ID MED19_HUMAN Reviewed; 244 AA. AC A0JLT2; Q8IV02; Q8IZD1; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 2. DT 14-DEC-2022, entry version 128. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 19; DE AltName: Full=Lung cancer metastasis-related protein 1; DE AltName: Full=Mediator complex subunit 19; GN Name=MED19; Synonyms=LCMR1; 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 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 (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-205 (ISOFORM 1). RC TISSUE=Brain, and 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-244 (ISOFORM 1). RA Chen L.A., Tian Q., Liu Y.N., Fan B.X.; RT "Cloning of a metastasis-related gene cDNA from a human lung cancer cell RT line."; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP INTERACTION WITH MED10 AND MED31. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [6] 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, 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 [8] 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 [9] RP IDENTIFICATION BY 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194 AND SER-226, 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:15175163}. CC -!- INTERACTION: CC A0JLT2; Q9NX70: MED29; NbExp=8; IntAct=EBI-394430, EBI-394656; CC A0JLT2-2; Q86UW9: DTX2; NbExp=3; IntAct=EBI-13288755, EBI-740376; CC A0JLT2-2; P62993: GRB2; NbExp=3; IntAct=EBI-13288755, EBI-401755; CC A0JLT2-2; P50747: HLCS; NbExp=3; IntAct=EBI-13288755, EBI-3915568; CC A0JLT2-2; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-13288755, EBI-2556193; CC A0JLT2-2; Q92993: KAT5; NbExp=3; IntAct=EBI-13288755, EBI-399080; CC A0JLT2-2; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-13288755, EBI-11742507; CC A0JLT2-2; Q14511-2: NEDD9; NbExp=3; IntAct=EBI-13288755, EBI-11746523; CC A0JLT2-2; P17252: PRKCA; NbExp=3; IntAct=EBI-13288755, EBI-1383528; CC A0JLT2-2; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-13288755, EBI-10226430; CC A0JLT2-2; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-13288755, EBI-9090795; CC A0JLT2-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-13288755, EBI-372899; CC A0JLT2-2; P61981: YWHAG; NbExp=3; IntAct=EBI-13288755, EBI-359832; CC A0JLT2-2; P36508: ZNF76; NbExp=3; IntAct=EBI-13288755, EBI-7254550; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=A0JLT2-1; Sequence=Displayed; CC Name=2; CC IsoId=A0JLT2-2; Sequence=VSP_028121, VSP_028122; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 19 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAN16075.1; Type=Erroneous initiation; 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; CH471076; EAW73775.1; -; Genomic_DNA. DR EMBL; BC009723; AAH09723.1; -; mRNA. DR EMBL; BC037223; AAH37223.1; -; mRNA. DR EMBL; AY148462; AAN16075.1; ALT_INIT; mRNA. DR CCDS; CCDS7966.2; -. [A0JLT2-2] DR CCDS; CCDS86203.1; -. [A0JLT2-1] DR RefSeq; NP_001304007.1; NM_001317078.1. DR RefSeq; NP_703151.2; NM_153450.2. [A0JLT2-2] DR PDB; 7EMF; EM; 3.50 A; S=1-244. DR PDB; 7ENA; EM; 4.07 A; s=1-244. DR PDB; 7ENC; EM; 4.13 A; s=1-244. DR PDB; 7ENJ; EM; 4.40 A; S=1-244. DR PDB; 7LBM; EM; 4.80 A; w=1-244. DR PDB; 7NVR; EM; 4.50 A; m=1-244. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; A0JLT2; -. DR SMR; A0JLT2; -. DR BioGRID; 128553; 99. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; A0JLT2; -. DR DIP; DIP-31467N; -. DR IntAct; A0JLT2; 139. DR MINT; A0JLT2; -. DR STRING; 9606.ENSP00000337340; -. DR iPTMnet; A0JLT2; -. DR PhosphoSitePlus; A0JLT2; -. DR BioMuta; MED19; -. DR EPD; A0JLT2; -. DR jPOST; A0JLT2; -. DR MassIVE; A0JLT2; -. DR MaxQB; A0JLT2; -. DR PaxDb; A0JLT2; -. DR PeptideAtlas; A0JLT2; -. DR ProteomicsDB; 38; -. [A0JLT2-1] DR ProteomicsDB; 39; -. [A0JLT2-2] DR TopDownProteomics; A0JLT2-2; -. [A0JLT2-2] DR Antibodypedia; 43279; 160 antibodies from 20 providers. DR DNASU; 219541; -. DR Ensembl; ENST00000337672.9; ENSP00000337340.4; ENSG00000156603.20. [A0JLT2-2] DR Ensembl; ENST00000645681.2; ENSP00000493863.2; ENSG00000156603.20. [A0JLT2-2] DR GeneID; 219541; -. DR KEGG; hsa:219541; -. DR UCSC; uc001nlb.4; human. [A0JLT2-1] DR CTD; 219541; -. DR DisGeNET; 219541; -. DR GeneCards; MED19; -. DR HGNC; HGNC:29600; MED19. DR HPA; ENSG00000156603; Low tissue specificity. DR MIM; 612385; gene. DR neXtProt; NX_A0JLT2; -. DR OpenTargets; ENSG00000156603; -. DR PharmGKB; PA134926032; -. DR VEuPathDB; HostDB:ENSG00000156603; -. DR eggNOG; KOG4043; Eukaryota. DR GeneTree; ENSGT00390000001774; -. DR InParanoid; A0JLT2; -. DR OrthoDB; 1484317at2759; -. DR PhylomeDB; A0JLT2; -. DR TreeFam; TF317417; -. DR PathwayCommons; A0JLT2; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; A0JLT2; -. DR SIGNOR; A0JLT2; -. DR BioGRID-ORCS; 219541; 378 hits in 1110 CRISPR screens. DR ChiTaRS; MED19; human. DR GenomeRNAi; 219541; -. DR Pharos; A0JLT2; Tbio. DR PRO; PR:A0JLT2; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; A0JLT2; protein. DR Bgee; ENSG00000156603; Expressed in oocyte and 192 other tissues. DR ExpressionAtlas; A0JLT2; baseline and differential. DR Genevisible; A0JLT2; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR019403; Mediator_Med19_met. DR PANTHER; PTHR22536; LUNG CANCER METASTASIS-RELATED LCMR1 PROTEIN; 1. DR Pfam; PF10278; Med19; 1. DR AGR; HGNC:29600; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..244 FT /note="Mediator of RNA polymerase II transcription subunit FT 19" FT /id="PRO_0000304766" FT REGION 1..56 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 171..244 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 11..51 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 205..226 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 229..244 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 226 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT VAR_SEQ 191..194 FT /note="ETPS -> GKPS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028121" FT VAR_SEQ 195..244 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028122" FT CONFLICT 198 FT /note="H -> P (in Ref. 3; AAN16075)" FT /evidence="ECO:0000305" FT STRAND 79..81 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 83..86 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 90..96 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 112..116 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 117..119 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 128..138 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 147..152 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 244 AA; 26273 MW; 9B85721364F33F02 CRC64; MENFTALFGA QADPPPPPTA LGFGPGKPPP PPPPPAGGGP GTAPPPTAAT APPGADKSGA GCGPFYLMRE LPGSTELTGS TNLITHYNLE QAYNKFCGKK VKEKLSNFLP DLPGMIDLPG SHDNSSLRSL IEKPPILSSS FNPITGTMLA GFRLHTGPLP EQCRLMHIQP PKKKNKHKHK QSRTQDPVPP ETPSDSDHKK KKKKKEEDPD RKRKKKEKKK KKNRHSPDHP GMGSSQASSS SSLR // ID MED26_HUMAN Reviewed; 600 AA. AC O95402; A1A4S3; Q0VGB6; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 2. DT 14-DEC-2022, entry version 178. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 26; DE AltName: Full=Activator-recruited cofactor 70 kDa component; DE Short=ARC70; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 7; DE Short=CRSP complex subunit 7; DE AltName: Full=Mediator complex subunit 26; DE AltName: Full=Transcriptional coactivator CRSP70; GN Name=MED26; Synonyms=ARC70, CRSP7; 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=9989412; DOI=10.1038/17141; RA Ryu S., Zhou S., Ladurner A.G., Tjian R.; RT "The transcriptional cofactor complex CRSP is required for activity of the RT enhancer-binding protein Sp1."; RL Nature 397:446-450(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 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 [3] RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 294-305 AND 478-489. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [5] RP INTERACTION WITH MED1 AND MED10, IDENTIFICATION BY MASS SPECTROMETRY, RP IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR RP COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [6] RP INTERACTION WITH CEBPB. RX PubMed=20111005; DOI=10.1038/emboj.2010.3; RA Kowenz-Leutz E., Pless O., Dittmar G., Knoblich M., Leutz A.; RT "Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and RT SWI/SNF/Mediator implies an indexing transcription factor code."; RL EMBO J. 29:1105-1115(2010). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447; SER-470 AND SER-535, 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 [8] RP STRUCTURE BY NMR OF 1-92. RX PubMed=26861138; DOI=10.1007/s12104-016-9673-z; RA Peruzzini R., Lens Z., Verger A., Dewitte F., Ferreira E., Baert J.L., RA Villeret V., Landrieu I., Cantrelle F.X.; RT "1H, 15N and 13C assignments of the N-terminal domain of the Mediator RT complex subunit MED26."; RL Biomol. NMR. Assign. 10:233-236(2016). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional pre-initiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CEBPB (when CC not methylated)(PubMed:20111005). {ECO:0000269|PubMed:10235267, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:20111005}. CC -!- INTERACTION: CC O95402; Q96JC9: EAF1; NbExp=5; IntAct=EBI-394392, EBI-769261; CC O95402; Q9NPJ6: MED4; NbExp=11; IntAct=EBI-394392, EBI-394607; CC O95402; O43513: MED7; NbExp=8; IntAct=EBI-394392, EBI-394632; CC O95402; Q8C1S0: Med19; Xeno; NbExp=2; IntAct=EBI-394392, EBI-398761; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95402-1; Sequence=Displayed; CC Name=2; CC IsoId=O95402-2; Sequence=VSP_028151, VSP_028152; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 26 family. CC {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; AF104253; AAD12722.1; -; mRNA. DR EMBL; BC110430; AAI10431.1; -; mRNA. DR EMBL; BC127215; AAI27216.1; -; mRNA. DR CCDS; CCDS12347.1; -. [O95402-1] DR RefSeq; NP_004822.2; NM_004831.3. [O95402-1] DR PDB; 5ODD; NMR; -; A=1-92. DR PDB; 6ZV3; NMR; -; A=1-87. DR PDB; 7EMF; EM; 3.50 A; Z=1-600. DR PDB; 7ENA; EM; 4.07 A; z=1-600. DR PDB; 7ENC; EM; 4.13 A; z=1-600. DR PDB; 7ENJ; EM; 4.40 A; Z=1-600. DR PDBsum; 5ODD; -. DR PDBsum; 6ZV3; -. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR AlphaFoldDB; O95402; -. DR SMR; O95402; -. DR BioGRID; 114831; 106. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; O95402; -. DR DIP; DIP-31464N; -. DR IntAct; O95402; 97. DR MINT; O95402; -. DR STRING; 9606.ENSP00000263390; -. DR iPTMnet; O95402; -. DR PhosphoSitePlus; O95402; -. DR BioMuta; MED26; -. DR EPD; O95402; -. DR jPOST; O95402; -. DR MassIVE; O95402; -. DR MaxQB; O95402; -. DR PaxDb; O95402; -. DR PeptideAtlas; O95402; -. DR ProteomicsDB; 50854; -. [O95402-1] DR ProteomicsDB; 50855; -. [O95402-2] DR TopDownProteomics; O95402-1; -. [O95402-1] DR Antibodypedia; 14206; 291 antibodies from 32 providers. DR DNASU; 9441; -. DR Ensembl; ENST00000263390.8; ENSP00000263390.3; ENSG00000105085.11. [O95402-1] DR Ensembl; ENST00000611692.4; ENSP00000484490.1; ENSG00000105085.11. [O95402-2] DR GeneID; 9441; -. DR KEGG; hsa:9441; -. DR MANE-Select; ENST00000263390.8; ENSP00000263390.3; NM_004831.5; NP_004822.2. DR UCSC; uc002nen.2; human. [O95402-1] DR CTD; 9441; -. DR DisGeNET; 9441; -. DR GeneCards; MED26; -. DR HGNC; HGNC:2376; MED26. DR HPA; ENSG00000105085; Tissue enhanced (testis). DR MIM; 605043; gene. DR neXtProt; NX_O95402; -. DR OpenTargets; ENSG00000105085; -. DR PharmGKB; PA162395623; -. DR VEuPathDB; HostDB:ENSG00000105085; -. DR eggNOG; KOG1105; Eukaryota. DR GeneTree; ENSGT00390000000259; -. DR HOGENOM; CLU_478915_0_0_1; -. DR InParanoid; O95402; -. DR OMA; SHSNQIC; -. DR OrthoDB; 459216at2759; -. DR PhylomeDB; O95402; -. DR TreeFam; TF328436; -. DR PathwayCommons; O95402; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; O95402; -. DR SIGNOR; O95402; -. DR BioGRID-ORCS; 9441; 600 hits in 1074 CRISPR screens. DR ChiTaRS; MED26; human. DR GeneWiki; MED26; -. DR GenomeRNAi; 9441; -. DR Pharos; O95402; Tbio. DR PRO; PR:O95402; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O95402; protein. DR Bgee; ENSG00000105085; Expressed in sperm and 190 other tissues. DR ExpressionAtlas; O95402; baseline and differential. DR Genevisible; O95402; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; TAS:ProtInc. DR Gene3D; 1.20.930.10; -; 1. DR InterPro; IPR042376; MED26. DR InterPro; IPR031416; Med26_C. DR InterPro; IPR031417; Med26_Mid. DR InterPro; IPR003617; TFIIS/CRSP70_N_sub. DR InterPro; IPR035441; TFIIS/LEDGF_dom_sf. DR InterPro; IPR017923; TFIIS_N. DR PANTHER; PTHR15201; CRSP70; 1. DR Pfam; PF08711; Med26; 1. DR Pfam; PF15693; Med26_C; 1. DR Pfam; PF15694; Med26_M; 1. DR SMART; SM00509; TFS2N; 1. DR SUPFAM; SSF47676; Conserved domain common to transcription factors TFIIS, elongin A, CRSP70; 1. DR PROSITE; PS51319; TFIIS_N; 1. DR AGR; HGNC:2376; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Nucleus; Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..600 FT /note="Mediator of RNA polymerase II transcription subunit FT 26" FT /id="PRO_0000079360" FT DOMAIN 10..87 FT /note="TFIIS N-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00649" FT REGION 99..330 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 348..402 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 431..461 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 125..157 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 171..195 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 204..222 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 276..295 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 387..402 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 445..461 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 447 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 470 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 535 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 76..92 FT /note="LLRSWQKLIEPAHQHEA -> LPGWQWACRPRGQPPGA (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028151" FT VAR_SEQ 93..600 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028152" FT CONFLICT 156 FT /note="L -> F (in Ref. 1; AAD12722)" FT /evidence="ECO:0000305" FT CONFLICT 241 FT /note="P -> A (in Ref. 2; AAI27216)" FT /evidence="ECO:0000305" FT CONFLICT 369 FT /note="R -> L (in Ref. 2; AAI10431)" FT /evidence="ECO:0000305" FT HELIX 8..18 FT /evidence="ECO:0007829|PDB:5ODD" FT HELIX 28..40 FT /evidence="ECO:0007829|PDB:5ODD" FT HELIX 45..50 FT /evidence="ECO:0007829|PDB:5ODD" FT TURN 51..53 FT /evidence="ECO:0007829|PDB:5ODD" FT HELIX 54..63 FT /evidence="ECO:0007829|PDB:5ODD" FT HELIX 67..81 FT /evidence="ECO:0007829|PDB:5ODD" FT TURN 82..84 FT /evidence="ECO:0007829|PDB:5ODD" FT HELIX 485..499 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 539..542 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 550..556 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 561..564 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 580..582 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 585..588 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 591..593 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 600 AA; 65446 MW; 4BEA264A3EB5A407 CRC64; MTAAPASPQQ IRDRLLQAID PQSNIRNMVA VLEVISSLEK YPITKEALEE TRLGKLINDV RKKTKNEELA KRAKKLLRSW QKLIEPAHQH EAALRGLAGA TGSANGGAHN CRPEVGAAGP PRSIHDLKSR NDLQRLPGQR LDRLGSRKRR GDQRDLGHPG PPPKVSKASH DPLVPNSSPL PTNGISGSPE SFASSLDGSG HAGPEGSRLE RDENDKHSGK IPVNAVRPHT SSPGLGKPPG PCLQPKASVL QQLDRVDETP GPPHPKGPPR CSFSPRNSRH EGSFARQQSL YAPKGSVPSP SPRPQALDAT QVPSPLPLAQ PSTPPVRRLE LLPSAESPVC WLEQPESHQR LAGPGCKAGL SPAEPLLSRA GFSPDSSKAD SDAASSGGSD SKKKKRYRPR DYTVNLDGQV AEAGVKPVRL KERKLTFDPM TRQIKPLTQK EPVRADSPVH MEQQSRTELD KQEAKASLQS PFEQTNWKEL SRNEIIQSYL SRQSSLLSSS GAQTPGAHHF MSEYLKQEES TRQGARQLHV LVPQSPPTDL PGLTREVTQD DLDRIQASQW PGVNGCQDTQ GNWYDWTQCI SLDPHGDDGR LNILPYVCLD // ID MED29_HUMAN Reviewed; 200 AA. AC Q9NX70; B4DNQ6; M0R2E4; Q5XX09; Q9NTF4; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 14-DEC-2022, entry version 147. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 29; DE AltName: Full=Intersex-like protein; DE AltName: Full=Mediator complex subunit 29; GN Name=MED29; Synonyms=IXL; 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), FUNCTION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RC TISSUE=Embryonic heart; RX PubMed=15555573; DOI=10.1016/j.bbrc.2004.10.159; RA Wang Y., Li Y., Zeng W., Zhu C., Xiao J., Yuan W., Wang Y., Cai Z., RA Zhou J., Liu M., Wu X.; RT "IXL, a new subunit of the mammalian Mediator complex, functions as a RT transcriptional suppressor."; RL Biochem. Biophys. Res. Commun. 325:1330-1338(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, and 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 IDENTIFICATION IN THE TRAP/SMCC MEDIATOR COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND INTERACTION WITH MED18 AND MED20. RX PubMed=14576168; DOI=10.1074/jbc.c300444200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Parmely T.J., Sorokina I., RA Brower C.S., Conaway R.C., Conaway J.W.; RT "A mammalian homolog of Drosophila melanogaster transcriptional coactivator RT intersex is a subunit of the mammalian Mediator complex."; RL J. Biol. Chem. 278:49671-49674(2003). RN [7] RP IDENTIFICATION IN THE TRAP/SMCC MEDIATOR COMPLEX. RX PubMed=14638676; DOI=10.1074/jbc.m312523200; RA Tomomori-Sato C., Sato S., Parmely T.J., Banks C.A.S., Sorokina I., RA Florens L., Zybailov B., Washburn M.P., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "A mammalian mediator subunit that shares properties with Saccharomyces RT cerevisiae mediator subunit Cse2."; RL J. Biol. Chem. 279:5846-5851(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [9] RP INTERACTION WITH CCNC; MED1; MED12; MED13; MED17; MED20 AND MED21, RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [10] 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:15555573}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Associates with the CC MED18/MED20 heteromer. {ECO:0000269|PubMed:14576168, CC ECO:0000269|PubMed:14638676, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9NX70; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-394656, EBI-11096309; CC Q9NX70; Q9P2A4: ABI3; NbExp=3; IntAct=EBI-394656, EBI-742038; CC Q9NX70; O75934: BCAS2; NbExp=3; IntAct=EBI-394656, EBI-1050106; CC Q9NX70; Q14232: EIF2B1; NbExp=3; IntAct=EBI-394656, EBI-491065; CC Q9NX70; Q9BUE0: MED18; NbExp=6; IntAct=EBI-394656, EBI-394640; CC Q9NX70; A0JLT2: MED19; NbExp=8; IntAct=EBI-394656, EBI-394430; CC Q9NX70; Q9H944: MED20; NbExp=6; IntAct=EBI-394656, EBI-394644; CC Q9NX70; Q15528: MED22; NbExp=4; IntAct=EBI-394656, EBI-394687; CC Q9NX70; Q9H204: MED28; NbExp=3; IntAct=EBI-394656, EBI-514199; CC Q9NX70; O75586: MED6; NbExp=3; IntAct=EBI-394656, EBI-394624; CC Q9NX70; Q9H7Z3: NRDE2; NbExp=3; IntAct=EBI-394656, EBI-1042642; CC Q9NX70; A1L4H1: SSC5D; NbExp=3; IntAct=EBI-394656, EBI-10172867; CC Q9NX70; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-394656, EBI-6260909; CC Q9NX70; Q9R0X0: Med20; Xeno; NbExp=2; IntAct=EBI-394656, EBI-398698; CC Q9NX70; Q9CQI9: Med30; Xeno; NbExp=2; IntAct=EBI-394656, EBI-309220; CC Q9NX70; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-394656, EBI-7990252; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15555573}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NX70-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NX70-2; Sequence=VSP_056133, VSP_056134; CC -!- TISSUE SPECIFICITY: Widely expressed in embryo and adult. CC {ECO:0000269|PubMed:15555573}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 29 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAU43732.1; Type=Erroneous initiation; 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; AY729650; AAU43732.1; ALT_INIT; mRNA. DR EMBL; AK000411; BAA91147.1; -; mRNA. DR EMBL; AK298014; BAG60318.1; -; mRNA. DR EMBL; AL137304; CAB70687.2; -; mRNA. DR EMBL; AC005239; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011500; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104106; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC019015; AAH19015.1; -; mRNA. DR CCDS; CCDS33021.1; -. [Q9NX70-1] DR PIR; T46497; T46497. DR RefSeq; NP_001304699.1; NM_001317770.1. [Q9NX70-2] DR RefSeq; NP_060062.1; NM_017592.2. [Q9NX70-1] DR PDB; 7EMF; EM; 3.50 A; 2=1-200. DR PDB; 7ENA; EM; 4.07 A; b=1-200. DR PDB; 7ENC; EM; 4.13 A; b=1-200. DR PDB; 7ENJ; EM; 4.40 A; 2=1-200. DR PDB; 7LBM; EM; 4.80 A; p=1-200. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR AlphaFoldDB; Q9NX70; -. DR SMR; Q9NX70; -. DR BioGRID; 120734; 105. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9NX70; -. DR IntAct; Q9NX70; 104. DR MINT; Q9NX70; -. DR STRING; 9606.ENSP00000314343; -. DR GlyGen; Q9NX70; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NX70; -. DR PhosphoSitePlus; Q9NX70; -. DR BioMuta; MED29; -. DR DMDM; 74734688; -. DR EPD; Q9NX70; -. DR jPOST; Q9NX70; -. DR MassIVE; Q9NX70; -. DR MaxQB; Q9NX70; -. DR PaxDb; Q9NX70; -. DR PeptideAtlas; Q9NX70; -. DR ProteomicsDB; 83050; -. [Q9NX70-1] DR Antibodypedia; 30311; 62 antibodies from 18 providers. DR DNASU; 55588; -. DR Ensembl; ENST00000315588.11; ENSP00000314343.5; ENSG00000063322.15. [Q9NX70-1] DR Ensembl; ENST00000594368.5; ENSP00000472501.2; ENSG00000063322.15. [Q9NX70-2] DR GeneID; 55588; -. DR KEGG; hsa:55588; -. DR MANE-Select; ENST00000315588.11; ENSP00000314343.5; NM_017592.4; NP_060062.2. DR UCSC; uc060ykk.1; human. [Q9NX70-1] DR CTD; 55588; -. DR DisGeNET; 55588; -. DR GeneCards; MED29; -. DR HGNC; HGNC:23074; MED29. DR HPA; ENSG00000063322; Low tissue specificity. DR MIM; 612914; gene. DR neXtProt; NX_Q9NX70; -. DR OpenTargets; ENSG00000063322; -. DR PharmGKB; PA162395655; -. DR VEuPathDB; HostDB:ENSG00000063322; -. DR eggNOG; ENOG502QRNJ; Eukaryota. DR GeneTree; ENSGT00390000007540; -. DR HOGENOM; CLU_1312718_0_0_1; -. DR InParanoid; Q9NX70; -. DR OrthoDB; 1362864at2759; -. DR PhylomeDB; Q9NX70; -. DR TreeFam; TF326632; -. DR PathwayCommons; Q9NX70; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9NX70; -. DR SIGNOR; Q9NX70; -. DR BioGRID-ORCS; 55588; 414 hits in 1090 CRISPR screens. DR ChiTaRS; MED29; human. DR GenomeRNAi; 55588; -. DR Pharos; Q9NX70; Tbio. DR PRO; PR:Q9NX70; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9NX70; protein. DR Bgee; ENSG00000063322; Expressed in prefrontal cortex and 181 other tissues. DR ExpressionAtlas; Q9NX70; baseline and differential. DR Genevisible; Q9NX70; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR021018; Mediator_Med29_met. DR PANTHER; PTHR28314; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 29; 1. DR Pfam; PF11568; Med29; 1. DR AGR; HGNC:23074; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Nucleus; KW Reference proteome; Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..200 FT /note="Mediator of RNA polymerase II transcription subunit FT 29" FT /id="PRO_0000288058" FT REGION 1..48 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..26 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT VAR_SEQ 121..196 FT /note="RLAHECLSQSCDSAKHSPTLVPTATKPDAVQPDSLPYPQYLAVIKAQISCAK FT DIHTALLDCANKVTGKTPAPPAGP -> PPSPTQCSLTASPTHSTWRSSKPRFPVPRTF FT TPPCWTVPTRSRARHPHHLLALGALCEVGDREWGRQWLVGGVQRE (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056133" FT VAR_SEQ 197..200 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056134" FT HELIX 56..89 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 102..135 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 157..185 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 200 AA; 21073 MW; E0CDA1DDD89635CA CRC64; MAASQQQASA ASSAAGVSGP SSAGGPGPQQ QPQPPAQLVG PAQSGLLQQQ QQDFDPVQRY KMLIPQLKES LQTLMKVAAQ NLIQNTNIDN GQKSSDGPIQ RFDKCLEEFY ALCDQLELCL RLAHECLSQS CDSAKHSPTL VPTATKPDAV QPDSLPYPQY LAVIKAQISC AKDIHTALLD CANKVTGKTP APPAGPGGTL // ID MED31_HUMAN Reviewed; 131 AA. AC Q9Y3C7; B2R4L9; DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 14-DEC-2022, entry version 159. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 31; DE AltName: Full=Mediator complex subunit 31; DE AltName: Full=Mediator complex subunit SOH1; DE Short=hSOH1; GN Name=MED31; Synonyms=SOH1; ORFNames=CGI-125; 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]. RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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]. 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=Prostate; 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 IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [6] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH ESR1 AND ESR2. RX PubMed=11867769; DOI=10.1073/pnas.261715899; RA Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G.; RT "The TRAP/Mediator coactivator complex interacts directly with estrogen RT receptors alpha and beta through the TRAP220 subunit and directly enhances RT estrogen receptor function in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002). RN [8] RP INTERACTION WITH MED19. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [11] 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 [12] 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 [13] 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=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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:11867769, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9Y3C7; O95257: GADD45G; NbExp=2; IntAct=EBI-394707, EBI-448202; CC Q9Y3C7; P42858: HTT; NbExp=9; IntAct=EBI-394707, EBI-466029; CC Q9Y3C7; O43513: MED7; NbExp=3; IntAct=EBI-394707, EBI-394632; CC Q9Y3C7; Q96HR8: NAF1; NbExp=3; IntAct=EBI-394707, EBI-2515597; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 31 family. CC {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; AF151883; AAD34120.1; -; mRNA. DR EMBL; AK311875; BAG34816.1; -; mRNA. DR EMBL; CH471108; EAW90301.1; -; Genomic_DNA. DR EMBL; BC012539; AAH12539.1; -; mRNA. DR CCDS; CCDS11078.1; -. DR RefSeq; NP_057144.1; NM_016060.2. DR PDB; 7EMF; EM; 3.50 A; 4=1-131. DR PDB; 7ENA; EM; 4.07 A; m=1-131. DR PDB; 7ENC; EM; 4.13 A; m=1-131. DR PDB; 7ENJ; EM; 4.40 A; 4=1-131. DR PDB; 7LBM; EM; 4.80 A; y=1-131. DR PDB; 7NVR; EM; 4.50 A; o=1-131. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9Y3C7; -. DR SMR; Q9Y3C7; -. DR BioGRID; 119211; 120. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9Y3C7; -. DR IntAct; Q9Y3C7; 105. DR MINT; Q9Y3C7; -. DR STRING; 9606.ENSP00000225728; -. DR iPTMnet; Q9Y3C7; -. DR PhosphoSitePlus; Q9Y3C7; -. DR SwissPalm; Q9Y3C7; -. DR BioMuta; MED31; -. DR DMDM; 38258656; -. DR EPD; Q9Y3C7; -. DR jPOST; Q9Y3C7; -. DR MassIVE; Q9Y3C7; -. DR MaxQB; Q9Y3C7; -. DR PaxDb; Q9Y3C7; -. DR PeptideAtlas; Q9Y3C7; -. DR ProteomicsDB; 86016; -. DR Antibodypedia; 23820; 117 antibodies from 24 providers. DR DNASU; 51003; -. DR Ensembl; ENST00000225728.8; ENSP00000225728.3; ENSG00000108590.11. DR GeneID; 51003; -. DR KEGG; hsa:51003; -. DR MANE-Select; ENST00000225728.8; ENSP00000225728.3; NM_016060.3; NP_057144.1. DR UCSC; uc002gdg.5; human. DR CTD; 51003; -. DR DisGeNET; 51003; -. DR GeneCards; MED31; -. DR HGNC; HGNC:24260; MED31. DR HPA; ENSG00000108590; Low tissue specificity. DR neXtProt; NX_Q9Y3C7; -. DR OpenTargets; ENSG00000108590; -. DR PharmGKB; PA134884310; -. DR VEuPathDB; HostDB:ENSG00000108590; -. DR eggNOG; KOG4086; Eukaryota. DR GeneTree; ENSGT00390000015531; -. DR HOGENOM; CLU_071681_5_1_1; -. DR InParanoid; Q9Y3C7; -. DR OMA; QILLWQH; -. DR OrthoDB; 1480492at2759; -. DR PhylomeDB; Q9Y3C7; -. DR TreeFam; TF105799; -. DR PathwayCommons; Q9Y3C7; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9Y3C7; -. DR SIGNOR; Q9Y3C7; -. DR BioGRID-ORCS; 51003; 515 hits in 1087 CRISPR screens. DR ChiTaRS; MED31; human. DR GeneWiki; MED31; -. DR GenomeRNAi; 51003; -. DR Pharos; Q9Y3C7; Tbio. DR PRO; PR:Q9Y3C7; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9Y3C7; protein. DR Bgee; ENSG00000108590; Expressed in lower esophagus mucosa and 164 other tissues. DR ExpressionAtlas; Q9Y3C7; baseline and differential. DR Genevisible; Q9Y3C7; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0060173; P:limb development; IEA:Ensembl. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR Gene3D; 1.10.10.1340; -; 1. DR InterPro; IPR038089; Med31_sf. DR InterPro; IPR008831; Mediator_Med31. DR PANTHER; PTHR13186; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 31; 1. DR Pfam; PF05669; Med31; 1. DR AGR; HGNC:24260; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..131 FT /note="Mediator of RNA polymerase II transcription subunit FT 31" FT /id="PRO_0000212527" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT HELIX 11..28 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 31..39 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 46..54 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 55..59 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 61..64 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 72..79 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 83..86 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 91..105 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 107..121 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 131 AA; 15805 MW; 5DC672ADB994D015 CRC64; MAAAVAMETD DAGNRLRFQL ELEFVQCLAN PNYLNFLAQR GYFKDKAFVN YLKYLLYWKD PEYAKYLKYP QCLHMLELLQ YEHFRKELVN AQCAKFIDEQ QILHWQHYSR KRMRLQQALA EQQQQNNTSG K // ID MED10_HUMAN Reviewed; 135 AA. AC Q9BTT4; C6G491; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 14-DEC-2022, entry version 150. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 10; DE AltName: Full=Mediator complex subunit 10; DE AltName: Full=Transformation-related gene 17 protein; DE Short=TRG-17; DE AltName: Full=Transformation-related gene 20 protein; DE Short=TRG-20; GN Name=MED10; ORFNames=L6, TRG17, TRG20; 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=15334068; DOI=10.1038/sj.onc.1207921; RA Petroziello J., Yamane A., Westendorf L., Thompson M., McDonagh C., RA Cerveny C., Law C.-L., Wahl A., Carter P.; RT "Suppression subtractive hybridization and expression profiling identifies RT a unique set of genes overexpressed in non-small-cell lung cancer."; RL Oncogene 23:7734-7745(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kim J.W.; RT "Identification of a human transforming gene."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2008) 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [7] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [8] RP INTERACTION WITH MED6. RX PubMed=10993082; DOI=10.1038/35024111; RA Akoulitchev S., Chuikov S., Reinberg D.; RT "TFIIH is negatively regulated by cdk8-containing mediator complexes."; RL Nature 407:102-106(2000). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [10] RP INTERACTION WITH CCNC; MED1; MED6; MED12; MED13; MED14; MED15; MED16; RP MED17; MED18; MED19; MED20; MED23; MED24 AND MED26, IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF RP THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [11] 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: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9BTT4; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-394354, EBI-11096309; CC Q9BTT4; Q99819: ARHGDIG; NbExp=3; IntAct=EBI-394354, EBI-10295284; CC Q9BTT4; P04066: FUCA1; NbExp=3; IntAct=EBI-394354, EBI-2512153; CC Q9BTT4; O43513: MED7; NbExp=7; IntAct=EBI-394354, EBI-394632; CC Q9BTT4; Q9H8W5-2: TRIM45; NbExp=3; IntAct=EBI-394354, EBI-11993364; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 10 family. CC {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; AY598325; AAT06736.1; -; mRNA. DR EMBL; AY277599; AAQ18038.1; -; mRNA. DR EMBL; AY453397; AAS47514.1; -; mRNA. DR EMBL; FJ515848; ACS13739.1; -; Genomic_DNA. DR EMBL; CH471102; EAX08110.1; -; Genomic_DNA. DR EMBL; BC003353; AAH03353.1; -; mRNA. DR CCDS; CCDS34134.1; -. DR RefSeq; NP_115662.2; NM_032286.2. DR PDB; 7EMF; EM; 3.50 A; J=1-135. DR PDB; 7ENA; EM; 4.07 A; j=1-135. DR PDB; 7ENC; EM; 4.13 A; j=1-135. DR PDB; 7ENJ; EM; 4.40 A; J=1-135. DR PDB; 7LBM; EM; 4.80 A; v=1-135. DR PDB; 7NVR; EM; 4.50 A; k=1-135. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9BTT4; -. DR SMR; Q9BTT4; -. DR BioGRID; 123974; 103. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9BTT4; -. DR DIP; DIP-31457N; -. DR IntAct; Q9BTT4; 84. DR MINT; Q9BTT4; -. DR STRING; 9606.ENSP00000255764; -. DR iPTMnet; Q9BTT4; -. DR PhosphoSitePlus; Q9BTT4; -. DR BioMuta; MED10; -. DR DMDM; 74733145; -. DR EPD; Q9BTT4; -. DR jPOST; Q9BTT4; -. DR MassIVE; Q9BTT4; -. DR MaxQB; Q9BTT4; -. DR PaxDb; Q9BTT4; -. DR PeptideAtlas; Q9BTT4; -. DR ProteomicsDB; 79008; -. DR TopDownProteomics; Q9BTT4; -. DR Antibodypedia; 43141; 38 antibodies from 18 providers. DR DNASU; 84246; -. DR Ensembl; ENST00000255764.4; ENSP00000255764.3; ENSG00000133398.4. DR GeneID; 84246; -. DR KEGG; hsa:84246; -. DR MANE-Select; ENST00000255764.4; ENSP00000255764.3; NM_032286.3; NP_115662.2. DR UCSC; uc003jdo.4; human. DR CTD; 84246; -. DR GeneCards; MED10; -. DR HGNC; HGNC:28760; MED10. DR HPA; ENSG00000133398; Low tissue specificity. DR MIM; 612382; gene. DR neXtProt; NX_Q9BTT4; -. DR OpenTargets; ENSG00000133398; -. DR PharmGKB; PA144596412; -. DR VEuPathDB; HostDB:ENSG00000133398; -. DR eggNOG; KOG3046; Eukaryota. DR GeneTree; ENSGT00390000014501; -. DR HOGENOM; CLU_096169_3_0_1; -. DR InParanoid; Q9BTT4; -. DR OMA; QYQRAKM; -. DR OrthoDB; 1403581at2759; -. DR PhylomeDB; Q9BTT4; -. DR TreeFam; TF315096; -. DR PathwayCommons; Q9BTT4; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9BTT4; -. DR SIGNOR; Q9BTT4; -. DR BioGRID-ORCS; 84246; 482 hits in 1102 CRISPR screens. DR ChiTaRS; MED10; human. DR GenomeRNAi; 84246; -. DR Pharos; Q9BTT4; Tdark. DR PRO; PR:Q9BTT4; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9BTT4; protein. DR Bgee; ENSG00000133398; Expressed in monocyte and 170 other tissues. DR Genevisible; Q9BTT4; HS. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR019145; Mediator_Med10. DR Pfam; PF09748; Med10; 1. DR AGR; HGNC:28760; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..135 FT /note="Mediator of RNA polymerase II transcription subunit FT 10" FT /id="PRO_0000303151" FT HELIX 8..28 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 36..59 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 65..72 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 78..116 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 118..127 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 135 AA; 15688 MW; F804CD76770149E1 CRC64; MAEKFDHLEE HLEKFVENIR QLGIIVSDFQ PSSQAGLNQK LNFIVTGLQD IDKCRQQLHD ITVPLEVFEY IDQGRNPQLY TKECLERALA KNEQVKGKID TMKKFKSLLI QELSKVFPED MAKYRSIRGE DHPPS // ID MED18_HUMAN Reviewed; 208 AA. AC Q9BUE0; D3DPM1; Q9NXU9; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 14-DEC-2022, entry version 156. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 18; DE AltName: Full=Mediator complex subunit 18; DE AltName: Full=p28b; GN Name=MED18; 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]. RC TISSUE=Lymphoma; RA Furumoto T., Malik S., Hayashi K., Tanaka A., Ito M., Roeder R.G., RA Hanaoka F., Ohkuma Y.; RT "Physical and functional connections between human Mediator complex and RT general transcription machinery."; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; 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=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP INTERACTION WITH MED10 AND MED20. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [8] RP INTERACTION WITH CCNC; MED1; MED12; MED13; MED17; MED20 AND MED21, RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66, AND IDENTIFICATION BY RP 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9BUE0; Q63HM1: AFMID; NbExp=3; IntAct=EBI-394640, EBI-13286382; CC Q9BUE0; Q13554: CAMK2B; NbExp=3; IntAct=EBI-394640, EBI-1058722; CC Q9BUE0; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-394640, EBI-10172004; CC Q9BUE0; Q9NVC6: MED17; NbExp=3; IntAct=EBI-394640, EBI-394562; CC Q9BUE0; Q9H944: MED20; NbExp=21; IntAct=EBI-394640, EBI-394644; CC Q9BUE0; Q15528: MED22; NbExp=3; IntAct=EBI-394640, EBI-394687; CC Q9BUE0; Q9NX70: MED29; NbExp=6; IntAct=EBI-394640, EBI-394656; CC Q9BUE0; O75586: MED6; NbExp=3; IntAct=EBI-394640, EBI-394624; CC Q9BUE0; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-394640, EBI-11139477; CC Q9BUE0; Q9HCM9: TRIM39; NbExp=3; IntAct=EBI-394640, EBI-739510; CC Q9BUE0; Q9HCM9-2: TRIM39; NbExp=3; IntAct=EBI-394640, EBI-11523450; CC Q9BUE0; Q9R0X0: Med20; Xeno; NbExp=6; IntAct=EBI-394640, EBI-398698; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 18 family. CC {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; AB107222; BAD06869.1; -; mRNA. DR EMBL; AK000052; BAA90910.1; -; mRNA. DR EMBL; AL353622; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07699.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07700.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07702.1; -; Genomic_DNA. DR EMBL; BC002694; AAH02694.1; -; mRNA. DR CCDS; CCDS322.1; -. DR RefSeq; NP_001120822.1; NM_001127350.1. DR RefSeq; NP_060108.2; NM_017638.2. DR RefSeq; XP_005245971.1; XM_005245914.4. DR PDB; 7EMF; EM; 3.50 A; R=1-208. DR PDB; 7ENA; EM; 4.07 A; r=1-208. DR PDB; 7ENC; EM; 4.13 A; r=1-208. DR PDB; 7ENJ; EM; 4.40 A; R=1-208. DR PDB; 7LBM; EM; 4.80 A; k=1-208. DR PDB; 7NVR; EM; 4.50 A; e=1-208. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9BUE0; -. DR SMR; Q9BUE0; -. DR BioGRID; 120156; 75. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9BUE0; -. DR IntAct; Q9BUE0; 65. DR MINT; Q9BUE0; -. DR STRING; 9606.ENSP00000362948; -. DR iPTMnet; Q9BUE0; -. DR MetOSite; Q9BUE0; -. DR PhosphoSitePlus; Q9BUE0; -. DR BioMuta; MED18; -. DR DMDM; 74752353; -. DR EPD; Q9BUE0; -. DR jPOST; Q9BUE0; -. DR MassIVE; Q9BUE0; -. DR MaxQB; Q9BUE0; -. DR PaxDb; Q9BUE0; -. DR PeptideAtlas; Q9BUE0; -. DR ProteomicsDB; 79079; -. DR Antibodypedia; 30928; 233 antibodies from 24 providers. DR DNASU; 54797; -. DR Ensembl; ENST00000373842.9; ENSP00000362948.4; ENSG00000130772.14. DR Ensembl; ENST00000398997.2; ENSP00000381963.2; ENSG00000130772.14. DR Ensembl; ENST00000645794.2; ENSP00000494184.1; ENSG00000284944.2. DR Ensembl; ENST00000647352.1; ENSP00000494048.1; ENSG00000284944.2. DR GeneID; 54797; -. DR KEGG; hsa:54797; -. DR MANE-Select; ENST00000373842.9; ENSP00000362948.4; NM_017638.3; NP_060108.2. DR UCSC; uc001bpt.5; human. DR CTD; 54797; -. DR DisGeNET; 54797; -. DR GeneCards; MED18; -. DR HGNC; HGNC:25944; MED18. DR HPA; ENSG00000130772; Low tissue specificity. DR MIM; 612384; gene. DR neXtProt; NX_Q9BUE0; -. DR OpenTargets; ENSG00000130772; -. DR PharmGKB; PA134884523; -. DR VEuPathDB; HostDB:ENSG00000130772; -. DR eggNOG; KOG3264; Eukaryota. DR GeneTree; ENSGT00390000003312; -. DR HOGENOM; CLU_084570_0_0_1; -. DR InParanoid; Q9BUE0; -. DR OMA; PTSPWHL; -. DR OrthoDB; 1140930at2759; -. DR PhylomeDB; Q9BUE0; -. DR TreeFam; TF313246; -. DR PathwayCommons; Q9BUE0; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9BUE0; -. DR SIGNOR; Q9BUE0; -. DR BioGRID-ORCS; 54797; 632 hits in 1095 CRISPR screens. DR GenomeRNAi; 54797; -. DR Pharos; Q9BUE0; Tbio. DR PRO; PR:Q9BUE0; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9BUE0; protein. DR Bgee; ENSG00000130772; Expressed in mucosa of transverse colon and 107 other tissues. DR Genevisible; Q9BUE0; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0006369; P:termination of RNA polymerase II transcription; IBA:GO_Central. DR InterPro; IPR019095; Mediator_Med18. DR PANTHER; PTHR13321; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION, SUBUNIT 18; 1. DR Pfam; PF09637; Med18; 1. DR AGR; HGNC:25944; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..208 FT /note="Mediator of RNA polymerase II transcription subunit FT 18" FT /id="PRO_0000304742" FT MOD_RES 66 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CONFLICT 148 FT /note="I -> T (in Ref. 2; BAA90910)" FT /evidence="ECO:0000305" FT STRAND 18..27 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 29..42 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 51..60 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 63..66 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 68..78 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 83..88 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 94..110 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 114..121 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 124..138 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 141..151 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 157..163 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 165..178 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 183..191 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 192..196 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 208 AA; 23663 MW; AE68984390532C33 CRC64; MEAPPVTMMP VTGGTINMME YLLQGSVLDH SLESLIHRLR GLCDNMEPET FLDHEMVFLL KGQQASPFVL RARRSMDRAG APWHLRYLGQ PEMGDKNRHA LVRNCVDIAT SENLTDFLME MGFRMDHEFV AKGHLFRKGI MKIMVYKIFR ILVPGNTDST EALSLSYLVE LSVVAPAGQD MVSDDMKNFA EQLKPLVHLE KIDPKRLM // ID MED14_HUMAN Reviewed; 1454 AA. AC O60244; Q4KMR7; Q9UNB3; DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 2. DT 14-DEC-2022, entry version 185. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 14; DE AltName: Full=Activator-recruited cofactor 150 kDa component; DE Short=ARC150; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 2; DE Short=CRSP complex subunit 2; DE AltName: Full=Mediator complex subunit 14; DE AltName: Full=RGR1 homolog; DE Short=hRGR1; DE AltName: Full=Thyroid hormone receptor-associated protein complex 170 kDa component; DE Short=Trap170; DE AltName: Full=Transcriptional coactivator CRSP150; DE AltName: Full=Vitamin D3 receptor-interacting protein complex 150 kDa component; DE Short=DRIP150; GN Name=MED14; GN Synonyms=ARC150, CRSP2, CXorf4, DRIP150, EXLM1, RGR1, TRAP170; 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 [GENOMIC DNA / MRNA]. RX PubMed=9598311; DOI=10.1006/geno.1998.5246; RA Yoshikawa H., Fujiyama A., Nakai K., Inazawa J., Matsubara K.; RT "Detection and isolation of a novel human gene located on Xp11.2-p11.4 that RT escapes X-inactivation using a two-dimensional DNA mapping method."; RL Genomics 49:237-246(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9989412; DOI=10.1038/17141; RA Ryu S., Zhou S., Ladurner A.G., Tjian R.; RT "The transcriptional cofactor complex CRSP is required for activity of the RT enhancer-binding protein Sp1."; RL Nature 397:446-450(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 250-263 AND 1106-1146, AND RP IDENTIFICATION IN ARC COMPLEX. RC TISSUE=Cervix carcinoma; RX PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors requires RT the DRIP complex."; RL Nature 398:824-828(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, AND RP IDENTIFICATION IN THE SMCC COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [5] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A FORM OF THE RP MEDIATOR COMPLEX. RX PubMed=9734358; DOI=10.1016/s1097-2765(00)80131-8; RA Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D.; RT "NAT, a human complex containing Srb polypeptides that functions as a RT negative regulator of activated transcription."; RL Mol. Cell 2:213-222(1998). RN [8] RP PROTEIN SEQUENCE OF 4-13 AND 1256-1264, AND IDENTIFICATION IN ARC COMPLEX. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [9] RP INTERACTION WITH AR. RX PubMed=12218053; DOI=10.1074/jbc.m206061200; RA Wang Q., Sharma D., Ren Y., Fondell J.D.; RT "A coregulatory role for the TRAP-mediator complex in androgen receptor- RT mediated gene expression."; RL J. Biol. Chem. 277:42852-42858(2002). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH ESR1 AND ESR2. RX PubMed=11867769; DOI=10.1073/pnas.261715899; RA Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G.; RT "The TRAP/Mediator coactivator complex interacts directly with estrogen RT receptors alpha and beta through the TRAP220 subunit and directly enhances RT estrogen receptor function in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002). RN [11] RP INTERACTION WITH STAT2. RX PubMed=12509459; DOI=10.1128/mcb.23.2.620-628.2003; RA Lau J.F., Nusinzon I., Burakov D., Freedman L.P., Horvath C.M.; RT "Role of metazoan mediator proteins in interferon-responsive RT transcription."; RL Mol. Cell. Biol. 23:620-628(2003). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [13] RP FUNCTION, AND INTERACTION WITH SREBF1. RX PubMed=15340088; DOI=10.1128/mcb.24.18.8288-8300.2004; RA Toth J.I., Datta S., Athanikar J.N., Freedman L.P., Osborne T.F.; RT "Selective coactivator interactions in gene activation by SREBP-1a and RT -1c."; RL Mol. Cell. Biol. 24:8288-8300(2004). RN [14] RP FUNCTION, AND INTERACTION WITH ESR1. RX PubMed=15625066; DOI=10.1074/jbc.m413184200; RA Lee J.E., Kim K., Sacchettini J.C., Smith C.V., Safe S.; RT "DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer RT cells is independent of LXXLL motifs."; RL J. Biol. Chem. 280:8819-8830(2005). RN [15] RP INTERACTION WITH MED1 AND MED10, IDENTIFICATION BY MASS SPECTROMETRY, RP IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR RP COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [16] RP FUNCTION, AND INTERACTION WITH MED1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617, 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1128; SER-1136 AND SER-1144, 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-617 AND SER-986, AND RP IDENTIFICATION BY 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1112; SER-1128 AND SER-1136, 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1112; SER-1119; SER-1128 AND RP SER-1136, 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 [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-617; SER-1112; SER-1119; RP SER-1128; SER-1136 AND SER-1144, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 VARIANT [LARGE SCALE ANALYSIS] LEU-1325. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:15340088, CC ECO:0000269|PubMed:15625066, ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Interacts with GATA1 (By similarity). Component of the CC Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, CC MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, CC MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, CC MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CC CCNC and CDK8 subunits form a distinct module termed the CDK8 module. CC Mediator containing the CDK8 module is less active than Mediator CC lacking this module in supporting transcriptional activation. CC Individual preparations of the Mediator complex lacking one or more CC distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC CC and TRAP. Interacts with AR, ESR1, SREBF1 and STAT2. {ECO:0000250, CC ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:10235266, CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:11867769, CC ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:12509459, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15340088, CC ECO:0000269|PubMed:15625066, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:9734358}. CC -!- INTERACTION: CC O60244; Q96RN5: MED15; NbExp=2; IntAct=EBI-394489, EBI-394506; CC O60244; Q9Y2X0: MED16; NbExp=2; IntAct=EBI-394489, EBI-394541; CC O60244; Q9ULK4: MED23; NbExp=4; IntAct=EBI-394489, EBI-311161; CC O60244; Q71SY5: MED25; NbExp=2; IntAct=EBI-394489, EBI-394558; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 14 family. CC {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; AB006651; BAA28626.1; -; mRNA. DR EMBL; AB006652; BAA28627.1; -; Genomic_DNA. DR EMBL; AF104256; AAD12725.1; -; mRNA. DR EMBL; AF304448; AAG22547.1; -; mRNA. DR EMBL; AF135802; AAD24360.1; -; mRNA. DR EMBL; BC098377; AAH98377.1; -; mRNA. DR EMBL; BC132672; AAI32673.1; -; mRNA. DR EMBL; BC132674; AAI32675.1; -; mRNA. DR CCDS; CCDS14254.1; -. DR RefSeq; NP_004220.2; NM_004229.3. DR PDB; 7EMF; EM; 3.50 A; N=1-1454. DR PDB; 7ENA; EM; 4.07 A; n=1-1454. DR PDB; 7ENC; EM; 4.13 A; n=1-1454. DR PDB; 7ENJ; EM; 4.40 A; N=1-1454. DR PDB; 7LBM; EM; 4.80 A; r=1-1454. DR PDB; 7NVR; EM; 4.50 A; l=1-1454. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; O60244; -. DR SMR; O60244; -. DR BioGRID; 114699; 170. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; O60244; -. DR DIP; DIP-31460N; -. DR IntAct; O60244; 64. DR MINT; O60244; -. DR STRING; 9606.ENSP00000323720; -. DR iPTMnet; O60244; -. DR MetOSite; O60244; -. DR PhosphoSitePlus; O60244; -. DR BioMuta; MED14; -. DR EPD; O60244; -. DR jPOST; O60244; -. DR MassIVE; O60244; -. DR MaxQB; O60244; -. DR PaxDb; O60244; -. DR PeptideAtlas; O60244; -. DR ProteomicsDB; 49278; -. DR Antibodypedia; 10773; 164 antibodies from 29 providers. DR DNASU; 9282; -. DR Ensembl; ENST00000324817.6; ENSP00000323720.1; ENSG00000180182.11. DR GeneID; 9282; -. DR KEGG; hsa:9282; -. DR MANE-Select; ENST00000324817.6; ENSP00000323720.1; NM_004229.4; NP_004220.2. DR UCSC; uc004dex.5; human. DR CTD; 9282; -. DR DisGeNET; 9282; -. DR GeneCards; MED14; -. DR HGNC; HGNC:2370; MED14. DR HPA; ENSG00000180182; Low tissue specificity. DR MIM; 300182; gene. DR neXtProt; NX_O60244; -. DR OpenTargets; ENSG00000180182; -. DR PharmGKB; PA26890; -. DR VEuPathDB; HostDB:ENSG00000180182; -. DR eggNOG; KOG1875; Eukaryota. DR GeneTree; ENSGT00390000001021; -. DR HOGENOM; CLU_001928_0_0_1; -. DR InParanoid; O60244; -. DR OMA; SPAGSFM; -. DR OrthoDB; 1215335at2759; -. DR PhylomeDB; O60244; -. DR TreeFam; TF314388; -. DR PathwayCommons; O60244; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; O60244; -. DR SIGNOR; O60244; -. DR BioGRID-ORCS; 9282; 372 hits in 727 CRISPR screens. DR ChiTaRS; MED14; human. DR GeneWiki; MED14; -. DR GenomeRNAi; 9282; -. DR Pharos; O60244; Tbio. DR PRO; PR:O60244; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O60244; protein. DR Bgee; ENSG00000180182; Expressed in secondary oocyte and 201 other tissues. DR ExpressionAtlas; O60244; baseline and differential. DR Genevisible; O60244; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0030374; F:nuclear receptor coactivator activity; NAS:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR InterPro; IPR013947; Mediator_Med14. DR PANTHER; PTHR12809; MEDIATOR COMPLEX SUBUNIT; 1. DR Pfam; PF08638; Med14; 1. DR AGR; HGNC:2370; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Direct protein sequencing; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation. FT CHAIN 1..1454 FT /note="Mediator of RNA polymerase II transcription subunit FT 14" FT /id="PRO_0000079357" FT REGION 1..34 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 188..566 FT /note="Interaction with STAT2" FT /evidence="ECO:0000269|PubMed:12509459" FT REGION 500..824 FT /note="Interaction with SREBF1" FT /evidence="ECO:0000269|PubMed:15340088" FT REGION 973..1167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 69..73 FT /note="LXXLL motif 1" FT MOTIF 1182..1186 FT /note="LXXLL motif 2" FT COMPBIAS 1011..1050 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1088..1115 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1135..1157 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 617 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163" FT MOD_RES 986 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 1112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1119 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1128 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1136 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1144 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VARIANT 1325 FT /note="F -> L (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036608" FT CONFLICT 309..310 FT /note="HS -> LT (in Ref. 4; AAD24360)" FT /evidence="ECO:0000305" FT CONFLICT 1265 FT /note="V -> L (in Ref. 1; BAA28626, 2; AAD12725 and 3; FT AAG22547)" FT /evidence="ECO:0000305" FT CONFLICT 1451 FT /note="G -> V (in Ref. 1; BAA28626, 2; AAD12725 and 3; FT AAG22547)" FT /evidence="ECO:0000305" FT HELIX 51..72 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 73..75 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 78..105 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 109..141 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 142..147 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 154..161 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 162..165 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 172..177 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 187..203 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 218..220 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 230..236 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 245..252 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 257..259 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 268..283 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 288..317 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 321..330 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 331..333 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 334..340 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 355..360 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 371..373 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 375..377 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 383..388 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 397..423 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 433..436 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 437..445 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 448..456 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 458..460 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 472..484 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 486..488 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 489..506 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 507..509 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 510..518 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 529..532 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 537..545 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 547..556 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 564..573 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 584..587 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 639..651 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 653..663 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 675..678 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 681..685 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 691..693 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 695..701 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 702..704 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 705..714 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 715..717 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 719..728 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 734..736 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 739..749 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 753..755 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 760..786 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 787..789 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 794..797 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 798..803 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 808..812 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 813..816 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 818..825 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 826..829 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 830..837 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 839..842 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 852..861 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 865..882 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 904..908 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 913..918 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 919..921 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 922..929 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 930..932 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 933..936 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 939..941 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 959..966 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 1180..1186 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 1206..1225 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1240..1242 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1245..1247 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1249..1253 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1255..1259 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1261..1264 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 1277..1288 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 1296..1305 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 1312..1324 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1342..1344 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 1358..1360 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 1454 AA; 160607 MW; 144308E3F08D3D9B CRC64; MAPVQLENHQ LVPPGGGGGG SGGPPSAPAP PPPGAAVAAA AAAAASPGYR LSTLIEFLLH RAYSELMVLT DLLPRKSDVE RKIEIVQFAS RTRQLFVRLL ALVKWANNAG KVEKCAMISS FLDQQAILFV DTADRLASLA RDALVHARLP SFAIPYAIDV LTTGSYPRLP TCIRDKIIPP DPITKIEKQA TLHQLNQILR HRLVTTDLPP QLANLTVANG RVKFRVEGEF EATLTVMGDD PDVPWRLLKL EILVEDKETG DGRALVHSMQ ISFIHQLVQS RLFADEKPLQ DMYNCLHSFC LSLQLEVLHS QTLMLIRERW GDLVQVERYH AGKCLSLSVW NQQVLGRKTG TASVHKVTIK IDENDVSKPL QIFHDPPLPA SDSKLVERAM KIDHLSIEKL LIDSVHARAH QKLQELKAIL RGFNANENSS IETALPALVV PILEPCGNSE CLHIFVDLHS GMFQLMLYGL DQATLDDMEK SVNDDMKRII PWIQQLKFWL GQQRCKQSIK HLPTISSETL QLSNYSTHPI GNLSKNKLFI KLTRLPQYYI VVEMLEVPNK PTQLSYKYYF MSVNAADRED SPAMALLLQQ FKENIQDLVF RTKTGKQTRT NAKRKLSDDP CPVESKKTKR AGEMCAFNKV LAHFVAMCDT NMPFVGLRLE LSNLEIPHQG VQVEGDGFSH AIRLLKIPPC KGITEETQKA LDRSLLDCTF RLQGRNNRTW VAELVFANCP LNGTSTREQG PSRHVYLTYE NLLSEPVGGR KVVEMFLNDW NSIARLYECV LEFARSLPDI PAHLNIFSEV RVYNYRKLIL CYGTTKGSSI SIQWNSIHQK FHISLGTVGP NSGCSNCHNT ILHQLQEMFN KTPNVVQLLQ VLFDTQAPLN AINKLPTVPM LGLTQRTNTA YQCFSILPQS STHIRLAFRN MYCIDIYCRS RGVVAIRDGA YSLFDNSKLV EGFYPAPGLK TFLNMFVDSN QDARRRSVNE DDNPPSPIGG DMMDSLISQL QPPPQQQPFP KQPGTSGAYP LTSPPTSYHS TVNQSPSMMH TQSPGNLHAA SSPSGALRAP SPASFVPTPP PSSHGISIGP GASFASPHGT LDPSSPYTMV SPSGRAGNWP GSPQVSGPSP AARMPGMSPA NPSLHSPVPD ASHSPRAGTS SQTMPTNMPP PRKLPQRSWA ASIPTILTHS ALNILLLPSP TPGLVPGLAG SYLCSPLERF LGSVIMRRHL QRIIQQETLQ LINSNEPGVI MFKTDALKCR VALSPKTNQT LQLKVTPENA GQWKPDELQV LEKFFETRVA GPPFKANTLI AFTKLLGAPT HILRDCVHIM KLELFPDQAT QLKWNVQFCL TIPPSAPPIA PPGTPAVVLK SKMLFFLQLT QKTSVPPQEP VSIIVPIIYD MASGTTQQAD IPRQQNSSVA APMMVSNILK RFAEMNPPRQ GECTIFAAVR DLMANLTLPP GGRP // ID MED7_HUMAN Reviewed; 233 AA. AC O43513; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 14-DEC-2022, entry version 186. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 7; DE Short=hMED7; DE AltName: Full=Activator-recruited cofactor 34 kDa component; DE Short=ARC34; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 9; DE Short=CRSP complex subunit 9; DE AltName: Full=Mediator complex subunit 7; DE AltName: Full=RNA polymerase transcriptional regulation mediator subunit 7 homolog; DE AltName: Full=Transcriptional coactivator CRSP33; GN Name=MED7; Synonyms=ARC34, CRSP9; 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=9671713; DOI=10.1073/pnas.95.15.8538; RA Jiang Y.W., Veschambre P., Erdjument-Bromage H., Tempst P., Conaway J.W., RA Conaway R.C., Kornberg R.D.; RT "Mammalian mediator of transcriptional regulation and its possible role as RT an end-point of signal transduction pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8538-8543(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9989412; DOI=10.1038/17141; RA Ryu S., Zhou S., Ladurner A.G., Tjian R.; RT "The transcriptional cofactor complex CRSP is required for activity of the RT enhancer-binding protein Sp1."; RL Nature 397:446-450(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=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 [4] RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 19-29 AND 212-222. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [7] 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, 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 [9] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, 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 [10] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, 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 [11] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, 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 [12] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [13] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, AND IDENTIFICATION BY MASS RP 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC O43513; Q9Y376: CAB39; NbExp=3; IntAct=EBI-394632, EBI-306905; CC O43513; A0A0S2Z4Q4: HGS; NbExp=3; IntAct=EBI-394632, EBI-16429135; CC O43513; O14964: HGS; NbExp=4; IntAct=EBI-394632, EBI-740220; CC O43513; Q15648: MED1; NbExp=6; IntAct=EBI-394632, EBI-394459; CC O43513; Q9BTT4: MED10; NbExp=7; IntAct=EBI-394632, EBI-394354; CC O43513; Q13503: MED21; NbExp=3; IntAct=EBI-394632, EBI-394678; CC O43513; O95402: MED26; NbExp=8; IntAct=EBI-394632, EBI-394392; CC O43513; Q9Y3C7: MED31; NbExp=3; IntAct=EBI-394632, EBI-394707; CC O43513; P03383: env; Xeno; NbExp=3; IntAct=EBI-394632, EBI-9676086; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- PTM: Constitutively sumoylated. {ECO:0000269|PubMed:17709345}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 7 family. CC {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; AF031383; AAC52115.1; -; mRNA. DR EMBL; AF104251; AAD12720.1; -; mRNA. DR EMBL; BC005250; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS4334.1; -. DR RefSeq; NP_001094286.1; NM_001100816.1. DR RefSeq; NP_004261.1; NM_004270.4. DR PDB; 7EMF; EM; 3.50 A; G=1-233. DR PDB; 7ENA; EM; 4.07 A; g=1-233. DR PDB; 7ENC; EM; 4.13 A; g=1-233. DR PDB; 7ENJ; EM; 4.40 A; G=1-233. DR PDB; 7LBM; EM; 4.80 A; t=1-233. DR PDB; 7NVR; EM; 4.50 A; i=1-233. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; O43513; -. DR SMR; O43513; -. DR BioGRID; 114833; 93. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; O43513; -. DR IntAct; O43513; 65. DR MINT; O43513; -. DR STRING; 9606.ENSP00000286317; -. DR iPTMnet; O43513; -. DR PhosphoSitePlus; O43513; -. DR BioMuta; MED7; -. DR EPD; O43513; -. DR jPOST; O43513; -. DR MassIVE; O43513; -. DR PaxDb; O43513; -. DR PeptideAtlas; O43513; -. DR ProteomicsDB; 49002; -. DR Antibodypedia; 16528; 249 antibodies from 25 providers. DR DNASU; 9443; -. DR Ensembl; ENST00000286317.6; ENSP00000286317.5; ENSG00000155868.8. DR Ensembl; ENST00000420343.1; ENSP00000401046.1; ENSG00000155868.8. DR GeneID; 9443; -. DR KEGG; hsa:9443; -. DR MANE-Select; ENST00000286317.6; ENSP00000286317.5; NM_004270.5; NP_004261.1. DR CTD; 9443; -. DR DisGeNET; 9443; -. DR GeneCards; MED7; -. DR HGNC; HGNC:2378; MED7. DR HPA; ENSG00000155868; Low tissue specificity. DR MIM; 605045; gene. DR neXtProt; NX_O43513; -. DR OpenTargets; ENSG00000155868; -. DR PharmGKB; PA162395669; -. DR VEuPathDB; HostDB:ENSG00000155868; -. DR eggNOG; KOG0570; Eukaryota. DR GeneTree; ENSGT00940000154444; -. DR InParanoid; O43513; -. DR OMA; PQHFDRR; -. DR OrthoDB; 1356482at2759; -. DR PhylomeDB; O43513; -. DR TreeFam; TF314411; -. DR PathwayCommons; O43513; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; O43513; -. DR SIGNOR; O43513; -. DR BioGRID-ORCS; 9443; 640 hits in 1102 CRISPR screens. DR ChiTaRS; MED7; human. DR GeneWiki; MED7; -. DR GenomeRNAi; 9443; -. DR Pharos; O43513; Tbio. DR PRO; PR:O43513; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O43513; protein. DR Bgee; ENSG00000155868; Expressed in choroid plexus epithelium and 210 other tissues. DR ExpressionAtlas; O43513; baseline and differential. DR Genevisible; O43513; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; TAS:ProtInc. DR Gene3D; 6.10.140.200; -; 1. DR InterPro; IPR037212; Med7/Med21-like. DR InterPro; IPR009244; Mediatior_Med7. DR InterPro; IPR044888; Mediatior_Med7_sf. DR Pfam; PF05983; Med7; 1. DR SUPFAM; SSF140718; Mediator hinge subcomplex-like; 1. DR AGR; HGNC:2378; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Direct protein sequencing; Isopeptide bond; KW Nucleus; Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..233 FT /note="Mediator of RNA polymerase II transcription subunit FT 7" FT /id="PRO_0000079408" FT REGION 187..213 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT CROSSLNK 185 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 185 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:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 60..63 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 74..98 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 104..124 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 126..174 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 233 AA; 27245 MW; 9D95A2A8360B9C62 CRC64; MGEPQQVSAL PPPPMQYIKE YTDENIQEGL APKPPPPIKD SYMMFGNQFQ CDDLIIRPLE SQGIERLHPM QFDHKKELRK LNMSILINFL DLLDILIRSP GSIKREEKLE DLKLLFVHVH HLINEYRPHQ ARETLRVMME VQKRQRLETA ERFQKHLERV IEMIQNCLAS LPDDLPHSEA GMRVKTEPMD ADDSNNCTGQ NEHQRENSGH RRDQIIEKDA ALCVLIDEMN ERP // ID MED24_HUMAN Reviewed; 989 AA. AC O75448; A8K4S5; B3KMR9; Q14143; Q9NNY5; DT 24-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 14-DEC-2022, entry version 193. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 24; DE AltName: Full=Activator-recruited cofactor 100 kDa component; DE Short=ARC100; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 4; DE Short=CRSP complex subunit 4; DE AltName: Full=Mediator complex subunit 24; DE AltName: Full=Thyroid hormone receptor-associated protein 4; DE AltName: Full=Thyroid hormone receptor-associated protein complex 100 kDa component; DE Short=Trap100; DE Short=hTRAP100; DE AltName: Full=Vitamin D3 receptor-interacting protein complex 100 kDa component; DE Short=DRIP100; GN Name=MED24; GN Synonyms=ARC100, CRSP4, DRIP100, KIAA0130, THRAP4, TRAP100; 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), PROTEIN SEQUENCE OF 1-15, AND RP TISSUE SPECIFICITY. RX PubMed=9653119; DOI=10.1073/pnas.95.14.7939; RA Yuan C.-X., Ito M., Fondell J.D., Fu Z.-Y., Roeder R.G.; RT "The TRAP220 component of a thyroid hormone receptor-associated protein RT (TRAP) coactivator complex interacts directly with nuclear receptors in a RT ligand-dependent fashion."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7939-7944(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND IDENTIFICATION IN DRIP COMPLEX. RX PubMed=9637681; DOI=10.1101/gad.12.12.1787; RA Rachez C., Suldan Z., Ward J., Chang C.-P.B., Burakov D., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "A novel protein complex that interacts with the vitamin D3 receptor in a RT ligand-dependent manner and enhances VDR transactivation in a cell-free RT system."; RL Genes Dev. 12:1787-1800(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-204. RC TISSUE=Bone marrow; RX PubMed=8590280; DOI=10.1093/dnares/2.4.167; RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. IV. The RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 2:167-174(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; 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 PROTEIN SEQUENCE OF 1-11 AND 957-965, AND IDENTIFICATION IN ARC COMPLEX. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [8] RP PROTEIN SEQUENCE OF 467-489, AND IDENTIFICATION IN ARC COMPLEX. RC TISSUE=Cervix carcinoma; RX PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors requires RT the DRIP complex."; RL Nature 398:824-828(1999). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [10] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [11] RP FUNCTION, AND INTERACTION WITH AR. RX PubMed=12218053; DOI=10.1074/jbc.m206061200; RA Wang Q., Sharma D., Ren Y., Fondell J.D.; RT "A coregulatory role for the TRAP-mediator complex in androgen receptor- RT mediated gene expression."; RL J. Biol. Chem. 277:42852-42858(2002). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [13] RP INTERACTION WITH MED1; MED10; MED21 AND MED30, IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF RP THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [14] RP FUNCTION, AND INTERACTION WITH MED1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862 AND SER-873, 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 [17] 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 [18] RP IDENTIFICATION BY 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862 AND SER-873, 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862 AND SER-873, 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862, 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 [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862 AND SER-873, 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:12218053, CC ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with AR. CC {ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:10235266, CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:12218053, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:9637681}. CC -!- INTERACTION: CC O75448; Q9Y2X0: MED16; NbExp=2; IntAct=EBI-394523, EBI-394541; CC O75448; Q71SY5: MED25; NbExp=2; IntAct=EBI-394523, EBI-394558; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75448-1; Sequence=Displayed; CC Name=2; CC IsoId=O75448-2; Sequence=VSP_041125; CC -!- TISSUE SPECIFICITY: Ubiquitous. Abundant in skeletal muscle, heart and CC placenta. {ECO:0000269|PubMed:9653119}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 24 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA09479.2; Type=Erroneous initiation; 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; AF055995; AAC39855.1; -; mRNA. DR EMBL; AF277379; AAF78764.1; -; mRNA. DR EMBL; D50920; BAA09479.2; ALT_INIT; mRNA. DR EMBL; AK022508; BAG51081.1; -; mRNA. DR EMBL; AK291040; BAF83729.1; -; mRNA. DR EMBL; AC090844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC102799; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC011375; AAH11375.1; -; mRNA. DR CCDS; CCDS11359.1; -. [O75448-1] DR CCDS; CCDS42315.1; -. [O75448-2] DR RefSeq; NP_001072986.1; NM_001079518.1. [O75448-2] DR RefSeq; NP_001254726.1; NM_001267797.1. [O75448-2] DR RefSeq; NP_055630.2; NM_014815.3. [O75448-1] DR RefSeq; XP_016880955.1; XM_017025466.1. DR PDB; 7EMF; EM; 3.50 A; X=1-989. DR PDB; 7ENA; EM; 4.07 A; x=1-989. DR PDB; 7ENC; EM; 4.13 A; x=1-989. DR PDB; 7ENJ; EM; 4.40 A; X=1-989. DR PDB; 7LBM; EM; 4.80 A; 2=1-989. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR AlphaFoldDB; O75448; -. DR SMR; O75448; -. DR BioGRID; 115196; 123. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; O75448; -. DR DIP; DIP-31462N; -. DR IntAct; O75448; 55. DR MINT; O75448; -. DR STRING; 9606.ENSP00000377686; -. DR iPTMnet; O75448; -. DR PhosphoSitePlus; O75448; -. DR BioMuta; MED24; -. DR CPTAC; CPTAC-933; -. DR EPD; O75448; -. DR jPOST; O75448; -. DR MassIVE; O75448; -. DR MaxQB; O75448; -. DR PaxDb; O75448; -. DR PeptideAtlas; O75448; -. DR ProteomicsDB; 50015; -. [O75448-1] DR ProteomicsDB; 50016; -. [O75448-2] DR Antibodypedia; 28479; 152 antibodies from 23 providers. DR DNASU; 9862; -. DR Ensembl; ENST00000356271.7; ENSP00000348610.3; ENSG00000008838.21. [O75448-2] DR Ensembl; ENST00000394127.6; ENSP00000377685.2; ENSG00000008838.21. [O75448-2] DR Ensembl; ENST00000394128.7; ENSP00000377686.2; ENSG00000008838.21. [O75448-1] DR GeneID; 9862; -. DR KEGG; hsa:9862; -. DR MANE-Select; ENST00000394128.7; ENSP00000377686.2; NM_014815.4; NP_055630.2. DR UCSC; uc002htt.4; human. [O75448-1] DR CTD; 9862; -. DR DisGeNET; 9862; -. DR GeneCards; MED24; -. DR HGNC; HGNC:22963; MED24. DR HPA; ENSG00000008838; Low tissue specificity. DR MIM; 607000; gene. DR neXtProt; NX_O75448; -. DR OpenTargets; ENSG00000008838; -. DR PharmGKB; PA162395566; -. DR VEuPathDB; HostDB:ENSG00000008838; -. DR eggNOG; ENOG502QPJD; Eukaryota. DR GeneTree; ENSGT00390000016438; -. DR HOGENOM; CLU_007484_0_0_1; -. DR InParanoid; O75448; -. DR OMA; TWQDICL; -. DR PhylomeDB; O75448; -. DR TreeFam; TF323565; -. DR PathwayCommons; O75448; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; O75448; -. DR SIGNOR; O75448; -. DR BioGRID-ORCS; 9862; 238 hits in 1108 CRISPR screens. DR ChiTaRS; MED24; human. DR GeneWiki; MED24; -. DR GenomeRNAi; 9862; -. DR Pharos; O75448; Tbio. DR PRO; PR:O75448; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O75448; protein. DR Bgee; ENSG00000008838; Expressed in right hemisphere of cerebellum and 179 other tissues. DR ExpressionAtlas; O75448; baseline and differential. DR Genevisible; O75448; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0004402; F:histone acetyltransferase activity; IEA:Ensembl. DR GO; GO:0030374; F:nuclear receptor coactivator activity; NAS:UniProtKB. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR021429; Mediator_Med24. DR PANTHER; PTHR12898; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 24; 1. DR Pfam; PF11277; Med24_N; 1. DR AGR; HGNC:22963; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation. FT CHAIN 1..989 FT /note="Mediator of RNA polymerase II transcription subunit FT 24" FT /id="PRO_0000065582" FT MOTIF 128..132 FT /note="LXXLL motif 1" FT MOTIF 344..348 FT /note="LXXLL motif 2" FT MOTIF 448..452 FT /note="LXXLL motif 3" FT MOTIF 557..561 FT /note="LXXLL motif 4" FT MOTIF 788..792 FT /note="LXXLL motif 5" FT MOTIF 857..861 FT /note="LXXLL motif 6" FT MOD_RES 862 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 873 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 72..84 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041125" FT VARIANT 204 FT /note="A -> T (in dbSNP:rs34585432)" FT /evidence="ECO:0000269|PubMed:8590280" FT /id="VAR_053969" FT CONFLICT 20 FT /note="D -> Y (in Ref. 3; BAA09479)" FT /evidence="ECO:0000305" FT CONFLICT 476 FT /note="Missing (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 555 FT /note="E -> G (in Ref. 2; AAF78764)" FT /evidence="ECO:0000305" FT CONFLICT 710 FT /note="V -> E (in Ref. 4; BAG51081)" FT /evidence="ECO:0000305" FT CONFLICT 741 FT /note="V -> A (in Ref. 4; BAG51081)" FT /evidence="ECO:0000305" FT CONFLICT 969 FT /note="A -> P (in Ref. 4; BAG51081)" FT /evidence="ECO:0000305" FT HELIX 6..15 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 20..30 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 38..41 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 42..48 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 51..55 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 58..69 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 75..83 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 91..104 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 105..107 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 114..145 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 157..170 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 172..184 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 188..205 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 211..224 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 242..253 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 260..273 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 278..294 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 300..310 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 312..323 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 330..342 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 345..355 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 359..369 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 375..390 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 406..423 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 424..426 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 427..430 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 432..443 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 447..457 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 461..477 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 483..506 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 510..512 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 518..520 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 524..532 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 545..547 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 552..561 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 574..594 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 599..610 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 615..630 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 637..646 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 647..649 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 659..674 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 677..680 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 696..699 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 703..705 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 707..721 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 726..753 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 758..772 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 776..785 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 787..793 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 797..800 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 803..822 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 830..838 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 843..846 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 896..913 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 919..934 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 943..946 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 950..957 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 966..969 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 970..972 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 976..987 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 989 AA; 110305 MW; CCEDE7D4E74D890C CRC64; MKVVNLKQAI LQAWKERWSD YQWAINMKKF FPKGATWDIL NLADALLEQA MIGPSPNPLI LSYLKYAISS QMVSYSSVLT AISKFDDFSR DLCVQALLDI MDMFCDRLSC HGKAEECIGL CRALLSALHW LLRCTAASAE RLREGLEAGT PAAGEKQLAM CLQRLEKTLS STKNRALLHI AKLEEASSWT AIEHSLLKLG EILANLSNPQ LRSQAEQCGT LIRSIPTMLS VHAEQMHKTG FPTVHAVILL EGTMNLTGET QSLVEQLTMV KRMQHIPTPL FVLEIWKACF VGLIESPEGT EELKWTAFTF LKIPQVLVKL KKYSHGDKDF TEDVNCAFEF LLKLTPLLDK ADQRCNCDCT NFLLQECGKQ GLLSEASVNN LMAKRKADRE HAPQQKSGEN ANIQPNIQLI LRAEPTVTNI LKTMDADHSK SPEGLLGVLG HMLSGKSLDL LLAAAAATGK LKSFARKFIN LNEFTTYGSE ESTKPASVRA LLFDISFLML CHVAQTYGSE VILSESRTGA EVPFFETWMQ TCMPEEGKIL NPDHPCFRPD STKVESLVAL LNNSSEMKLV QMKWHEACLS ISAAILEILN AWENGVLAFE SIQKITDNIK GKVCSLAVCA VAWLVAHVRM LGLDEREKSL QMIRQLAGPL FSENTLQFYN ERVVIMNSIL ERMCADVLQQ TATQIKFPST GVDTMPYWNL LPPKRPIKEV LTDIFAKVLE KGWVDSRSIH IFDTLLHMGG VYWFCNNLIK ELLKETRKEH TLRAVELLYS IFCLDMQQVT LVLLGHILPG LLTDSSKWHS LMDPPGTALA KLAVWCALSS YSSHKGQAST RQKKRHREDI EDYISLFPLD DVQPSKLMRL LSSNEDDANI LSSPTDRSMS SSLSASQLHT VNMRDPLNRV LANLFLLISS ILGSRTAGPH TQFVQWFMEE CVDCLEQGGR GSVLQFMPFT TVSELVKVSA MSSPKVVLAI TDLSLPLGRQ VAAKAIAAL // ID MED11_HUMAN Reviewed; 117 AA. AC Q9P086; Q6NS89; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 2. DT 14-DEC-2022, entry version 143. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 11; DE AltName: Full=Mediator complex subunit 11; GN Name=MED11; ORFNames=HSPC296; 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=Umbilical cord blood; RA Ye M., Zhang Q.-H., Zhou J., Shen Y., Wu X.-Y., Guan Z.Q., Wang L., RA Fan H.-Y., Mao Y.-F., Dai M., Huang Q.-H., Chen S.-J., Chen Z.; RT "Human partial CDS from CD34+ stem cells."; RL Submitted (MAY-1999) 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 (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [4] RP INTERACTION WITH MED10 AND MED22. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [7] 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=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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9P086; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-394704, EBI-11096309; CC Q9P086; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-394704, EBI-744556; CC Q9P086; P23434: GCSH; NbExp=3; IntAct=EBI-394704, EBI-715444; CC Q9P086; Q15528: MED22; NbExp=3; IntAct=EBI-394704, EBI-394687; CC Q9P086; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-394704, EBI-928842; CC Q9P086; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-394704, EBI-744782; CC Q9P086; Q96ES7: SGF29; NbExp=3; IntAct=EBI-394704, EBI-743117; CC Q9P086; A1L4H1: SSC5D; NbExp=3; IntAct=EBI-394704, EBI-10172867; CC Q9P086; Q6PIF2: SYCE2; NbExp=3; IntAct=EBI-394704, EBI-11958386; CC Q9P086; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-394704, EBI-739895; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 11 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF28974.1; Type=Erroneous initiation; 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; AF161414; AAF28974.1; ALT_INIT; mRNA. DR EMBL; CH471108; EAW90417.1; -; Genomic_DNA. DR EMBL; BC070377; AAH70377.1; -; mRNA. DR CCDS; CCDS32533.1; -. DR RefSeq; NP_001001683.1; NM_001001683.3. DR RefSeq; NP_001291929.1; NM_001305000.1. DR PDB; 7EMF; EM; 3.50 A; K=1-117. DR PDB; 7ENA; EM; 4.07 A; k=1-117. DR PDB; 7ENC; EM; 4.13 A; k=1-117. DR PDB; 7ENJ; EM; 4.40 A; K=1-117. DR PDB; 7LBM; EM; 4.80 A; i=1-117. DR PDB; 7NVR; EM; 4.50 A; c=1-117. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9P086; -. DR SMR; Q9P086; -. DR BioGRID; 134637; 69. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9P086; -. DR IntAct; Q9P086; 39. DR MINT; Q9P086; -. DR STRING; 9606.ENSP00000293777; -. DR iPTMnet; Q9P086; -. DR PhosphoSitePlus; Q9P086; -. DR BioMuta; MED11; -. DR DMDM; 158564056; -. DR EPD; Q9P086; -. DR jPOST; Q9P086; -. DR MassIVE; Q9P086; -. DR MaxQB; Q9P086; -. DR PaxDb; Q9P086; -. DR PeptideAtlas; Q9P086; -. DR ProteomicsDB; 83546; -. DR TopDownProteomics; Q9P086; -. DR Antibodypedia; 58423; 32 antibodies from 14 providers. DR DNASU; 400569; -. DR Ensembl; ENST00000293777.6; ENSP00000293777.5; ENSG00000161920.11. DR GeneID; 400569; -. DR KEGG; hsa:400569; -. DR MANE-Select; ENST00000293777.6; ENSP00000293777.5; NM_001001683.4; NP_001001683.1. DR UCSC; uc002fyp.4; human. DR CTD; 400569; -. DR DisGeNET; 400569; -. DR GeneCards; MED11; -. DR HGNC; HGNC:32687; MED11. DR HPA; ENSG00000161920; Low tissue specificity. DR MIM; 612383; gene. DR neXtProt; NX_Q9P086; -. DR OpenTargets; ENSG00000161920; -. DR PharmGKB; PA144596413; -. DR VEuPathDB; HostDB:ENSG00000161920; -. DR eggNOG; KOG4057; Eukaryota. DR GeneTree; ENSGT00390000010184; -. DR HOGENOM; CLU_123010_2_0_1; -. DR InParanoid; Q9P086; -. DR OMA; IAMVLQC; -. DR OrthoDB; 1616309at2759; -. DR PhylomeDB; Q9P086; -. DR TreeFam; TF318328; -. DR PathwayCommons; Q9P086; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9P086; -. DR SIGNOR; Q9P086; -. DR BioGRID-ORCS; 400569; 808 hits in 1092 CRISPR screens. DR ChiTaRS; MED11; human. DR GenomeRNAi; 400569; -. DR Pharos; Q9P086; Tdark. DR PRO; PR:Q9P086; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9P086; protein. DR Bgee; ENSG00000161920; Expressed in right adrenal gland and 183 other tissues. DR ExpressionAtlas; Q9P086; baseline and differential. DR Genevisible; Q9P086; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR019404; Mediator_Med11. DR PANTHER; PTHR22890; UNCHARACTERIZED; 1. DR Pfam; PF10280; Med11; 1. DR AGR; HGNC:32687; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..117 FT /note="Mediator of RNA polymerase II transcription subunit FT 11" FT /id="PRO_0000304308" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT CONFLICT 112 FT /note="E -> G (in Ref. 1; AAF28974)" FT /evidence="ECO:0000305" FT HELIX 7..34 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 42..72 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 84..115 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 117 AA; 13129 MW; D01CAA8D211D6FC7 CRC64; MATYSLANER LRALEDIERE IGAILQNAGT VILELSKEKT NERLLDRQAA AFTASVQHVE AELSAQIRYL TQVATGQPHE GSSYSSRKDC QMALKRVDYA RLKLSDVART CEQMLEN // ID MD13L_HUMAN Reviewed; 2210 AA. AC Q71F56; A1L469; Q68DN4; Q9H8C0; Q9NSY9; Q9UFD8; Q9UPX5; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 14-DEC-2022, entry version 152. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 13-like; DE AltName: Full=Mediator complex subunit 13-like; DE AltName: Full=Thyroid hormone receptor-associated protein 2; DE AltName: Full=Thyroid hormone receptor-associated protein complex 240 kDa component-like; GN Name=MED13L; Synonyms=KIAA1025, PROSIT240, THRAP2, TRAP240L; 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], TISSUE SPECIFICITY, VARIANT MRFACD GLY-251, RP VARIANTS HIS-1872 AND GLY-2023, AND CHROMOSOMAL TRANSLOCATION. RX PubMed=14638541; DOI=10.1161/01.cir.0000103684.77636.cd; RA Muncke N., Jung C., Ruediger H., Ulmer H., Roeth R., Hubert A., RA Goldmuntz E., Driscoll D., Goodship J., Schoen K., Rappold G.; RT "Missense mutations and gene interruption in PROSIT240, a novel TRAP240- RT like gene, in patients with congenital heart defect (transposition of the RT great arteries)."; RL Circulation 108:2843-2850(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=15145061; DOI=10.1016/j.gene.2004.02.044; RA Musante L., Bartsch O., Ropers H.-H., Kalscheuer V.M.; RT "cDNA cloning and characterization of the human THRAP2 gene which maps to RT chromosome 12q24, and its mouse ortholog Thrap2."; RL Gene 332:119-127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 142-2210. RC TISSUE=Fetal kidney; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 294-2210. RC TISSUE=Brain; RX PubMed=10470851; DOI=10.1093/dnares/6.3.197; RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:197-205(1999). RN [6] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1077-2210. RC TISSUE=Placenta; 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 [8] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-817; SER-826 AND SER-2083, RP AND 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-817 AND SER-2083, AND RP IDENTIFICATION BY 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553; SER-560 AND SER-817, 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-923 AND SER-2083, 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 [14] RP INVOLVEMENT IN MRFACD. RX PubMed=25167861; DOI=10.1136/jmedgenet-2014-102554; RA Redin C., Gerard B., Lauer J., Herenger Y., Muller J., Quartier A., RA Masurel-Paulet A., Willems M., Lesca G., El-Chehadeh S., Le Gras S., RA Vicaire S., Philipps M., Dumas M., Geoffroy V., Feger C., Haumesser N., RA Alembik Y., Barth M., Bonneau D., Colin E., Dollfus H., Doray B., RA Delrue M.A., Drouin-Garraud V., Flori E., Fradin M., Francannet C., RA Goldenberg A., Lumbroso S., Mathieu-Dramard M., Martin-Coignard D., RA Lacombe D., Morin G., Polge A., Sukno S., Thauvin-Robinet C., Thevenon J., RA Doco-Fenzy M., Genevieve D., Sarda P., Edery P., Isidor B., Jost B., RA Olivier-Faivre L., Mandel J.L., Piton A.; RT "Efficient strategy for the molecular diagnosis of intellectual disability RT using targeted high-throughput sequencing."; RL J. Med. Genet. 51:724-736(2014). RN [15] RP INVOLVEMENT IN MRFACD. RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772; RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L., RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E., RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S., RA Rouleau G.A., Michaud J.L.; RT "De novo mutations in moderate or severe intellectual disability."; RL PLoS Genet. 10:E1004772-E1004772(2014). RN [16] RP VARIANT MRFACD 160-SER--GLU-174 DEL. RX PubMed=24781760; DOI=10.1038/ejhg.2014.69; RA van Haelst M.M., Monroe G.R., Duran K., van Binsbergen E., Breur J.M., RA Giltay J.C., van Haaften G.; RT "Further confirmation of the MED13L haploinsufficiency syndrome."; RL Eur. J. Hum. Genet. 23:135-138(2015). RN [17] RP INVOLVEMENT IN MRFACD. RX PubMed=25758992; DOI=10.1038/ejhg.2015.26; RA Adegbola A., Musante L., Callewaert B., Maciel P., Hu H., Isidor B., RA Picker-Minh S., Le Caignec C., Delle Chiaie B., Vanakker O., Menten B., RA Dheedene A., Bockaert N., Roelens F., Decaestecker K., Silva J., Soares G., RA Lopes F., Najmabadi H., Kahrizi K., Cox G.F., Angus S.P., Staropoli J.F., RA Fischer U., Suckow V., Bartsch O., Chess A., Ropers H.H., Wienker T.F., RA Huebner C., Kaindl A.M., Kalscheuer V.M.; RT "Redefining the MED13L syndrome."; RL Eur. J. Hum. Genet. 23:1308-1317(2015). RN [18] RP INVOLVEMENT IN MRFACD. RX PubMed=25712080; DOI=10.1038/ejhg.2015.19; RA Cafiero C., Marangi G., Orteschi D., Ali M., Asaro A., Ponzi E., RA Moncada A., Ricciardi S., Murdolo M., Mancano G., Contaldo I., Leuzzi V., RA Battaglia D., Mercuri E., Slavotinek A.M., Zollino M.; RT "Novel de novo heterozygous loss-of-function variants in MED13L and further RT delineation of the MED13L haploinsufficiency syndrome."; RL Eur. J. Hum. Genet. 23:1499-1504(2015). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. This subunit may specifically CC regulate transcription of targets of the Wnt signaling pathway and SHH CC signaling pathway. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Highly expressed in brain (cerebellum), heart CC (aorta), skeletal muscle, kidney, placenta and peripheral blood CC leukocytes. Highly expressed in fetal brain. CC {ECO:0000269|PubMed:14638541, ECO:0000269|PubMed:15145061}. CC -!- DISEASE: Note=A chromosomal aberration involving MED13L is found in a CC patient with transposition of the great arteries, dextro-looped and CC intellectual disability. Translocation t(12;17)(q24.1;q21). CC {ECO:0000269|PubMed:14638541}. CC -!- DISEASE: Impaired intellectual development and distinctive facial CC features with or without cardiac defects (MRFACD) [MIM:616789]: An CC autosomal dominant syndrome characterized by intellectual disability, CC delayed psychomotor development, profound language impairment, and CC facial dysmorphism, including frontal bossing, upslanting palpebral CC fissures, depressed nasal bridge with bulbous tip, and macrostomia. CC There is variable penetrance of cardiac malformations, ranging from no CC malformations to patent foramen ovale to septal defects and/or CC transposition of the great arteries. {ECO:0000269|PubMed:14638541, CC ECO:0000269|PubMed:24781760, ECO:0000269|PubMed:25167861, CC ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:25712080, CC ECO:0000269|PubMed:25758992}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 13 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14697.1; Type=Erroneous initiation; 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; AF515599; AAQ08182.1; -; mRNA. DR EMBL; AY338463; AAR08418.1; -; mRNA. DR EMBL; BC130422; AAI30423.1; -; mRNA. DR EMBL; AL133033; CAB61363.1; -; mRNA. DR EMBL; AL137644; CAB70855.1; -; mRNA. DR EMBL; CR749332; CAH18186.1; -; mRNA. DR EMBL; AB028948; BAA82977.2; -; mRNA. DR EMBL; AK023837; BAB14697.1; ALT_INIT; mRNA. DR CCDS; CCDS9177.1; -. DR PIR; T42707; T42707. DR RefSeq; NP_056150.1; NM_015335.4. DR AlphaFoldDB; Q71F56; -. DR BioGRID; 116964; 69. DR CORUM; Q71F56; -. DR IntAct; Q71F56; 31. DR MINT; Q71F56; -. DR STRING; 9606.ENSP00000281928; -. DR iPTMnet; Q71F56; -. DR PhosphoSitePlus; Q71F56; -. DR BioMuta; MED13L; -. DR DMDM; 74749769; -. DR EPD; Q71F56; -. DR jPOST; Q71F56; -. DR MassIVE; Q71F56; -. DR MaxQB; Q71F56; -. DR PaxDb; Q71F56; -. DR PeptideAtlas; Q71F56; -. DR ProteomicsDB; 68600; -. DR Antibodypedia; 31301; 97 antibodies from 23 providers. DR DNASU; 23389; -. DR Ensembl; ENST00000281928.9; ENSP00000281928.3; ENSG00000123066.9. DR GeneID; 23389; -. DR KEGG; hsa:23389; -. DR MANE-Select; ENST00000281928.9; ENSP00000281928.3; NM_015335.5; NP_056150.1. DR UCSC; uc001tvw.4; human. DR CTD; 23389; -. DR DisGeNET; 23389; -. DR GeneCards; MED13L; -. DR HGNC; HGNC:22962; MED13L. DR HPA; ENSG00000123066; Low tissue specificity. DR MalaCards; MED13L; -. DR MIM; 608771; gene. DR MIM; 616789; phenotype. DR neXtProt; NX_Q71F56; -. DR OpenTargets; ENSG00000123066; -. DR Orphanet; 369891; Developmental delay-facial dysmorphism syndrome due to MED13L deficiency. DR Orphanet; 216718; Isolated congenitally uncorrected transposition of the great arteries. DR PharmGKB; PA162395233; -. DR VEuPathDB; HostDB:ENSG00000123066; -. DR eggNOG; KOG3600; Eukaryota. DR GeneTree; ENSGT00390000013680; -. DR HOGENOM; CLU_000508_0_0_1; -. DR InParanoid; Q71F56; -. DR OrthoDB; 177884at2759; -. DR PhylomeDB; Q71F56; -. DR TreeFam; TF316867; -. DR PathwayCommons; Q71F56; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q71F56; -. DR SIGNOR; Q71F56; -. DR BioGRID-ORCS; 23389; 48 hits in 1091 CRISPR screens. DR ChiTaRS; MED13L; human. DR GenomeRNAi; 23389; -. DR Pharos; Q71F56; Tbio. DR PRO; PR:Q71F56; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q71F56; protein. DR Bgee; ENSG00000123066; Expressed in calcaneal tendon and 211 other tissues. DR ExpressionAtlas; Q71F56; baseline and differential. DR Genevisible; Q71F56; HS. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR InterPro; IPR009401; Med13_C. DR InterPro; IPR041285; MID_MedPIWI. DR Pfam; PF06333; Med13_C; 1. DR Pfam; PF18296; MID_MedPIWI; 1. DR AGR; HGNC:22962; -. PE 1: Evidence at protein level; KW Activator; Chromosomal rearrangement; Disease variant; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Repressor; Transcription; Transcription regulation. FT CHAIN 1..2210 FT /note="Mediator of RNA polymerase II transcription subunit FT 13-like" FT /id="PRO_0000076352" FT REGION 391..414 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 435..489 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 519..582 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 736..770 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1016..1096 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1380..1401 FT /note="Leucine-zipper" FT REGION 1530..1656 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2045..2080 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 669..673 FT /note="LXXLL motif 1" FT MOTIF 1225..1229 FT /note="LXXLL motif 2" FT COMPBIAS 391..405 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 443..464 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 467..484 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 519..548 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 736..751 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 756..770 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1016..1038 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1060..1096 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1558..1625 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1633..1650 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 553 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 560 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 817 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332" FT MOD_RES 826 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 923 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2083 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163" FT VARIANT 160..174 FT /note="Missing (in MRFACD)" FT /evidence="ECO:0000269|PubMed:24781760" FT /id="VAR_076332" FT VARIANT 251 FT /note="E -> G (in MRFACD; unknown pathological FT significance; dbSNP:rs28940309)" FT /evidence="ECO:0000269|PubMed:14638541" FT /id="VAR_024024" FT VARIANT 1872 FT /note="R -> H (in a patient with dextro-looped FT transposition of the great arteries; unknown pathological FT significance; dbSNP:rs28940310)" FT /evidence="ECO:0000269|PubMed:14638541" FT /id="VAR_024025" FT VARIANT 2023 FT /note="D -> G (in a patient with dextro-looped FT transposition of the great arteries; unknown pathological FT significance; dbSNP:rs121918333)" FT /evidence="ECO:0000269|PubMed:14638541" FT /id="VAR_024026" FT CONFLICT 295..299 FT /note="PQSVA -> SISLI (in Ref. 5; BAA82977)" FT /evidence="ECO:0000305" FT CONFLICT 861 FT /note="L -> S (in Ref. 4; CAH18186)" FT /evidence="ECO:0000305" FT CONFLICT 1258 FT /note="S -> G (in Ref. 4; CAH18186)" FT /evidence="ECO:0000305" FT CONFLICT 1455 FT /note="P -> L (in Ref. 7; BAB14697)" FT /evidence="ECO:0000305" FT CONFLICT 1577 FT /note="S -> N (in Ref. 7; BAB14697)" FT /evidence="ECO:0000305" FT CONFLICT 1703 FT /note="L -> M (in Ref. 7; BAB14697)" FT /evidence="ECO:0000305" FT CONFLICT 1971 FT /note="V -> F (in Ref. 7; BAB14697)" FT /evidence="ECO:0000305" FT CONFLICT 2194 FT /note="V -> A (in Ref. 7; BAB14697)" FT /evidence="ECO:0000305" SQ SEQUENCE 2210 AA; 242602 MW; A8B566B1662B570C CRC64; MTAAANWVAN GASLEDCHSN LFSLAELTGI KWRRYNFGGH GDCGPIISAP AQDDPILLSF IRCLQANLLC VWRRDVKPDC KELWIFWWGD EPNLVGVIHH ELQVVEEGLW ENGLSYECRT LLFKAIHNLL ERCLMDKNFV RIGKWFVRPY EKDEKPVNKS EHLSCAFTFF LHGESNVCTS VEIAQHQPIY LINEEHIHMA QSSPAPFQVL VSPYGLNGTL TGQAYKMSDP ATRKLIEEWQ YFYPMVLKKK EESKEEDELG YDDDFPVAVE VIVGGVRMVY PSAFVLISQN DIPVPQSVAS AGGHIAVGQQ GLGSVKDPSN CGMPLTPPTS PEQAILGESG GMQSAASHLV SQDGGMITMH SPKRSGKIPP KLHNHMVHRV WKECILNRTQ SKRSQMSTPT LEEEPASNPA TWDFVDPTQR VSCSCSRHKL LKRCAVGPNR PPTVSQPGFS AGPSSSSSLP PPASSKHKTA ERQEKGDKLQ KRPLIPFHHR PSVAEELCME QDTPGQKLGL AGIDSSLEVS SSRKYDKQMA VPSRNTSKQM NLNPMDSPHS PISPLPPTLS PQPRGQETES LDPPSVPVNP ALYGNGLELQ QLSTLDDRTV LVGQRLPLMA EVSETALYCG IRPSNPESSE KWWHSYRLPP SDDAEFRPPE LQGERCDAKM EVNSESTALQ RLLAQPNKRF KIWQDKQPQL QPLHFLDPLP LSQQPGDSLG EVNDPYTFED GDIKYIFTAN KKCKQGTEKD SLKKNKSEDG FGTKDVTTPG HSTPVPDGKN AMSIFSSATK TDVRQDNAAG RAGSSSLTQV TDLAPSLHDL DNIFDNSDDD ELGAVSPALR SSKMPAVGTE DRPLGKDGRA AVPYPPTVAD LQRMFPTPPS LEQHPAFSPV MNYKDGISSE TVTALGMMES PMVSMVSTQL TEFKMEVEDG LGSPKPEEIK DFSYVHKVPS FQPFVGSSMF APLKMLPSHC LLPLKIPDAC LFRPSWAIPP KIEQLPMPPA ATFIRDGYNN VPSVGSLADP DYLNTPQMNT PVTLNSAAPA SNSGAGVLPS PATPRFSVPT PRTPRTPRTP RGGGTASGQG SVKYDSTDQG SPASTPSTTR PLNSVEPATM QPIPEAHSLY VTLILSDSVM NIFKDRNFDS CCICACNMNI KGADVGLYIP DSSNEDQYRC TCGFSAIMNR KLGYNSGLFL EDELDIFGKN SDIGQAAERR LMMCQSTFLP QVEGTKKPQE PPISLLLLLQ NQHTQPFASL NFLDYISSNN RQTLPCVSWS YDRVQADNND YWTECFNALE QGRQYVDNPT GGKVDEALVR SATVHSWPHS NVLDISMLSS QDVVRMLLSL QPFLQDAIQK KRTGRTWENI QHVQGPLTWQ QFHKMAGRGT YGSEESPEPL PIPTLLVGYD KDFLTISPFS LPFWERLLLD PYGGHRDVAY IVVCPENEAL LEGAKTFFRD LSAVYEMCRL GQHKPICKVL RDGIMRVGKT VAQKLTDELV SEWFNQPWSG EENDNHSRLK LYAQVCRHHL APYLATLQLD SSLLIPPKYQ TPPAAAQGQA TPGNAGPLAP NGSAAPPAGS AFNPTSNSSS TNPAASSSAS GSSVPPVSSS ASAPGISQIS TTSSSGFSGS VGGQNPSTGG ISADRTQGNI GCGGDTDPGQ SSSQPSQDGQ ESVTERERIG IPTEPDSADS HAHPPAVVIY MVDPFTYAAE EDSTSGNFWL LSLMRCYTEM LDNLPEHMRN SFILQIVPCQ YMLQTMKDEQ VFYIQYLKSM AFSVYCQCRR PLPTQIHIKS LTGFGPAASI EMTLKNPERP SPIQLYSPPF ILAPIKDKQT ELGETFGEAS QKYNVLFVGY CLSHDQRWLL ASCTDLHGEL LETCVVNIAL PNRSRRSKVS ARKIGLQKLW EWCIGIVQMT SLPWRVVIGR LGRLGHGELK DWSILLGECS LQTISKKLKD VCRMCGISAA DSPSILSACL VAMEPQGSFV VMPDAVTMGS VFGRSTALNM QSSQLNTPQD ASCTHILVFP TSSTIQVAPA NYPNEDGFSP NNDDMFVDLP FPDDMDNDIG ILMTGNLHSS PNSSPVPSPG SPSGIGVGSH FQHSRSQGER LLSREAPEEL KQQPLALGYF VSTAKAENLP QWFWSSCPQA QNQCPLFLKA SLHHHISVAQ TDELLPARNS QRVPHPLDSK TTSDVLRFVL EQYNALSWLT CNPATQDRTS CLPVHFVVLT QLYNAIMNIL // ID MED6_HUMAN Reviewed; 246 AA. AC O75586; B4DU17; B4E2P0; O15401; Q53FE3; Q53HJ3; Q6FHQ4; Q9BTH1; Q9UHL1; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 28-FEB-2003, sequence version 2. DT 14-DEC-2022, entry version 181. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 6; DE AltName: Full=Activator-recruited cofactor 33 kDa component; DE Short=ARC33; DE AltName: Full=Mediator complex subunit 6; DE Short=hMed6; DE AltName: Full=Renal carcinoma antigen NY-REN-28; GN Name=MED6; Synonyms=ARC33; 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), IDENTIFICATION BY MASS RP SPECTROMETRY, AND IDENTIFICATION IN A FORM OF THE MEDIATOR COMPLEX. RX PubMed=9734358; DOI=10.1016/s1097-2765(00)80131-8; RA Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D.; RT "NAT, a human complex containing Srb polypeptides that functions as a RT negative regulator of activated transcription."; RL Mol. Cell 2:213-222(1998). RN [2] 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Placenta, and Trachea; 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 MRNA] (ISOFORM 1). RC TISSUE=Coronary arterial endothelium, and Testis; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-157 (ISOFORM 1). RA Kim Y.-J.; RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-246 (ISOFORM 1), AND IDENTIFICATION AS A RP 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 [10] RP PROTEIN SEQUENCE OF 200-208 AND 227-236, AND IDENTIFICATION IN THE ARC RP COMPLEX. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [12] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [13] RP INTERACTION WITH CCNC; MED10 AND MED23. RX PubMed=10993082; DOI=10.1038/35024111; RA Akoulitchev S., Chuikov S., Reinberg D.; RT "TFIIH is negatively regulated by cdk8-containing mediator complexes."; RL Nature 407:102-106(2000). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH ESR1 AND ESR2. RX PubMed=11867769; DOI=10.1073/pnas.261715899; RA Kang Y.K., Guermah M., Yuan C.-X., Roeder R.G.; RT "The TRAP/Mediator coactivator complex interacts directly with estrogen RT receptors alpha and beta through the TRAP220 subunit and directly enhances RT estrogen receptor function in vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 99:2642-2647(2002). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [16] RP INTERACTION WITH MED1; MED21 AND MED30, IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF RP THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [17] RP ASSOCIATION WITH PROMOTER REGIONS. RX PubMed=16574658; DOI=10.1074/jbc.m600163200; RA Udayakumar T.S., Belakavadi M., Choi K.-H., Pandey P.K., Fondell J.D.; RT "Regulation of Aurora-A kinase gene expression via GABP recruitment of RT TRAP220/MED1."; RL J. Biol. Chem. 281:14691-14699(2006). RN [18] RP FUNCTION, AND INTERACTION WITH MED 1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [19] RP INTERACTION WITH CDK8; CTNNB1 AND GLI3. RX PubMed=17000779; DOI=10.1128/mcb.00443-06; RA Zhou H., Kim S., Ishii S., Boyer T.G.; RT "Mediator modulates Gli3-dependent Sonic hedgehog signaling."; RL Mol. Cell. Biol. 26:8667-8682(2006). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-236 AND LYS-241, 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 [21] 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 [22] 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 [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-208, AND IDENTIFICATION BY MASS RP 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CTNNB1 and CC GLI3. {ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:10235267, CC ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:11867769, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:17000779, CC ECO:0000269|PubMed:9734358}. CC -!- INTERACTION: CC O75586; Q13616: CUL1; NbExp=2; IntAct=EBI-394624, EBI-359390; CC O75586; Q9NVC6: MED17; NbExp=2; IntAct=EBI-394624, EBI-394562; CC O75586; Q9BUE0: MED18; NbExp=3; IntAct=EBI-394624, EBI-394640; CC O75586; Q6P2C8: MED27; NbExp=2; IntAct=EBI-394624, EBI-394603; CC O75586; Q9NX70: MED29; NbExp=3; IntAct=EBI-394624, EBI-394656; CC O75586; Q9R0X0: Med20; Xeno; NbExp=2; IntAct=EBI-394624, EBI-398698; CC O75586; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-394624, EBI-7990252; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O75586-1; Sequence=Displayed; CC Name=2; CC IsoId=O75586-2; Sequence=VSP_054589; CC Name=3; CC IsoId=O75586-3; Sequence=VSP_054590; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 6 family. CC {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; AF074723; AAC26869.1; -; mRNA. DR EMBL; BT006831; AAP35477.1; -; mRNA. DR EMBL; CR541697; CAG46498.1; -; mRNA. DR EMBL; AK300460; BAG62179.1; -; mRNA. DR EMBL; AK304361; BAG65202.1; -; mRNA. DR EMBL; AK222587; BAD96307.1; -; mRNA. DR EMBL; AK223346; BAD97066.1; -; mRNA. DR EMBL; AL357153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC004106; AAH04106.1; -; mRNA. DR EMBL; U78082; AAB84363.1; -; mRNA. DR EMBL; AF155104; AAD42870.1; -; mRNA. DR CCDS; CCDS61483.1; -. [O75586-3] DR CCDS; CCDS61484.1; -. [O75586-2] DR CCDS; CCDS9805.1; -. [O75586-1] DR RefSeq; NP_001271138.1; NM_001284209.1. [O75586-2] DR RefSeq; NP_001271139.1; NM_001284210.1. [O75586-3] DR RefSeq; NP_001271140.1; NM_001284211.1. DR RefSeq; NP_005457.2; NM_005466.3. [O75586-1] DR PDB; 7EMF; EM; 3.50 A; F=1-246. DR PDB; 7ENA; EM; 4.07 A; f=1-246. DR PDB; 7ENC; EM; 4.13 A; f=1-246. DR PDB; 7ENJ; EM; 4.40 A; F=1-246. DR PDB; 7LBM; EM; 4.80 A; g=1-246. DR PDB; 7NVR; EM; 4.50 A; a=1-246. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; O75586; -. DR SMR; O75586; -. DR BioGRID; 115319; 94. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; O75586; -. DR DIP; DIP-31456N; -. DR IntAct; O75586; 47. DR MINT; O75586; -. DR STRING; 9606.ENSP00000481920; -. DR iPTMnet; O75586; -. DR PhosphoSitePlus; O75586; -. DR BioMuta; MED6; -. DR EPD; O75586; -. DR jPOST; O75586; -. DR MassIVE; O75586; -. DR MaxQB; O75586; -. DR PaxDb; O75586; -. DR PeptideAtlas; O75586; -. DR ProteomicsDB; 50100; -. [O75586-1] DR ProteomicsDB; 5142; -. DR ProteomicsDB; 5839; -. DR Antibodypedia; 25135; 299 antibodies from 27 providers. DR DNASU; 10001; -. DR Ensembl; ENST00000256379.10; ENSP00000256379.5; ENSG00000133997.12. [O75586-1] DR Ensembl; ENST00000430055.6; ENSP00000413343.2; ENSG00000133997.12. [O75586-2] DR Ensembl; ENST00000440435.2; ENSP00000394502.2; ENSG00000133997.12. [O75586-3] DR GeneID; 10001; -. DR KEGG; hsa:10001; -. DR MANE-Select; ENST00000256379.10; ENSP00000256379.5; NM_005466.4; NP_005457.2. DR UCSC; uc001xmf.5; human. [O75586-1] DR CTD; 10001; -. DR GeneCards; MED6; -. DR HGNC; HGNC:19970; MED6. DR HPA; ENSG00000133997; Low tissue specificity. DR MIM; 602984; gene. DR neXtProt; NX_O75586; -. DR OpenTargets; ENSG00000133997; -. DR PharmGKB; PA134868263; -. DR VEuPathDB; HostDB:ENSG00000133997; -. DR eggNOG; KOG3169; Eukaryota. DR GeneTree; ENSGT00390000017666; -. DR HOGENOM; CLU_077754_1_0_1; -. DR InParanoid; O75586; -. DR OMA; HLHNMIG; -. DR OrthoDB; 1251252at2759; -. DR PhylomeDB; O75586; -. DR TreeFam; TF313577; -. DR PathwayCommons; O75586; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; O75586; -. DR SIGNOR; O75586; -. DR BioGRID-ORCS; 10001; 765 hits in 1095 CRISPR screens. DR GeneWiki; MED6; -. DR GenomeRNAi; 10001; -. DR Pharos; O75586; Tbio. DR PRO; PR:O75586; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O75586; protein. DR Bgee; ENSG00000133997; Expressed in calcaneal tendon and 178 other tissues. DR ExpressionAtlas; O75586; baseline and differential. DR Genevisible; O75586; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003677; F:DNA binding; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI. DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR Gene3D; 3.10.450.580; -; 1. DR InterPro; IPR007018; Mediator_Med6. DR InterPro; IPR016820; Mediator_Med6_met/pln. DR InterPro; IPR038566; Mediator_Med6_sf. DR PANTHER; PTHR13104; MED-6-RELATED; 1. DR Pfam; PF04934; Med6; 1. DR PIRSF; PIRSF023869; Mediator_MED6_meta/pln; 1. DR AGR; HGNC:19970; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Direct protein sequencing; Isopeptide bond; Nucleus; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..246 FT /note="Mediator of RNA polymerase II transcription subunit FT 6" FT /id="PRO_0000096388" FT REGION 193..246 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 202..226 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 236 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 241 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 208 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 119 FT /note="V -> VSLFSFYK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054589" FT VAR_SEQ 156..246 FT /note="DKVRPKAKRKEEPSSIFQRQRVDALLLDLRQKFPPKFVQLKPGEKPVPVDQT FT KKEAEPIPETVKPEEKETTKNVQQTVSAKGPPEKRMRLQ -> AKAWRKACSSGSNKER FT GRTYTRNCKT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054590" FT CONFLICT 151 FT /note="D -> V (in Ref. 1; AAC26869)" FT /evidence="ECO:0000305" FT CONFLICT 156 FT /note="D -> G (in Ref. 9; AAB84363)" FT /evidence="ECO:0000305" FT CONFLICT 203 FT /note="P -> S (in Ref. 5; BAD97066)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="E -> G (in Ref. 5; BAD96307)" FT /evidence="ECO:0000305" FT HELIX 10..12 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 18..20 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 26..32 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 39..41 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 43..45 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 46..52 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 56..61 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 65..73 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 79..88 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 91..101 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 104..107 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 111..136 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 137..140 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 141..143 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 144..147 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 174..187 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 246 AA; 28425 MW; 9B173626F583B48B CRC64; MAAVDIRDNL LGISWVDSSW IPILNSGSVL DYFSERSNPF YDRTCNNEVV KMQRLTLEHL NQMVGIEYIL LHAQEPILFI IRKQQRQSPA QVIPLADYYI IAGVIYQAPD LGSVINSRVL TAVHGIQSAF DEAMSYCRYH PSKGYWWHFK DHEEQDKVRP KAKRKEEPSS IFQRQRVDAL LLDLRQKFPP KFVQLKPGEK PVPVDQTKKE AEPIPETVKP EEKETTKNVQ QTVSAKGPPE KRMRLQ // ID MED20_HUMAN Reviewed; 212 AA. AC Q9H944; B4DE08; O95821; Q5T8J4; Q9Y429; DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 14-DEC-2022, entry version 180. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 20; DE AltName: Full=Mediator complex subunit 20; DE AltName: Full=TRF-proximal protein homolog; DE Short=hTRFP; GN Name=MED20; Synonyms=TRFP; 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), PROTEIN SEQUENCE OF 16-26; 36-51 RP AND 205-212, AND INTERACTION WITH RNA POLYMERASE II AND MED21. RX PubMed=9933582; DOI=10.1074/jbc.274.7.3937; RA Xiao H., Tao Y., Roeder R.G.; RT "The human homologue of Drosophila TRF-proximal protein is associated with RT an RNA polymerase II-SRB complex."; RL J. Biol. Chem. 274:3937-3940(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Liver, Prostate, Testis, and 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 120-212 (ISOFORM 1). RC TISSUE=Uterus; 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 [6] RP INTERACTION WITH MED18. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [8] RP INTERACTION WITH MED1; MED18; MED21; MED28; MED29 AND MED31, IDENTIFICATION RP BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND RP ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [9] 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: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Interacts with PPARG (By similarity). Component of the CC Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, CC MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, CC MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, CC MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CC CCNC and CDK8 subunits form a distinct module termed the CDK8 module. CC Mediator containing the CDK8 module is less active than Mediator CC lacking this module in supporting transcriptional activation. CC Individual preparations of the Mediator complex lacking one or more CC distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC CC and TRAP. {ECO:0000250, ECO:0000269|PubMed:12584197, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:9933582}. CC -!- INTERACTION: CC Q9H944; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-394644, EBI-11954519; CC Q9H944; Q6BCY4-2: CYB5R2; NbExp=3; IntAct=EBI-394644, EBI-12102608; CC Q9H944; Q96DN0: ERP27; NbExp=3; IntAct=EBI-394644, EBI-953772; CC Q9H944; Q06547: GABPB1; NbExp=3; IntAct=EBI-394644, EBI-618165; CC Q9H944; Q6IPE9: MARK4; NbExp=3; IntAct=EBI-394644, EBI-10250211; CC Q9H944; Q9BUE0: MED18; NbExp=21; IntAct=EBI-394644, EBI-394640; CC Q9H944; Q9NX70: MED29; NbExp=6; IntAct=EBI-394644, EBI-394656; CC Q9H944; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-394644, EBI-10232538; CC Q9H944; Q9UIG4: PSORS1C2; NbExp=3; IntAct=EBI-394644, EBI-11974061; CC Q9H944; Q6ZRS2-3: SRCAP; NbExp=3; IntAct=EBI-394644, EBI-12029182; CC Q9H944; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-394644, EBI-11525489; CC Q9H944; P25490: YY1; NbExp=3; IntAct=EBI-394644, EBI-765538; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H944-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H944-2; Sequence=VSP_057052; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 20 family. CC {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; AF097725; AAD16169.1; -; mRNA. DR EMBL; AK023092; BAB14399.1; -; mRNA. DR EMBL; AK293412; BAG56919.1; -; mRNA. DR EMBL; AL160163; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC012618; AAH12618.1; -; mRNA. DR EMBL; BC019866; AAH19866.1; -; mRNA. DR EMBL; BC032552; AAH32552.1; -; mRNA. DR EMBL; BC040950; AAH40950.1; -; mRNA. DR EMBL; AL050196; CAB43314.1; -; mRNA. DR CCDS; CCDS4862.1; -. [Q9H944-1] DR CCDS; CCDS83085.1; -. [Q9H944-2] DR PIR; T08801; T08801. DR RefSeq; NP_001292384.1; NM_001305455.1. DR RefSeq; NP_001292385.1; NM_001305456.1. DR RefSeq; NP_001292386.1; NM_001305457.1. [Q9H944-2] DR RefSeq; NP_004266.2; NM_004275.4. [Q9H944-1] DR PDB; 7EMF; EM; 3.50 A; T=1-212. DR PDB; 7ENA; EM; 4.07 A; t=1-212. DR PDB; 7ENC; EM; 4.13 A; t=1-212. DR PDB; 7ENJ; EM; 4.40 A; T=1-212. DR PDB; 7LBM; EM; 4.80 A; l=1-212. DR PDB; 7NVR; EM; 4.50 A; f=1-212. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9H944; -. DR SMR; Q9H944; -. DR BioGRID; 114862; 177. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9H944; -. DR DIP; DIP-31449N; -. DR IntAct; Q9H944; 137. DR MINT; Q9H944; -. DR STRING; 9606.ENSP00000265350; -. DR GlyGen; Q9H944; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9H944; -. DR MetOSite; Q9H944; -. DR PhosphoSitePlus; Q9H944; -. DR SwissPalm; Q9H944; -. DR BioMuta; MED20; -. DR DMDM; 29428258; -. DR EPD; Q9H944; -. DR jPOST; Q9H944; -. DR MassIVE; Q9H944; -. DR MaxQB; Q9H944; -. DR PaxDb; Q9H944; -. DR PeptideAtlas; Q9H944; -. DR ProteomicsDB; 3912; -. DR ProteomicsDB; 81283; -. [Q9H944-1] DR TopDownProteomics; Q9H944-1; -. [Q9H944-1] DR Antibodypedia; 30105; 105 antibodies from 23 providers. DR DNASU; 9477; -. DR Ensembl; ENST00000265350.9; ENSP00000265350.4; ENSG00000124641.16. [Q9H944-1] DR Ensembl; ENST00000409312.5; ENSP00000386816.1; ENSG00000124641.16. [Q9H944-2] DR GeneID; 9477; -. DR KEGG; hsa:9477; -. DR MANE-Select; ENST00000265350.9; ENSP00000265350.4; NM_004275.5; NP_004266.2. DR UCSC; uc003ork.4; human. [Q9H944-1] DR CTD; 9477; -. DR DisGeNET; 9477; -. DR GeneCards; MED20; -. DR HGNC; HGNC:16840; MED20. DR HPA; ENSG00000124641; Low tissue specificity. DR MIM; 612915; gene. DR neXtProt; NX_Q9H944; -. DR OpenTargets; ENSG00000124641; -. DR PharmGKB; PA162395472; -. DR VEuPathDB; HostDB:ENSG00000124641; -. DR eggNOG; KOG4309; Eukaryota. DR GeneTree; ENSGT00390000002060; -. DR HOGENOM; CLU_080044_1_0_1; -. DR InParanoid; Q9H944; -. DR OMA; QSTFSIC; -. DR OrthoDB; 1112080at2759; -. DR PhylomeDB; Q9H944; -. DR TreeFam; TF315156; -. DR PathwayCommons; Q9H944; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9H944; -. DR SIGNOR; Q9H944; -. DR BioGRID-ORCS; 9477; 652 hits in 1032 CRISPR screens. DR ChiTaRS; MED20; human. DR GenomeRNAi; 9477; -. DR Pharos; Q9H944; Tbio. DR PRO; PR:Q9H944; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9H944; protein. DR Bgee; ENSG00000124641; Expressed in secondary oocyte and 168 other tissues. DR ExpressionAtlas; Q9H944; baseline and differential. DR Genevisible; Q9H944; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003899; F:DNA-directed 5'-3' RNA polymerase activity; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central. DR GO; GO:0006351; P:DNA-templated transcription; NAS:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc. DR InterPro; IPR013921; Mediator_Med20. DR PANTHER; PTHR12465; UBIQUITIN SPECIFIC PROTEASE HOMOLOG 49; 1. DR Pfam; PF08612; Med20; 1. DR AGR; HGNC:16840; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Nucleus; Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..212 FT /note="Mediator of RNA polymerase II transcription subunit FT 20" FT /id="PRO_0000065731" FT VAR_SEQ 117..212 FT /note="YQYCDFLVKVGTVTMGPSARGISVEVEYGPCVVASDCWSLLLEFLQSFLGSH FT TPGAPAVFGNRHDAVYGPADTMVQYMELFNKIRKQQQVPVAGIR -> WSMAPVW (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057052" FT CONFLICT 134..136 FT /note="SAR -> VP (in Ref. 1; AAD16169)" FT /evidence="ECO:0000305" FT CONFLICT 206..207 FT /note="Missing (in Ref. 1; AAD16169)" FT /evidence="ECO:0000305" FT STRAND 3..9 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 13..15 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 17..31 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 34..47 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 62..67 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 69..71 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 74..82 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 84..88 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 91..98 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 100..103 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 110..131 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 134..146 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 150..152 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 154..164 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 174..177 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 186..203 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 212 AA; 23222 MW; 5AA7A39981EB1498 CRC64; MGVTCVSQMP VAEGKSVQQT VELLTRKLEM LGAEKQGTFC VDCETYHTAA STLGSQGQTG KLMYVMHNSE YPLSCFALFE NGPCLIADTN FDVLMVKLKG FFQSAKASKI ETRGTRYQYC DFLVKVGTVT MGPSARGISV EVEYGPCVVA SDCWSLLLEF LQSFLGSHTP GAPAVFGNRH DAVYGPADTM VQYMELFNKI RKQQQVPVAG IR // ID MED21_HUMAN Reviewed; 144 AA. AC Q13503; B2R4I3; Q6IB05; Q92811; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 14-DEC-2022, entry version 175. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 21; DE AltName: Full=Mediator complex subunit 21; DE AltName: Full=RNA polymerase II holoenzyme component SRB7; DE Short=RNAPII complex component SRB7; DE Short=hSrb7; GN Name=MED21; Synonyms=SRB7, SURB7; 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 INTERACTION WITH RNA POLYMERASE II. RX PubMed=8598913; DOI=10.1038/380082a0; RA Chao D.M., Gadbois E.L., Murray P.J., Anderson S.F., Sonu M.S., RA Parvin J.D., Young R.A.; RT "A mammalian SRB protein associated with an RNA polymerase II holoenzyme."; RL Nature 380:82-85(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH RNA POLYMERASE II. RC TISSUE=Liver; RX PubMed=8609996; DOI=10.1038/381086a0; RA Maldonado E., Shiekhattar R., Sheldon M., Cho H., Drapkin R., Rickert P., RA Lees E., Anderson C.W., Linn S., Reinberg D.; RT "A human RNA polymerase II complex associated with SRB and DNA-repair RT proteins."; RL Nature 381:86-89(1996). RN [3] RP ERRATUM OF PUBMED:8609996. RA Maldonado E., Shiekhattar R., Sheldon M., Cho H., Drapkin R., Rickert P., RA Lees E., Anderson C.W., Linn S., Reinberg D.; RL Nature 384:384-384(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain cortex; 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 [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]. RC TISSUE=Kidney; 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 FUNCTION. RX PubMed=9660976; DOI=10.1016/s1097-2765(00)80092-1; RA Oelgeschlaeger T., Tao Y., Kang Y.K., Roeder R.G.; RT "Transcription activation via enhanced preinitiation complex assembly in a RT human cell-free system lacking TAFIIs."; RL Mol. Cell 1:925-931(1998). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A FORM OF THE RP MEDIATOR COMPLEX. RX PubMed=9734358; DOI=10.1016/s1097-2765(00)80131-8; RA Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D.; RT "NAT, a human complex containing Srb polypeptides that functions as a RT negative regulator of activated transcription."; RL Mol. Cell 2:213-222(1998). RN [10] RP INTERACTION WITH RNA POLYMERASE II AND MED21. RX PubMed=9933582; DOI=10.1074/jbc.274.7.3937; RA Xiao H., Tao Y., Roeder R.G.; RT "The human homologue of Drosophila TRF-proximal protein is associated with RT an RNA polymerase II-SRB complex."; RL J. Biol. Chem. 274:3937-3940(1999). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC RP COMPLEX. RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1; RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in RT transcription regulation."; RL Mol. Cell 3:97-108(1999). RN [12] RP ERRATUM OF PUBMED:10024883. RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E., RA Qin J., Roeder R.G.; RL Mol. Cell 3:541-541(1999). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [14] RP FUNCTION, AND INTERACTION WITH THRA. RX PubMed=15249124; DOI=10.1016/j.mce.2004.05.003; RA Nevado J., Tenbaum S.P., Aranda A.; RT "hSrb7, an essential human Mediator component, acts as a coactivator for RT the thyroid hormone receptor."; RL Mol. Cell. Endocrinol. 222:41-51(2004). RN [15] RP INTERACTION WITH MED1; MED6; MED12; MED13; MED16; MED17; MED18; MED20; RP MED24; MED28 AND MED30, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION RP IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA RP POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:15249124, CC ECO:0000269|PubMed:9660976}. CC -!- SUBUNIT: Interacts with PPARG (By similarity). Component of the CC Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, CC MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, CC MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, CC MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CC CCNC and CDK8 subunits form a distinct module termed the CDK8 module. CC Mediator containing the CDK8 module is less active than Mediator CC lacking this module in supporting transcriptional activation. CC Individual preparations of the Mediator complex lacking one or more CC distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC CC and TRAP. Interacts with THRA in a ligand-dependent fashion. CC {ECO:0000250, ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15249124, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:8598913, ECO:0000269|PubMed:8609996, CC ECO:0000269|PubMed:9734358, ECO:0000269|PubMed:9933582}. CC -!- INTERACTION: CC Q13503; Q9UL45: BLOC1S6; NbExp=3; IntAct=EBI-394678, EBI-465781; CC Q13503; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-394678, EBI-10193358; CC Q13503; O14964: HGS; NbExp=3; IntAct=EBI-394678, EBI-740220; CC Q13503; O14901: KLF11; NbExp=3; IntAct=EBI-394678, EBI-948266; CC Q13503; Q13449: LSAMP; NbExp=3; IntAct=EBI-394678, EBI-4314821; CC Q13503; O15481: MAGEB4; NbExp=6; IntAct=EBI-394678, EBI-751857; CC Q13503; Q15648: MED1; NbExp=3; IntAct=EBI-394678, EBI-394459; CC Q13503; Q9NPJ6: MED4; NbExp=5; IntAct=EBI-394678, EBI-394607; CC Q13503; O43513: MED7; NbExp=3; IntAct=EBI-394678, EBI-394632; CC Q13503; Q9NWA0: MED9; NbExp=5; IntAct=EBI-394678, EBI-394653; CC Q13503; Q9NQG6: MIEF1; NbExp=3; IntAct=EBI-394678, EBI-740987; CC Q13503; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-394678, EBI-2811583; CC Q13503; P63208-1: SKP1; NbExp=5; IntAct=EBI-394678, EBI-307497; CC Q13503; A1L4H1: SSC5D; NbExp=6; IntAct=EBI-394678, EBI-10172867; CC Q13503; Q6ZMU5: TRIM72; NbExp=3; IntAct=EBI-394678, EBI-2341648; CC Q13503; Q8N720: ZNF655; NbExp=3; IntAct=EBI-394678, EBI-625509; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 21 family. CC {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; U46837; AAA98511.1; -; mRNA. DR EMBL; U52960; AAB06944.1; -; mRNA. DR EMBL; CR456999; CAG33280.1; -; mRNA. DR EMBL; AK311838; BAG34780.1; -; mRNA. DR EMBL; CH471094; EAW96545.1; -; Genomic_DNA. DR EMBL; BC008380; AAH08380.1; -; mRNA. DR CCDS; CCDS8711.1; -. DR PIR; S68454; S68454. DR RefSeq; NP_004255.2; NM_004264.4. DR PDB; 7EMF; EM; 3.50 A; U=1-144. DR PDB; 7ENA; EM; 4.07 A; u=1-144. DR PDB; 7ENC; EM; 4.13 A; u=1-144. DR PDB; 7ENJ; EM; 4.40 A; U=1-144. DR PDB; 7LBM; EM; 4.80 A; x=1-144. DR PDB; 7NVR; EM; 4.50 A; n=1-144. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q13503; -. DR SMR; Q13503; -. DR BioGRID; 114807; 147. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q13503; -. DR DIP; DIP-31471N; -. DR IntAct; Q13503; 118. DR MINT; Q13503; -. DR STRING; 9606.ENSP00000282892; -. DR iPTMnet; Q13503; -. DR PhosphoSitePlus; Q13503; -. DR BioMuta; MED21; -. DR DMDM; 7531204; -. DR EPD; Q13503; -. DR jPOST; Q13503; -. DR MassIVE; Q13503; -. DR MaxQB; Q13503; -. DR PaxDb; Q13503; -. DR PeptideAtlas; Q13503; -. DR ProteomicsDB; 59498; -. DR TopDownProteomics; Q13503; -. DR Antibodypedia; 1803; 168 antibodies from 24 providers. DR DNASU; 9412; -. DR Ensembl; ENST00000282892.4; ENSP00000282892.3; ENSG00000152944.9. DR GeneID; 9412; -. DR KEGG; hsa:9412; -. DR MANE-Select; ENST00000282892.4; ENSP00000282892.3; NM_004264.5; NP_004255.2. DR UCSC; uc001rhp.3; human. DR CTD; 9412; -. DR DisGeNET; 9412; -. DR GeneCards; MED21; -. DR HGNC; HGNC:11473; MED21. DR HPA; ENSG00000152944; Low tissue specificity. DR MIM; 603800; gene. DR neXtProt; NX_Q13503; -. DR OpenTargets; ENSG00000152944; -. DR PharmGKB; PA162395485; -. DR VEuPathDB; HostDB:ENSG00000152944; -. DR eggNOG; KOG1510; Eukaryota. DR GeneTree; ENSGT00390000014557; -. DR HOGENOM; CLU_126757_0_0_1; -. DR InParanoid; Q13503; -. DR OrthoDB; 1583203at2759; -. DR PhylomeDB; Q13503; -. DR PathwayCommons; Q13503; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q13503; -. DR SIGNOR; Q13503; -. DR BioGRID-ORCS; 9412; 638 hits in 1097 CRISPR screens. DR ChiTaRS; MED21; human. DR GeneWiki; MED21; -. DR GenomeRNAi; 9412; -. DR Pharos; Q13503; Tbio. DR PRO; PR:Q13503; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q13503; protein. DR Bgee; ENSG00000152944; Expressed in secondary oocyte and 205 other tissues. DR ExpressionAtlas; Q13503; baseline and differential. DR Genevisible; Q13503; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003899; F:DNA-directed 5'-3' RNA polymerase activity; TAS:ProtInc. DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR InterPro; IPR037212; Med7/Med21-like. DR InterPro; IPR021384; Mediator_Med21. DR PANTHER; PTHR13381; RNA POLYMERASE II HOLOENZYME COMPONENT SRB7; 1. DR Pfam; PF11221; Med21; 1. DR SUPFAM; SSF140718; Mediator hinge subcomplex-like; 1. DR AGR; HGNC:11473; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..144 FT /note="Mediator of RNA polymerase II transcription subunit FT 21" FT /id="PRO_0000096375" FT CONFLICT 104 FT /note="L -> V (in Ref. 2; AAB06944)" FT /evidence="ECO:0000305" FT HELIX 4..28 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 49..75 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 83..132 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 144 AA; 15564 MW; F786169620EDC126 CRC64; MADRLTQLQD AVNSLADQFC NAIGVLQQCG PPASFNNIQT AINKDQPANP TEEYAQLFAA LIARTAKDID VLIDSLPSEE STAALQAASL YKLEEENHEA ATCLEDVVYR GDMLLEKIQS ALADIAQSQL KTRSGTHSQS LPDS // ID MED30_HUMAN Reviewed; 178 AA. AC Q96HR3; C6GKU9; DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 14-DEC-2022, entry version 162. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 30; DE AltName: Full=Mediator complex subunit 30; DE AltName: Full=TRAP/Mediator complex component TRAP25; DE AltName: Full=Thyroid hormone receptor-associated protein 6; DE AltName: Full=Thyroid hormone receptor-associated protein complex 25 kDa component; DE Short=Trap25; GN Name=MED30; Synonyms=THRAP6, TRAP25; 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), IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, FUNCTION, AND TISSUE RP SPECIFICITY. RX PubMed=11909976; DOI=10.1128/mcb.22.8.2842-2852.2002; RA Baek H.J., Malik S., Qin J., Roeder R.G.; RT "Requirement of TRAP/mediator for both activator-independent and activator- RT dependent transcription in conjunction with TFIID-associated TAF(II)s."; RL Mol. Cell. Biol. 22:2842-2852(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING. RC TISSUE=Bone marrow, and Peripheral blood; RA Rienzo M., Casamassimi A., Giovane A., Napoli C.; RT "Identification of MED30 alternative mRNA in human progenitor cells."; RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; 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 MED22. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [7] RP INTERACTION WITH MED1; MED6; MED12; MED13; MED16; MED17; MED20; MED21 AND RP MED24, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [8] RP FUNCTION, AND INTERACTION WITH MED1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [9] 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 [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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 [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [14] RP IDENTIFICATION BY 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:11909976, CC ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:11909976, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q96HR3; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-394659, EBI-10174653; CC Q96HR3; O14964: HGS; NbExp=5; IntAct=EBI-394659, EBI-740220; CC Q96HR3; P42858: HTT; NbExp=3; IntAct=EBI-394659, EBI-466029; CC Q96HR3; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-394659, EBI-9091197; CC Q96HR3; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-394659, EBI-10172052; CC Q96HR3; Q9H204: MED28; NbExp=6; IntAct=EBI-394659, EBI-514199; CC Q96HR3; Q9ULW6: NAP1L2; NbExp=3; IntAct=EBI-394659, EBI-3911716; CC Q96HR3; Q9Y5B8: NME7; NbExp=5; IntAct=EBI-394659, EBI-744782; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96HR3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96HR3-2; Sequence=VSP_053904; CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, lung, CC pancreas, placenta and skeletal muscle. {ECO:0000269|PubMed:11909976}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 30 family. CC {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; AY083305; AAL89787.1; -; mRNA. DR EMBL; FM179284; CAQ76893.1; -; mRNA. DR EMBL; AC024329; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087361; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008226; AAH08226.1; -; mRNA. DR CCDS; CCDS6323.1; -. [Q96HR3-1] DR CCDS; CCDS64959.1; -. [Q96HR3-2] DR RefSeq; NP_001269915.1; NM_001282986.1. [Q96HR3-2] DR RefSeq; NP_542382.1; NM_080651.3. [Q96HR3-1] DR PDB; 7EMF; EM; 3.50 A; 3=1-178. DR PDB; 7ENA; EM; 4.07 A; l=1-178. DR PDB; 7ENC; EM; 4.13 A; l=1-178. DR PDB; 7ENJ; EM; 4.40 A; 3=1-178. DR PDB; 7LBM; EM; 4.80 A; q=1-178. DR PDB; 7NVR; EM; 4.50 A; s=1-178. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q96HR3; -. DR SMR; Q96HR3; -. DR BioGRID; 124707; 83. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q96HR3; -. DR IntAct; Q96HR3; 58. DR MINT; Q96HR3; -. DR STRING; 9606.ENSP00000297347; -. DR GlyGen; Q96HR3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96HR3; -. DR PhosphoSitePlus; Q96HR3; -. DR BioMuta; MED30; -. DR DMDM; 74731968; -. DR EPD; Q96HR3; -. DR jPOST; Q96HR3; -. DR MassIVE; Q96HR3; -. DR MaxQB; Q96HR3; -. DR PaxDb; Q96HR3; -. DR PeptideAtlas; Q96HR3; -. DR ProteomicsDB; 7605; -. DR ProteomicsDB; 76778; -. [Q96HR3-1] DR Antibodypedia; 26728; 200 antibodies from 24 providers. DR DNASU; 90390; -. DR Ensembl; ENST00000297347.7; ENSP00000297347.3; ENSG00000164758.7. [Q96HR3-1] DR Ensembl; ENST00000522839.1; ENSP00000431051.1; ENSG00000164758.7. [Q96HR3-2] DR GeneID; 90390; -. DR KEGG; hsa:90390; -. DR MANE-Select; ENST00000297347.7; ENSP00000297347.3; NM_080651.4; NP_542382.1. DR UCSC; uc003yoj.4; human. [Q96HR3-1] DR CTD; 90390; -. DR DisGeNET; 90390; -. DR GeneCards; MED30; -. DR HGNC; HGNC:23032; MED30. DR HPA; ENSG00000164758; Low tissue specificity. DR MIM; 610237; gene. DR neXtProt; NX_Q96HR3; -. DR OpenTargets; ENSG00000164758; -. DR PharmGKB; PA162395656; -. DR VEuPathDB; HostDB:ENSG00000164758; -. DR eggNOG; ENOG502QV3C; Eukaryota. DR GeneTree; ENSGT00390000010887; -. DR HOGENOM; CLU_074190_1_1_1; -. DR InParanoid; Q96HR3; -. DR OMA; KHDDRGV; -. DR OrthoDB; 1549016at2759; -. DR PhylomeDB; Q96HR3; -. DR TreeFam; TF324588; -. DR PathwayCommons; Q96HR3; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q96HR3; -. DR SIGNOR; Q96HR3; -. DR BioGRID-ORCS; 90390; 777 hits in 1091 CRISPR screens. DR ChiTaRS; MED30; human. DR GeneWiki; MED30; -. DR GenomeRNAi; 90390; -. DR Pharos; Q96HR3; Tbio. DR PRO; PR:Q96HR3; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q96HR3; protein. DR Bgee; ENSG00000164758; Expressed in oocyte and 188 other tissues. DR Genevisible; Q96HR3; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0030374; F:nuclear receptor coactivator activity; NAS:UniProtKB. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR InterPro; IPR021019; Mediator_Med30_met. DR PANTHER; PTHR31705; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 30; 1. DR Pfam; PF11315; Med30; 1. DR AGR; HGNC:23032; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Coiled coil; KW Nucleus; Reference proteome; Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..178 FT /note="Mediator of RNA polymerase II transcription subunit FT 30" FT /id="PRO_0000239406" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 70..94 FT /evidence="ECO:0000255" FT COILED 133..173 FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22814378" FT VAR_SEQ 113..147 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_053904" FT HELIX 30..57 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 70..101 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 137..175 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 178 AA; 20277 MW; 1FD31212EDDF6238 CRC64; MSTPPLAASG MAPGPFAGPQ AQQAAREVNT ASLCRIGQET VQDIVYRTME IFQLLRNMQL PNGVTYHTGT YQDRLTKLQD NLRQLSVLFR KLRLVYDKCN ENCGGMDPIP VEQLIPYVEE DGSKNDDRAG PPRFASEERR EIAEVNKKLK QKNQQLKQIM DQLRNLIWDI NAMLAMRN // ID MED22_HUMAN Reviewed; 200 AA. AC Q15528; B3KW83; B3KWX4; O76072; Q5T8U0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 14-DEC-2022, entry version 175. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 22; DE AltName: Full=Mediator complex subunit 22; DE AltName: Full=Surfeit locus protein 5; DE Short=Surf-5; GN Name=MED22; Synonyms=SURF5; 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 SURF5A). RX PubMed=8586415; DOI=10.1006/geno.1995.9889; RA Garson K., Duhig T., Armes N., Colombo P., Fried M.; RT "Surf5: a gene in the tightly clustered mouse surfeit locus is highly RT conserved and transcribed divergently from the rpL7A (Surf3) gene."; RL Genomics 30:163-170(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING. RX PubMed=11891058; DOI=10.1016/s0378-1119(02)00379-7; RA Angiolillo A., Russo G., Porcellini A., Smaldone S., D'Alessandro F., RA Pietropaolo C.; RT "The human homologue of the mouse Surf5 gene encodes multiple alternatively RT spliced transcripts."; RL Gene 284:169-178(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SURF5B AND SURF5A). RC TISSUE=Cerebellum, and 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 [4] 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 [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] (ISOFORM SURF5A). RC TISSUE=Muscle, and Skin; 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 MED10; MED11 AND MED30. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [9] 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: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q15528; Q9P086: MED11; NbExp=3; IntAct=EBI-394687, EBI-394704; CC Q15528; Q9NVC6: MED17; NbExp=4; IntAct=EBI-394687, EBI-394562; CC Q15528; Q9BUE0: MED18; NbExp=3; IntAct=EBI-394687, EBI-394640; CC Q15528; Q6P2C8: MED27; NbExp=3; IntAct=EBI-394687, EBI-394603; CC Q15528; Q9H204: MED28; NbExp=2; IntAct=EBI-394687, EBI-514199; CC Q15528; Q9NX70: MED29; NbExp=4; IntAct=EBI-394687, EBI-394656; CC Q15528; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-394687, EBI-6260909; CC Q15528; Q9CQI9: Med30; Xeno; NbExp=6; IntAct=EBI-394687, EBI-309220; CC Q15528; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-394687, EBI-7990252; CC Q15528-2; O14964: HGS; NbExp=3; IntAct=EBI-12954271, EBI-740220; CC Q15528-2; P42858: HTT; NbExp=12; IntAct=EBI-12954271, EBI-466029; CC Q15528-2; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-12954271, EBI-741158; CC Q15528-2; P60891: PRPS1; NbExp=3; IntAct=EBI-12954271, EBI-749195; CC Q15528-2; O14530: TXNDC9; NbExp=3; IntAct=EBI-12954271, EBI-707554; CC Q15528-2; O76024: WFS1; NbExp=3; IntAct=EBI-12954271, EBI-720609; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Surf5B; CC IsoId=Q15528-1; Sequence=Displayed; CC Name=Surf5A; CC IsoId=Q15528-2; Sequence=VSP_006309; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 22 family. CC {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; X85178; CAA59462.1; -; mRNA. DR EMBL; AJ224639; CAA12052.1; -; Genomic_DNA. DR EMBL; AJ224639; CAA12053.1; -; Genomic_DNA. DR EMBL; AJ224358; CAA11915.1; -; mRNA. DR EMBL; AJ224359; CAA11916.1; -; mRNA. DR EMBL; AK124518; BAG54045.1; -; mRNA. DR EMBL; AK126069; BAG54286.1; -; mRNA. DR EMBL; AL158826; CAI12827.1; -; Genomic_DNA. DR EMBL; CH471090; EAW88056.1; -; Genomic_DNA. DR EMBL; CH471090; EAW88060.1; -; Genomic_DNA. DR EMBL; BC024225; AAH24225.1; -; mRNA. DR EMBL; BC040111; AAH40111.1; -; mRNA. DR CCDS; CCDS6963.1; -. [Q15528-1] DR CCDS; CCDS6964.1; -. [Q15528-2] DR RefSeq; NP_598395.1; NM_133640.4. [Q15528-1] DR RefSeq; NP_852468.1; NM_181491.2. [Q15528-2] DR PDB; 7EMF; EM; 3.50 A; V=1-200. DR PDB; 7ENA; EM; 4.07 A; v=1-200. DR PDB; 7ENC; EM; 4.13 A; v=1-200. DR PDB; 7ENJ; EM; 4.40 A; V=1-200. DR PDB; 7LBM; EM; 4.80 A; m=1-200. DR PDB; 7NVR; EM; 4.50 A; g=1-200. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q15528; -. DR SMR; Q15528; -. DR BioGRID; 112704; 86. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q15528; -. DR IntAct; Q15528; 42. DR MINT; Q15528; -. DR STRING; 9606.ENSP00000482438; -. DR iPTMnet; Q15528; -. DR PhosphoSitePlus; Q15528; -. DR BioMuta; MED22; -. DR DMDM; 6175074; -. DR EPD; Q15528; -. DR jPOST; Q15528; -. DR MassIVE; Q15528; -. DR MaxQB; Q15528; -. DR PaxDb; Q15528; -. DR PeptideAtlas; Q15528; -. DR ProteomicsDB; 60619; -. [Q15528-1] DR ProteomicsDB; 60620; -. [Q15528-2] DR TopDownProteomics; Q15528-2; -. [Q15528-2] DR Antibodypedia; 18330; 176 antibodies from 25 providers. DR DNASU; 6837; -. DR Ensembl; ENST00000343730.10; ENSP00000342343.5; ENSG00000148297.16. [Q15528-1] DR Ensembl; ENST00000610672.4; ENSP00000482438.1; ENSG00000148297.16. [Q15528-1] DR Ensembl; ENST00000610888.4; ENSP00000478773.1; ENSG00000148297.16. [Q15528-2] DR Ensembl; ENST00000614493.4; ENSP00000481493.1; ENSG00000148297.16. [Q15528-2] DR Ensembl; ENST00000626118.2; ENSP00000485715.1; ENSG00000281022.3. [Q15528-2] DR Ensembl; ENST00000629522.2; ENSP00000485880.1; ENSG00000281022.3. [Q15528-1] DR Ensembl; ENST00000629975.2; ENSP00000486722.1; ENSG00000281022.3. [Q15528-2] DR Ensembl; ENST00000631196.3; ENSP00000487580.1; ENSG00000281022.3. [Q15528-1] DR GeneID; 6837; -. DR KEGG; hsa:6837; -. DR MANE-Select; ENST00000343730.10; ENSP00000342343.5; NM_133640.5; NP_598395.1. DR UCSC; uc004cdc.5; human. [Q15528-1] DR CTD; 6837; -. DR DisGeNET; 6837; -. DR GeneCards; MED22; -. DR HGNC; HGNC:11477; MED22. DR HPA; ENSG00000148297; Low tissue specificity. DR MIM; 185641; gene. DR neXtProt; NX_Q15528; -. DR OpenTargets; ENSG00000148297; -. DR PharmGKB; PA162395486; -. DR VEuPathDB; HostDB:ENSG00000148297; -. DR eggNOG; KOG3304; Eukaryota. DR GeneTree; ENSGT00390000004339; -. DR HOGENOM; CLU_117242_0_0_1; -. DR InParanoid; Q15528; -. DR OMA; TQCEQDT; -. DR PhylomeDB; Q15528; -. DR TreeFam; TF323390; -. DR PathwayCommons; Q15528; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q15528; -. DR SIGNOR; Q15528; -. DR BioGRID-ORCS; 6837; 703 hits in 1092 CRISPR screens. DR ChiTaRS; MED22; human. DR GeneWiki; MED22; -. DR GenomeRNAi; 6837; -. DR Pharos; Q15528; Tbio. DR PRO; PR:Q15528; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q15528; protein. DR Bgee; ENSG00000148297; Expressed in cortical plate and 97 other tissues. DR ExpressionAtlas; Q15528; baseline and differential. DR Genevisible; Q15528; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR009332; Med22. DR PANTHER; PTHR12434; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 22; 1. DR Pfam; PF06179; Med22; 1. DR AGR; HGNC:11477; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Coiled coil; Nucleus; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..200 FT /note="Mediator of RNA polymerase II transcription subunit FT 22" FT /id="PRO_0000178838" FT REGION 166..200 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 93..122 FT /evidence="ECO:0000255" FT VAR_SEQ 138..200 FT /note="SSSLCEANDLPLCEAYGRLDLDTDSADGLSAPLLASPEPSAGPLQVAAPAHS FT HAGGPGPTEHA -> RYK (in isoform Surf5A)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8586415" FT /id="VSP_006309" FT HELIX 11..39 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 50..89 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 91..135 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 200 AA; 22221 MW; 113BBF7C35B03F7B CRC64; MAQQRALPQS KETLLQSYNK RLKDDIKSIM DNFTEIIKTA KIEDETQVSR ATQGEQDNYE MHVRAANIVR AGESLMKLVS DLKQFLILND FPSVNEAIDQ RNQQLRTLQE ECDRKLITLR DEISIDLYEL EEEYYSSSSS LCEANDLPLC EAYGRLDLDT DSADGLSAPL LASPEPSAGP LQVAAPAHSH AGGPGPTEHA // ID MD12L_HUMAN Reviewed; 2145 AA. AC Q86YW9; Q96PC7; Q96PC8; Q9H9M5; Q9HCD7; Q9UI69; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 15-JAN-2008, sequence version 2. DT 14-DEC-2022, entry version 141. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 12-like protein; DE AltName: Full=Mediator complex subunit 12-like protein; DE AltName: Full=Thyroid hormone receptor-associated-like protein; DE AltName: Full=Trinucleotide repeat-containing gene 11 protein-like; GN Name=MED12L; Synonyms=KIAA1635, TNRC11L, TRALP, TRALPUSH; GN ORFNames=PRO0314; 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 2 AND 3). RX PubMed=11524702; DOI=10.1086/323610; RA Joensuu T., Haemaelaeinen R., Yuan B., Johnson C., Tegelberg S., RA Gasparini P., Zelante L., Pirvola U., Pakarinen L., Lehesjoki A.-E., RA de la Chapelle A., Sankila E.-M.; RT "Mutations in a novel gene with transmembrane domains underlie Usher RT syndrome type 3."; RL Am. J. Hum. Genet. 69:673-684(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Adato A., Avidan N., Ben-Asher E., Khen M., Man O., Beckmann J.S., RA Bonne-Tamir B., Lancet D.; RT "Tralpush, a novel transcription-related gene, that spans the entire USHER RT syndrome type-3 linkage interval encloses five G-protein-coupled receptor RT genes nested within its introns."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. 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] OF 711-2145 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10997877; DOI=10.1093/dnares/7.4.271; RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:273-281(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 808-1763 (ISOFORM 4). 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1175-1608 (ISOFORMS 1/4). RC TISSUE=Fetal liver; RX PubMed=11483580; DOI=10.1101/gr.175501; RA Yu Y., Zhang C., Zhou G., Wu S., Qu X., Wei H., Xing G., Dong C., Zhai Y., RA Wan J., Ouyang S., Li L., Zhang S., Zhou K., Zhang Y., Wu C., He F.; RT "Gene expression profiling in human fetal liver and identification of RT tissue- and developmental-stage-specific genes through compiled expression RT profiles and efficient cloning of full-length cDNAs."; RL Genome Res. 11:1392-1403(2001). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-462, 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 [8] RP INVOLVEMENT IN NIZIDS, AND VARIANT NIZIDS 1998-GLN--PHE-2145 DEL. RX PubMed=31155615; DOI=10.1038/s41436-019-0557-3; RA Nizon M., Laugel V., Flanigan K.M., Pastore M., Waldrop M.A., RA Rosenfeld J.A., Marom R., Xiao R., Gerard A., Pichon O., Le Caignec C., RA Gerard M., Dieterich K., Truitt Cho M., McWalter K., Hiatt S., RA Thompson M.L., Bezieau S., Wadley A., Wierenga K.J., Egly J.M., Isidor B.; RT "Variants in MED12L, encoding a subunit of the mediator kinase module, are RT responsible for intellectual disability associated with transcriptional RT defect."; RL Genet. Med. 21:2713-2722(2019). CC -!- FUNCTION: May be a component of the Mediator complex, a coactivator CC involved in the regulated transcription of nearly all RNA polymerase CC II-dependent genes. Mediator functions as a bridge to convey CC information from gene-specific regulatory proteins to the basal RNA CC polymerase II transcription machinery. Mediator is recruited to CC promoters by direct interactions with regulatory proteins and serves as CC a scaffold for the assembly of a functional preinitiation complex with CC RNA polymerase II and the general transcription factors (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: May be a component of the Mediator complex, which is known to CC be composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, CC MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, CC MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CC CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a CC distinct module termed the CDK8 module. Mediator containing the CDK8 CC module is less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity). CC {ECO:0000250}. CC -!- INTERACTION: CC Q86YW9; P61024: CKS1B; NbExp=3; IntAct=EBI-3957138, EBI-456371; CC Q86YW9; P45984: MAPK9; NbExp=3; IntAct=EBI-3957138, EBI-713568; CC Q86YW9; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-3957138, EBI-10699187; CC Q86YW9; Q08117-2: TLE5; NbExp=3; IntAct=EBI-3957138, EBI-11741437; CC Q86YW9; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-3957138, EBI-9090990; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q86YW9-1; Sequence=Displayed; CC Name=2; Synonyms=NOPAR; CC IsoId=Q86YW9-2; Sequence=VSP_029995, VSP_029996; CC Name=3; Synonyms=NOPAR2; CC IsoId=Q86YW9-3; Sequence=VSP_029994, VSP_029995, VSP_029996; CC Name=4; CC IsoId=Q86YW9-4; Sequence=VSP_029997; CC -!- DISEASE: Nizon-Isidor syndrome (NIZIDS) [MIM:618872]: An autosomal CC dominant neurodevelopmental disorder characterized by intellectual CC disability, global developmental delay, speech impairment, and CC behavioral abnormalities including autism spectrum disorder and CC aggressive behavior. Other features include a thin corpus callosum, and CC mild facial dysmorphism. Disease onset is in infancy or early CC childhood. {ECO:0000269|PubMed:31155615}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 12 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF24035.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part and potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAB14198.1; Type=Erroneous initiation; 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; AF388364; AAL09579.1; -; mRNA. DR EMBL; AF388365; AAL09580.1; -; mRNA. DR EMBL; AF399708; AAO38813.1; -; mRNA. DR EMBL; CH471052; EAW78800.1; -; Genomic_DNA. DR EMBL; AB046855; BAB13461.1; -; mRNA. DR EMBL; AK022714; BAB14198.1; ALT_INIT; mRNA. DR EMBL; AF090917; AAF24035.1; ALT_SEQ; mRNA. DR CCDS; CCDS33876.1; -. [Q86YW9-1] DR RefSeq; NP_443728.3; NM_053002.5. [Q86YW9-1] DR RefSeq; XP_011510692.1; XM_011512390.2. [Q86YW9-1] DR AlphaFoldDB; Q86YW9; -. DR BioGRID; 125538; 45. DR IntAct; Q86YW9; 21. DR MINT; Q86YW9; -. DR STRING; 9606.ENSP00000417235; -. DR iPTMnet; Q86YW9; -. DR PhosphoSitePlus; Q86YW9; -. DR BioMuta; MED12L; -. DR DMDM; 166232934; -. DR EPD; Q86YW9; -. DR jPOST; Q86YW9; -. DR MassIVE; Q86YW9; -. DR MaxQB; Q86YW9; -. DR PaxDb; Q86YW9; -. DR PeptideAtlas; Q86YW9; -. DR ProteomicsDB; 70486; -. [Q86YW9-1] DR ProteomicsDB; 70487; -. [Q86YW9-2] DR ProteomicsDB; 70488; -. [Q86YW9-3] DR ProteomicsDB; 70489; -. [Q86YW9-4] DR Antibodypedia; 46744; 25 antibodies from 14 providers. DR DNASU; 116931; -. DR Ensembl; ENST00000309237.8; ENSP00000310760.4; ENSG00000144893.13. [Q86YW9-3] DR Ensembl; ENST00000422248.6; ENSP00000403308.2; ENSG00000144893.13. [Q86YW9-2] DR Ensembl; ENST00000474524.5; ENSP00000417235.1; ENSG00000144893.13. [Q86YW9-1] DR GeneID; 116931; -. DR KEGG; hsa:116931; -. DR UCSC; uc003eyn.3; human. [Q86YW9-1] DR CTD; 116931; -. DR DisGeNET; 116931; -. DR GeneCards; MED12L; -. DR HGNC; HGNC:16050; MED12L. DR HPA; ENSG00000144893; Tissue enriched (choroid). DR MalaCards; MED12L; -. DR MIM; 611318; gene. DR MIM; 618872; phenotype. DR neXtProt; NX_Q86YW9; -. DR OpenTargets; ENSG00000144893; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR PharmGKB; PA134884590; -. DR VEuPathDB; HostDB:ENSG00000144893; -. DR eggNOG; KOG3598; Eukaryota. DR GeneTree; ENSGT00440000037505; -. DR HOGENOM; CLU_383529_0_0_1; -. DR InParanoid; Q86YW9; -. DR OMA; HSMILQK; -. DR OrthoDB; 15873at2759; -. DR PhylomeDB; Q86YW9; -. DR TreeFam; TF324178; -. DR PathwayCommons; Q86YW9; -. DR SignaLink; Q86YW9; -. DR BioGRID-ORCS; 116931; 11 hits in 1072 CRISPR screens. DR ChiTaRS; MED12L; human. DR GenomeRNAi; 116931; -. DR Pharos; Q86YW9; Tdark. DR PRO; PR:Q86YW9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q86YW9; protein. DR Bgee; ENSG00000144893; Expressed in monocyte and 102 other tissues. DR ExpressionAtlas; Q86YW9; baseline and differential. DR Genevisible; Q86YW9; HS. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0008013; F:beta-catenin binding; IEA:InterPro. DR GO; GO:0003713; F:transcription coactivator activity; IBA:GO_Central. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central. DR InterPro; IPR019035; Mediator_Med12. DR InterPro; IPR021989; Mediator_Med12_catenin-bd. DR InterPro; IPR021990; Mediator_Med12_LCEWAV. DR Pfam; PF09497; Med12; 1. DR Pfam; PF12145; Med12-LCEWAV; 1. DR Pfam; PF12144; Med12-PQL; 1. DR SMART; SM01281; Med12; 1. DR AGR; HGNC:16050; -. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Autism spectrum disorder; Disease variant; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation. FT CHAIN 1..2145 FT /note="Mediator of RNA polymerase II transcription subunit FT 12-like protein" FT /id="PRO_0000313053" FT REGION 1..30 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1436..1460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1721..1802 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2029..2145 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1436..1457 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1749..1780 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1781..1802 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2052..2069 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2079..2145 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 462 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT VAR_SEQ 656 FT /note="E -> EEQSIMAHMGIDSGTTNIFDEVDKSDFKTDFGSEFP (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:11524702" FT /id="VSP_029994" FT VAR_SEQ 716..721 FT /note="DESSSH -> VSHCFS (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11524702" FT /id="VSP_029995" FT VAR_SEQ 722..2145 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11524702" FT /id="VSP_029996" FT VAR_SEQ 951 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_029997" FT VARIANT 401 FT /note="Q -> P (in dbSNP:rs17290219)" FT /id="VAR_037647" FT VARIANT 464 FT /note="E -> K (in dbSNP:rs3108728)" FT /id="VAR_037648" FT VARIANT 903 FT /note="Q -> H (in dbSNP:rs2131100)" FT /id="VAR_037649" FT VARIANT 1210 FT /note="R -> Q (in dbSNP:rs3732765)" FT /id="VAR_037650" FT VARIANT 1698 FT /note="R -> Q (in dbSNP:rs2276761)" FT /id="VAR_037651" FT VARIANT 1998..2145 FT /note="Missing (in NIZIDS)" FT /evidence="ECO:0000269|PubMed:31155615" FT /id="VAR_084189" FT CONFLICT 1088 FT /note="I -> T (in Ref. 5; BAB14198)" FT /evidence="ECO:0000305" SQ SEQUENCE 2145 AA; 240120 MW; 578F84E1C76004C9 CRC64; MAAFGLLSYE QRPLKRPRLG PPDVYPQDPK QKEDELTAVN VKQGFNNQPA FTGDEHGSAR NIVINPSKIG AYFSSILAEK LKLNTFQDTG KKKPQVNAKD NYWLVTARSQ SAIHSWFSDL AGNKPLSILA KKVPILSKKE DVFAYLAKYS VPMVRATWLI KMTCAYYSAI SEAKIKKRQA PDPNLEWTQI STRYLREQLA KISDFYHMAS STGDGPVPVP PEVEQAMKQW EYNEKLAFHM FQEGMLEKHE YLTWILDVLE KIRPMDDDLL KLLLPLMLQY SDEFVQSAYL SRRLAYFCAR RLSLLLSDSP NLLAAHSPHM MIGPNNSSIG APSPGPPGPG MSPVQLAFSD FLSCAQHGPL VYGLSCMLQT VTLCCPSALV WNYSTNENKS ANPGSPLDLL QVAPSSLPMP GGNTAFNQQV RARIYEVEQQ IKQRGRAVEV RWSFDKCQES TAGVTISRVL HTLEVLDRHC FDRTDSSNSM ETLYHKIFWA NQNKDNQEVA PNDEAVVTLL CEWAVSCKRS GKHRAMAVAK LLEKRQAEIE AERCGESEVL DEKESISSSS LAGSSLPVFQ NVLLRFLDTQ APSLSDPNSE CEKVEFVNLV LLFCEFIRHD VFSHDAYMCT LISRGDLSVT ASTRPRSPVG ENADEHYSKD HDVKMEIFSP MPGESCENAN TSLGRRMSVN CEKLVKREKP RELIFPSNYD LLRHLQYATH FPIPLDESSS HECNQRTILL YGVGKERDEA RHQLKKITKD ILKILNKKST TETGVGDEGQ KARKNKQETF PTLETVFTKL QLLSYFDQHQ VTSQISNNVL EQITSFASGT SYHLPLAHHI QLIFDLMEPA LNINGLIDFA IQLLNELSVV EAELLLKSSS LAGSYTTGLC VCIVAVLRRY HSCLILNPDQ TAQVFEGLCG VVKHVVNPSE CSSPERCILA YLYDLYVSCS HLRSKFGDLF SSACSKVKQT IYNNVMPANS NLRWDPDFMM DFIENPSARS INYSMLGKIL SDNAANRYSF VCNTLMNVCM GHQDAGRIND IANFSSELTA CCTVLSSEWL GVLKALCCSS NHVWGFNDVL CTVDVSDLSF HDSLATFIAI LIARQCFSLE DVVQHVALPS LLAAACGDAD AEPGARMTCR LLLHLFRAPQ ACFLPQATGK PFPGIRSSCD RHLLAAAHNS IEVGAVFAVL KAIMMLGDAK IGNNSVSSLK NDDFTMRGLR CDGNADDIWT ASQNPKSCGK SISIETANLR EYARYVLRTI CQQEWVGEHC LKEPERLCTD KELILDPVLS NMQAQKLLQL ICYPHGIKEC TEGDNLQRQH IKRILQNLEQ WTLRQSWLEL QLMIKQCLKD PGSGSVAEMN NLLDNIAKAT IEVFQQSADL NNSSNSGMSL FNPNSIGSAD TSSTRQNGIK TFLSSSERRG VWLVAPLIAR LPTSVQGRVL KAAGEELEKG QHLGSSSKKE RDRQKQKSMS LLSQQPFLSL VLTCLKGQDE QREGLLTSLQ NQVNQILSNW REERYQDDIK ARQMMHEALQ LRLNLVGGMF DTVQRSTQWT TDWALLLLQI ITSGTVDMHT NNELFTTVLD MLGVLINGTL ASDLSNASPG GSEENKRAYM NLVKKLKKEL GDKRSESIDK VRQLLPLPKQ TCDVITCEPM GSLIDTKGNK IAGFDSIDKK QGLQVSTKQK VSPWDLFEGQ KNPAPLSWAW FGTVRVDRRV IKYEEQHHLL LYHTHPMPKP RSYYLQPLPL PPEEEEEEPT SPVSQEPERK SAELSDQGKT TTDEEKKTKG RKRKTKSSSR VDEYPQSNIY RVPPNYSPIS SQMMHHPQST LWGYNLVGQP QQPGFFLQNQ SLTPGGSRLD PAGSFVPTNT KQALSNMLQR RSGAMMQPPS LHAITSQQQL IQMKLLQQQQ QQRLLRQAQT RPFQQGQPGD QAALFAAQAR PSPQLPQYPG LQQAQTMPQG YTMYGTQMPL QQTSQQQAGS VVLSPSYNSR AYPAAHSNPV LMERLRQIQQ QPSGYVQQQA SPYLQPLTGS QRLNHQALQQ SPLVGGGIDA VLTSAHPNLP SVPLPQDPMR PRQPQVRQQQ RLLQMQQPQQ PQPQQPPQPQ QSSQSQSQTL GLQAMQPQQP LFPRQGLQQT QQQQQTAALV RQLQKQLSSN QPQQGVTPYG HPSHF // ID MED13_HUMAN Reviewed; 2174 AA. AC Q9UHV7; B2RU05; O60334; DT 22-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 14-DEC-2022, entry version 185. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 13 {ECO:0000305}; DE AltName: Full=Activator-recruited cofactor 250 kDa component; DE Short=ARC250; DE AltName: Full=Mediator complex subunit 13; DE AltName: Full=Thyroid hormone receptor-associated protein 1; DE AltName: Full=Thyroid hormone receptor-associated protein complex 240 kDa component; DE Short=Trap240; DE AltName: Full=Vitamin D3 receptor-interacting protein complex component DRIP250; DE Short=DRIP250; GN Name=MED13 {ECO:0000312|HGNC:HGNC:22474}; GN Synonyms=ARC250, KIAA0593, THRAP1, TRAP240; 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], PROTEIN SEQUENCE OF 696-713, TISSUE RP SPECIFICITY, AND IDENTIFICATION IN TRAP COMPLEX. RC TISSUE=Cervix carcinoma; RX PubMed=10198638; DOI=10.1016/s1097-2765(00)80463-3; RA Ito M., Yuan C.-X., Malik S., Gu W., Fondell J.D., Yamamura S., Fu Z.-Y., RA Zhang X., Qin J., Roeder R.G.; RT "Identity between TRAP and SMCC complexes indicates novel pathways for the RT function of nuclear receptors and diverse mammalian activators."; RL Mol. Cell 3:361-370(1999). RN [2] 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 [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=Brain; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 170-2174. RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [6] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Ishikawa K.; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP PROTEIN SEQUENCE OF 1401-1408 AND 1358-1367, AND IDENTIFICATION IN ARC RP COMPLEX. RC TISSUE=Cervix carcinoma; RX PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors requires RT the DRIP complex."; RL Nature 398:824-828(1999). RN [8] RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 1429-1438; 1772-1783 RP AND 2073-2084. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND INTERACTION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [10] RP INTERACTION WITH MED1; MED18; MED21; MED28; MED29 AND MED30, IDENTIFICATION RP BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND RP ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [11] RP FUNCTION, AND INTERACTION WITH MED1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-500 AND SER-1029, 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-504 AND SER-537, 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 [14] RP IDENTIFICATION BY 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 [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-504; SER-826 AND RP SER-890, AND 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1029, 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 [18] RP INVOLVEMENT IN MRD61, VARIANTS MRD61 131-LEU--LEU-2174 DEL; ILE-326; RP THR-326 DEL; GLN-327; SER-327; THR-540; 582-LEU--LEU-2174 DEL; RP 1400-ARG--LEU-2174 DEL; LYS-2060 AND VAL-2064, AND CHARACTERIZATION OF RP VARIANT MRD61 1400-ARG--LEU-2174 DEL. RX PubMed=29740699; DOI=10.1007/s00439-018-1887-y; RG DDD study; RA Snijders Blok L., Hiatt S.M., Bowling K.M., Prokop J.W., Engel K.L., RA Cochran J.N., Bebin E.M., Bijlsma E.K., Ruivenkamp C.A.L., Terhal P., RA Simon M.E.H., Smith R., Hurst J.A., McLaughlin H., Person R., Crunk A., RA Wangler M.F., Streff H., Symonds J.D., Zuberi S.M., Elliott K.S., RA Sanders V.R., Masunga A., Hopkin R.J., Dubbs H.A., Ortiz-Gonzalez X.R., RA Pfundt R., Brunner H.G., Fisher S.E., Kleefstra T., Cooper G.M.; RT "De novo mutations in MED13, a component of the Mediator complex, are RT associated with a novel neurodevelopmental disorder."; RL Hum. Genet. 137:375-388(2018). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266, CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10198638}. CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 61 CC (MRD61) [MIM:618009]: An autosomal dominant form of intellectual CC disability, a disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. MRD61 CC is characterized by global developmental delay apparent in infancy with CC mildly impaired intellectual development, expressive speech delay, and CC behavioral abnormalities, including autism spectrum disorder and CC attention deficit-hyperactivity disorder. Additional features are CC highly variable and may include non-specific dysmorphic features, CC obstipation, ocular anomalies, and poor overall growth. CC {ECO:0000269|PubMed:29740699}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 13 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD22032.1; 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; AF117754; AAD22032.1; ALT_FRAME; mRNA. DR EMBL; AC008158; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018628; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC060798; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471179; EAW51438.1; -; Genomic_DNA. DR EMBL; BC140891; AAI40892.1; -; mRNA. DR EMBL; AB011165; BAA25519.2; -; mRNA. DR CCDS; CCDS42366.1; -. DR PIR; T01238; T01238. DR RefSeq; NP_005112.2; NM_005121.2. DR AlphaFoldDB; Q9UHV7; -. DR BioGRID; 115294; 87. DR ComplexPortal; CPX-3232; CKM complex variant 1. DR ComplexPortal; CPX-3263; CKM complex variant 2. DR CORUM; Q9UHV7; -. DR DIP; DIP-31468N; -. DR IntAct; Q9UHV7; 37. DR MINT; Q9UHV7; -. DR STRING; 9606.ENSP00000380888; -. DR iPTMnet; Q9UHV7; -. DR PhosphoSitePlus; Q9UHV7; -. DR BioMuta; MED13; -. DR DMDM; 317373421; -. DR EPD; Q9UHV7; -. DR jPOST; Q9UHV7; -. DR MassIVE; Q9UHV7; -. DR MaxQB; Q9UHV7; -. DR PaxDb; Q9UHV7; -. DR PeptideAtlas; Q9UHV7; -. DR ProteomicsDB; 84417; -. DR Antibodypedia; 31215; 81 antibodies from 22 providers. DR DNASU; 9969; -. DR Ensembl; ENST00000397786.7; ENSP00000380888.2; ENSG00000108510.10. DR GeneID; 9969; -. DR KEGG; hsa:9969; -. DR MANE-Select; ENST00000397786.7; ENSP00000380888.2; NM_005121.3; NP_005112.2. DR UCSC; uc002izo.3; human. DR CTD; 9969; -. DR DisGeNET; 9969; -. DR GeneCards; MED13; -. DR HGNC; HGNC:22474; MED13. DR HPA; ENSG00000108510; Low tissue specificity. DR MalaCards; MED13; -. DR MIM; 603808; gene. DR MIM; 618009; phenotype. DR neXtProt; NX_Q9UHV7; -. DR OpenTargets; ENSG00000108510; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA162395168; -. DR VEuPathDB; HostDB:ENSG00000108510; -. DR eggNOG; KOG3600; Eukaryota. DR GeneTree; ENSGT00390000013680; -. DR HOGENOM; CLU_000508_0_0_1; -. DR InParanoid; Q9UHV7; -. DR OMA; WWGEDPS; -. DR OrthoDB; 177884at2759; -. DR PhylomeDB; Q9UHV7; -. DR TreeFam; TF316867; -. DR PathwayCommons; Q9UHV7; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9UHV7; -. DR SIGNOR; Q9UHV7; -. DR BioGRID-ORCS; 9969; 34 hits in 1099 CRISPR screens. DR ChiTaRS; MED13; human. DR GeneWiki; MED13; -. DR GenomeRNAi; 9969; -. DR Pharos; Q9UHV7; Tbio. DR PRO; PR:Q9UHV7; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q9UHV7; protein. DR Bgee; ENSG00000108510; Expressed in endothelial cell and 208 other tissues. DR ExpressionAtlas; Q9UHV7; baseline and differential. DR Genevisible; Q9UHV7; HS. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0030374; F:nuclear receptor coactivator activity; NAS:UniProtKB. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl. DR InterPro; IPR009401; Med13_C. DR InterPro; IPR041285; MID_MedPIWI. DR Pfam; PF06333; Med13_C; 1. DR Pfam; PF18296; MID_MedPIWI; 1. DR AGR; HGNC:22474; -. PE 1: Evidence at protein level; KW Activator; Direct protein sequencing; Disease variant; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Repressor; Transcription; Transcription regulation. FT CHAIN 1..2174 FT /note="Mediator of RNA polymerase II transcription subunit FT 13" FT /id="PRO_0000065584" FT REGION 435..477 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 709..735 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 749..769 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 787..816 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 959..1054 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1484..1505 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1557..1617 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2015..2048 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1188..1192 FT /note="LXXLL motif 1" FT MOTIF 1279..1283 FT /note="LXXLL motif 2" FT COMPBIAS 435..455 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 456..473 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 709..731 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 753..769 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 970..1002 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1032..1054 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1557..1612 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 395 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 500 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 504 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 530 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q5SWW4" FT MOD_RES 537 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 826 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 890 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1029 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:24275569" FT VARIANT 131..2174 FT /note="Missing (in MRD61)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083556" FT VARIANT 326 FT /note="T -> I (in MRD61; dbSNP:rs1603405457)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083557" FT VARIANT 326 FT /note="Missing (in MRD61)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083558" FT VARIANT 327 FT /note="P -> Q (in MRD61)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083559" FT VARIANT 327 FT /note="P -> S (in MRD61)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083560" FT VARIANT 540 FT /note="P -> T (in MRD61; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083561" FT VARIANT 582..2174 FT /note="Missing (in MRD61)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083562" FT VARIANT 1370 FT /note="A -> P (in dbSNP:rs34805963)" FT /id="VAR_057792" FT VARIANT 1385 FT /note="A -> P (in dbSNP:rs35996128)" FT /id="VAR_057793" FT VARIANT 1400..2174 FT /note="Missing (in MRD61; no effect on protein levels)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083563" FT VARIANT 2060 FT /note="Q -> K (in MRD61; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083564" FT VARIANT 2064 FT /note="A -> V (in MRD61; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:29740699" FT /id="VAR_083565" FT CONFLICT 106 FT /note="V -> M (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 392 FT /note="R -> K (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 467 FT /note="K -> E (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 712 FT /note="K -> A (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 800 FT /note="K -> R (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 930 FT /note="P -> L (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 984 FT /note="F -> C (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" FT CONFLICT 1090 FT /note="F -> S (in Ref. 1; AAD22032)" FT /evidence="ECO:0000305" SQ SEQUENCE 2174 AA; 239297 MW; 0FA54C84FE2C91E2 CRC64; MSASFVPNGA SLEDCHCNLF CLADLTGIKW KKYVWQGPTS APILFPVTEE DPILSSFSRC LKADVLGVWR RDQRPGRREL WIFWWGEDPS FADLIHHDLS EEEDGVWENG LSYECRTLLF KAVHNLLERC LMNRNFVRIG KWFVKPYEKD EKPINKSEHL SCSFTFFLHG DSNVCTSVEI NQHQPVYLLS EEHITLAQQS NSPFQVILCP FGLNGTLTGQ AFKMSDSATK KLIGEWKQFY PISCCLKEMS EEKQEDMDWE DDSLAAVEVL VAGVRMIYPA CFVLVPQSDI PTPSPVGSTH CSSSCLGVHQ VPASTRDPAM SSVTLTPPTS PEEVQTVDPQ SVQKWVKFSS VSDGFNSDST SHHGGKIPRK LANHVVDRVW QECNMNRAQN KRKYSASSGG LCEEATAAKV ASWDFVEATQ RTNCSCLRHK NLKSRNAGQQ GQAPSLGQQQ QILPKHKTNE KQEKSEKPQK RPLTPFHHRV SVSDDVGMDA DSASQRLVIS APDSQVRFSN IRTNDVAKTP QMHGTEMANS PQPPPLSPHP CDVVDEGVTK TPSTPQSQHF YQMPTPDPLV PSKPMEDRID SLSQSFPPQY QEAVEPTVYV GTAVNLEEDE ANIAWKYYKF PKKKDVEFLP PQLPSDKFKD DPVGPFGQES VTSVTELMVQ CKKPLKVSDE LVQQYQIKNQ CLSAIASDAE QEPKIDPYAF VEGDEEFLFP DKKDRQNSER EAGKKHKVED GTSSVTVLSH EEDAMSLFSP SIKQDAPRPT SHARPPSTSL IYDSDLAVSY TDLDNLFNSD EDELTPGSKK SANGSDDKAS CKESKTGNLD PLSCISTADL HKMYPTPPSL EQHIMGFSPM NMNNKEYGSM DTTPGGTVLE GNSSSIGAQF KIEVDEGFCS PKPSEIKDFS YVYKPENCQI LVGCSMFAPL KTLPSQYLPP IKLPEECIYR QSWTVGKLEL LSSGPSMPFI KEGDGSNMDQ EYGTAYTPQT HTSFGMPPSS APPSNSGAGI LPSPSTPRFP TPRTPRTPRT PRGAGGPASA QGSVKYENSD LYSPASTPST CRPLNSVEPA TVPSIPEAHS LYVNLILSES VMNLFKDCNF DSCCICVCNM NIKGADVGVY IPDPTQEAQY RCTCGFSAVM NRKFGNNSGL FLEDELDIIG RNTDCGKEAE KRFEALRATS AEHVNGGLKE SEKLSDDLIL LLQDQCTNLF SPFGAADQDP FPKSGVISNW VRVEERDCCN DCYLALEHGR QFMDNMSGGK VDEALVKSSC LHPWSKRNDV SMQCSQDILR MLLSLQPVLQ DAIQKKRTVR PWGVQGPLTW QQFHKMAGRG SYGTDESPEP LPIPTFLLGY DYDYLVLSPF ALPYWERLML EPYGSQRDIA YVVLCPENEA LLNGAKSFFR DLTAIYESCR LGQHRPVSRL LTDGIMRVGS TASKKLSEKL VAEWFSQAAD GNNEAFSKLK LYAQVCRYDL GPYLASLPLD SSLLSQPNLV APTSQSLITP PQMTNTGNAN TPSATLASAA SSTMTVTSGV AISTSVATAN STLTTASTSS SSSSNLNSGV SSNKLPSFPP FGSMNSNAAG SMSTQANTVQ SGQLGGQQTS ALQTAGISGE SSSLPTQPHP DVSESTMDRD KVGIPTDGDS HAVTYPPAIV VYIIDPFTYE NTDESTNSSS VWTLGLLRCF LEMVQTLPPH IKSTVSVQII PCQYLLQPVK HEDREIYPQH LKSLAFSAFT QCRRPLPTST NVKTLTGFGP GLAMETALRS PDRPECIRLY APPFILAPVK DKQTELGETF GEAGQKYNVL FVGYCLSHDQ RWILASCTDL YGELLETCII NIDVPNRARR KKSSARKFGL QKLWEWCLGL VQMSSLPWRV VIGRLGRIGH GELKDWSCLL SRRNLQSLSK RLKDMCRMCG ISAADSPSIL SACLVAMEPQ GSFVIMPDSV STGSVFGRST TLNMQTSQLN TPQDTSCTHI LVFPTSASVQ VASATYTTEN LDLAFNPNND GADGMGIFDL LDTGDDLDPD IINILPASPT GSPVHSPGSH YPHGGDAGKG QSTDRLLSTE PHEEVPNILQ QPLALGYFVS TAKAGPLPDW FWSACPQAQY QCPLFLKASL HLHVPSVQSD ELLHSKHSHP LDSNQTSDVL RFVLEQYNAL SWLTCDPATQ DRRSCLPIHF VVLNQLYNFI MNML // ID RIPP1_HUMAN Reviewed; 151 AA. AC Q0D2K3; A0JP63; Q0VGB3; Q5JRB8; Q5JRB9; DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 1. DT 14-DEC-2022, entry version 114. DE RecName: Full=Protein ripply1; GN Name=RIPPLY1 {ECO:0000312|HGNC:HGNC:25117}; 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] {ECO:0000312|EMBL:CAI40160.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [2] {ECO:0000312|EMBL:EAX02733.1} 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 [3] {ECO:0000305, ECO:0000312|EMBL:AAI05692.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [4] {ECO:0000305} RP IDENTIFICATION AS RIPPLY1. RX PubMed=16326386; DOI=10.1016/j.devcel.2005.09.021; RA Kawamura A., Koshida S., Hijikata H., Ohbayashi A., Kondoh H., Takada S.; RT "Groucho-associated transcriptional repressor ripply1 is required for RT proper transition from the presomitic mesoderm to somites."; RL Dev. Cell 9:735-744(2005). CC -!- FUNCTION: Plays a role in somitogenesis. Essential for transcriptional CC repression of the segmental patterning genes, thus terminating the CC segmentation program in the presomitic mesoderm, and also required for CC the maintenance of rostrocaudal polarity in somites (By similarity). CC {ECO:0000250|UniProtKB:Q2WG80}. CC -!- INTERACTION: CC Q0D2K3; Q5T686: AVPI1; NbExp=3; IntAct=EBI-10226430, EBI-8640233; CC Q0D2K3; Q8N7W2-2: BEND7; NbExp=3; IntAct=EBI-10226430, EBI-10181188; CC Q0D2K3; Q5T655: CFAP58; NbExp=3; IntAct=EBI-10226430, EBI-10245749; CC Q0D2K3; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-10226430, EBI-11962928; CC Q0D2K3; Q66K64: DCAF15; NbExp=3; IntAct=EBI-10226430, EBI-2559052; CC Q0D2K3; Q96HU8: DIRAS2; NbExp=3; IntAct=EBI-10226430, EBI-911391; CC Q0D2K3; Q14192: FHL2; NbExp=3; IntAct=EBI-10226430, EBI-701903; CC Q0D2K3; Q8TC17: GRAPL; NbExp=3; IntAct=EBI-10226430, EBI-18300553; CC Q0D2K3; Q8TE85-2: GRHL3; NbExp=3; IntAct=EBI-10226430, EBI-12827521; CC Q0D2K3; Q16695: H3-4; NbExp=3; IntAct=EBI-10226430, EBI-358900; CC Q0D2K3; P61296-2: HAND2; NbExp=3; IntAct=EBI-10226430, EBI-13086076; CC Q0D2K3; Q8WUI4-5: HDAC7; NbExp=3; IntAct=EBI-10226430, EBI-10276431; CC Q0D2K3; Q8WUI4-6: HDAC7; NbExp=6; IntAct=EBI-10226430, EBI-12094670; CC Q0D2K3; Q5VVH5: IRAK1BP1; NbExp=3; IntAct=EBI-10226430, EBI-9658404; CC Q0D2K3; O76011: KRT34; NbExp=3; IntAct=EBI-10226430, EBI-1047093; CC Q0D2K3; P59942: MCCD1; NbExp=3; IntAct=EBI-10226430, EBI-11987923; CC Q0D2K3; Q99750: MDFI; NbExp=6; IntAct=EBI-10226430, EBI-724076; CC Q0D2K3; A0JLT2-2: MED19; NbExp=3; IntAct=EBI-10226430, EBI-13288755; CC Q0D2K3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-10226430, EBI-16439278; CC Q0D2K3; P17568: NDUFB7; NbExp=3; IntAct=EBI-10226430, EBI-1246238; CC Q0D2K3; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-10226430, EBI-11022007; CC Q0D2K3; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-10226430, EBI-10302990; CC Q0D2K3; Q99471: PFDN5; NbExp=3; IntAct=EBI-10226430, EBI-357275; CC Q0D2K3; Q9UPG8: PLAGL2; NbExp=5; IntAct=EBI-10226430, EBI-2876622; CC Q0D2K3; P86480: PRR20D; NbExp=3; IntAct=EBI-10226430, EBI-12754095; CC Q0D2K3; Q9NZH5-2: PTTG2; NbExp=3; IntAct=EBI-10226430, EBI-17630019; CC Q0D2K3; Q93062: RBPMS; NbExp=3; IntAct=EBI-10226430, EBI-740322; CC Q0D2K3; Q04864: REL; NbExp=3; IntAct=EBI-10226430, EBI-307352; CC Q0D2K3; Q15669: RHOH; NbExp=3; IntAct=EBI-10226430, EBI-1244971; CC Q0D2K3; Q5SSQ6-2: SAPCD1; NbExp=3; IntAct=EBI-10226430, EBI-13072754; CC Q0D2K3; Q9NVV9: THAP1; NbExp=6; IntAct=EBI-10226430, EBI-741515; CC Q0D2K3; Q08117-2: TLE5; NbExp=3; IntAct=EBI-10226430, EBI-11741437; CC Q0D2K3; Q13077: TRAF1; NbExp=3; IntAct=EBI-10226430, EBI-359224; CC Q0D2K3; Q12933: TRAF2; NbExp=6; IntAct=EBI-10226430, EBI-355744; CC Q0D2K3; Q13114: TRAF3; NbExp=3; IntAct=EBI-10226430, EBI-357631; CC Q0D2K3; Q08AM6: VAC14; NbExp=3; IntAct=EBI-10226430, EBI-2107455; CC Q0D2K3; Q99990: VGLL1; NbExp=3; IntAct=EBI-10226430, EBI-11983165; CC Q0D2K3; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-10226430, EBI-12030590; CC Q0D2K3; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-10226430, EBI-4395669; CC Q0D2K3; Q8NCA9: ZNF784; NbExp=3; IntAct=EBI-10226430, EBI-7138303; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q2WG80}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15772651}; CC IsoId=Q0D2K3-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15772651}; CC IsoId=Q0D2K3-2; Sequence=VSP_052555; CC -!- DOMAIN: The ripply homology domain is required for transcriptional CC repression. {ECO:0000250}. CC -!- DOMAIN: The WRPW motif is required for binding to TLE/GROUCHO proteins. CC {ECO:0000250|UniProtKB:Q2WG80}. CC -!- SIMILARITY: Belongs to the ripply family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI10437.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC Sequence=CAI40159.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI40160.1; Type=Erroneous initiation; 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; AL591849; CAI40159.1; ALT_INIT; Genomic_DNA. DR EMBL; AL591849; CAI40160.1; ALT_INIT; Genomic_DNA. DR EMBL; CH471120; EAX02733.1; -; Genomic_DNA. DR EMBL; BC105691; AAI05692.1; -; mRNA. DR EMBL; BC105692; AAI05693.1; -; mRNA. DR EMBL; BC110436; AAI10437.1; ALT_SEQ; mRNA. DR EMBL; BC127250; AAI27251.1; -; mRNA. DR CCDS; CCDS48145.1; -. [Q0D2K3-1] DR CCDS; CCDS55471.1; -. [Q0D2K3-2] DR RefSeq; NP_001165177.1; NM_001171706.1. [Q0D2K3-2] DR RefSeq; NP_612391.1; NM_138382.2. [Q0D2K3-1] DR AlphaFoldDB; Q0D2K3; -. DR BioGRID; 124912; 56. DR IntAct; Q0D2K3; 44. DR STRING; 9606.ENSP00000276173; -. DR PhosphoSitePlus; Q0D2K3; -. DR BioMuta; RIPPLY1; -. DR MassIVE; Q0D2K3; -. DR PaxDb; Q0D2K3; -. DR PeptideAtlas; Q0D2K3; -. DR Antibodypedia; 63924; 12 antibodies from 8 providers. DR DNASU; 92129; -. DR Ensembl; ENST00000276173.5; ENSP00000276173.4; ENSG00000147223.6. [Q0D2K3-1] DR Ensembl; ENST00000411805.1; ENSP00000400539.1; ENSG00000147223.6. [Q0D2K3-2] DR GeneID; 92129; -. DR KEGG; hsa:92129; -. DR MANE-Select; ENST00000276173.5; ENSP00000276173.4; NM_138382.3; NP_612391.1. DR UCSC; uc004emr.3; human. [Q0D2K3-1] DR CTD; 92129; -. DR DisGeNET; 92129; -. DR GeneCards; RIPPLY1; -. DR HGNC; HGNC:25117; RIPPLY1. DR HPA; ENSG00000147223; Group enriched (kidney, liver). DR MIM; 300575; gene. DR neXtProt; NX_Q0D2K3; -. DR OpenTargets; ENSG00000147223; -. DR PharmGKB; PA162401348; -. DR VEuPathDB; HostDB:ENSG00000147223; -. DR eggNOG; ENOG502S6U6; Eukaryota. DR GeneTree; ENSGT00940000161952; -. DR HOGENOM; CLU_117697_0_0_1; -. DR InParanoid; Q0D2K3; -. DR OMA; ADSEFHH; -. DR PhylomeDB; Q0D2K3; -. DR TreeFam; TF336045; -. DR PathwayCommons; Q0D2K3; -. DR SignaLink; Q0D2K3; -. DR BioGRID-ORCS; 92129; 15 hits in 697 CRISPR screens. DR GenomeRNAi; 92129; -. DR Pharos; Q0D2K3; Tdark. DR PRO; PR:Q0D2K3; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q0D2K3; protein. DR Bgee; ENSG00000147223; Expressed in right lobe of liver and 63 other tissues. DR Genevisible; Q0D2K3; HS. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0032525; P:somite rostral/caudal axis specification; ISS:UniProtKB. DR GO; GO:0001757; P:somite specification; ISS:UniProtKB. DR InterPro; IPR028127; Ripply_fam. DR PANTHER; PTHR16770; -; 1. DR Pfam; PF14998; Ripply; 1. DR AGR; HGNC:25117; -. PE 1: Evidence at protein level; KW Alternative splicing; Developmental protein; Nucleus; Reference proteome; KW Repressor; Transcription; Transcription regulation. FT CHAIN 1..151 FT /note="Protein ripply1" FT /id="PRO_0000307756" FT REGION 96..131 FT /note="Ripply homology domain" FT /evidence="ECO:0000255" FT REGION 130..151 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 57..60 FT /note="WRPW motif" FT /evidence="ECO:0000255" FT COMPBIAS 132..151 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 53..99 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:15772651" FT /id="VSP_052555" SQ SEQUENCE 151 AA; 16379 MW; 201C7BA5C5C8025F CRC64; MDSAACAAAA TPVPALALAL APDLAQAPLA LPGLLSPSCL LSSGQEVNGS ERGTCLWRPW LSSTNDSPRQ MRKLVDLAAG GATAAEVTKA ESKFHHPVRL FWPKSRSFDY LYSAGEILLQ NFPVQATINL YEDSDSEEEE EDEEQEDEEE K // ID MED8_HUMAN Reviewed; 268 AA. AC Q96G25; A9IZ91; A9IZ92; Q5JUY8; Q96FQ4; DT 23-MAY-2003, integrated into UniProtKB/Swiss-Prot. DT 23-MAY-2003, sequence version 2. DT 14-DEC-2022, entry version 177. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 8; DE AltName: Full=Activator-recruited cofactor 32 kDa component; DE Short=ARC32; DE AltName: Full=Mediator complex subunit 8; GN Name=MED8; 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), IDENTIFICATION IN AN E3 UBIQUITIN RP LIGASE COMPLEX, INTERACTION WITH MED10, AND MUTAGENESIS OF LEU-143 AND RP CYS-147. RX PubMed=12149480; DOI=10.1073/pnas.162424199; RA Brower C.S., Sato S., Tomomori-Sato C., Kamura T., Pause A., Stearman R., RA Klausner R.D., Malik S., Lane W.S., Sorokina I., Roeder R.G., Conaway J.W., RA Conaway R.C.; RT "Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that RT can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase."; RL Proc. Natl. Acad. Sci. U.S.A. 99:10353-10358(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 1-259 (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [LARGE RP SCALE MRNA] OF 5-268 (ISOFORM 2). RC TISSUE=Cervix carcinoma, Melanoma, 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 [4] RP IDENTIFICATION IN THE ARC COMPLEX, AND PROTEIN SEQUENCE OF 72-83 AND RP 189-200. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [5] RP INTERACTION WITH MED10. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, 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 [9] 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82, 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). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. May play a role as a target CC recruitment subunit in E3 ubiquitin-protein ligase complexes and thus CC in ubiquitination and subsequent proteasomal degradation of target CC proteins. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. May be part of a CC multisubunit E3 ubiquitin-protein ligase complex with the elongin BC CC complex (ELOB and ELOC), CUL2 and RBX1. {ECO:0000269|PubMed:10235267, CC ECO:0000269|PubMed:12149480, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q96G25; Q15370: ELOB; NbExp=5; IntAct=EBI-394405, EBI-301238; CC Q96G25; Q15369: ELOC; NbExp=3; IntAct=EBI-394405, EBI-301231; CC Q96G25-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-10286267, EBI-10171697; CC Q96G25-2; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-10286267, EBI-302345; CC Q96G25-2; P31321: PRKAR1B; NbExp=3; IntAct=EBI-10286267, EBI-2805516; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96G25-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96G25-2; Sequence=VSP_007524; CC Name=3; CC IsoId=Q96G25-3; Sequence=VSP_035507; CC -!- DOMAIN: The elongin BC complex binding domain is also known as BC-box CC with the consensus [APST]-L-x(3)-C-x(3)-[AILV]. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 8 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BG722466; 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; AF521562; AAM76709.1; -; mRNA. DR EMBL; AL139289; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010019; AAH10019.3; -; mRNA. DR EMBL; BC010543; AAH10543.2; -; mRNA. DR EMBL; BG722466; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS486.2; -. [Q96G25-2] DR CCDS; CCDS487.2; -. [Q96G25-1] DR CCDS; CCDS60108.1; -. [Q96G25-3] DR RefSeq; NP_001001653.1; NM_001001653.2. [Q96G25-3] DR RefSeq; NP_443109.2; NM_052877.4. [Q96G25-2] DR RefSeq; NP_963836.2; NM_201542.4. [Q96G25-1] DR PDB; 7EMF; EM; 3.50 A; H=1-268. DR PDB; 7ENA; EM; 4.07 A; h=1-268. DR PDB; 7ENC; EM; 4.13 A; h=1-268. DR PDB; 7ENJ; EM; 4.40 A; H=1-268. DR PDB; 7LBM; EM; 4.80 A; h=1-268. DR PDB; 7NVR; EM; 4.50 A; b=1-268. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q96G25; -. DR SMR; Q96G25; -. DR BioGRID; 125219; 114. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q96G25; -. DR IntAct; Q96G25; 60. DR MINT; Q96G25; -. DR STRING; 9606.ENSP00000290663; -. DR iPTMnet; Q96G25; -. DR PhosphoSitePlus; Q96G25; -. DR BioMuta; MED8; -. DR DMDM; 31076772; -. DR EPD; Q96G25; -. DR jPOST; Q96G25; -. DR MassIVE; Q96G25; -. DR MaxQB; Q96G25; -. DR PaxDb; Q96G25; -. DR PeptideAtlas; Q96G25; -. DR ProteomicsDB; 76585; -. [Q96G25-1] DR ProteomicsDB; 76586; -. [Q96G25-2] DR ProteomicsDB; 76587; -. [Q96G25-3] DR Antibodypedia; 32328; 179 antibodies from 27 providers. DR DNASU; 112950; -. DR Ensembl; ENST00000290663.10; ENSP00000290663.6; ENSG00000159479.17. [Q96G25-2] DR Ensembl; ENST00000372455.4; ENSP00000361533.4; ENSG00000159479.17. [Q96G25-3] DR Ensembl; ENST00000372457.9; ENSP00000361535.4; ENSG00000159479.17. [Q96G25-1] DR GeneID; 112950; -. DR KEGG; hsa:112950; -. DR MANE-Select; ENST00000372457.9; ENSP00000361535.4; NM_201542.5; NP_963836.2. DR UCSC; uc001cje.3; human. [Q96G25-1] DR CTD; 112950; -. DR DisGeNET; 112950; -. DR GeneCards; MED8; -. DR HGNC; HGNC:19971; MED8. DR HPA; ENSG00000159479; Low tissue specificity. DR MIM; 607956; gene. DR neXtProt; NX_Q96G25; -. DR OpenTargets; ENSG00000159479; -. DR PharmGKB; PA134893073; -. DR VEuPathDB; HostDB:ENSG00000159479; -. DR eggNOG; KOG3583; Eukaryota. DR GeneTree; ENSGT00390000011838; -. DR HOGENOM; CLU_085476_0_0_1; -. DR InParanoid; Q96G25; -. DR OMA; IIMRVND; -. DR OrthoDB; 1392867at2759; -. DR PhylomeDB; Q96G25; -. DR TreeFam; TF316778; -. DR PathwayCommons; Q96G25; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q96G25; -. DR SIGNOR; Q96G25; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 112950; 549 hits in 1110 CRISPR screens. DR ChiTaRS; MED8; human. DR GeneWiki; MED8; -. DR GenomeRNAi; 112950; -. DR Pharos; Q96G25; Tbio. DR PRO; PR:Q96G25; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q96G25; protein. DR Bgee; ENSG00000159479; Expressed in oocyte and 201 other tissues. DR Genevisible; Q96G25; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR InterPro; IPR019364; Mediatior_Med8_fun/met. DR PANTHER; PTHR13074; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 8; 1. DR Pfam; PF10232; Med8; 1. DR AGR; HGNC:19971; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Coiled coil; KW Direct protein sequencing; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation pathway. FT CHAIN 1..268 FT /note="Mediator of RNA polymerase II transcription subunit FT 8" FT /id="PRO_0000096394" FT REGION 142..151 FT /note="Interaction with the Elongin BC complex" FT REGION 156..176 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 193..268 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 1..28 FT /evidence="ECO:0000255" FT COILED 133..163 FT /evidence="ECO:0000255" FT COMPBIAS 214..240 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 253..268 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..89 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_035507" FT VAR_SEQ 268 FT /note="R -> RPSCLGFILAIPLRRKVKKLLGQEGKKNAHLQLW (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_007524" FT MUTAGEN 143 FT /note="L->P: Impairs interaction with the Elongin BC FT complex; when associated with F-147." FT /evidence="ECO:0000269|PubMed:12149480" FT MUTAGEN 147 FT /note="C->F: Impairs interaction with the Elongin BC FT complex; when associated with P-143." FT /evidence="ECO:0000269|PubMed:12149480" FT CONFLICT 257 FT /note="N -> K (in Ref. 3; BG722466)" FT /evidence="ECO:0000305" FT HELIX 4..35 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 42..65 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 71..73 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 74..77 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 87..93 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 104..108 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 115..128 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 135..157 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 175..186 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 268 AA; 29080 MW; 6C186A4CECD1AFB3 CRC64; MQREEKQLEA SLDALLSQVA DLKNSLGSFI CKLENEYGRL TWPSVLDSFA LLSGQLNTLN KVLKHEKTPL FRNQVIIPLV LSPDRDEDLM RQTEGRVPVF SHEVVPDHLR TKPDPEVEEQ EKQLTTDAAR IGADAAQKQI QSLNKMCSNL LEKISKEERE SESGGLRPNK QTFNPTDTNA LVAAVAFGKG LSNWRPSGSS GPGQAGQPGA GTILAGTSGL QQVQMAGAPS QQQPMLSGVQ MAQAGQPGKM PSGIKTNIKS ASMHPYQR // ID MED16_HUMAN Reviewed; 877 AA. AC Q9Y2X0; Q6PJT2; Q96AD4; Q96I35; Q9Y652; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 12-APR-2005, sequence version 2. DT 14-DEC-2022, entry version 169. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 16; DE AltName: Full=Mediator complex subunit 16; DE AltName: Full=Thyroid hormone receptor-associated protein 5; DE AltName: Full=Thyroid hormone receptor-associated protein complex 95 kDa component; DE Short=Trap95; DE AltName: Full=Vitamin D3 receptor-interacting protein complex 92 kDa component; DE Short=DRIP92; GN Name=MED16; Synonyms=DRIP92 {ECO:0000312|EMBL:AAD31087.1}, THRAP5; 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] {ECO:0000305, ECO:0000312|EMBL:AAD30032.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 277-283, RP IDENTIFICATION IN TRAP COMPLEX, AND FUNCTION OF TRAP COMPLEX. RC TISSUE=Cervix carcinoma; RX PubMed=10198638; DOI=10.1016/s1097-2765(00)80463-3; RA Ito M., Yuan C.-X., Malik S., Gu W., Fondell J.D., Yamamura S., Fu Z.-Y., RA Zhang X., Qin J., Roeder R.G.; RT "Identity between TRAP and SMCC complexes indicates novel pathways for the RT function of nuclear receptors and diverse mammalian activators."; RL Mol. Cell 3:361-370(1999). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD31087.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF 27-42 AND RP 755-772, IDENTIFICATION IN ARC COMPLEX, AND FUNCTION OF ARC COMPLEX. RC TISSUE=B-cell {ECO:0000269|PubMed:10235266}; RX PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors requires RT the DRIP complex."; RL Nature 398:824-828(1999). RN [3] {ECO:0000312|EMBL:AAH11841.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 248-877 (ISOFORM 4). RC TISSUE=Skin {ECO:0000312|EMBL:AAH17282.1}, and Uterus RC {ECO:0000312|EMBL:AAH11841.1}; 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 [4] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [5] RP INTERACTION WITH MED1; MED10; MED21 AND MED30, IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND ASSOCIATION OF RP THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:10198638, CC ECO:0000269|PubMed:10235266}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9Y2X0; O60244: MED14; NbExp=2; IntAct=EBI-394541, EBI-394489; CC Q9Y2X0; Q9ULK4: MED23; NbExp=4; IntAct=EBI-394541, EBI-311161; CC Q9Y2X0; O75448: MED24; NbExp=2; IntAct=EBI-394541, EBI-394523; CC Q9Y2X0; Q71SY5: MED25; NbExp=3; IntAct=EBI-394541, EBI-394558; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1 {ECO:0000269|PubMed:10198638}; CC IsoId=Q9Y2X0-1; Sequence=Displayed; CC Name=2 {ECO:0000305}; CC IsoId=Q9Y2X0-2; Sequence=VSP_051724; CC Name=3 {ECO:0000305}; CC IsoId=Q9Y2X0-3; Sequence=VSP_051722, VSP_051724; CC Name=4 {ECO:0000305}; CC IsoId=Q9Y2X0-4; Sequence=VSP_051721, VSP_051723; CC Name=5; CC IsoId=Q9Y2X0-5; Sequence=VSP_028749, VSP_028750; CC -!- SIMILARITY: Belongs to the Mediator complex subunit 16 family. CC {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-13 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD31087.1; 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; AF121228; AAD30032.1; -; mRNA. DR EMBL; AF106934; AAD31087.1; ALT_FRAME; mRNA. DR EMBL; BC004554; AAH04554.1; -; mRNA. DR EMBL; BC007853; AAH07853.2; -; mRNA. DR EMBL; BC011841; AAH11841.1; -; mRNA. DR EMBL; BC017282; AAH17282.1; -; mRNA. DR CCDS; CCDS12047.1; -. [Q9Y2X0-1] DR RefSeq; NP_005472.2; NM_005481.2. [Q9Y2X0-1] DR PDB; 7EMF; EM; 3.50 A; P=1-828. DR PDB; 7ENA; EM; 4.07 A; p=1-828. DR PDB; 7ENC; EM; 4.13 A; p=1-828. DR PDB; 7ENJ; EM; 4.40 A; P=1-877. DR PDB; 7LBM; EM; 4.80 A; 0=1-828. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR AlphaFoldDB; Q9Y2X0; -. DR SMR; Q9Y2X0; -. DR BioGRID; 115342; 103. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9Y2X0; -. DR DIP; DIP-31463N; -. DR IntAct; Q9Y2X0; 45. DR MINT; Q9Y2X0; -. DR STRING; 9606.ENSP00000325612; -. DR iPTMnet; Q9Y2X0; -. DR PhosphoSitePlus; Q9Y2X0; -. DR SwissPalm; Q9Y2X0; -. DR BioMuta; MED16; -. DR DMDM; 62511180; -. DR EPD; Q9Y2X0; -. DR jPOST; Q9Y2X0; -. DR MassIVE; Q9Y2X0; -. DR MaxQB; Q9Y2X0; -. DR PaxDb; Q9Y2X0; -. DR PeptideAtlas; Q9Y2X0; -. DR ProteomicsDB; 85922; -. [Q9Y2X0-1] DR ProteomicsDB; 85923; -. [Q9Y2X0-2] DR ProteomicsDB; 85924; -. [Q9Y2X0-3] DR ProteomicsDB; 85925; -. [Q9Y2X0-4] DR ProteomicsDB; 85926; -. [Q9Y2X0-5] DR Antibodypedia; 10226; 192 antibodies from 24 providers. DR DNASU; 10025; -. DR Ensembl; ENST00000312090.10; ENSP00000308528.4; ENSG00000175221.16. [Q9Y2X0-3] DR Ensembl; ENST00000325464.6; ENSP00000325612.1; ENSG00000175221.16. [Q9Y2X0-1] DR Ensembl; ENST00000395808.7; ENSP00000379153.1; ENSG00000175221.16. [Q9Y2X0-2] DR GeneID; 10025; -. DR KEGG; hsa:10025; -. DR MANE-Select; ENST00000325464.6; ENSP00000325612.1; NM_005481.3; NP_005472.2. DR UCSC; uc002lqd.2; human. [Q9Y2X0-1] DR CTD; 10025; -. DR DisGeNET; 10025; -. DR GeneCards; MED16; -. DR HGNC; HGNC:17556; MED16. DR HPA; ENSG00000175221; Low tissue specificity. DR MIM; 604062; gene. DR neXtProt; NX_Q9Y2X0; -. DR OpenTargets; ENSG00000175221; -. DR PharmGKB; PA162395406; -. DR VEuPathDB; HostDB:ENSG00000175221; -. DR eggNOG; ENOG502QQ3H; Eukaryota. DR GeneTree; ENSGT00390000003821; -. DR HOGENOM; CLU_018773_0_0_1; -. DR InParanoid; Q9Y2X0; -. DR OMA; DSHAQLH; -. DR OrthoDB; 493637at2759; -. DR PhylomeDB; Q9Y2X0; -. DR PathwayCommons; Q9Y2X0; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9Y2X0; -. DR SIGNOR; Q9Y2X0; -. DR BioGRID-ORCS; 10025; 148 hits in 1104 CRISPR screens. DR ChiTaRS; MED16; human. DR GeneWiki; MED16; -. DR GenomeRNAi; 10025; -. DR Pharos; Q9Y2X0; Tbio. DR PRO; PR:Q9Y2X0; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9Y2X0; protein. DR Bgee; ENSG00000175221; Expressed in lower esophagus mucosa and 93 other tissues. DR ExpressionAtlas; Q9Y2X0; baseline and differential. DR Genevisible; Q9Y2X0; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; NAS:UniProtKB. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc. DR Gene3D; 2.130.10.10; -; 1. DR InterPro; IPR021665; Mediator_Med16. DR InterPro; IPR011041; Quinoprot_gluc/sorb_DH. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR PANTHER; PTHR13224; THYROID HORMONE RECEPTOR-ASSOCIATED PROTEIN-RELATED; 1. DR Pfam; PF11635; Med16; 1. DR SMART; SM00320; WD40; 1. DR SUPFAM; SSF50952; Soluble quinoprotein glucose dehydrogenase; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR AGR; HGNC:17556; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Nucleus; Reference proteome; Repeat; Transcription; KW Transcription regulation; WD repeat. FT CHAIN 1..877 FT /note="Mediator of RNA polymerase II transcription subunit FT 16" FT /id="PRO_0000051292" FT REPEAT 21..71 FT /note="WD 1" FT REPEAT 72..119 FT /note="WD 2" FT REPEAT 120..165 FT /note="WD 3" FT REPEAT 166..203 FT /note="WD 4" FT REPEAT 204..257 FT /note="WD 5" FT REPEAT 258..334 FT /note="WD 6" FT REPEAT 335..415 FT /note="WD 7" FT REPEAT 416..460 FT /note="WD 8" FT REPEAT 461..495 FT /note="WD 9" FT REGION 848..877 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 863..877 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 636..751 FT /note="GSLLRPGHSFLRDGTSLGMLRELMVVIRIWGLLKPSCLPVYTATSDTQDSMS FT LLFRLLTKLWICCRDEGPASEPDEALVDECCLLPSQLLIPSLDWLPASDGLVSRLQPKQ FT PLRLQ -> VAMRAQRASRTRRWWMNAACCPASCLSPAWTGCQPATAWLAACSPSSPFV FT CSLAGRPRCLAVLPPCSSTASPGPQASPRSTTCGGCTLALAPRRNARPAPGAAVSPCSS FT RPTEPRR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_051721" FT VAR_SEQ 636..663 FT /note="GSLLRPGHSFLRDGTSLGMLRELMVVIR -> PCPTSEPCPTSEPSPTSEPS FT PTSEPSSP (in isoform 5)" FT /evidence="ECO:0000303|PubMed:10235266" FT /id="VSP_028749" FT VAR_SEQ 664..877 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:10235266" FT /id="VSP_028750" FT VAR_SEQ 700 FT /note="C -> FPSTGPCSVWVLLGWQPLPG (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_051722" FT VAR_SEQ 752..877 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_051723" FT VAR_SEQ 829..877 FT /note="AVEGRGPDACVTSRASEEAPAFVQLGPQSTHHSPRTPRSLDHLHPEDRP -> FT CGGLWWRVPLSYP (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10235266, FT ECO:0000303|PubMed:15489334" FT /id="VSP_051724" FT VARIANT 770 FT /note="L -> F (in dbSNP:rs34859566)" FT /id="VAR_053958" FT VARIANT 874 FT /note="E -> K (in dbSNP:rs13090)" FT /id="VAR_053959" FT CONFLICT 46 FT /note="A -> T (in Ref. 1; AAD30032)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="G -> A (in Ref. 2; AAD31087)" FT /evidence="ECO:0000305" FT CONFLICT 412 FT /note="R -> K (in Ref. 1; AAD30032)" FT /evidence="ECO:0000305" FT STRAND 13..20 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 37..39 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 41..48 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 57..59 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 60..66 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 73..77 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 84..89 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 91..103 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 114..124 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 131..136 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 147..149 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 155..158 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 167..169 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 171..173 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 177..193 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 199..209 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 214..220 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 226..231 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 235..237 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 239..249 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 252..259 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 279..287 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 290..299 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 304..310 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 340..344 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 365..373 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 378..389 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 391..398 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 401..405 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 431..436 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 438..450 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 452..457 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 459..462 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 467..483 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 489..492 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 497..499 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 500..511 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 518..521 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 523..534 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 538..540 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 541..543 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 544..563 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 576..586 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 592..597 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 610..613 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 615..631 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 641..646 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 649..668 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 670..672 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 685..700 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 701..704 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 711..718 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 720..723 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 738..741 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 748..751 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 752..754 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 781..783 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 795..801 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 804..808 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 812..814 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 817..820 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 821..823 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 824..826 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 877 AA; 96793 MW; 15173F237A75D230 CRC64; MCDLRRPAAG GMMDLAYVCE WEKWSKSTHC PSVPLACAWS CRNLIAFTMD LRSDDQDLTR MIHILDTEHP WDLHSIPSEH HEAITCLEWD QSGSRLLSAD ADGQIKCWSM ADHLANSWES SVGSLVEGDP IVALSWLHNG VKLALHVEKS GASSFGEKFS RVKFSPSLTL FGGKPMEGWI AVTVSGLVTV SLLKPSGQVL TSTESLCRLR GRVALADIAF TGGGNIVVAT ADGSSASPVQ FYKVCVSVVS EKCRIDTEIL PSLFMRCTTD LNRKDKFPAI THLKFLARDM SEQVLLCASS QTSSIVECWS LRKEGLPVNN IFQQISPVVG DKQPTILKWR ILSATNDLDR VSAVALPKLP ISLTNTDLKV ASDTQFYPGL GLALAFHDGS VHIVHRLSLQ TMAVFYSSAA PRPVDEPAMK RPRTAGPAVH LKAMQLSWTS LALVGIDSHG KLSVLRLSPS MGHPLEVGLA LRHLLFLLEY CMVTGYDWWD ILLHVQPSMV QSLVEKLHEE YTRQTAALQQ VLSTRILAMK ASLCKLSPCT VTRVCDYHTK LFLIAISSTL KSLLRPHFLN TPDKSPGDRL TEICTKITDV DIDKVMINLK TEEFVLDMNT LQALQQLLQW VGDFVLYLLA SLPNQGSLLR PGHSFLRDGT SLGMLRELMV VIRIWGLLKP SCLPVYTATS DTQDSMSLLF RLLTKLWICC RDEGPASEPD EALVDECCLL PSQLLIPSLD WLPASDGLVS RLQPKQPLRL QFGRAPTLPG SAATLQLDGL ARAPGQPKID HLRRLHLGAC PTEECKACTR CGCVTMLKSP NRTTAVKQWE QRWIKNCLAV EGRGPDACVT SRASEEAPAF VQLGPQSTHH SPRTPRSLDH LHPEDRP // ID MED15_HUMAN Reviewed; 788 AA. AC Q96RN5; D3DX31; D3DX32; O15413; Q6IC31; Q8NF16; Q96CT0; Q96IH7; Q9P1T3; DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 10-JAN-2003, sequence version 2. DT 14-DEC-2022, entry version 194. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 15; DE AltName: Full=Activator-recruited cofactor 105 kDa component; DE Short=ARC105; DE AltName: Full=CTG repeat protein 7a; DE AltName: Full=Mediator complex subunit 15; DE AltName: Full=Positive cofactor 2 glutamine/Q-rich-associated protein; DE Short=PC2 glutamine/Q-rich-associated protein; DE AltName: Full=TPA-inducible gene 1 protein; DE Short=TIG-1; DE AltName: Full=Trinucleotide repeat-containing gene 7 protein; GN Name=MED15; Synonyms=ARC105, CTG7A, PCQAP, TIG1, TNRC7; 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 2), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND INDUCTION. RC TISSUE=Megakaryocyte, and Placenta; RX PubMed=11024300; DOI=10.1016/s0378-1119(00)00292-4; RA Abraham S., Solomon W.B.; RT "A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), RT preferentially expressed in placental and bone-marrow tissues."; RL Gene 255:389-400(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND POLYMORPHISM OF POLY-GLN RP REGION. RC TISSUE=Cervix carcinoma; RX PubMed=11414760; DOI=10.1006/geno.2001.6566; RA Berti L., Mittler G., Przemeck G.K.H., Stelzer G., Guenzler B., Amati F., RA Conti E., Dallapiccola B., Hrabe' de Angelis M., Novelli G., RA Meisterernst M.; RT "Isolation and characterization of a novel gene from the DiGeorge RT chromosomal region that encodes for a mediator subunit."; RL Genomics 74:320-332(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hepatoma, and Spleen; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 405-788 (ISOFORM 1). RC TISSUE=Eye, and Kidney; 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 185-573 (ISOFORM 2). RC TISSUE=Brain cortex; RX PubMed=9225980; DOI=10.1007/s004390050476; RA Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S., RA Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A.; RT "cDNAs with long CAG trinucleotide repeats from human brain."; RL Hum. Genet. 100:114-122(1997). RN [8] RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 39-48 AND 525-536. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [9] RP FUNCTION, AND INTERACTION WITH SMAD1; SMAD2 AND SMAD3. RX PubMed=12167862; DOI=10.1038/nature00969; RA Kato Y., Habas R., Katsuyama Y., Naeaer A.M., He X.; RT "A component of the ARC/Mediator complex required for TGF beta/Nodal RT signalling."; RL Nature 418:641-646(2002). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [12] RP INTERACTION WITH TRIM11, UBIQUITINATION, AND SUBCELLULAR LOCATION. RX PubMed=16904669; DOI=10.1016/j.febslet.2006.07.066; RA Ishikawa H., Tachikawa H., Miura Y., Takahashi N.; RT "TRIM11 binds to and destabilizes a key component of the activator-mediated RT cofactor complex (ARC105) through the ubiquitin-proteasome system."; RL FEBS Lett. 580:4784-4792(2006). RN [13] RP FUNCTION. RX PubMed=16630888; DOI=10.1016/j.molcel.2006.03.023; RA Andrau J.-C., van de Pasch L., Lijnzaad P., Bijma T., Koerkamp M.G., RA van de Peppel J., Werner M., Holstege F.C.P.; RT "Genome-wide location of the coactivator mediator: binding without RT activation and transient Cdk8 interaction on DNA."; RL Mol. Cell 22:179-192(2006). RN [14] RP INTERACTION WITH WWTR1. RX PubMed=18568018; DOI=10.1038/ncb1748; RA Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M., RA Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.; RT "TAZ controls Smad nucleocytoplasmic shuttling and regulates human RT embryonic stem-cell self-renewal."; RL Nat. Cell Biol. 10:837-848(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-603, 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 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 [17] 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 [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-603, 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-603, 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 [20] RP STRUCTURE BY NMR OF 5-78, FUNCTION, INTERACTION WITH SREBF1 AND SREBF2, AND RP MUTAGENESIS OF GLU-42; LEU-58 AND ALA-60. RX PubMed=16799563; DOI=10.1038/nature04942; RA Yang F., Vought B.W., Satterlee J.S., Walker A.K., Jim Sun Z.-Y., RA Watts J.L., DeBeaumont R., Saito R.M., Hyberts S.G., Yang S., Macol C., RA Iyer L., Tjian R., van den Heuvel S., Hart A.C., Wagner G., Naeaer A.M.; RT "An ARC/Mediator subunit required for SREBP control of cholesterol and RT lipid homeostasis."; RL Nature 442:700-704(2006). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. Required for cholesterol- CC dependent gene regulation. Positively regulates the Nodal signaling CC pathway. {ECO:0000269|PubMed:12167862, ECO:0000269|PubMed:16630888, CC ECO:0000269|PubMed:16799563}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with SMAD2, CC SMAD3, SREBF1 and SREBF2. Interacts with WWTR1. Interacts with TRIM11. CC {ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:12167862, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:16799563, ECO:0000269|PubMed:16904669, CC ECO:0000269|PubMed:18568018}. CC -!- INTERACTION: CC Q96RN5; P42858: HTT; NbExp=3; IntAct=EBI-394506, EBI-466029; CC Q96RN5; O60244: MED14; NbExp=2; IntAct=EBI-394506, EBI-394489; CC Q96RN5; Q71SY5: MED25; NbExp=2; IntAct=EBI-394506, EBI-394558; CC Q96RN5; P36956-1: SREBF1; NbExp=7; IntAct=EBI-394506, EBI-948328; CC Q96RN5; P36956-3: SREBF1; NbExp=2; IntAct=EBI-394506, EBI-948338; CC Q96RN5; Q12772: SREBF2; NbExp=2; IntAct=EBI-394506, EBI-465059; CC Q96RN5; Q96F44: TRIM11; NbExp=5; IntAct=EBI-394506, EBI-851809; CC Q96RN5-2; P54253: ATXN1; NbExp=6; IntAct=EBI-11030807, EBI-930964; CC Q96RN5-2; P42858: HTT; NbExp=6; IntAct=EBI-11030807, EBI-466029; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96RN5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96RN5-2; Sequence=VSP_003922; CC Name=3; CC IsoId=Q96RN5-3; Sequence=VSP_013024, VSP_003922; CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined, including heart, CC brain, lung, spleen, thymus, pancreas, blood leukocyte and placenta. CC However, the level of expression varied, with highest expression in the CC placenta and peripheral blood and lowest in the pancreas and kidney. CC {ECO:0000269|PubMed:11024300}. CC -!- INDUCTION: By 12-O-tetradecanoylphorbol-13-acetate (TPA). CC {ECO:0000269|PubMed:11024300}. CC -!- PTM: Ubiquitinated by TRIM11, leading to proteasomal degradation. CC {ECO:0000269|PubMed:16904669}. CC -!- POLYMORPHISM: The poly-Gln region from amino acids 235-262 of PCQAP is CC polymorphic. There are from 15 to 18 repeats in the Italian population. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 15 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC12944.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB85034.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305}; CC Sequence=BAC03446.1; Type=Erroneous initiation; 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; AF056191; AAC12944.1; ALT_FRAME; mRNA. DR EMBL; AF328769; AAK58423.1; -; mRNA. DR EMBL; AK074268; BAB85034.1; ALT_SEQ; mRNA. DR EMBL; AK090465; BAC03446.1; ALT_INIT; mRNA. DR EMBL; CR456537; CAG30423.1; -; mRNA. DR EMBL; CH471176; EAX02951.1; -; Genomic_DNA. DR EMBL; CH471176; EAX02952.1; -; Genomic_DNA. DR EMBL; CH471176; EAX02954.1; -; Genomic_DNA. DR EMBL; CH471176; EAX02956.1; -; Genomic_DNA. DR EMBL; BC007529; AAH07529.1; -; mRNA. DR EMBL; BC013985; AAH13985.1; -; mRNA. DR EMBL; U80745; AAB91443.1; -; mRNA. DR CCDS; CCDS13781.1; -. [Q96RN5-2] DR CCDS; CCDS33602.1; -. [Q96RN5-1] DR CCDS; CCDS74824.1; -. [Q96RN5-3] DR RefSeq; NP_001003891.1; NM_001003891.2. [Q96RN5-1] DR RefSeq; NP_001280164.1; NM_001293235.1. DR RefSeq; NP_001280165.1; NM_001293236.1. [Q96RN5-3] DR RefSeq; NP_056973.2; NM_015889.4. [Q96RN5-2] DR PDB; 2GUT; NMR; -; A=5-78. DR PDB; 7EMF; EM; 3.50 A; O=1-788. DR PDB; 7ENA; EM; 4.07 A; o=1-788. DR PDB; 7ENC; EM; 4.13 A; o=1-788. DR PDB; 7ENJ; EM; 4.40 A; O=1-788. DR PDB; 7LBM; EM; 4.80 A; z=1-788. DR PDBsum; 2GUT; -. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR AlphaFoldDB; Q96RN5; -. DR BMRB; Q96RN5; -. DR SMR; Q96RN5; -. DR BioGRID; 119623; 118. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q96RN5; -. DR DIP; DIP-32908N; -. DR IntAct; Q96RN5; 56. DR MINT; Q96RN5; -. DR STRING; 9606.ENSP00000263205; -. DR GlyGen; Q96RN5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96RN5; -. DR PhosphoSitePlus; Q96RN5; -. DR BioMuta; MED15; -. DR DMDM; 27734440; -. DR EPD; Q96RN5; -. DR jPOST; Q96RN5; -. DR MassIVE; Q96RN5; -. DR MaxQB; Q96RN5; -. DR PaxDb; Q96RN5; -. DR PeptideAtlas; Q96RN5; -. DR ProteomicsDB; 77993; -. [Q96RN5-1] DR ProteomicsDB; 77994; -. [Q96RN5-2] DR ProteomicsDB; 77995; -. [Q96RN5-3] DR Antibodypedia; 282; 305 antibodies from 31 providers. DR DNASU; 51586; -. DR Ensembl; ENST00000263205.11; ENSP00000263205.7; ENSG00000099917.17. [Q96RN5-1] DR Ensembl; ENST00000292733.11; ENSP00000292733.7; ENSG00000099917.17. [Q96RN5-2] DR Ensembl; ENST00000382974.6; ENSP00000372434.2; ENSG00000099917.17. [Q96RN5-3] DR GeneID; 51586; -. DR KEGG; hsa:51586; -. DR MANE-Select; ENST00000263205.11; ENSP00000263205.7; NM_001003891.3; NP_001003891.1. DR UCSC; uc002zsp.4; human. [Q96RN5-1] DR CTD; 51586; -. DR DisGeNET; 51586; -. DR GeneCards; MED15; -. DR HGNC; HGNC:14248; MED15. DR HPA; ENSG00000099917; Low tissue specificity. DR MIM; 607372; gene. DR neXtProt; NX_Q96RN5; -. DR OpenTargets; ENSG00000099917; -. DR PharmGKB; PA33088; -. DR VEuPathDB; HostDB:ENSG00000099917; -. DR eggNOG; KOG4274; Eukaryota. DR GeneTree; ENSGT00730000111140; -. DR HOGENOM; CLU_023921_0_0_1; -. DR InParanoid; Q96RN5; -. DR OMA; CCLDDKR; -. DR PhylomeDB; Q96RN5; -. DR TreeFam; TF324988; -. DR PathwayCommons; Q96RN5; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q96RN5; -. DR SIGNOR; Q96RN5; -. DR BioGRID-ORCS; 51586; 126 hits in 1098 CRISPR screens. DR ChiTaRS; MED15; human. DR EvolutionaryTrace; Q96RN5; -. DR GeneWiki; MED15; -. DR GenomeRNAi; 51586; -. DR Pharos; Q96RN5; Tbio. DR PRO; PR:Q96RN5; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q96RN5; protein. DR Bgee; ENSG00000099917; Expressed in sural nerve and 191 other tissues. DR ExpressionAtlas; Q96RN5; baseline and differential. DR Genevisible; Q96RN5; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016592; C:mediator complex; IEA:InterPro. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR Gene3D; 1.10.246.20; -; 1. DR InterPro; IPR036529; KIX_dom_sf. DR InterPro; IPR019087; Med15. DR Pfam; PF09606; Med15; 1. DR AGR; HGNC:14248; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Triplet repeat expansion; Ubl conjugation. FT CHAIN 1..788 FT /note="Mediator of RNA polymerase II transcription subunit FT 15" FT /id="PRO_0000058264" FT REGION 9..73 FT /note="Interaction with SREBF1" FT /evidence="ECO:0000269|PubMed:16799563" FT REGION 95..139 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 260..329 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 412..530 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 547..564 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 271..285 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 286..300 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 301..315 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 412..442 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 443..461 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..476 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 477..491 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 492..530 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 349 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q924H2" FT MOD_RES 603 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT VAR_SEQ 80..151 FT /note="DPMNALQSLTGGPAAGAAGIGMPPRGPGQSLGGMGSLGAMGQPMSLSGQPPP FT GTSGMAPHSMAVVSTATPQT -> A (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15461802" FT /id="VSP_013024" FT VAR_SEQ 385..424 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11024300, FT ECO:0000303|PubMed:11414760, ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15461802, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9225980" FT /id="VSP_003922" FT VARIANT 261..262 FT /note="Missing" FT /id="VAR_013136" FT MUTAGEN 42 FT /note="E->A: Abrogates interaction with SREBF1." FT /evidence="ECO:0000269|PubMed:16799563" FT MUTAGEN 58 FT /note="L->D: Abrogates interaction with SREBF1." FT /evidence="ECO:0000269|PubMed:16799563" FT MUTAGEN 60 FT /note="A->D: Abrogates interaction with SREBF1." FT /evidence="ECO:0000269|PubMed:16799563" FT CONFLICT 12 FT /note="S -> R (in Ref. 1; AAC12944)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="L -> F (in Ref. 1; AAC12944)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="Q -> H (in Ref. 3; BAC03446)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="Q -> R (in Ref. 3; BAB85034)" FT /evidence="ECO:0000305" FT CONFLICT 185..186 FT /note="QQ -> EL (in Ref. 7; AAB91443)" FT /evidence="ECO:0000305" FT CONFLICT 186..187 FT /note="Missing (in Ref. 4; CAG30423)" FT /evidence="ECO:0000305" FT CONFLICT 218 FT /note="Missing (in Ref. 4; CAG30423)" FT /evidence="ECO:0000305" FT CONFLICT 232..287 FT /note="Missing (in Ref. 3; BAB85034)" FT /evidence="ECO:0000305" FT CONFLICT 265 FT /note="Q -> E (in Ref. 1; AAC12944 and 7; AAB91443)" FT /evidence="ECO:0000305" FT CONFLICT 572..573 FT /note="IL -> GI (in Ref. 7; AAB91443)" FT /evidence="ECO:0000305" FT CONFLICT 685 FT /note="L -> V (in Ref. 3; BAB85034)" FT /evidence="ECO:0000305" FT HELIX 13..30 FT /evidence="ECO:0007829|PDB:2GUT" FT HELIX 38..48 FT /evidence="ECO:0007829|PDB:2GUT" FT HELIX 52..71 FT /evidence="ECO:0007829|PDB:2GUT" FT TURN 616..618 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 619..627 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 634..649 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 676..683 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 695..697 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 700..707 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 713..715 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 722..725 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 735..737 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 740..743 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 747..761 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 769..787 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 788 AA; 86753 MW; BB6AC6C63ED2F97E CRC64; MDVSGQETDW RSTAFRQKLV SQIEDAMRKA GVAHSKSSKD MESHVFLKAK TRDEYLSLVA RLIIHFRDIH NKKSQASVSD PMNALQSLTG GPAAGAAGIG MPPRGPGQSL GGMGSLGAMG QPMSLSGQPP PGTSGMAPHS MAVVSTATPQ TQLQLQQVAL QQQQQQQQFQ QQQQAALQQQ QQQQQQQQFQ AQQSAMQQQF QAVVQQQQQL QQQQQQQQHL IKLHHQNQQQ IQQQQQQLQR IAQLQLQQQQ QQQQQQQQQQ QQALQAQPPI QQPPMQQPQP PPSQALPQQL QQMHHTQHHQ PPPQPQQPPV AQNQPSQLPP QSQTQPLVSQ AQALPGQMLY TQPPLKFVRA PMVVQQPPVQ PQVQQQQTAV QTAQAAQMVA PGVQMITEAL AQGGMHIRAR FPPTTAVSAI PSSSIPLGRQ PMAQVSQSSL PMLSSPSPGQ QVQTPQSMPP PPQPSPQPGQ PSSQPNSNVS SGPAPSPSSF LPSPSPQPSQ SPVTARTPQN FSVPSPGPLN TPVNPSSVMS PAGSSQAEEQ QYLDKLKQLS KYIEPLRRMI NKIDKNEDRK KDLSKMKSLL DILTDPSKRC PLKTLQKCEI ALEKLKNDMA VPTPPPPPVP PTKQQYLCQP LLDAVLANIR SPVFNHSLYR TFVPAMTAIH GPPITAPVVC TRKRRLEDDE RQSIPSVLQG EVARLDPKFL VNLDPSHCSN NGTVHLICKL DDKDLPSVPP LELSVPADYP AQSPLWIDRQ WQYDANPFLQ SVHRCMTSRL LQLPDKHSVT ALLNTWAQSV HQACLSAA // ID MED27_HUMAN Reviewed; 311 AA. AC Q6P2C8; O95401; Q4F964; Q5VTA4; Q5VTA5; Q9BU57; Q9NYR4; V9GYV9; DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 14-DEC-2022, entry version 151. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 27; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 8; DE Short=CRSP complex subunit 8; DE AltName: Full=Mediator complex subunit 27; DE AltName: Full=P37 TRAP/SMCC/PC2 subunit; DE AltName: Full=Transcriptional coactivator CRSP34; GN Name=MED27; Synonyms=CRSP34 {ECO:0000312|EMBL:AAD12721.1}, CRSP8; 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] (ISOFORM 3). RX PubMed=8889548; DOI=10.1101/gr.6.9.791; RA Bonaldo M.F., Lennon G., Soares M.B.; RT "Normalization and subtraction: two approaches to facilitate gene RT discovery."; RL Genome Res. 6:791-806(1996). RN [2] {ECO:0000305} 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] {ECO:0000305, ECO:0000312|EMBL:AAH64608.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung {ECO:0000312|EMBL:AAH02878.1}, and Skin RC {ECO:0000312|EMBL:AAH64608.1}; 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 [4] {ECO:0000305, ECO:0000312|EMBL:AAD12721.1} RP NUCLEOTIDE SEQUENCE [MRNA] OF 39-311 (ISOFORM 1), FUNCTION, IDENTIFICATION RP IN CRSP COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=9989412; DOI=10.1038/17141; RA Ryu S., Zhou S., Ladurner A.G., Tjian R.; RT "The transcriptional cofactor complex CRSP is required for activity of the RT enhancer-binding protein Sp1."; RL Nature 397:446-450(1999). RN [5] {ECO:0000305, ECO:0000312|EMBL:AAF37290.1} RP NUCLEOTIDE SEQUENCE [MRNA] OF 39-311 (ISOFORM 1), FUNCTION, IDENTIFICATION RP IN CRSP COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=10882111; DOI=10.1016/s1097-2765(00)80254-3; RA Malik S., Gu W., Wu W., Qin J., Roeder R.G.; RT "The USA-derived transcriptional coactivator PC2 is a submodule of RT TRAP/SMCC and acts synergistically with other PCs."; RL Mol. Cell 5:753-760(2000). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 39-311 (ISOFORM 2). RA Lin L., Nong W., Zhou G., Ke R., Shen C., Zhong G., Zheng Z., Liang M., RA Huang B., Li H., Yang S.; RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [9] 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, 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 [11] RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-134, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [12] RP INVOLVEMENT IN NEDSCAC, AND VARIANTS NEDSCAC GLY-63; PHE-232; ALA-242; RP LEU-259; LEU-280; SER-291 AND LEU-293. RX PubMed=33443317; DOI=10.1002/ana.26019; RA Meng L., Isohanni P., Shao Y., Graham B.H., Hickey S.E., Brooks S., RA Suomalainen A., Joset P., Steindl K., Rauch A., Hackenberg A., High F.A., RA Armstrong-Javors A., Mencacci N.E., Gonzalez-Latapi P., Kamel W.A., RA Al-Hashel J.Y., Bustos B.I., Hernandez A.V., Krainc D., Lubbe S.J., RA Van Esch H., De Luca C., Ballon K., Ravelli C., Burglen L., Qebibo L., RA Calame D.G., Mitani T., Marafi D., Pehlivan D., Saadi N.W., Sahin Y., RA Maroofian R., Efthymiou S., Houlden H., Maqbool S., Rahman F., Gu S., RA Posey J.E., Lupski J.R., Hunter J.V., Wangler M.F., Carroll C.J., Yang Y.; RT "MED27 variants cause developmental delay, dystonia, and cerebellar RT hypoplasia."; RL Ann. Neurol. 89:828-833(2021). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:10882111, CC ECO:0000269|PubMed:9989412}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. CC {ECO:0000269|PubMed:10882111, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:9989412}. CC -!- INTERACTION: CC Q6P2C8; Q9NVC6: MED17; NbExp=3; IntAct=EBI-394603, EBI-394562; CC Q6P2C8; Q15528: MED22; NbExp=3; IntAct=EBI-394603, EBI-394687; CC Q6P2C8; O75586: MED6; NbExp=2; IntAct=EBI-394603, EBI-394624; CC Q6P2C8; Q9R0X0: Med20; Xeno; NbExp=2; IntAct=EBI-394603, EBI-398698; CC Q6P2C8; Q9CQI9: Med30; Xeno; NbExp=2; IntAct=EBI-394603, EBI-309220; CC Q6P2C8; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-394603, EBI-7990252; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10882111, CC ECO:0000269|PubMed:9989412}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1 {ECO:0000269|PubMed:10882111, ECO:0000269|PubMed:9989412, CC ECO:0000303|PubMed:15164053, ECO:0000305}; CC IsoId=Q6P2C8-1; Sequence=Displayed; CC Name=2 {ECO:0000303|PubMed:15164053}; CC IsoId=Q6P2C8-2; Sequence=VSP_051869; CC Name=3; CC IsoId=Q6P2C8-4; Sequence=VSP_055411, VSP_055412; CC -!- DISEASE: Neurodevelopmental disorder with spasticity, cataracts, and CC cerebellar hypoplasia (NEDSCAC) [MIM:619286]: An autosomal recessive CC disorder characterized by global developmental delay, impaired CC intellectual development, and poor or absent speech. More severely CC affected individuals do not achieve independent ambulation, whereas CC others develop some speech and can walk, or show regression later in CC childhood. Additional features include axial hypotonia, peripheral CC spasticity, dystonia, cataracts, and seizures. Brain imaging usually CC shows cerebellar hypoplasia, thin corpus callosum, cerebral atrophy, CC and hypomyelination. {ECO:0000269|PubMed:33443317}. Note=The disease CC may be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 27 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH02878.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH02878.1; 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; BQ189678; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL603649; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513102; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL160271; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL713892; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002878; AAH02878.1; ALT_SEQ; mRNA. DR EMBL; BC064608; AAH64608.1; -; mRNA. DR EMBL; AF104252; AAD12721.1; -; mRNA. DR EMBL; AF230382; AAF37290.1; -; mRNA. DR EMBL; DQ099387; AAZ13763.1; -; mRNA. DR CCDS; CCDS59153.1; -. [Q6P2C8-2] DR CCDS; CCDS6945.1; -. [Q6P2C8-1] DR CCDS; CCDS69689.1; -. [Q6P2C8-4] DR RefSeq; NP_001240810.1; NM_001253881.1. [Q6P2C8-2] DR RefSeq; NP_001240811.1; NM_001253882.1. [Q6P2C8-4] DR RefSeq; NP_004260.2; NM_004269.3. [Q6P2C8-1] DR PDB; 7EMF; EM; 3.50 A; 0=1-311. DR PDB; 7ENA; EM; 4.07 A; c=1-311. DR PDB; 7ENC; EM; 4.13 A; c=1-311. DR PDB; 7ENJ; EM; 4.40 A; 0=1-311. DR PDB; 7LBM; EM; 4.80 A; n=1-311. DR PDB; 7NVR; EM; 4.50 A; p=1-311. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q6P2C8; -. DR SMR; Q6P2C8; -. DR BioGRID; 114832; 92. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q6P2C8; -. DR DIP; DIP-31465N; -. DR IntAct; Q6P2C8; 46. DR MINT; Q6P2C8; -. DR STRING; 9606.ENSP00000292035; -. DR iPTMnet; Q6P2C8; -. DR PhosphoSitePlus; Q6P2C8; -. DR BioMuta; MED27; -. DR DMDM; 74737195; -. DR EPD; Q6P2C8; -. DR jPOST; Q6P2C8; -. DR MassIVE; Q6P2C8; -. DR MaxQB; Q6P2C8; -. DR PaxDb; Q6P2C8; -. DR PeptideAtlas; Q6P2C8; -. DR ProteomicsDB; 66886; -. [Q6P2C8-1] DR ProteomicsDB; 66887; -. [Q6P2C8-2] DR Antibodypedia; 1810; 162 antibodies from 26 providers. DR DNASU; 9442; -. DR Ensembl; ENST00000292035.10; ENSP00000292035.5; ENSG00000160563.14. [Q6P2C8-1] DR Ensembl; ENST00000357028.6; ENSP00000349530.3; ENSG00000160563.14. [Q6P2C8-2] DR Ensembl; ENST00000474263.1; ENSP00000477136.1; ENSG00000160563.14. [Q6P2C8-4] DR GeneID; 9442; -. DR KEGG; hsa:9442; -. DR MANE-Select; ENST00000292035.10; ENSP00000292035.5; NM_004269.4; NP_004260.2. DR UCSC; uc004cbe.3; human. [Q6P2C8-1] DR CTD; 9442; -. DR DisGeNET; 9442; -. DR GeneCards; MED27; -. DR HGNC; HGNC:2377; MED27. DR HPA; ENSG00000160563; Low tissue specificity. DR MalaCards; MED27; -. DR MIM; 605044; gene. DR MIM; 619286; phenotype. DR neXtProt; NX_Q6P2C8; -. DR OpenTargets; ENSG00000160563; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA162395634; -. DR VEuPathDB; HostDB:ENSG00000160563; -. DR eggNOG; ENOG502QS6H; Eukaryota. DR GeneTree; ENSGT00390000012207; -. DR HOGENOM; CLU_056015_0_0_1; -. DR InParanoid; Q6P2C8; -. DR OMA; HAAMLHF; -. DR OrthoDB; 1256412at2759; -. DR PhylomeDB; Q6P2C8; -. DR TreeFam; TF323728; -. DR PathwayCommons; Q6P2C8; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q6P2C8; -. DR SIGNOR; Q6P2C8; -. DR BioGRID-ORCS; 9442; 509 hits in 1075 CRISPR screens. DR ChiTaRS; MED27; human. DR GeneWiki; MED27; -. DR GenomeRNAi; 9442; -. DR Pharos; Q6P2C8; Tbio. DR PRO; PR:Q6P2C8; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q6P2C8; protein. DR Bgee; ENSG00000160563; Expressed in oocyte and 182 other tissues. DR ExpressionAtlas; Q6P2C8; baseline and differential. DR Genevisible; Q6P2C8; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; TAS:ProtInc. DR InterPro; IPR021627; Mediator_Med27. DR PANTHER; PTHR13130; 34 KDA TRANSCRIPTIONAL CO-ACTIVATOR-RELATED; 1. DR Pfam; PF11571; Med27; 1. DR AGR; HGNC:2377; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cataract; KW Intellectual disability; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..311 FT /note="Mediator of RNA polymerase II transcription subunit FT 27" FT /id="PRO_0000079361" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 134 FT /note="N6-methyllysine" FT /evidence="ECO:0007744|PubMed:24129315" FT VAR_SEQ 117..130 FT /note="LQYHAGLASGLLNQ -> KEQLSIPRIFHWKV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8889548" FT /id="VSP_055411" FT VAR_SEQ 131..311 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8889548" FT /id="VSP_055412" FT VAR_SEQ 192..227 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15164053, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_051869" FT VARIANT 63 FT /note="V -> G (in NEDSCAC; unknown pathological FT significance; dbSNP:rs774752053)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085606" FT VARIANT 232 FT /note="S -> F (in NEDSCAC; unknown pathological FT significance; dbSNP:rs1056298725)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085607" FT VARIANT 242 FT /note="V -> A (in NEDSCAC; unknown pathological FT significance; dbSNP:rs1589166413)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085608" FT VARIANT 259 FT /note="P -> L (in NEDSCAC; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085609" FT VARIANT 280 FT /note="P -> L (in NEDSCAC; unknown pathological FT significance; dbSNP:rs778593272)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085610" FT VARIANT 291 FT /note="G -> S (in NEDSCAC; unknown pathological FT significance; dbSNP:rs774276967)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085611" FT VARIANT 293 FT /note="P -> L (in NEDSCAC; unknown pathological FT significance; dbSNP:rs1218659650)" FT /evidence="ECO:0000269|PubMed:33443317" FT /id="VAR_085612" FT CONFLICT 64 FT /note="N -> D (in Ref. 6; AAZ13763)" FT /evidence="ECO:0000305" FT CONFLICT 79 FT /note="K -> E (in Ref. 6; AAZ13763)" FT /evidence="ECO:0000305" FT CONFLICT 94 FT /note="L -> S (in Ref. 4; AAD12721)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="L -> C (in Ref. 4; AAD12721)" FT /evidence="ECO:0000305" FT CONFLICT 235 FT /note="N -> D (in Ref. 6; AAZ13763)" FT /evidence="ECO:0000305" FT CONFLICT 279 FT /note="A -> G (in Ref. 4; AAD12721)" FT /evidence="ECO:0000305" FT HELIX 8..37 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 45..76 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 104..130 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 159..171 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 176..181 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 189..194 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 195..197 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 198..219 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 226..228 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 237..252 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 260..271 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 272..275 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 276..278 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 282..284 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 311 AA; 35432 MW; 996D675993E393CB CRC64; MADVINVSVN LEAFSQAISA IQALRSSVSR VFDCLKDGMR NKETLEGREK AFIAHFQDNL HSVNRDLNEL ERLSNLVGKP SENHPLHNSG LLSLDPVQDK TPLYSQLLQA YKWSNKLQYH AGLASGLLNQ QSLKRSANQM GVSAKRRPKA QPTTLVLPPQ YVDDVISRID RMFPEMSIHL SRPNGTSAML LVTLGKVLKV IVVMRSLFID RTIVKGYNEN VYTEDGKLDI WSKSNYQVFQ KVTDHATTAL LHYQLPQMPD VVVRSFMTWL RSYIKLFQAP CQRCGKFLQD GLPPTWRDFR TLEAFHDTCR Q // ID MED17_HUMAN Reviewed; 651 AA. AC Q9NVC6; B3KN07; Q9HA81; Q9UNP7; Q9Y2W0; Q9Y660; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 14-DEC-2022, entry version 174. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 17; DE AltName: Full=Activator-recruited cofactor 77 kDa component; DE Short=ARC77; DE AltName: Full=Cofactor required for Sp1 transcriptional activation subunit 6; DE Short=CRSP complex subunit 6; DE AltName: Full=Mediator complex subunit 17; DE AltName: Full=Thyroid hormone receptor-associated protein complex 80 kDa component; DE Short=Trap80; DE AltName: Full=Transcriptional coactivator CRSP77; DE AltName: Full=Vitamin D3 receptor-interacting protein complex 80 kDa component; DE Short=DRIP80; GN Name=MED17; Synonyms=ARC77, CRSP6, DRIP77, DRIP80, TRAP80; 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), PROTEIN SEQUENCE OF 306-319; RP 405-415 AND 592-602, TISSUE SPECIFICITY, IDENTIFICATION IN TRAP COMPLEX, RP AND VARIANT ASP-69. RC TISSUE=Cervix carcinoma; RX PubMed=10198638; DOI=10.1016/s1097-2765(00)80463-3; RA Ito M., Yuan C.-X., Malik S., Gu W., Fondell J.D., Yamamura S., Fu Z.-Y., RA Zhang X., Qin J., Roeder R.G.; RT "Identity between TRAP and SMCC complexes indicates novel pathways for the RT function of nuclear receptors and diverse mammalian activators."; RL Mol. Cell 3:361-370(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 88-99 AND RP 607-619, IDENTIFICATION IN ARC COMPLEX, AND VARIANT ASP-69. RC TISSUE=Cervix carcinoma; RX PubMed=10235266; DOI=10.1038/19783; RA Rachez C., Lemon B.D., Suldan Z., Bromleigh V., Gamble M., Naeaer A.M., RA Erdjument-Bromage H., Tempst P., Freedman L.P.; RT "Ligand-dependent transcription activation by nuclear receptors requires RT the DRIP complex."; RL Nature 398:824-828(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ASP-69. 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 [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-69. RC TISSUE=Skin; 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 [MRNA] OF 269-651 (ISOFORM 1). RX PubMed=9989412; DOI=10.1038/17141; RA Ryu S., Zhou S., Ladurner A.G., Tjian R.; RT "The transcriptional cofactor complex CRSP is required for activity of the RT enhancer-binding protein Sp1."; RL Nature 397:446-450(1999). RN [7] RP IDENTIFICATION IN ARC COMPLEX, AND PROTEIN SEQUENCE OF 168-179 AND 355-361. RX PubMed=10235267; DOI=10.1038/19789; RA Naeaer A.M., Beaurang P.A., Zhou S., Abraham S., Solomon W.B., Tjian R.; RT "Composite co-activator ARC mediates chromatin-directed transcriptional RT activation."; RL Nature 398:828-832(1999). RN [8] RP INTERACTION WITH MED10. RX PubMed=12584197; DOI=10.1074/jbc.c300054200; RA Sato S., Tomomori-Sato C., Banks C.A.S., Sorokina I., Parmely T.J., RA Kong S.E., Jin J., Cai Y., Lane W.S., Brower C.S., Conaway R.C., RA Conaway J.W.; RT "Identification of mammalian Mediator subunits with similarities to yeast RT Mediator subunits Srb5, Srb6, Med11, and Rox3."; RL J. Biol. Chem. 278:15123-15127(2003). RN [9] RP INTERACTION WITH STAT2. RX PubMed=12509459; DOI=10.1128/mcb.23.2.620-628.2003; RA Lau J.F., Nusinzon I., Burakov D., Freedman L.P., Horvath C.M.; RT "Role of metazoan mediator proteins in interferon-responsive RT transcription."; RL Mol. Cell. Biol. 23:620-628(2003). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [11] RP INTERACTION WITH MED1; MED10; MED18; MED21; MED28 AND MED30, IDENTIFICATION RP BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR COMPLEX, AND RP ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [12] RP FUNCTION, AND INTERACTION WITH MED1 AND MED10. RX PubMed=16595664; DOI=10.1074/jbc.m601983200; RA Baek H.J., Kang Y.K., Roeder R.G.; RT "Human Mediator enhances basal transcription by facilitating recruitment of RT transcription factor IIB during preinitiation complex assembly."; RL J. Biol. Chem. 281:15172-15181(2006). RN [13] 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 [14] RP VARIANT [LARGE SCALE ANALYSIS] ASP-69, AND IDENTIFICATION BY MASS RP 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 [15] RP VARIANT [LARGE SCALE ANALYSIS] ASP-69, AND IDENTIFICATION BY MASS RP 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 [16] RP VARIANT MCPHSBA PRO-371. RX PubMed=20950787; DOI=10.1016/j.ajhg.2010.09.016; RA Kaufmann R., Straussberg R., Mandel H., Fattal-Valevski A., Ben-Zeev B., RA Naamati A., Shaag A., Zenvirt S., Konen O., Mimouni-Bloch A., Dobyns W.B., RA Edvardson S., Pines O., Elpeleg O.; RT "Infantile cerebral and cerebellar atrophy is associated with a mutation in RT the MED17 subunit of the transcription preinitiation mediator complex."; RL Am. J. Hum. Genet. 87:667-670(2010). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. {ECO:0000269|PubMed:16595664}. CC -!- SUBUNIT: Interacts with GATA1 and PPARG (By similarity). Component of CC the Mediator complex, which is composed of MED1, MED4, MED6, MED7, CC MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, CC MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, CC MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, CC MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 CC module. Mediator containing the CDK8 module is less active than CC Mediator lacking this module in supporting transcriptional activation. CC Individual preparations of the Mediator complex lacking one or more CC distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC CC and TRAP. Interacts with STAT2. {ECO:0000250, CC ECO:0000269|PubMed:10198638, ECO:0000269|PubMed:10235266, CC ECO:0000269|PubMed:10235267, ECO:0000269|PubMed:12509459, CC ECO:0000269|PubMed:12584197, ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16595664}. CC -!- INTERACTION: CC Q9NVC6; Q9BUE0: MED18; NbExp=3; IntAct=EBI-394562, EBI-394640; CC Q9NVC6; Q15528: MED22; NbExp=4; IntAct=EBI-394562, EBI-394687; CC Q9NVC6; Q6P2C8: MED27; NbExp=3; IntAct=EBI-394562, EBI-394603; CC Q9NVC6; Q9H204: MED28; NbExp=2; IntAct=EBI-394562, EBI-514199; CC Q9NVC6; O75586: MED6; NbExp=2; IntAct=EBI-394562, EBI-394624; CC Q9NVC6; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-394562, EBI-6260909; CC Q9NVC6; Q9CQI9: Med30; Xeno; NbExp=2; IntAct=EBI-394562, EBI-309220; CC Q9NVC6; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-394562, EBI-7990252; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NVC6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NVC6-2; Sequence=VSP_028115, VSP_028116; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10198638}. CC -!- DISEASE: Microcephaly, postnatal progressive, with seizures and brain CC atrophy (MCPHSBA) [MIM:613668]: A disorder characterized by postnatal CC progressive microcephaly and severe developmental retardation CC associated with cerebral and cerebellar atrophy. Infants manifest CC swallowing difficulties leading to failure to thrive, jitteriness, poor CC visual fixation, truncal arching, seizures. There is no acquisition of CC developmental milestones and patients suffer from marked spasticity and CC profound retardation. Progressive microcephaly becomes evident few CC months after birth. {ECO:0000269|PubMed:20950787}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 17 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD30856.1; 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; AF117657; AAD22031.2; -; mRNA. DR EMBL; AF105421; AAD30856.1; ALT_FRAME; mRNA. DR EMBL; AK001674; BAA91827.1; -; mRNA. DR EMBL; AK022156; BAB13973.1; -; mRNA. DR EMBL; AK023209; BAG51169.1; -; mRNA. DR EMBL; AC022150; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC021101; AAH21101.1; -; mRNA. DR EMBL; AF104254; AAD12723.1; -; mRNA. DR CCDS; CCDS8295.1; -. [Q9NVC6-1] DR RefSeq; NP_004259.3; NM_004268.4. [Q9NVC6-1] DR PDB; 7EMF; EM; 3.50 A; Q=1-651. DR PDB; 7ENA; EM; 4.07 A; q=1-651. DR PDB; 7ENC; EM; 4.13 A; q=1-651. DR PDB; 7ENJ; EM; 4.40 A; Q=1-651. DR PDB; 7LBM; EM; 4.80 A; j=1-651. DR PDB; 7NVR; EM; 4.50 A; d=1-651. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9NVC6; -. DR SMR; Q9NVC6; -. DR BioGRID; 114830; 209. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9NVC6; -. DR DIP; DIP-31451N; -. DR IntAct; Q9NVC6; 68. DR MINT; Q9NVC6; -. DR STRING; 9606.ENSP00000251871; -. DR iPTMnet; Q9NVC6; -. DR PhosphoSitePlus; Q9NVC6; -. DR BioMuta; MED17; -. DR DMDM; 296437366; -. DR EPD; Q9NVC6; -. DR jPOST; Q9NVC6; -. DR MassIVE; Q9NVC6; -. DR MaxQB; Q9NVC6; -. DR PaxDb; Q9NVC6; -. DR PeptideAtlas; Q9NVC6; -. DR ProteomicsDB; 82777; -. [Q9NVC6-1] DR ProteomicsDB; 82778; -. [Q9NVC6-2] DR Antibodypedia; 17843; 293 antibodies from 32 providers. DR DNASU; 9440; -. DR Ensembl; ENST00000251871.9; ENSP00000251871.3; ENSG00000042429.12. [Q9NVC6-1] DR GeneID; 9440; -. DR KEGG; hsa:9440; -. DR MANE-Select; ENST00000251871.9; ENSP00000251871.3; NM_004268.5; NP_004259.3. DR UCSC; uc001pel.3; human. [Q9NVC6-1] DR CTD; 9440; -. DR DisGeNET; 9440; -. DR GeneCards; MED17; -. DR HGNC; HGNC:2375; MED17. DR HPA; ENSG00000042429; Low tissue specificity. DR MalaCards; MED17; -. DR MIM; 603810; gene. DR MIM; 613668; phenotype. DR neXtProt; NX_Q9NVC6; -. DR OpenTargets; ENSG00000042429; -. DR Orphanet; 402364; Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly. DR PharmGKB; PA162395443; -. DR VEuPathDB; HostDB:ENSG00000042429; -. DR eggNOG; KOG4512; Eukaryota. DR GeneTree; ENSGT00390000011810; -. DR HOGENOM; CLU_028003_1_0_1; -. DR InParanoid; Q9NVC6; -. DR OMA; CQIYQHQ; -. DR OrthoDB; 976669at2759; -. DR PhylomeDB; Q9NVC6; -. DR TreeFam; TF323615; -. DR PathwayCommons; Q9NVC6; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9NVC6; -. DR SIGNOR; Q9NVC6; -. DR BioGRID-ORCS; 9440; 725 hits in 1087 CRISPR screens. DR ChiTaRS; MED17; human. DR GeneWiki; MED17; -. DR GenomeRNAi; 9440; -. DR Pharos; Q9NVC6; Tbio. DR PRO; PR:Q9NVC6; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9NVC6; protein. DR Bgee; ENSG00000042429; Expressed in sural nerve and 126 other tissues. DR ExpressionAtlas; Q9NVC6; baseline and differential. DR Genevisible; Q9NVC6; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; IDA:UniProtKB. DR GO; GO:0042809; F:nuclear vitamin D receptor binding; NAS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; TAS:ProtInc. DR InterPro; IPR019313; Mediator_Med17. DR PANTHER; PTHR13114; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 17; 1. DR Pfam; PF10156; Med17; 1. DR AGR; HGNC:2375; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Direct protein sequencing; KW Disease variant; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..651 FT /note="Mediator of RNA polymerase II transcription subunit FT 17" FT /id="PRO_0000079359" FT REGION 51..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 140..145 FT /note="NPQTLQ -> VFVDFN (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_028115" FT VAR_SEQ 146..651 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_028116" FT VARIANT 69 FT /note="E -> D (in dbSNP:rs2848477)" FT /evidence="ECO:0000269|PubMed:10198638, FT ECO:0000269|PubMed:10235266, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT /id="VAR_063126" FT VARIANT 357 FT /note="F -> L (in dbSNP:rs35313315)" FT /id="VAR_057781" FT VARIANT 371 FT /note="L -> P (in MCPHSBA; dbSNP:rs267607232)" FT /evidence="ECO:0000269|PubMed:20950787" FT /id="VAR_065066" FT CONFLICT 21 FT /note="E -> G (in Ref. 3; BAB13973)" FT /evidence="ECO:0000305" FT CONFLICT 58 FT /note="E -> G (in Ref. 3; BAB13973)" FT /evidence="ECO:0000305" FT CONFLICT 356 FT /note="K -> N (in Ref. 2; AAD30856)" FT /evidence="ECO:0000305" FT CONFLICT 409 FT /note="G -> Q (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 531 FT /note="Q -> H (in Ref. 6; AAD12723)" FT /evidence="ECO:0000305" FT HELIX 37..46 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 97..120 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 140..171 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 183..193 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 194..199 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 202..206 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 209..213 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 221..226 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 255..263 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 290..317 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 328..333 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 340..347 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 369..386 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 389..391 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 394..398 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 403..407 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 408..412 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 415..421 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 427..454 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 485..487 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 492..497 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 502..506 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 511..514 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 520..543 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 547..555 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 557..559 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 562..564 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 566..573 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 576..584 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 586..588 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 591..595 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 602..604 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 614..616 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 622..625 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 633..635 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 636..645 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 651 AA; 72890 MW; 47011210952D287B CRC64; MSGVRAVRIS IESACEKQVH EVGLDGTETY LPPLSMSQNL ARLAQRIDFS QGSGSEEEEA AGTEGDAQEW PGAGSSADQD DEEGVVKFQP SLWPWDSVRN NLRSALTEMC VLYDVLSIVR DKKFMTLDPV SQDALPPKQN PQTLQLISKK KSLAGAAQIL LKGAERLTKS VTENQENKLQ RDFNSELLRL RQHWKLRKVG DKILGDLSYR SAGSLFPHHG TFEVIKNTDL DLDKKIPEDY CPLDVQIPSD LEGSAYIKVS IQKQAPDIGD LGTVNLFKRP LPKSKPGSPH WQTKLEAAQN VLLCKEIFAQ LSREAVQIKS QVPHIVVKNQ IISQPFPSLQ LSISLCHSSN DKKSQKFATE KQCPEDHLYV LEHNLHLLIR EFHKQTLSSI MMPHPASAPF GHKRMRLSGP QAFDKNEINS LQSSEGLLEK IIKQAKHIFL RSRAAATIDS LASRIEDPQI QAHWSNINDV YESSVKVLIT SQGYEQICKS IQLQLNIGVE QIRVVHRDGR VITLSYQEQE LQDFLLSQMS QHQVHAVQQL AKVMGWQVLS FSNHVGLGPI ESIGNASAIT VASPSGDYAI SVRNGPESGS KIMVQFPRNQ CKDLPKSDVL QDNKWSHLRG PFKEVQWNKM EGRNFVYKME LLMSALSPCL L // ID MED28_HUMAN Reviewed; 178 AA. AC Q9H204; Q9BZJ5; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 14-DEC-2022, entry version 162. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 28; DE AltName: Full=Endothelial-derived protein 1; DE AltName: Full=Mediator complex subunit 28; DE AltName: Full=Merlin and Grb2-interacting cytoskeletal protein; DE Short=Magicin; DE AltName: Full=Tumor angiogenesis marker EG-1; GN Name=MED28; Synonyms=EG1; ORFNames=FKSG20; 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 INDUCTION. RX PubMed=11779215; DOI=10.1006/bbrc.2001.6119; RA Liu C., Zhang L., Shao Z.-M., Beatty P., Sartippour M., Lane T.F., RA Barsky S.H., Livingston E., Nguyen M.H.; RT "Identification of a novel endothelial-derived gene EG-1."; RL Biochem. Biophys. Res. Commun. 290:602-612(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Wang Y.-G., Gong L.; RT "Cloning of FKSG20, a novel gene expressed in adrenal gland tumor RT tissues."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Mai N., Liu C.; RT "A gene from tumor."; RL Submitted (NOV-2000) 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 IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [6] RP FUNCTION IN SIGNALING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP INTERACTION WITH ACTIN; NF2 AND GRB2. RX PubMed=15467741; DOI=10.1038/sj.onc.1208110; RA Wiederhold T., Lee M.-F., James M., Neujahr R., Smith N., Murthy A., RA Hartwig J., Gusella J.F., Ramesh V.; RT "Magicin, a novel cytoskeletal protein associates with the NF2 tumor RT suppressor merlin and Grb2."; RL Oncogene 23:8815-8825(2004). RN [7] RP INTERACTION WITH CCNC; MED1; MED6; MED12; MED13; MED16; MED17; MED20; MED21 RP AND MED24, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RP MEDIATOR COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA RP POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [8] 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: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. May be part of a complex CC containing NF2/merlin that participates in cellular signaling to the CC actin cytoskeleton downstream of tyrosine kinase signaling pathways. CC {ECO:0000269|PubMed:15467741}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Forms a ternary complex CC with NF2/merlin and GRB2. Binds to actin. {ECO:0000269|PubMed:15175163, CC ECO:0000269|PubMed:15989967}. CC -!- INTERACTION: CC Q9H204; Q8NA61: CBY2; NbExp=3; IntAct=EBI-514199, EBI-741724; CC Q9H204; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-514199, EBI-11524851; CC Q9H204; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-514199, EBI-21603100; CC Q9H204; P06241: FYN; NbExp=6; IntAct=EBI-514199, EBI-515315; CC Q9H204; P62993: GRB2; NbExp=3; IntAct=EBI-514199, EBI-401755; CC Q9H204; P42858: HTT; NbExp=9; IntAct=EBI-514199, EBI-466029; CC Q9H204; P06239: LCK; NbExp=4; IntAct=EBI-514199, EBI-1348; CC Q9H204; Q5TCQ9: MAGI3; NbExp=2; IntAct=EBI-514199, EBI-310506; CC Q9H204; Q9NVC6: MED17; NbExp=2; IntAct=EBI-514199, EBI-394562; CC Q9H204; Q15528: MED22; NbExp=2; IntAct=EBI-514199, EBI-394687; CC Q9H204; Q9NX70: MED29; NbExp=3; IntAct=EBI-514199, EBI-394656; CC Q9H204; Q96HR3: MED30; NbExp=6; IntAct=EBI-514199, EBI-394659; CC Q9H204; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-514199, EBI-2801965; CC Q9H204; Q92597: NDRG1; NbExp=3; IntAct=EBI-514199, EBI-716486; CC Q9H204; P35240: NF2; NbExp=4; IntAct=EBI-514199, EBI-1014472; CC Q9H204; P35240-1: NF2; NbExp=2; IntAct=EBI-514199, EBI-1014500; CC Q9H204; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-514199, EBI-912440; CC Q9H204; Q9UHX1: PUF60; NbExp=6; IntAct=EBI-514199, EBI-1053259; CC Q9H204; P12931: SRC; NbExp=3; IntAct=EBI-514199, EBI-621482; CC Q9H204; P51687: SUOX; NbExp=3; IntAct=EBI-514199, EBI-3921347; CC Q9H204; Q8WWU5-7: TCP11; NbExp=3; IntAct=EBI-514199, EBI-17721485; CC Q9H204; P07947: YES1; NbExp=2; IntAct=EBI-514199, EBI-515331; CC Q9H204; Q9D8C6: Med11; Xeno; NbExp=2; IntAct=EBI-514199, EBI-6260909; CC Q9H204; Q9CQI9: Med30; Xeno; NbExp=2; IntAct=EBI-514199, EBI-309220; CC Q9H204; Q9D7W5: Med8; Xeno; NbExp=2; IntAct=EBI-514199, EBI-7990252; CC Q9H204; P03255; Xeno; NbExp=2; IntAct=EBI-514199, EBI-2603114; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15467741}. Cytoplasm CC {ECO:0000269|PubMed:15467741}. Membrane {ECO:0000269|PubMed:15467741}; CC Peripheral membrane protein {ECO:0000269|PubMed:15467741}. CC Note=According to PubMed:15467741, it is cytoplasmic and mainly CC membrane-associated. CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in vascular CC tissues such as placenta, testis and liver. CC {ECO:0000269|PubMed:15467741}. CC -!- INDUCTION: Up-regulated by endothelial cells when exposed to tumor CC conditional media. {ECO:0000269|PubMed:11779215}. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 28 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK11563.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MED28ID50131ch4p15.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; AF321617; AAG38612.1; -; mRNA. DR EMBL; AF358829; AAK32724.1; -; mRNA. DR EMBL; AF318059; AAL26906.1; -; mRNA. DR EMBL; AF317680; AAK11563.1; ALT_FRAME; mRNA. DR EMBL; BC011936; AAH11936.1; -; mRNA. DR CCDS; CCDS33963.1; -. DR RefSeq; NP_079481.2; NM_025205.4. DR PDB; 7EMF; EM; 3.50 A; 1=1-178. DR PDB; 7ENA; EM; 4.07 A; e=1-178. DR PDB; 7ENC; EM; 4.13 A; e=1-178. DR PDB; 7ENJ; EM; 4.40 A; 1=1-178. DR PDB; 7LBM; EM; 4.80 A; o=1-178. DR PDB; 7NVR; EM; 4.50 A; q=1-178. DR PDBsum; 7EMF; -. DR PDBsum; 7ENA; -. DR PDBsum; 7ENC; -. DR PDBsum; 7ENJ; -. DR PDBsum; 7LBM; -. DR PDBsum; 7NVR; -. DR AlphaFoldDB; Q9H204; -. DR SMR; Q9H204; -. DR BioGRID; 123219; 115. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q9H204; -. DR IntAct; Q9H204; 77. DR MINT; Q9H204; -. DR STRING; 9606.ENSP00000237380; -. DR iPTMnet; Q9H204; -. DR PhosphoSitePlus; Q9H204; -. DR BioMuta; MED28; -. DR DMDM; 59799838; -. DR EPD; Q9H204; -. DR jPOST; Q9H204; -. DR MassIVE; Q9H204; -. DR MaxQB; Q9H204; -. DR PaxDb; Q9H204; -. DR PeptideAtlas; Q9H204; -. DR ProteomicsDB; 80465; -. DR Antibodypedia; 23086; 173 antibodies from 27 providers. DR DNASU; 80306; -. DR Ensembl; ENST00000237380.12; ENSP00000237380.6; ENSG00000118579.13. DR GeneID; 80306; -. DR KEGG; hsa:80306; -. DR MANE-Select; ENST00000237380.12; ENSP00000237380.6; NM_025205.5; NP_079481.2. DR UCSC; uc003gpk.2; human. DR CTD; 80306; -. DR DisGeNET; 80306; -. DR GeneCards; MED28; -. DR HGNC; HGNC:24628; MED28. DR HPA; ENSG00000118579; Low tissue specificity. DR MIM; 610311; gene. DR neXtProt; NX_Q9H204; -. DR OpenTargets; ENSG00000118579; -. DR PharmGKB; PA134935853; -. DR VEuPathDB; HostDB:ENSG00000118579; -. DR eggNOG; ENOG502QSN9; Eukaryota. DR GeneTree; ENSGT00390000006192; -. DR InParanoid; Q9H204; -. DR OMA; MQPSPQH; -. DR OrthoDB; 1504193at2759; -. DR PhylomeDB; Q9H204; -. DR TreeFam; TF326988; -. DR PathwayCommons; Q9H204; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q9H204; -. DR SIGNOR; Q9H204; -. DR BioGRID-ORCS; 80306; 707 hits in 1099 CRISPR screens. DR ChiTaRS; MED28; human. DR GeneWiki; MED28; -. DR GenomeRNAi; 80306; -. DR Pharos; Q9H204; Tbio. DR PRO; PR:Q9H204; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q9H204; protein. DR Bgee; ENSG00000118579; Expressed in amniotic fluid and 201 other tissues. DR ExpressionAtlas; Q9H204; baseline and differential. DR Genevisible; Q9H204; HS. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR InterPro; IPR021640; Mediator_Med28. DR PANTHER; PTHR13512; MEDIATOR COMPLEX SUBUNIT 28; 1. DR AGR; HGNC:24628; -. PE 1: Evidence at protein level; KW 3D-structure; Actin-binding; Activator; Coiled coil; Cytoplasm; Membrane; KW Nucleus; Reference proteome; Transcription; Transcription regulation. FT CHAIN 1..178 FT /note="Mediator of RNA polymerase II transcription subunit FT 28" FT /id="PRO_0000113981" FT REGION 1..44 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 109..145 FT /evidence="ECO:0000255" FT HELIX 44..55 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 57..59 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 70..105 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 108..143 FT /evidence="ECO:0007829|PDB:7EMF" SQ SEQUENCE 178 AA; 19520 MW; 63DE023972908066 CRC64; MAAPLGGMFS GQPPGPPQAP PGLPGQASLL QAAPGAPRPS SSTLVDELES SFEACFASLV SQDYVNGTDQ EEIRTGVDQC IQKFLDIARQ TECFFLQKRL QLSVQKPEQV IKEDVSELRN ELQRKDALVQ KHLTKLRHWQ QVLEDINVQH KKPADIPQGS LAYLEQASAN IPAPLKPT //