AAQ97180.1; -; Genomic_DNA. DR EMBL; EU332858; ABY87547.1; -; Genomic_DNA. DR EMBL; AC005601; AAC34207.1; -; Genomic_DNA. DR EMBL; AC004782; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091925; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61872.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61873.1; -; Genomic_DNA. DR EMBL; BC015610; AAH15610.1; -; mRNA. DR EMBL; M69104; AAA88049.1; -; Genomic_DNA. DR EMBL; AH002750; AAA53151.1; -; Genomic_DNA. DR EMBL; S68378; AAB20466.1; -; Genomic_DNA. DR CCDS; CCDS34258.1; -. [P04150-3] DR CCDS; CCDS4278.1; -. [P04150-1] DR CCDS; CCDS47298.1; -. [P04150-2] DR PIR; A93370; QRHUGA. DR PIR; B93370; QRHUGB. DR RefSeq; NP_000167.1; NM_000176.2. [P04150-1] DR RefSeq; NP_001018084.1; NM_001018074.1. [P04150-1] DR RefSeq; NP_001018085.1; NM_001018075.1. [P04150-1] DR RefSeq; NP_001018086.1; NM_001018076.1. [P04150-1] DR RefSeq; NP_001018087.1; NM_001018077.1. [P04150-1] DR RefSeq; NP_001018661.1; NM_001020825.1. [P04150-2] DR RefSeq; NP_001019265.1; NM_001024094.1. [P04150-3] DR RefSeq; NP_001191187.1; NM_001204258.1. [P04150-8] DR RefSeq; NP_001191188.1; NM_001204259.1. [P04150-11] DR RefSeq; NP_001191189.1; NM_001204260.1. [P04150-12] DR RefSeq; NP_001191190.1; NM_001204261.1. [P04150-13] DR RefSeq; NP_001191191.1; NM_001204262.1. [P04150-14] DR RefSeq; NP_001191192.1; NM_001204263.1. [P04150-15] DR RefSeq; NP_001191193.1; NM_001204264.1. [P04150-16] DR RefSeq; XP_005268476.1; XM_005268419.3. DR RefSeq; XP_005268477.1; XM_005268420.4. DR RefSeq; XP_005268479.1; XM_005268422.3. [P04150-3] DR RefSeq; XP_005268480.1; XM_005268423.3. [P04150-3] DR RefSeq; XP_016864886.1; XM_017009397.1. DR RefSeq; XP_016864887.1; XM_017009398.1. DR PDB; 1M2Z; X-ray; 2.50 A; A/D=521-777. DR PDB; 1NHZ; X-ray; 2.30 A; A=500-777. DR PDB; 1P93; X-ray; 2.70 A; A/B/C/D=500-777. DR PDB; 3BQD; X-ray; 2.50 A; A=525-777. DR PDB; 3CLD; X-ray; 2.84 A; A/B=521-777. DR PDB; 3E7C; X-ray; 2.15 A; A/B=521-777. DR PDB; 3H52; X-ray; 2.80 A; A/B/C/D=528-777. DR PDB; 3K22; X-ray; 2.10 A; A/B=521-777. DR PDB; 3K23; X-ray; 3.00 A; A/B/C=521-777. DR PDB; 4CSJ; X-ray; 2.30 A; A=500-777. DR PDB; 4HN5; X-ray; 1.90 A; A/B=417-506. DR PDB; 4HN6; X-ray; 2.55 A; A/B=417-506. DR PDB; 4LSJ; X-ray; 2.35 A; A=522-777. DR PDB; 4MDD; X-ray; 2.40 A; A/B=522-777. DR PDB; 4P6W; X-ray; 1.95 A; A=526-777. DR PDB; 4P6X; X-ray; 2.50 A; A/C/E/G/I/K=523-777. DR PDB; 4UDC; X-ray; 2.50 A; A=500-777. DR PDB; 4UDD; X-ray; 1.80 A; A=500-777. DR PDB; 5CBX; X-ray; 2.00 A; A/B/E/F=415-495. DR PDB; 5CBY; X-ray; 2.00 A; A/B=415-495. DR PDB; 5CBZ; X-ray; 2.20 A; A/B/E/F=419-495. DR PDB; 5CC1; X-ray; 2.30 A; A/B/W/X=417-506. DR PDB; 5E69; X-ray; 1.85 A; A/B=417-506. DR PDB; 5E6A; X-ray; 2.20 A; A/B=417-506. DR PDB; 5E6B; X-ray; 2.25 A; A/B=417-506. DR PDB; 5E6C; X-ray; 2.20 A; A/B=417-506. DR PDB; 5E6D; X-ray; 2.40 A; A/B=417-506. DR PDB; 5EMC; X-ray; 2.30 A; A/B=411-500. DR PDB; 5EMP; X-ray; 2.30 A; A/B=411-500. DR PDB; 5EMQ; X-ray; 2.30 A; A/B=411-500. DR PDB; 5G3J; X-ray; 2.40 A; A=500-777. DR PDB; 5G5W; X-ray; 2.20 A; A=500-777. DR PDB; 5NFP; X-ray; 2.10 A; A=500-777. DR PDB; 5NFT; X-ray; 2.30 A; A=500-777. DR PDB; 5UC3; X-ray; 2.01 A; A/B=522-777. DR PDB; 5VA0; X-ray; 2.29 A; A/B=419-490. DR PDB; 5VA7; X-ray; 2.15 A; A/B=419-488. DR PDB; 6BQU; X-ray; 2.50 A; A/B=421-490. DR PDB; 6CFN; X-ray; 2.50 A; A/B/C/D/E/F/G/H=418-506. DR PDB; 6DXK; X-ray; 3.05 A; A/B=522-777. DR PDB; 6EL6; X-ray; 2.40 A; A=500-777. DR PDB; 6EL7; X-ray; 2.18 A; A=500-777. DR PDB; 6EL9; X-ray; 2.19 A; A=500-777. DR PDB; 6X6D; X-ray; 2.48 A; A/B=417-490. DR PDB; 6X6E; X-ray; 2.00 A; A/B=417-491. DR PDB; 6YMO; X-ray; 2.02 A; C/D=611-623. DR PDB; 6YO8; X-ray; 2.09 A; E/F/G/H=518-530. DR PDB; 6YOS; X-ray; 2.75 A; C=518-530, C=611-623. DR PDB; 7KRJ; EM; 2.56 A; D=520-777. DR PDB; 7KW7; EM; 3.57 A; F=1-777. DR PDBsum; 1M2Z; -. DR PDBsum; 1NHZ; -. DR PDBsum; 1P93; -. DR PDBsum; 3BQD; -. DR PDBsum; 3CLD; -. DR PDBsum; 3E7C; -. DR PDBsum; 3H52; -. DR PDBsum; 3K22; -. DR PDBsum; 3K23; -. DR PDBsum; 4CSJ; -. DR PDBsum; 4HN5; -. DR PDBsum; 4HN6; -. DR PDBsum; 4LSJ; -. DR PDBsum; 4MDD; -. DR PDBsum; 4P6W; -. DR PDBsum; 4P6X; -. DR PDBsum; 4UDC; -. DR PDBsum; 4UDD; -. DR PDBsum; 5CBX; -. DR PDBsum; 5CBY; -. DR PDBsum; 5CBZ; -. DR PDBsum; 5CC1; -. DR PDBsum; 5E69; -. DR PDBsum; 5E6A; -. DR PDBsum; 5E6B; -. DR PDBsum; 5E6C; -. DR PDBsum; 5E6D; -. DR PDBsum; 5EMC; -. DR PDBsum; 5EMP; -. DR PDBsum; 5EMQ; -. DR PDBsum; 5G3J; -. DR PDBsum; 5G5W; -. DR PDBsum; 5NFP; -. DR PDBsum; 5NFT; -. DR PDBsum; 5UC3; -. DR PDBsum; 5VA0; -. DR PDBsum; 5VA7; -. DR PDBsum; 6BQU; -. DR PDBsum; 6CFN; -. DR PDBsum; 6DXK; -. DR PDBsum; 6EL6; -. DR PDBsum; 6EL7; -. DR PDBsum; 6EL9; -. DR PDBsum; 6X6D; -. DR PDBsum; 6X6E; -. DR PDBsum; 6YMO; -. DR PDBsum; 6YO8; -. DR PDBsum; 6YOS; -. DR PDBsum; 7KRJ; -. DR PDBsum; 7KW7; -. DR AlphaFoldDB; P04150; -. DR SMR; P04150; -. DR BioGRID; 109165; 1495. DR CORUM; P04150; -. DR DIP; DIP-576N; -. DR ELM; P04150; -. DR IntAct; P04150; 92. DR MINT; P04150; -. DR STRING; 9606.ENSP00000231509; -. DR BindingDB; P04150; -. DR ChEMBL; CHEMBL2034; -. DR DrugBank; DB00240; Alclometasone. DR DrugBank; DB04630; Aldosterone. DR DrugBank; DB00288; Amcinonide. DR DrugBank; DB00394; Beclomethasone dipropionate. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB14669; Betamethasone phosphate. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB01410; Ciclesonide. DR DrugBank; DB01013; Clobetasol propionate. DR DrugBank; DB13158; Clobetasone. DR DrugBank; DB00838; Clocortolone. DR DrugBank; DB01380; Cortisone acetate. DR DrugBank; DB13003; Cortivazol. DR DrugBank; DB11921; Deflazacort. DR DrugBank; DB01260; Desonide. DR DrugBank; DB00547; Desoximetasone. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB00223; Diflorasone. DR DrugBank; DB09095; Difluocortolone. DR DrugBank; DB06781; Difluprednate. DR DrugBank; DB01395; Drospirenone. DR DrugBank; DB00687; Fludrocortisone. DR DrugBank; DB00663; Flumethasone. DR DrugBank; DB00180; Flunisolide. DR DrugBank; DB00591; Fluocinolone acetonide. DR DrugBank; DB01047; Fluocinonide. DR DrugBank; DB00324; Fluorometholone. DR DrugBank; DB01185; Fluoxymesterone. DR DrugBank; DB00846; Flurandrenolide. DR DrugBank; DB13867; Fluticasone. DR DrugBank; DB08906; Fluticasone furoate. DR DrugBank; DB00588; Fluticasone propionate. DR DrugBank; DB11619; Gestrinone. DR DrugBank; DB02210; Hexane-1,6-Diol. DR DrugBank; DB00769; Hydrocortamate. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB14538; Hydrocortisone aceponate. DR DrugBank; DB14539; Hydrocortisone acetate. DR DrugBank; DB14540; Hydrocortisone butyrate. DR DrugBank; DB14541; Hydrocortisone cypionate. DR DrugBank; DB14542; Hydrocortisone phosphate. DR DrugBank; DB14543; Hydrocortisone probutate. DR DrugBank; DB14544; Hydrocortisone valerate. DR DrugBank; DB00367; Levonorgestrel. DR DrugBank; DB14596; Loteprednol etabonate. DR DrugBank; DB00253; Medrysone. DR DrugBank; DB00351; Megestrol acetate. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB00764; Mometasone. DR DrugBank; DB14512; Mometasone furoate. DR DrugBank; DB00717; Norethisterone. DR DrugBank; DB12637; Onapristone. DR DrugBank; DB05423; ORG-34517. DR DrugBank; DB01384; Paramethasone. DR DrugBank; DB01130; Prednicarbate. DR DrugBank; DB00860; Prednisolone. DR DrugBank; DB15566; Prednisolone acetate. DR DrugBank; DB14631; Prednisolone phosphate. DR DrugBank; DB00635; Prednisone. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB00896; Rimexolone. DR DrugBank; DB14583; Segesterone acetate. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB09091; Tixocortol. DR DrugBank; DB00620; Triamcinolone. DR DrugBank; DB08867; Ulipristal. DR DrugBank; DB00596; Ulobetasol. DR DrugCentral; P04150; -. DR GuidetoPHARMACOLOGY; 625; -. DR GlyGen; P04150; 6 sites, 2 O-linked glycans (6 sites). DR iPTMnet; P04150; -. DR PhosphoSitePlus; P04150; -. DR BioMuta; NR3C1; -. DR DMDM; 121069; -. DR EPD; P04150; -. DR jPOST; P04150; -. DR MassIVE; P04150; -. DR MaxQB; P04150; -. DR PaxDb; P04150; -. DR PeptideAtlas; P04150; -. DR ProteomicsDB; 51657; -. [P04150-1] DR ProteomicsDB; 51658; -. [P04150-10] DR ProteomicsDB; 51659; -. [P04150-2] DR ProteomicsDB; 51660; -. [P04150-3] DR ProteomicsDB; 51661; -. [P04150-5] DR ProteomicsDB; 51662; -. [P04150-6] DR ProteomicsDB; 51663; -. [P04150-7] DR ProteomicsDB; 51664; -. [P04150-8] DR ProteomicsDB; 51665; -. [P04150-9] DR Antibodypedia; 1329; 1339 antibodies from 43 providers. DR DNASU; 2908; -. DR Ensembl; ENST00000231509.7; ENSP00000231509.3; ENSG00000113580.15. [P04150-3] DR Ensembl; ENST00000343796.6; ENSP00000343205.2; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000394464.7; ENSP00000377977.2; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000394466.6; ENSP00000377979.2; ENSG00000113580.15. [P04150-3] DR Ensembl; ENST00000415690.6; ENSP00000387672.2; ENSG00000113580.15. [P04150-2] DR Ensembl; ENST00000424646.6; ENSP00000405282.2; ENSG00000113580.15. [P04150-10] DR Ensembl; ENST00000503201.1; ENSP00000427672.1; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000504572.5; ENSP00000422518.1; ENSG00000113580.15. [P04150-3] DR GeneID; 2908; -. DR KEGG; hsa:2908; -. DR MANE-Select; ENST00000394464.7; ENSP00000377977.2; NM_000176.3; NP_000167.1. DR UCSC; uc003lmy.4; human. [P04150-1] DR CTD; 2908; -. DR DisGeNET; 2908; -. DR GeneCards; NR3C1; -. DR HGNC; HGNC:7978; NR3C1. DR HPA; ENSG00000113580; Low tissue specificity. DR MalaCards; NR3C1; -. DR MIM; 138040; gene. DR MIM; 615962; phenotype. DR neXtProt; NX_P04150; -. DR OpenTargets; ENSG00000113580; -. DR Orphanet; 96253; Cushing disease. DR Orphanet; 786; Generalized glucocorticoid resistance syndrome. DR PharmGKB; PA181; -. DR VEuPathDB; HostDB:ENSG00000113580; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000156385; -. DR HOGENOM; CLU_020317_0_0_1; -. DR InParanoid; P04150; -. DR OMA; NLPCMYD; -. DR PhylomeDB; P04150; -. DR TreeFam; TF106510; -. DR PathwayCommons; P04150; -. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-400253; Circadian Clock. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR Reactome; R-HSA-8849473; PTK6 Expression. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SignaLink; P04150; -. DR SIGNOR; P04150; -. DR BioGRID-ORCS; 2908; 13 hits in 1109 CRISPR screens. DR ChiTaRS; NR3C1; human. DR EvolutionaryTrace; P04150; -. DR GeneWiki; Glucocorticoid_receptor; -. DR GenomeRNAi; 2908; -. DR Pharos; P04150; Tclin. DR PRO; PR:P04150; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P04150; protein. DR Bgee; ENSG00000113580; Expressed in endothelial cell and 210 other tissues. DR ExpressionAtlas; P04150; baseline and differential. DR Genevisible; P04150; HS. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; IEA:Ensembl. DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell. DR GO; GO:0005759; C:mitochondrial matrix; TAS:ProtInc. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:CAFA. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0140677; F:molecular function activator activity; IDA:DisProt. DR GO; GO:0004883; F:nuclear glucocorticoid receptor activity; TAS:ProtInc. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0005496; F:steroid binding; IDA:UniProtKB. DR GO; GO:1990239; F:steroid hormone binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IMP:CAFA. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IDA:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:CAFA. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0008211; P:glucocorticoid metabolic process; IEA:Ensembl. DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central. DR GO; GO:0060603; P:mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0042711; P:maternal behavior; IEA:Ensembl. DR GO; GO:0014004; P:microglia differentiation; IEA:Ensembl. DR GO; GO:0061744; P:motor behavior; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0150076; P:neuroinflammatory response; IEA:Ensembl. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:ARUK-UCL. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0031946; P:regulation of glucocorticoid biosynthetic process; IEA:Ensembl. DR GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl. DR DisProt; DP00030; -. DR Gene3D; 1.10.565.10; -; 1. DR Gene3D; 3.30.50.10; -; 1. DR IDEAL; IID00014; -. DR InterPro; IPR001409; Glcrtcd_rcpt. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Pfam; PF02155; GCR; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00528; GLCORTICOIDR. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR AGR; HGNC:7978; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing; KW Apoptosis; Cell cycle; Cell division; Chromatin regulator; KW Chromosome partition; Cytoplasm; Cytoskeleton; Disease variant; KW DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; Methylation; KW Mitochondrion; Mitosis; Nucleus; Phosphoprotein; Pseudohermaphroditism; KW Receptor; Reference proteome; RNA-binding; Steroid-binding; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..777 FT /note="Glucocorticoid receptor" FT /id="PRO_0000019937" FT DOMAIN 524..758 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 418..493 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 421..441 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 457..476 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..420 FT /note="Modulating" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 98..115 FT /note="Required for high transcriptional activity of FT isoform Alpha-C3" FT /evidence="ECO:0000269|PubMed:23820903" FT REGION 130..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 394..415 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 485..777 FT /note="Interaction with CLOCK" FT REGION 487..523 FT /note="Hinge" FT REGION 532..697 FT /note="Interaction with CRY1" FT /evidence="ECO:0000269|PubMed:22170608" FT COMPBIAS 130..149 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 166..183 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 8 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 23 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 113 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 141 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12000743, FT ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:25847991, FT ECO:0007744|PubMed:24275569" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12000743, FT ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:25847991" FT MOD_RES 226 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18483179, FT ECO:0007744|PubMed:18669648" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 404 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:18838540" FT MOD_RES 480 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 492 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 494 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 495 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT CROSSLNK 258 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 277 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:12144530" FT CROSSLNK 277 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 293 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:12144530" FT CROSSLNK 293 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 419 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P06537" FT CROSSLNK 703 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12144530" FT VAR_SEQ 1..335 FT /note="Missing (in isoform Alpha-D3)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058312" FT VAR_SEQ 1..330 FT /note="Missing (in isoform Alpha-D2)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058313" FT VAR_SEQ 1..315 FT /note="Missing (in isoform Alpha-D1)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058314" FT VAR_SEQ 1..97 FT /note="Missing (in isoform Alpha-C3)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058315" FT VAR_SEQ 1..89 FT /note="Missing (in isoform Alpha-C2)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058316" FT VAR_SEQ 1..85 FT /note="Missing (in isoform Alpha-C1)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058317" FT VAR_SEQ 1..26 FT /note="Missing (in isoform Alpha-B and isoform Beta-B)" FT /evidence="ECO:0000305" FT /id="VSP_018773" FT VAR_SEQ 313..338 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:17404046" FT /id="VSP_043908" FT VAR_SEQ 451 FT /note="G -> GR (in isoform Alpha-2 and isoform Beta-2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007363" FT VAR_SEQ 491..674 FT /note="Missing (in isoform GR-A alpha and isoform GR-A FT beta)" FT /evidence="ECO:0000305" FT /id="VSP_013340" FT VAR_SEQ 728..777 FT /note="VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK FT -> NVMWLKPESTSHTLI (in isoform Beta, isoform Beta-B, FT isoform Beta-2 and isoform GR-A beta)" FT /evidence="ECO:0000303|PubMed:2867473" FT /id="VSP_003703" FT VARIANT 23 FT /note="R -> K (reduces transactivation activity; does not FT affect transrepression activity; dbSNP:rs6190)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10898924, ECO:0000269|PubMed:12351458, FT ECO:0000269|PubMed:15276593, ECO:0000269|PubMed:15292341, FT ECO:0000269|PubMed:16030164, ECO:0000269|PubMed:9150737, FT ECO:0000269|Ref.9" FT /id="VAR_014140" FT VARIANT 29 FT /note="F -> L (in dbSNP:rs148102613)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015628" FT VARIANT 65 FT /note="F -> V (in dbSNP:rs6192)" FT /evidence="ECO:0000269|PubMed:10391209, ECO:0000269|Ref.9" FT /id="VAR_014622" FT VARIANT 72 FT /note="N -> D (variant of uncertain significance; FT associated in cis with A-321 and S-766 in one individual; FT doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075797" FT VARIANT 112 FT /note="L -> F (in dbSNP:rs542110718)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015629" FT VARIANT 233 FT /note="D -> N (in dbSNP:rs1241576112)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015630" FT VARIANT 321 FT /note="V -> A (variant of uncertain significance; FT associated in cis with D-72 and S-766 in one individual; FT doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075798" FT VARIANT 363 FT /note="N -> S (enhances transactivation activity; does not FT affect transrepression activity; may increase sensitivity FT to exogenously administered glucocorticoids; may contribute FT to central obesity in men and show lack of association with FT other risk factors for coronary heart disease and diabetes FT mellitus; dbSNP:rs56149945)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10898924, ECO:0000269|PubMed:11344238, FT ECO:0000269|PubMed:16030164, ECO:0000269|PubMed:8445027, FT ECO:0000269|PubMed:9150737" FT /id="VAR_004675" FT VARIANT 421 FT /note="C -> Y" FT /evidence="ECO:0000269|PubMed:8358735" FT /id="VAR_015631" FT VARIANT 423 FT /note="V -> A (in GCCR; unknown pathological significance; FT reduces transactivation activity; delays nuclear FT translocation; does not exert a dominant negative effect; FT impairs DNA binding)" FT /evidence="ECO:0000269|PubMed:23426617" FT /id="VAR_075799" FT VARIANT 477 FT /note="R -> H (in GCCR; dbSNP:rs104893913)" FT /evidence="ECO:0000269|PubMed:11589680" FT /id="VAR_013472" FT VARIANT 477 FT /note="R -> S (in GCCR; loss of DNA-binding and of FT transactivation activity; incomplete dexamethasone-induced FT translocation to the nucleus; no effect on FT dexamethasone-binding affinity compared with wild-type)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077143" FT VARIANT 478 FT /note="Y -> C (in GCCR; decreased DNA-binding and FT transactivation activity; incomplete dexamethasone-induced FT translocation to the nucleus; no effect on FT dexamethasone-binding affinity compared with wild-type)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077144" FT VARIANT 556 FT /note="T -> I (in GCCR; reduces transactivation activity; FT enhances transrepression activity; reduces affinity for FT ligand; delays nuclear translocation; does not exert a FT dominant negative effect; does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:21362280, FT ECO:0000269|PubMed:26541474" FT /id="VAR_075800" FT VARIANT 559 FT /note="I -> N (in GCCR; interferes with translocation to FT the nucleus and thereby strongly reduces transcription FT activation; is equally impaired in nuclear export; acts as FT dominant negative mutant; dbSNP:rs104893909)" FT /evidence="ECO:0000269|PubMed:11701741" FT /id="VAR_015632" FT VARIANT 571 FT /note="V -> A (in pseudohermaphroditism; female with FT hypokalemia due to glucocorticoid resistance; 6-fold FT reduction in binding affinity compared with the wild-type FT receptor; dbSNP:rs104893911)" FT /evidence="ECO:0000269|PubMed:11932321" FT /id="VAR_025014" FT VARIANT 575 FT /note="V -> G (in GCCR; unknown pathological significance; FT reduces transactivation activity; enhances transrepression FT activity; reduces affinity for ligand; delays nuclear FT translocation; does not exert a dominant negative effect; FT does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:24483153" FT /id="VAR_075801" FT VARIANT 641 FT /note="D -> V (in GCCR; dbSNP:rs104893908)" FT /evidence="ECO:0000269|PubMed:1704018" FT /id="VAR_004676" FT VARIANT 672 FT /note="L -> P (in GCCR; loss of dexamethasone-binding, FT dexamethasone-induced translocation to the nucleus and of FT transactivation activity)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077145" FT VARIANT 679 FT /note="G -> S (in GCCR; has 50% binding affinity; FT dbSNP:rs104893914)" FT /evidence="ECO:0000269|PubMed:11589680" FT /id="VAR_013473" FT VARIANT 714 FT /note="R -> Q (in GCCR; unknown pathological significance; FT reduces transactivation; reduces affinity for ligand; FT exerts a dominant negative effect; does not impair DNA FT binding)" FT /evidence="ECO:0000269|PubMed:20335448" FT /id="VAR_075802" FT VARIANT 726 FT /note="H -> R (in GCCR; unknown pathological significance; FT reduces transactivation and transrepression activity; FT reduces affinity for ligand; delays nuclear translocation; FT does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:26031419" FT /id="VAR_075803" FT VARIANT 729 FT /note="V -> I (in GCCR; dbSNP:rs1027058734)" FT /evidence="ECO:0000269|PubMed:7683692" FT /id="VAR_004677" FT VARIANT 737 FT /note="F -> L (in GCCR; reduces transactivation of the FT glucocorticoid-inducible tumor virus promoter; reduces FT affinity for ligand; delays its nuclear translocation; acts FT as dominant negative mutant; dbSNP:rs121909727)" FT /evidence="ECO:0000269|PubMed:17635946" FT /id="VAR_071935" FT VARIANT 747 FT /note="I -> M (in GCCR; alters interaction with NCOA2 and FT strongly reduces transcription activation; acts as dominant FT negative mutant; dbSNP:rs104893910)" FT /evidence="ECO:0000269|PubMed:12050230" FT /id="VAR_015633" FT VARIANT 753 FT /note="L -> F (in dbSNP:rs121909726)" FT /evidence="ECO:0000269|PubMed:8316249, FT ECO:0000269|PubMed:8358735" FT /id="VAR_004678" FT VARIANT 766 FT /note="N -> S (variant of uncertain significance; FT associated in cis with D-72 and A-321 in one individual; FT doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075804" FT VARIANT 773 FT /note="L -> P (in GCCR; reduces transactivation of the FT glucocorticoid-inducible tumor virus promoter; reduces FT affinity for ligand; delays its nuclear translocation; acts FT as dominant negative mutant; dbSNP:rs104893912)" FT /evidence="ECO:0000269|PubMed:15769988" FT /id="VAR_071936" FT MUTAGEN 1 FT /note="M->T: Abolishes expression of A-type isoforms." FT /evidence="ECO:0000269|PubMed:11435610, FT ECO:0000269|PubMed:15866175" FT MUTAGEN 27 FT /note="M->T: Abolishes expression of B-type isoforms." FT /evidence="ECO:0000269|PubMed:11435610, FT ECO:0000269|PubMed:15866175" FT MUTAGEN 86 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-90 and I-98." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 90 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-86 and I-98." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 98 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-86 and I-90." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 101 FT /note="D->A: Reduces transcription activation activity of FT isoform Alpha-C3 by half." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 101 FT /note="D->K: Reduces transcription activation activity of FT isoform Alpha-C3 by half. Suppresses apoptosis-inducing FT activity of isoform Alpha-C3. Impairs recruitment of FT selected coregulators onto DNA binding sites." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 106..107 FT /note="QQ->LL: Reduces activity of isoform Alpha-C3 by FT half." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 113..114 FT /note="SS->AA: Does not affect the activity of isoform FT Alpha-C3." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 191 FT /note="F->D: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 193 FT /note="I->D: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 194 FT /note="L->A: Strongly reduces transactivation by the ADA FT complex; when associated with V-224 and F-225." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 197 FT /note="L->E: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 211 FT /note="S->A: Reduces expression of target genes IGFBP1 and FT IRF8." FT /evidence="ECO:0000269|PubMed:18483179" FT MUTAGEN 213 FT /note="W->A: Strongly reduces transactivation by the ADA FT complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 224 FT /note="L->V: Strongly reduces transactivation by the ADA FT complex; when associated with A-194 and F-225." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 225 FT /note="L->F: Strongly reduces transactivation by the ADA FT complex; when associated with A-194 and V-224." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 226 FT /note="S->A: Abolishes phosphorylation and enhances FT transcriptional activation." FT /evidence="ECO:0000269|PubMed:18483179" FT MUTAGEN 235 FT /note="F->L: Strongly reduces transactivation by the ADA FT complex; when associated with V-236." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 236 FT /note="L->V: Strongly reduces transactivation by the ADA FT complex; when associated with L-235." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 277 FT /note="K->R: Strongly reduces sumoylation. Almost complete FT loss of sumoylation; when associated with R-293." FT /evidence="ECO:0000269|PubMed:12144530" FT MUTAGEN 293 FT /note="K->R: Strongly reduces sumoylation. Almost complete FT loss of sumoylation; when associated with R-277." FT /evidence="ECO:0000269|PubMed:12144530" FT MUTAGEN 316 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-331 and I-336." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 331 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-316 and I-336." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 336 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-316 and I-331." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 404 FT /note="S->A: Abolishes phosphorylation. Does not affect FT translocation to the nucleus following ligand stimulation. FT Increases protein half-life and transcriptional repressor FT activity. Alters repertoire of regulated genes. Increases FT cell death." FT /evidence="ECO:0000269|PubMed:18838540" FT MUTAGEN 404 FT /note="S->D: Does not affect translocation to the nucleus FT following ligand stimulation." FT /evidence="ECO:0000269|PubMed:18838540" FT MUTAGEN 480 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer. FT Complete loss in acetylation and in repression of its FT transcriptional activity by CLOCK-BMAL1 heterodimer; when FT associated with A-492; A-494 and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 492 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer. FT Complete loss in acetylation and in repression of its FT transcriptional activity by CLOCK-BMAL1 heterodimer; when FT associated with A-480; A-494 and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 494 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer; FT when associated with A-495. Complete loss in acetylation FT and in repression of its transcriptional activity by FT CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 FT and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 495 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer; FT when associated with A-494. Complete loss in acetylation FT and in repression of its transcriptional activity by FT CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 FT and A-494." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 585 FT /note="R->A: Reduces activation mediated by ligand binding FT domain; when associated with A-590." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 590 FT /note="D->A: Reduces activation mediated by ligand binding FT domain; when associated with A-585." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 602 FT /note="F->S: Increases solubility. No effect on FT transactivation by dexamethasone." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 625 FT /note="P->A: Decreases transactivation by dexamethasone by FT 95%." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 628 FT /note="I->A: Decreases dimerization and transactivation by FT dexamethasone; when associated with S-602." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 703 FT /note="K->R: Slightly reduces sumoylation. Inhibits the FT stimulatory effect of RWDD3 on its transcriptional FT activity." FT /evidence="ECO:0000269|PubMed:12144530, FT ECO:0000269|PubMed:23508108" FT CONFLICT 399 FT /note="R -> G (in Ref. 7; BAD97314)" FT /evidence="ECO:0000305" FT CONFLICT 754 FT /note="A -> T (in Ref. 7; BAD97314)" FT /evidence="ECO:0000305" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 435..437 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 439..450 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 458..461 FT /evidence="ECO:0007829|PDB:5E69" FT TURN 467..472 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 474..484 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 488..497 FT /evidence="ECO:0007829|PDB:6CFN" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:1M2Z" FT HELIX 532..538 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:3K22" FT HELIX 556..579 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 584..586 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 589..615 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 617..619 FT /evidence="ECO:0007829|PDB:4P6W" FT STRAND 621..624 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 627..629 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 631..634 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 639..655 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 660..671 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 673..675 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 683..702 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 704..706 FT /evidence="ECO:0007829|PDB:4P6W" FT HELIX 708..741 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 743..745 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 751..765 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 766..768 FT /evidence="ECO:0007829|PDB:6DXK" FT STRAND 769..771 FT /evidence="ECO:0007829|PDB:5UC3" FT MOD_RES P04150-8:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES P04150-9:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 777 AA; 85659 MW; C5C90C9A5DD16AAB CRC64; MDSKESLTPG REENPSSVLA QERGDVMDFY KTLRGGATVK VSASSPSLAV ASQSDSKQRR LLVDFPKGSV SNAQQPDLSK AVSLSMGLYM GETETKVMGN DLGFPQQGQI SLSSGETDLK LLEESIANLN RSTSVPENPK SSASTAVSAA PTEKEFPKTH SDVSSEQQHL KGQTGTNGGN VKLYTTDQST FDILQDLEFS SGSPGKETNE SPWRSDLLID ENCLLSPLAG EDDSFLLEGN SNEDCKPLIL PDTKPKIKDN GDLVLSSPSN VTLPQVKTEK EDFIELCTPG VIKQEKLGTV YCQASFPGAN IIGNKMSAIS VHGVSTSGGQ MYHYDMNTAS LSQQQDQKPI FNVIPPIPVG SENWNRCQGS GDDNLTSLGT LNFPGRTVFS NGYSSPSMRP DVSSPPSSSS TATTGPPPKL CLVCSDEASG CHYGVLTCGS CKVFFKRAVE GQHNYLCAGR NDCIIDKIRR KNCPACRYRK CLQAGMNLEA RKTKKKIKGI QQATTGVSQE TSENPGNKTI VPATLPQLTP TLVSLLEVIE PEVLYAGYDS SVPDSTWRIM TTLNMLGGRQ VIAAVKWAKA IPGFRNLHLD DQMTLLQYSW MFLMAFALGW RSYRQSSANL LCFAPDLIIN EQRMTLPCMY DQCKHMLYVS SELHRLQVSY EEYLCMKTLL LLSSVPKDGL KSQELFDEIR MTYIKELGKA IVKREGNSSQ NWQRFYQLTK LLDSMHEVVE NLLNYCFQTF LDKTMSIEFP EMLAEIITNQ IPKYSNGNIK KLLFHQK // ID F10A5_HUMAN Reviewed; 369 AA. AC Q8NFI4; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 14-DEC-2022, entry version 126. DE RecName: Full=Putative protein FAM10A5; DE AltName: Full=Suppression of tumorigenicity 13 pseudogene 5; GN Name=ST13P5; Synonyms=FAM10A5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12079276; DOI=10.1006/geno.2002.6792; RA Sossey-Alaoui K., Kitamura E., Head K., Cowell J.K.; RT "Characterization of FAM10A4, a member of the ST13 tumor suppressor gene RT family that maps to the 13q14.3 region associated with B-Cell leukemia, RT multiple myeloma, and prostate cancer."; RL Genomics 80:5-7(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- SIMILARITY: Belongs to the FAM10 family. {ECO:0000305}. CC -!- CAUTION: Could be the product of a pseudogene. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF512499; AAM44055.1; -; mRNA. DR EMBL; AC107948; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR AlphaFoldDB; Q8NFI4; -. DR SMR; Q8NFI4; -. DR IntAct; Q8NFI4; 1. DR GlyConnect; 2066; 1 N-Linked glycan (1 site). DR GlyGen; Q8NFI4; 1 site, 1 Asn glycan (1 site), 1 N-linked glycan (1 site). DR iPTMnet; Q8NFI4; -. DR SwissPalm; Q8NFI4; -. DR BioMuta; HGNC:18556; -. DR DMDM; 74762570; -. DR EPD; Q8NFI4; -. DR jPOST; Q8NFI4; -. DR MassIVE; Q8NFI4; -. DR MaxQB; Q8NFI4; -. DR PeptideAtlas; Q8NFI4; -. DR ProteomicsDB; 73315; -. DR GeneCards; ST13P5; -. DR HGNC; HGNC:18556; ST13P5. DR neXtProt; NX_Q8NFI4; -. DR InParanoid; Q8NFI4; -. DR PhylomeDB; Q8NFI4; -. DR PathwayCommons; Q8NFI4; -. DR Pharos; Q8NFI4; Tdark. DR Proteomes; UP000005640; Unplaced. DR RNAct; Q8NFI4; protein. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR CDD; cd14438; Hip_N; 1. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR034649; Hip_N. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF18253; HipN; 1. DR Pfam; PF17830; STI1; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. DR AGR; HGNC:18556; -. PE 5: Uncertain; KW Acetylation; Cytoplasm; Phosphoprotein; Reference proteome; Repeat; KW TPR repeat. FT CHAIN 1..369 FT /note="Putative protein FAM10A5" FT /id="PRO_0000190817" FT REPEAT 114..147 FT /note="TPR 1" FT REPEAT 149..181 FT /note="TPR 2" FT REPEAT 183..215 FT /note="TPR 3" FT DOMAIN 319..358 FT /note="STI1" FT REGION 38..98 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 256..300 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..71 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 256..274 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 346 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P50502" FT MOD_RES 353 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99L47" FT MOD_RES 360 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99L47" SQ SEQUENCE 369 AA; 41378 MW; 9BAD620C24E2D137 CRC64; MDPCKVNELR AFVKMCKQDP SVLHTEEMRF LREWVESMGG KVPPATQKAK SEENTKEEKP DSKKVEEDLK ADEPSTEESD LEIDKEGVIE PDTDAPQEMG DENVEITEEM MDQANDKKVA AIEVLNDGEL QKAIDLFTDA IKLNPRLAIL YAKRASVFVK LQKPNAAIQD CDRAIEINPD SAQPYKWRGK AHRLLGHWEE AAHDLAFACK LDYDEDASAM LKEVQPRAQK IAEHWRKYER KHEEREIKER IERVKKAQEE QERAQREEEA RRQSGAHYGP FPGGFPGGMP GNFPGGMPGM GGDMPGMAGM PGLNEILSDP EALAAMQDPE VMVAFQDVAQ NPANMSKYQS NPKVMNLISK LSAKFGGQA // ID HSOP_PLAF7 Reviewed; 564 AA. AC Q8ILC1; A0A144A2J9; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 14-DEC-2022, entry version 123. DE RecName: Full=Hsp70-Hsp90 organising protein {ECO:0000303|PubMed:22005844}; DE Short=PfHOP {ECO:0000303|PubMed:22005844}; DE AltName: Full=Stress-inducible protein 1 {ECO:0000303|PubMed:32343703}; GN Name=HOP {ECO:0000303|PubMed:22005844}; GN Synonyms=STI1 {ECO:0000303|PubMed:32343703}; GN ORFNames=PF14_0324, PF3D7_1434300; OS Plasmodium falciparum (isolate 3D7). OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida; OC Plasmodiidae; Plasmodium; Plasmodium (Laverania). OX NCBI_TaxID=36329; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=3D7; RX PubMed=12368864; DOI=10.1038/nature01097; RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W., RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D., RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S., RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M., RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A., RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I., RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J., RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.; RT "Genome sequence of the human malaria parasite Plasmodium falciparum."; RL Nature 419:498-511(2002). RN [2] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH HSP70 AND HSP90, SUBCELLULAR RP LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=22005844; DOI=10.1007/s12192-011-0299-x; RA Gitau G.W., Mandal P., Blatch G.L., Przyborski J., Shonhai A.; RT "Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising RT protein (PfHop)."; RL Cell Stress Chaperones 17:191-202(2012). RN [3] RP FUNCTION, SUBUNIT, INTERACTION WITH HSP70 AND HSP90, AND INDUCTION. RX PubMed=26267894; DOI=10.1371/journal.pone.0135326; RA Zininga T., Makumire S., Gitau G.W., Njunge J.M., Pooe O.J., Klimek H., RA Scheurr R., Raifer H., Prinsloo E., Przyborski J.M., Hoppe H., Shonhai A.; RT "Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a RT Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity."; RL PLoS ONE 10:e0135326-e0135326(2015). RN [4] RP FUNCTION, AND SUBUNIT. RX PubMed=31525467; DOI=10.1016/j.bbapap.2019.140282; RA Silva N.S.M., Bertolino-Reis D.E., Dores-Silva P.R., Anneta F.B., RA Seraphim T.V., Barbosa L.R.S., Borges J.C.; RT "Structural studies of the Hsp70/Hsp90 organizing protein of Plasmodium RT falciparum and its modulation of Hsp70 and Hsp90 ATPase activities."; RL Biochim. Biophys. Acta 1868:140282-140282(2020). RN [5] RP SUBUNIT. RX PubMed=32343703; DOI=10.1371/journal.pone.0226657; RA Makumire S., Zininga T., Vahokoski J., Kursula I., Shonhai A.; RT "Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising RT protein (PfHop) reveals a monomer that is characterised by folded segments RT connected by flexible linkers."; RL PLoS ONE 15:e0226657-e0226657(2020). CC -!- FUNCTION: Acts as a co-chaperone and mediates the association of the CC chaperones HSP70 and HSP90 probably facilitating substrate transfer CC from HSP70 to HSP90 (PubMed:22005844, PubMed:26267894). Stimulates CC HSP70 ATPase activity and, in contrast, inhibits HSP90 ATPase activity CC (PubMed:31525467). {ECO:0000269|PubMed:22005844, CC ECO:0000269|PubMed:26267894, ECO:0000269|PubMed:31525467}. CC -!- SUBUNIT: Monomer (PubMed:32343703). Homodimer (PubMed:26267894, CC PubMed:31525467). Forms a complex composed of HOP and chaperones HSP70 CC and HSP90; the interaction is stronger in the absence of ATP CC (PubMed:22005844). Interacts (via TPR 1, 2, 3, 7, 8 and 9 repeats) with CC HSP70 (via C-terminus); the interaction is direct and is stronger in CC the absence of ATP (PubMed:26267894). Interacts (via TPR 4, 5 and 6 CC repeats) with HSP90 (via C-terminus); the interaction is direct CC (PubMed:26267894). {ECO:0000269|PubMed:22005844, CC ECO:0000269|PubMed:26267894, ECO:0000269|PubMed:31525467, CC ECO:0000269|PubMed:32343703}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22005844}. CC -!- DEVELOPMENTAL STAGE: Expressed during the parasite blood stage, in CC trophozoites (at protein level). {ECO:0000269|PubMed:22005844}. CC -!- INDUCTION: By heat stress (at protein level). CC {ECO:0000269|PubMed:26267894}. CC -!- DOMAIN: The TPR repeats form 3 domains; the TPR 1 domain is composed of CC TPR 1, 2 and 3 repeats, the TPR2A domain of TPR 4, 5 and 6 repeats and CC TPR2B domain of TPR 7, 8 and 9 repeats. {ECO:0000303|PubMed:22005844}. CC -!- CAUTION: Showed to form heterodimers (PubMed:26267894, CC PubMed:31525467). However in a later study, showed to exist CC predominantly as a monomer (PubMed:32343703). CC {ECO:0000269|PubMed:26267894, ECO:0000269|PubMed:31525467, CC ECO:0000269|PubMed:32343703}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; LN999946; CZU00040.1; -; Genomic_DNA. DR RefSeq; XP_001348498.1; XM_001348462.1. DR AlphaFoldDB; Q8ILC1; -. DR SASBDB; Q8ILC1; -. DR SMR; Q8ILC1; -. DR BioGRID; 1207264; 5. DR IntAct; Q8ILC1; 4. DR STRING; 5833.PF14_0324; -. DR EnsemblProtists; CZU00040; CZU00040; PF3D7_1434300. DR GeneID; 811906; -. DR KEGG; pfa:PF3D7_1434300; -. DR VEuPathDB; PlasmoDB:PF3D7_1434300; -. DR HOGENOM; CLU_000134_46_5_1; -. DR InParanoid; Q8ILC1; -. DR OMA; HYSKAWE; -. DR PhylomeDB; Q8ILC1; -. DR Reactome; R-PFA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Proteomes; UP000001450; Chromosome 14. DR GO; GO:0101031; C:chaperone complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:GeneDB. DR GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:UniProtKB. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 1. DR Pfam; PF00515; TPR_1; 1. DR Pfam; PF13181; TPR_8; 4. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 9. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 8. DR PROSITE; PS50293; TPR_REGION; 2. PE 1: Evidence at protein level; KW Chaperone; Coiled coil; Cytoplasm; Reference proteome; Repeat; TPR repeat. FT CHAIN 1..564 FT /note="Hsp70-Hsp90 organising protein" FT /id="PRO_0000295632" FT REPEAT 7..40 FT /note="TPR 1" FT /evidence="ECO:0000255" FT REPEAT 42..74 FT /note="TPR 2" FT /evidence="ECO:0000255" FT REPEAT 76..108 FT /note="TPR 3" FT /evidence="ECO:0000255" FT REPEAT 243..276 FT /note="TPR 4" FT /evidence="ECO:0000255" FT REPEAT 278..310 FT /note="TPR 5" FT /evidence="ECO:0000255" FT REPEAT 318..351 FT /note="TPR 6" FT /evidence="ECO:0000255" FT REPEAT 378..411 FT /note="TPR 7" FT /evidence="ECO:0000255" FT REPEAT 413..445 FT /note="TPR 8" FT /evidence="ECO:0000255" FT REPEAT 446..479 FT /note="TPR 9" FT /evidence="ECO:0000255" FT DOMAIN 513..552 FT /note="STI1" FT /evidence="ECO:0000255" FT REGION 199..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 197..239 FT /evidence="ECO:0000255" SQ SEQUENCE 564 AA; 66057 MW; 215FA96B9A1B67B5 CRC64; MVNKEEAQRL KELGNKCFQE GKYEEAVKYF SDAITNDPLD HVLYSNLSGA FASLGRFYEA LESANKCISI KKDWPKGYIR KGCAEHGLRQ LSNAEKTYLE GLKIDPNNKS LQDALSKVRN ENMLENAQLI AHLNNIIEND PQLKSYKEEN SNYPHELLNT IKSINSNPMN IRIILSTCHP KISEGVEKFF GFKFTGEGND AEERQRQQRE EEERRKKKEE EERKKKEEEE MKKQNRTPEQ IQGDEHKLKG NEFYKQKKFD EALKEYEEAI QINPNDIMYH YNKAAVHIEM KNYDKAVETC LYAIENRYNF KAEFIQVAKL YNRLAISYIN MKKYDLAIEA YRKSLVEDNN RATRNALKEL ERRKEKEEKE AYIDPDKAEE HKNKGNEYFK NNDFPNAKKE YDEAIRRNPN DAKLYSNRAA ALTKLIEYPS ALEDVMKAIE LDPTFVKAYS RKGNLHFFMK DYYKALQAYN KGLELDPNNK ECLEGYQRCA FKIDEMSKSE KVDEEQFKKS MADPEIQQII SDPQFQIILQ KLNENPNSIS EYIKDPKIFN GLQKLIAAGI LKVR // ID ALL3_HUMJA Reviewed; 86 AA. AC I1SKR9; P86278; DT 01-OCT-2014, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2012, sequence version 1. DT 25-MAY-2022, entry version 9. DE RecName: Full=Allergen Hum j 3 {ECO:0000303|Ref.2}; DE AltName: Allergen=Hum j 3 {ECO:0000303|Ref.2}; OS Humulus japonicus (Japanese hop). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae; OC rosids; fabids; Rosales; Cannabaceae; Humulus. OX NCBI_TaxID=3485; RN [1] {ECO:0000305, ECO:0000312|EMBL:ADB97919.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pollen {ECO:0000269|Ref.1}; RA Yin J., Zhou J., Cheng X.; RT "cDNA cloning and identification of a major allergen from Humulus scandens RT pollen, Hum s 3."; RL Submitted (APR-2009) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000305, ECO:0000312|EMBL:ADB97919.1} RP PROTEIN SEQUENCE OF 1-10, MASS SPECTROMETRY, AND ALLERGEN. RC TISSUE=Pollen {ECO:0000269|Ref.2}; RA Yin J., Cheng X., Zhou J.X., Sun J.L.; RT "cDNA cloning and identification of a major allergen from Humulus scandens RT pollen, Hum j 3."; RL Submitted (APR-2009) to UniProtKB. RN [3] {ECO:0000305} RP PROTEIN SEQUENCE OF 2-21, AND ALLERGEN. RC TISSUE=Pollen {ECO:0000269|PubMed:10457112}; RX PubMed=10457112; DOI=10.1046/j.1365-2222.1999.00615.x; RA Park J.W., Ko S.H., Kim C.W., Jeoung B.J., Hong C.S.; RT "Identification and characterization of the major allergen of the Humulus RT japonicus pollen."; RL Clin. Exp. Allergy 29:1080-1086(1999). CC -!- MASS SPECTROMETRY: Mass=9607; Mass_error=0.2; Method=MALDI; CC Evidence={ECO:0000269|Ref.2}; CC -!- ALLERGEN: Causes an allergic reaction in human. CC {ECO:0000269|PubMed:10457112, ECO:0000269|Ref.2}. CC -!- MISCELLANEOUS: On the 2D-gel the determined pI of this protein is: 5.1, CC its MW is: 10 kDa. {ECO:0000269|PubMed:10457112}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; FJ967117; ADB97919.1; -; mRNA. DR AlphaFoldDB; I1SKR9; -. DR Allergome; 1239; Hum j 3. PE 1: Evidence at protein level; KW Allergen; Direct protein sequencing. FT CHAIN 1..86 FT /note="Allergen Hum j 3" FT /id="PRO_0000430497" SQ SEQUENCE 86 AA; 9614 MW; 56CCD2E8BD09D11E CRC64; MDNPFENGMK ACTSLYDKYY QNCVMKLPPG ACIDSENYRK CLTNHIGSCD IDTCFEDVSI ACRSIYPSNY AECATTHHNI CGDLQG // ID V9HW72_HUMAN Unreviewed; 543 AA. AC V9HW72; DT 19-MAR-2014, integrated into UniProtKB/TrEMBL. DT 19-MAR-2014, sequence version 1. DT 14-DEC-2022, entry version 69. DE RecName: Full=Stress-induced-phosphoprotein 1 {ECO:0000256|ARBA:ARBA00026193}; DE AltName: Full=Hsc70/Hsp90-organizing protein {ECO:0000256|ARBA:ARBA00032536}; GN Name=HEL-S-94n {ECO:0000313|EMBL:ACI46042.1}; GN Synonyms=STIP1 {ECO:0000313|EMBL:EAW74198.1}; GN ORFNames=hCG_21368 {ECO:0000313|EMBL:EAW74198.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:ACI46042.1}; RN [1] {ECO:0000313|EMBL:EAW74198.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11181995; DOI=10.1126/science.1058040; RA Venter J.C., Adams M.D., Myers E.W., Li P.W., Mural R.J., Sutton G.G., RA Smith H.O., Yandell M., Evans C.A., Holt R.A., Gocayne J.D., Amanatides P., RA Ballew R.M., Huson D.H., Wortman J.R., Zhang Q., Kodira C.D., Zheng X.H., RA Chen L., Skupski M., Subramanian G., Thomas P.D., Zhang J., RA Gabor Miklos G.L., Nelson C., Broder S., Clark A.G., Nadeau J., RA McKusick V.A., Zinder N., Levine A.J., Roberts R.J., Simon M., Slayman C., RA Hunkapiller M., Bolanos R., Delcher A., Dew I., Fasulo D., Flanigan M., RA Florea L., Halpern A., Hannenhalli S., Kravitz S., Levy S., Mobarry C., RA Reinert K., Remington K., Abu-Threideh J., Beasley E., Biddick K., RA Bonazzi V., Brandon R., Cargill M., Chandramouliswaran I., Charlab R., RA Chaturvedi K., Deng Z., Di Francesco V., Dunn P., Eilbeck K., RA Evangelista C., Gabrielian A.E., Gan W., Ge W., Gong F., Gu Z., Guan P., RA Heiman T.J., Higgins M.E., Ji R.R., Ke Z., Ketchum K.A., Lai Z., Lei Y., RA Li Z., Li J., Liang Y., Lin X., Lu F., Merkulov G.V., Milshina N., RA Moore H.M., Naik A.K., Narayan V.A., Neelam B., Nusskern D., Rusch D.B., RA Salzberg S., Shao W., Shue B., Sun J., Wang Z., Wang A., Wang X., Wang J., RA Wei M., Wides R., Xiao C., Yan C., Yao A., Ye J., Zhan M., Zhang W., RA Zhang H., Zhao Q., Zheng L., Zhong F., Zhong W., Zhu S., Zhao S., RA Gilbert D., Baumhueter S., Spier G., Carter C., Cravchik A., Woodage T., RA Ali F., An H., Awe A., Baldwin D., Baden H., Barnstead M., Barrow I., RA Beeson K., Busam D., Carver A., Center A., Cheng M.L., Curry L., RA Danaher S., Davenport L., Desilets R., Dietz S., Dodson K., Doup L., RA Ferriera S., Garg N., Gluecksmann A., Hart B., Haynes J., Haynes C., RA Heiner C., Hladun S., Hostin D., Houck J., Howland T., Ibegwam C., RA Johnson J., Kalush F., Kline L., Koduru S., Love A., Mann F., May D., RA McCawley S., McIntosh T., McMullen I., Moy M., Moy L., Murphy B., RA Nelson K., Pfannkoch C., Pratts E., Puri V., Qureshi H., Reardon M., RA Rodriguez R., Rogers Y.H., Romblad D., Ruhfel B., Scott R., Sitter C., RA Smallwood M., Stewart E., Strong R., Suh E., Thomas R., Tint N.N., Tse S., RA Vech C., Wang G., Wetter J., Williams S., Williams M., Windsor S., RA Winn-Deen E., Wolfe K., Zaveri J., Zaveri K., Abril J.F., Guigo R., RA Campbell M.J., Sjolander K.V., Karlak B., Kejariwal A., Mi H., Lazareva B., RA Hatton T., Narechania A., Diemer K., Muruganujan A., Guo N., Sato S., RA Bafna V., Istrail S., Lippert R., Schwartz R., Walenz B., Yooseph S., RA Allen D., Basu A., Baxendale J., Blick L., Caminha M., Carnes-Stine J., RA Caulk P., Chiang Y.H., Coyne M., Dahlke C., Mays A., Dombroski M., RA Donnelly M., Ely D., Esparham S., Fosler C., Gire H., Glanowski S., RA Glasser K., Glodek A., Gorokhov M., Graham K., Gropman B., Harris M., RA Heil J., Henderson S., Hoover J., Jennings D., Jordan C., Jordan J., RA Kasha J., Kagan L., Kraft C., Levitsky A., Lewis M., Liu X., Lopez J., RA Ma D., Majoros W., McDaniel J., Murphy S., Newman M., Nguyen T., Nguyen N., RA Nodell M., Pan S., Peck J., Peterson M., Rowe W., Sanders R., Scott J., RA Simpson M., Smith T., Sprague A., Stockwell T., Turner R., Venter E., RA Wang M., Wen M., Wu D., Wu M., Xia A., Zandieh A., Zhu X.; RT "The sequence of the human genome."; RL Science 291:1304-1351(2001). RN [2] {ECO:0000313|EMBL:EAW74198.1} RP NUCLEOTIDE SEQUENCE. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000313|EMBL:ACI46042.1} RP NUCLEOTIDE SEQUENCE. RA Li J.Y., Wang H.Y., Liu J., Liu F.J.; RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases. RN [4] {ECO:0000313|EMBL:ADO22226.1} RP NUCLEOTIDE SEQUENCE. RA Hoernsten L., Su C., Osbourn A.E., Hellman U., Wernstedt C., Oliw E.H.; RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; FJ224350; ACI46042.1; -; mRNA. DR EMBL; GQ891364; ADO22226.1; -; mRNA. DR EMBL; CH471076; EAW74198.1; -; Genomic_DNA. DR RefSeq; NP_006810.1; NM_006819.2. DR AlphaFoldDB; V9HW72; -. DR SMR; V9HW72; -. DR IntAct; V9HW72; 1. DR MaxQB; V9HW72; -. DR Antibodypedia; 15273; 439 antibodies from 39 providers. DR DNASU; 10963; -. DR GeneID; 10963; -. DR KEGG; hsa:10963; -. DR MANE-Select; ENST00000305218.9; ENSP00000305958.5; NM_006819.3; NP_006810.1. DR UCSC; uc001nyk.2; human. DR CTD; 10963; -. DR VEuPathDB; HostDB:ENSG00000168439; -. DR OMA; HYSKAWE; -. DR BioGRID-ORCS; 10963; 94 hits in 1086 CRISPR screens. DR ChiTaRS; STIP1; human. DR GenomeRNAi; 10963; -. DR ExpressionAtlas; V9HW72; baseline and differential. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:InterPro. DR GO; GO:0098761; P:cellular response to interleukin-7; IEA:Ensembl. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 2. DR Pfam; PF07719; TPR_2; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 2. DR SMART; SM00028; TPR; 9. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 7. PE 2: Evidence at transcript level; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 4..37 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 38..71 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 130..169 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REPEAT 225..258 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 300..333 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 360..393 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 394..427 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 428..461 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 492..531 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 192..233 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 208..233 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 543 AA; 62639 MW; 8E58ECA13825CB0E CRC64; MEQVNELKEK GNKALSVGNI DDALQCYSEA IKLDPHNHVL YSNRSAAYAK KGDYQKAYED GCKTVDLKPD WGKGYSRKAA ALEFLNRFEE AKRTYEEGLK HEANNPQLKE GLQNMEARLA ERKFMNPFNM PNLYQKLESD PRTRTLLSDP TYRELIEQLR NKPSDLGTKL QDPRIMTTLS VLLGVDLGSM DEEEEIATPP PPPPPKKETK PEPMEEDLPE NKKQALKEKE LGNDAYKKKD FDTALKHYDK AKELDPTNMT YITNQAAVYF EKGDYNKCRE LCEKAIEVGR ENREDYRQIA KAYARIGNSY FKEEKYKDAI HFYNKSLAEH RTPDVLKKCQ QAEKILKEQE RLAYINPDLA LEEKNKGNEC FQKGDYPQAM KHYTEAIKRN PKDAKLYSNR AACYTKLLEF QLALKDCEEC IQLEPTFIKG YTRKAAALEA MKDYTKAMDV YQKALDLDSS CKEAADGYQR CMMAQYNRHD SPEDVKRRAM ADPEVQQIMS DPAMRLILEQ MQKDPQALSE HLKNPVIAQK IQKLMDVGLI AIR // ID A8K690_HUMAN Unreviewed; 543 AA. AC A8K690; DT 04-DEC-2007, integrated into UniProtKB/TrEMBL. DT 04-DEC-2007, sequence version 1. DT 14-DEC-2022, entry version 76. DE RecName: Full=Stress-induced-phosphoprotein 1 {ECO:0000256|ARBA:ARBA00026193}; DE AltName: Full=Hsc70/Hsp90-organizing protein {ECO:0000256|ARBA:ARBA00032536}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAF84244.1}; RN [1] {ECO:0000313|EMBL:BAF84244.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Placenta {ECO:0000313|EMBL:BAF84244.1}; RA Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A., RA Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y., RA Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T., RA Sugano S., Nomura N., Isogai T.; RT "NEDO human cDNA sequencing project."; RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK291555; BAF84244.1; -; mRNA. DR AlphaFoldDB; A8K690; -. DR IntAct; A8K690; 1. DR PeptideAtlas; A8K690; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:InterPro. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 2. DR Pfam; PF00515; TPR_1; 1. DR Pfam; PF07719; TPR_2; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 2. DR SMART; SM00028; TPR; 9. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 6. PE 2: Evidence at transcript level; KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|ARBA:ARBA00022803, ECO:0000256|PROSITE- KW ProRule:PRU00339}. FT REPEAT 4..37 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 38..71 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 130..169 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REPEAT 225..258 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 300..333 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 394..427 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 428..461 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 492..531 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 192..233 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 208..233 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 543 AA; 62655 MW; 269C3920E425D6CF CRC64; MEQVNELKEK GNKALSVGNI DDALQCYSEA IKLDPHNHVL YSNRSAAYAK KGDYQKAYED GCKTVDLKPD WGKGYSRKAA ALEFLNRFEE AKRTYEEGLK HEANNPQLKE GLQNMEARLA ERKFMNPFNM PNLYQKLESD PRTRTLLSDP TYRELIEQLR NKPSDLGTKL QDPRIMTTLS VLLGVDLGSM DEEEEIATPP PPPPPKKETK PEPMEEDLPE NKKQALKEKE LGNDAYKKKD FDTALKHYDK AKELDPTNMT YITNQAAVYF EKGDYNKCRE LCEKAIEVGR ENREDYRQIA KAYARIGNSY FKEEKYKDAI HFYNKSLAEH RTPDVLKKCQ QAEKILKEQE RLAYINPDLA LEEKNKGNEC FQKGDYPQAM KHYTEAIKRN LKDAKLYSNR AACYTKLLEF QLALKDCEEC IQLEPTFIKG YTRKAAALEA MKDYTKAMDV YQKALDLDSS CKEAADGYQR CMMAQYNRHD SPEDVKRRAM ADPEVQQIMS DPAMRLILEQ MQKDPQALSE HLKNPVIAQK IQKLMDVGLI AIR // ID A0A140VKA6_HUMAN Unreviewed; 369 AA. AC A0A140VKA6; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 14-DEC-2022, entry version 43. DE SubName: Full=Testis secretory sperm-binding protein Li 233m {ECO:0000313|EMBL:AEE61243.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:AEE61243.1}; RN [1] {ECO:0000313|EMBL:AEE61243.1} RP NUCLEOTIDE SEQUENCE. RA Li J.Y.; RT "Human testis protein."; RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases. CC -!- SIMILARITY: Belongs to the FAM10 family. CC {ECO:0000256|ARBA:ARBA00009015}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; HM005646; AEE61243.1; -; mRNA. DR RefSeq; NP_003923.2; NM_003932.4. DR AlphaFoldDB; A0A140VKA6; -. DR SMR; A0A140VKA6; -. DR IntAct; A0A140VKA6; 1. DR Antibodypedia; 3378; 389 antibodies from 33 providers. DR DNASU; 6767; -. DR GeneID; 6767; -. DR KEGG; hsa:6767; -. DR MANE-Select; ENST00000216218.8; ENSP00000216218.3; NM_003932.5; NP_003923.2. DR CTD; 6767; -. DR VEuPathDB; HostDB:ENSG00000100380; -. DR OMA; TVLNMPQ; -. DR OrthoDB; 1282821at2759; -. DR PhylomeDB; A0A140VKA6; -. DR BioGRID-ORCS; 6767; 36 hits in 1035 CRISPR screens. DR GenomeRNAi; 6767; -. DR ExpressionAtlas; A0A140VKA6; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR CDD; cd14438; Hip_N; 1. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR034649; Hip_N. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF18253; HipN; 1. DR Pfam; PF17830; STI1; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 1. PE 2: Evidence at transcript level; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 148..181 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 319..358 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 38..97 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 256..300 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 50..71 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 256..273 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 369 AA; 41332 MW; 98FCC65BEE14CDD7 CRC64; MDPRKVNELR AFVKMCKQDP SVLHTEEMRF LREWVESMGG KVPPATQKAK SEENTKEEKP DSKKVEEDLK ADEPSSEESD LEIDKEGVIE PDTDAPQEMG DENAEITEEM MDQANDKKVA AIEALNDGEL QKAIDLFTDA IKLNPRLAIL YAKRASVFVK LQKPNAAIRD CDRAIEINPD SAQPYKWRGK AHRLLGHWEE AAHDLALACK LDYDEDASAM LKEVQPRAQK IAEHRRKYER KREEREIKER IERVKKAREE HERAQREEEA RRQSGAQYGS FPGGFPGGMP GNFPGGMPGM GGGMPGMAGM PGLNEILSDP EVLAAMQDPE VMVAFQDVAQ NPANMSKYQS NPKVMNLISK LSAKFGGQA // ID A0A0W4ZUD6_PNEJ7 Unreviewed; 574 AA. AC A0A0W4ZUD6; DT 16-MAR-2016, integrated into UniProtKB/TrEMBL. DT 16-MAR-2016, sequence version 1. DT 14-DEC-2022, entry version 29. DE RecName: Full=TPR_REGION domain-containing protein {ECO:0000256|Google:UnProtein}; GN ORFNames=T551_00619 {ECO:0000313|EMBL:KTW31936.1}; OS Pneumocystis jirovecii (strain RU7) (Human pneumocystis pneumonia agent). OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; OC Pneumocystidomycetes; Pneumocystidaceae; Pneumocystis. OX NCBI_TaxID=1408657 {ECO:0000313|EMBL:KTW31936.1, ECO:0000313|Proteomes:UP000053447}; RN [1] {ECO:0000313|Proteomes:UP000053447} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=RU7 {ECO:0000313|Proteomes:UP000053447}; RX PubMed=26899007; DOI=10.1038/ncomms10740; RA Ma L., Chen Z., Huang D.W., Kutty G., Ishihara M., Wang H., Abouelleil A., RA Bishop L., Davey E., Deng R., Deng X., Fan L., Fantoni G., Fitzgerald M., RA Gogineni E., Goldberg J.M., Handley G., Hu X., Huber C., Jiao X., Jones K., RA Levin J.Z., Liu Y., Macdonald P., Melnikov A., Raley C., Sassi M., RA Sherman B.T., Song X., Sykes S., Tran B., Walsh L., Xia Y., Yang J., RA Young S., Zeng Q., Zheng X., Stephens R., Nusbaum C., Birren B.W., RA Azadi P., Lempicki R.A., Cuomo C.A., Kovacs J.A.; RT "Genome analysis of three Pneumocystis species reveals adaptation RT mechanisms to life exclusively in mammalian hosts."; RL Nat. Commun. 7:10740-10740(2016). CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:KTW31936.1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; LFWA01000003; KTW31936.1; -; Genomic_DNA. DR RefSeq; XP_018230628.1; XM_018372885.1. DR AlphaFoldDB; A0A0W4ZUD6; -. DR STRING; 1408657.A0A0W4ZUD6; -. DR GeneID; 28939140; -. DR VEuPathDB; FungiDB:T551_00619; -. DR eggNOG; KOG0548; Eukaryota. DR OrthoDB; 933764at2759; -. DR Proteomes; UP000053447; Unassembled WGS sequence. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:InterPro. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 2. DR Pfam; PF07719; TPR_2; 2. DR Pfam; PF13181; TPR_8; 3. DR SMART; SM00727; STI1; 2. DR SMART; SM00028; TPR; 8. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 6. PE 4: Predicted; KW Reference proteome {ECO:0000313|Proteomes:UP000053447}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 2..35 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 36..69 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 70..103 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 140..179 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REPEAT 320..353 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 380..413 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 414..447 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 521..560 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 200..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..224 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 233..249 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 574 AA; 65538 MW; 9033092276D2C1FA CRC64; MSEEIRQEAN SLFSAKKYEE AIKMYTEAIT LEPGNHVLYS NRSACYASLK NFDEALKDAL KCIEINPNWA KGWSRKGVAL HGKGNLEESK HAYEKGLELE PENQQIKAAL KTVEESISRD FSKNFQKNDP FTQIAMKLNS PDFLSKVASN PKTSGLLSNP QFMEKLKKIQ ENPRIIFQEL NDPNMASILP LLLGLDTDTS NHINGDSKET HSPPSEKSSE SEVEADQELM EEDEDTKAQR ENKEKAEKEK ALGNECYKKR QFEKSVQHYL SAWEIYKDIT YLTNCSAAYY EDGKYEECIK CCEEAITYGR EVLADFKLIA RAFGRIGTAY MKQENYELAI KNFNSSLTEH RTPDILKKLR EAEKIKEEKD RLAYIDHNKA DEAREQGNKL FKEGDFGGAI KMYSEMIKRS PDDPRGYGNR AAAYIKVMSM VEALKDCEKA ISLDPNFTKA YIRKASCYFT MKEYNKCIDA CHSATKADEN SNNKGMHAKE IEAQLQKCMS AMYAQRENET EEQTLQRIQN DPEILSILQD PVMQSILNQA RENPAALEEH MKNAQVASKI QKLIHSGVIK LSRR // ID L0PAL8_PNEJ8 Unreviewed; 574 AA. AC L0PAL8; DT 06-MAR-2013, integrated into UniProtKB/TrEMBL. DT 06-MAR-2013, sequence version 1. DT 14-DEC-2022, entry version 39. DE RecName: Full=TPR_REGION domain-containing protein {ECO:0000256|Google:UnProtein}; GN ORFNames=PNEJI1_002819 {ECO:0000313|EMBL:CCJ29149.1}; OS Pneumocystis jirovecii (strain SE8) (Human pneumocystis pneumonia agent). OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; OC Pneumocystidomycetes; Pneumocystidaceae; Pneumocystis. OX NCBI_TaxID=1209962 {ECO:0000313|Proteomes:UP000010422}; RN [1] {ECO:0000313|EMBL:CCJ29149.1, ECO:0000313|Proteomes:UP000010422} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=SE8 {ECO:0000313|EMBL:CCJ29149.1, RC ECO:0000313|Proteomes:UP000010422}; RX PubMed=23269827; DOI=10.1128/mBio.00428-12; RA Cisse O.H., Pagni M., Hauser P.M.; RT "De novo assembly of the Pneumocystis jirovecii genome from a single RT bronchoalveolar lavage fluid specimen from a patient."; RL MBio 3:E428-E428(2012). CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ CC whole genome shotgun (WGS) entry which is preliminary data. CC {ECO:0000313|EMBL:CCJ29149.1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CAKM01000160; CCJ29149.1; -; Genomic_DNA. DR AlphaFoldDB; L0PAL8; -. DR STRING; 1209962.L0PAL8; -. DR VEuPathDB; FungiDB:PNEJI1_002819; -. DR InParanoid; L0PAL8; -. DR Proteomes; UP000010422; Unassembled WGS sequence. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:InterPro. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 2. DR Pfam; PF07719; TPR_2; 2. DR Pfam; PF13181; TPR_8; 3. DR SMART; SM00727; STI1; 2. DR SMART; SM00028; TPR; 8. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 6. PE 4: Predicted; KW Reference proteome {ECO:0000313|Proteomes:UP000010422}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 2..35 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 36..69 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 70..103 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 140..179 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REPEAT 320..353 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 380..413 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 414..447 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 521..560 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 200..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..224 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 233..249 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 574 AA; 65538 MW; 9033092276D2C1FA CRC64; MSEEIRQEAN SLFSAKKYEE AIKMYTEAIT LEPGNHVLYS NRSACYASLK NFDEALKDAL KCIEINPNWA KGWSRKGVAL HGKGNLEESK HAYEKGLELE PENQQIKAAL KTVEESISRD FSKNFQKNDP FTQIAMKLNS PDFLSKVASN PKTSGLLSNP QFMEKLKKIQ ENPRIIFQEL NDPNMASILP LLLGLDTDTS NHINGDSKET HSPPSEKSSE SEVEADQELM EEDEDTKAQR ENKEKAEKEK ALGNECYKKR QFEKSVQHYL SAWEIYKDIT YLTNCSAAYY EDGKYEECIK CCEEAITYGR EVLADFKLIA RAFGRIGTAY MKQENYELAI KNFNSSLTEH RTPDILKKLR EAEKIKEEKD RLAYIDHNKA DEAREQGNKL FKEGDFGGAI KMYSEMIKRS PDDPRGYGNR AAAYIKVMSM VEALKDCEKA ISLDPNFTKA YIRKASCYFT MKEYNKCIDA CHSATKADEN SNNKGMHAKE IEAQLQKCMS AMYAQRENET EEQTLQRIQN DPEILSILQD PVMQSILNQA RENPAALEEH MKNAQVASKI QKLIHSGVIK LSRR // ID E0VNU4_PEDHC Unreviewed; 541 AA. AC E0VNU4; DT 02-NOV-2010, integrated into UniProtKB/TrEMBL. DT 02-NOV-2010, sequence version 1. DT 14-DEC-2022, entry version 61. DE RecName: Full=Stress-induced-phosphoprotein 1 {ECO:0000256|ARBA:ARBA00026193}; GN Name=8231875 {ECO:0000313|EnsemblMetazoa:PHUM345830-PA}; GN ORFNames=Phum_PHUM345830 {ECO:0000313|EMBL:EEB15050.1}; OS Pediculus humanus subsp. corporis (Body louse). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Paraneoptera; Psocodea; Phthiraptera; Anoplura; Pediculidae; OC Pediculus. OX NCBI_TaxID=121224; RN [1] {ECO:0000313|EMBL:EEB15050.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=USDA {ECO:0000313|EMBL:EEB15050.1}; RA Kirkness E., Hannick L., Hass B., Bruggner R., Lawson D., Bidwell S., RA Joardar V., Caler E., Walenz B., Inman J., Schobel S., Galinsky K., RA Amedeo P., Strausberg R.; RT "Annotation of Pediculus humanus corporis strain USDA."; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:EEB15050.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=USDA {ECO:0000313|EMBL:EEB15050.1}; RG The Human Body Louse Genome Consortium; RA Kirkness E., Walenz B., Hass B., Bruggner R., Strausberg R.; RT "The genome of the human body louse."; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000313|EnsemblMetazoa:PHUM345830-PA} RP IDENTIFICATION. RC STRAIN=USDA {ECO:0000313|EnsemblMetazoa:PHUM345830-PA}; RG EnsemblMetazoa; RL Submitted (FEB-2021) to UniProtKB. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AAZO01004031; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; DS235354; EEB15050.1; -; Genomic_DNA. DR RefSeq; XP_002427788.1; XM_002427743.1. DR STRING; 121225.PHUM345830-PA; -. DR EnsemblMetazoa; PHUM345830-RA; PHUM345830-PA; PHUM345830. DR GeneID; 8231875; -. DR KEGG; phu:Phum_PHUM345830; -. DR CTD; 8231875; -. DR VEuPathDB; VectorBase:PHUM345830; -. DR eggNOG; KOG0548; Eukaryota. DR HOGENOM; CLU_000134_46_5_1; -. DR OMA; HYSKAWE; -. DR Proteomes; UP000009046; Unplaced. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0030544; F:Hsp70 protein binding; IEA:InterPro. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:InterPro. DR GO; GO:0006457; P:protein folding; IEA:InterPro. DR Gene3D; 1.25.40.10; -; 3. DR InterPro; IPR045248; Sti1-like. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR22904; TPR REPEAT CONTAINING PROTEIN; 1. DR Pfam; PF17830; STI1; 1. DR Pfam; PF00515; TPR_1; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 9. DR SUPFAM; SSF48452; TPR-like; 3. DR PROSITE; PS50005; TPR; 4. PE 4: Predicted; KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490}; KW Reference proteome {ECO:0000313|Proteomes:UP000009046}; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|ARBA:ARBA00022803, ECO:0000256|PROSITE- KW ProRule:PRU00339}. FT REPEAT 4..37 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 226..259 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 361..394 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT REPEAT 429..462 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 490..529 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 187..223 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 209..223 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 541 AA; 61972 MW; A7A46974FB4EF291 CRC64; MDQVQILKDK GNAALSANNS EEAIKWYTEA IALDPNNHVL YSNRSAAYAK SHKYDLALLD ANKTIELKPD WSKGYSRKGS ALAFLGRHRE SICAYEEGLK HEPDNIQLKQ GLNEAHIQLA YESRLAIAEL FKQLRSNQNT KNYVDDPEFL LFLEQYVDDP VKARANASNP RLQNFLRAIC DPNILEEPMD LDPPPQCTKP NNSSKTAEPT TKIDEDSNLS PEKREAIKEK MLGNEAYKKK DFETALKHYF RAVELDPTEI TYYNNVAAVY FELKEYEKCI KECEKGIEIG RENRADFKLI AKAFKRIGNS YKKLNDVRKA KIYYEKSMSE FRTPEIRTLL SDVEKIIKEE ERKAYIDPVK AEEEKEEGNK LFKKGDYAGA IKHYTEAIKR NPDDVKYYSN RAACYTKLAA FDLGLKDCKM CLELDPTFIK GWVRKGKILQ GMQQYGKAVE AYQKALDLDP NNAEALEGYR SCSVAFHSDP EEVRKRALAD PEVRKILFDP AMRLILDQMQ NDPKALNDHL KNPEIAAKIQ KLLESGLIAI H // ID Q1XBU6_HUMAN Unreviewed; 255 AA. AC Q1XBU6; DT 02-MAY-2006, integrated into UniProtKB/TrEMBL. DT 02-MAY-2006, sequence version 1. DT 14-DEC-2022, entry version 83. DE SubName: Full=Aging-associated protein 14b {ECO:0000313|EMBL:AAX18645.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:AAX18645.1}; RN [1] {ECO:0000313|EMBL:AAX18645.1} RP NUCLEOTIDE SEQUENCE. RA Kim J.W.; RT "Identification of a human aging-related gene."; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY826825; AAX18645.1; -; mRNA. DR AlphaFoldDB; Q1XBU6; -. DR SMR; Q1XBU6; -. DR PeptideAtlas; Q1XBU6; -. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF17830; STI1; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 1. PE 2: Evidence at transcript level; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 34..67 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 205..244 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 142..186 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 142..159 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 255 AA; 28367 MW; 476FE44C1FD4257B CRC64; MIKKVAAIEA LNDGELQKAI DLFTDAIKLN PRLAILYAKR ASVFVKLQKP NAAIRDCDRA IEINPDSAQP YKWRGKAHRL LGHWEEAAHD LALACKLDYD EDASAMLKEV QPRAQKIAEH RRKYERKREE REIKERIERV KKAREEHERA QREEEARRQS GAQYGSFPGG FPGGMPGNFP GGMPGMGGGM PGMAGMPGLN EILSDPEVLA AMQDPEVMVA FQDVAQNPAN MSKYQSNPKV MNLISKLSAK FGGQA // ID B7ZA40_HUMAN Unreviewed; 271 AA. AC B7ZA40; DT 03-MAR-2009, integrated into UniProtKB/TrEMBL. DT 03-MAR-2009, sequence version 1. DT 14-DEC-2022, entry version 67. DE SubName: Full=cDNA, FLJ79054, highly similar to Hsc70-interacting protein {ECO:0000313|EMBL:BAH14526.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000313|EMBL:BAH14526.1}; RN [1] {ECO:0000313|EMBL:BAH14526.1} RP NUCLEOTIDE SEQUENCE. RA Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A., RA Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y., RA Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T., RA Sugano S., Nomura N., Isogai T.; RT "NEDO human cDNA sequencing project."; RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK316155; BAH14526.1; -; mRNA. DR AlphaFoldDB; B7ZA40; -. DR PeptideAtlas; B7ZA40; -. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR041243; STI1/HOP_DP. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR Pfam; PF17830; STI1; 1. DR Pfam; PF13181; TPR_8; 1. DR SMART; SM00727; STI1; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50005; TPR; 1. PE 2: Evidence at transcript level; KW Repeat {ECO:0000256|ARBA:ARBA00022737}; KW TPR repeat {ECO:0000256|PROSITE-ProRule:PRU00339}. FT REPEAT 50..83 FT /note="TPR" FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00339" FT DOMAIN 221..260 FT /note="STI1" FT /evidence="ECO:0000259|SMART:SM00727" FT REGION 158..202 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 158..175 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 271 AA; 30147 MW; B077DB33B480299F CRC64; MGDENAEITE EMMDQANDKK VAAIEALNDG ELQKAIDLFT DAIKLNPRLA ILYAKRASVF VKLQKPNAAI RDCDRAIEIN PDSAQPYKWR GKAHRLLGHW EEAAHDLALA CKLDYDEDAS AMLKEVQPRA QKIAEHRRKY ERKREEREIK ERIERVKKAR EEHERAQREE EARRQSGAQY GSFPGGFPGG MPGNFPGGMP GMGGGMPGMA GMPGLNEILS DPEVLAAMQD PEVMVAFQDV AQNPANMSKY QSNPKVMNLI SKLSAKFGGQ A //