ID S22AI_HUMAN Reviewed; 424 AA. AC Q96BI1; O14906; O43562; O60485; O60680; Q7LDS5; Q7LGF7; DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 26-MAY-2009, sequence version 3. DT 24-JAN-2024, entry version 173. DE RecName: Full=Solute carrier family 22 member 18; DE AltName: Full=Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene A protein; DE AltName: Full=Efflux transporter-like protein; DE AltName: Full=Imprinted multi-membrane-spanning polyspecific transporter-related protein 1; DE AltName: Full=Organic cation transporter-like protein 2; DE Short=ORCTL-2; DE AltName: Full=Solute carrier family 22 member 1-like; DE AltName: Full=Tumor-suppressing STF cDNA 5 protein; DE AltName: Full=Tumor-suppressing subchromosomal transferable fragment candidate gene 5 protein; DE AltName: Full=p45-Beckwith-Wiedemann region 1 A; DE Short=p45-BWR1A; GN Name=SLC22A18; GN Synonyms=BWR1A, BWSCR1A, HET, IMPT1, ITM, ORCTL2, SLC22A1L, TSSC5; 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], VARIANT GLN-309, AND VARIANT LUNG CANCER RP PHE-233. RX PubMed=9751628; RA Lee M.P., Reeves C., Schmitt A., Su K., Connors T.D., Hu R.J., RA Brandenburg S., Lee M.J., Miller G., Feinberg A.P.; RT "Somatic mutation of TSSC5, a novel imprinted gene from human chromosome RT 11p15.5."; RL Cancer Res. 58:4155-4159(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9802569; DOI=10.1093/dnares/5.4.235; RA Morisaki H., Hatada I., Morisaki T., Mukai T.; RT "A novel gene, ITM, located between p57KIP2 and IPL, is imprinted in RT mice."; RL DNA Res. 5:235-240(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT GLN-12. RX PubMed=9570947; DOI=10.1006/geno.1998.5221; RA Cooper P.R., Smilinich N.J., Day C.D., Nowak N.J., Reid L.H., RA Pearsall R.S., Reece M., Prawitt D., Landers J., Housman D.E., RA Winterpacht A., Zabel B.U., Pelletier J., Weissman B.E., Shows T.B., RA Higgins M.J.; RT "Divergently transcribed overlapping genes expressed in liver and kidney RT and located in the 11p15.5 imprinted domain."; RL Genomics 49:38-51(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Placenta; RX PubMed=9499412; DOI=10.1093/hmg/7.4.597; RA Dao D., Frank D., Qian N., O'Keefe D., Vosatka R.J., Walsh C.P., Tycko B.; RT "IMPT1, an imprinted gene similar to polyspecific transporter and multi- RT drug resistance genes."; RL Hum. Mol. Genet. 7:597-608(1998). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-6 AND GLN-12; CYS-86, AND TISSUE RP SPECIFICITY. RX PubMed=9520460; DOI=10.1073/pnas.95.7.3873; RA Schwienbacher C., Sabbioni S., Campi M., Veronese A., Bernardi G., RA Menegatti A., Hatada I., Mukai T., Ohashi H., Barbanti-Brodano G., RA Croce C.M., Negrini M.; RT "Transcriptional map of 170-kb region at chromosome 11p15.5: identification RT and mutational analysis of the BWR1A gene reveals the presence of mutations RT in tumor samples."; RL Proc. Natl. Acad. Sci. U.S.A. 95:3873-3878(1998). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-12. RA Chen P., Shen W., Karnik P.; RT "Monoallelic expression of the gene encoding a human efflux transporter RT like protein (HET), on chromosome 11p15.5."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-12. 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 [8] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9744804; DOI=10.1016/s0014-5793(98)00907-7; RA Reece M., Prawitt D., Landers J., Kast C., Gros P., Housman D., Zabel B.U., RA Pelletier J.; RT "Functional characterization of ORCTL2 -- an organic cation transporter RT expressed in the renal proximal tubules."; RL FEBS Lett. 433:245-250(1998). RN [9] RP INTERACTION WITH RNF167. RX PubMed=16314844; DOI=10.1038/sj.onc.1209167; RA Yamada H.Y., Gorbsky G.J.; RT "Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel RT ubiquitin ligase RING105."; RL Oncogene 25:1330-1339(2006). CC -!- FUNCTION: May act as a transporter of organic cations based on a proton CC efflux antiport mechanism. May play a role in the transport of CC chloroquine and quinidine-related compounds in kidney. CC {ECO:0000269|PubMed:9744804}. CC -!- SUBUNIT: Interacts with RNF167. {ECO:0000269|PubMed:16314844}. CC -!- INTERACTION: CC Q96BI1; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-11721845, EBI-1052304; CC Q96BI1; Q99801: NKX3-1; NbExp=3; IntAct=EBI-11721845, EBI-1385894; CC Q96BI1; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-11721845, EBI-12947623; CC Q96BI1; Q9Y320: TMX2; NbExp=3; IntAct=EBI-11721845, EBI-6447886; CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000305}; Multi-pass CC membrane protein {ECO:0000305}. Note=Localized at the apical membrane CC surface of renal proximal tubules. {ECO:0000269|PubMed:9744804}. CC -!- TISSUE SPECIFICITY: Expressed at high levels in adult and fetal kidney CC and liver, and adult colon. Expressed in fetal renal proximal tubules CC (at protein level). Expressed at lower levels in heart, brain and lung. CC {ECO:0000269|PubMed:9499412, ECO:0000269|PubMed:9520460, CC ECO:0000269|PubMed:9570947, ECO:0000269|PubMed:9744804}. CC -!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting CC tissues of the lung. The most common form of lung cancer is non-small CC cell lung cancer (NSCLC) that can be divided into 3 major histologic CC subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung CC cancer. NSCLC is often diagnosed at an advanced stage and has a poor CC prognosis. {ECO:0000269|PubMed:9751628}. Note=The gene represented in CC this entry may be involved in disease pathogenesis. CC -!- DISEASE: Rhabdomyosarcoma, embryonal, 1 (RMSE1) [MIM:268210]: A form of CC rhabdomyosarcoma, a highly malignant tumor of striated muscle derived CC from primitive mesenchymal cells and exhibiting differentiation along CC rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently CC occurring soft tissue sarcomas and the most common in children. It CC occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal CC rhabdomyosarcomas. Note=The disease may be caused by variants affecting CC the gene represented in this entry. CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily. CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB82727.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA32779.1; 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; AF059663; AAC14725.1; -; mRNA. DR EMBL; AB012083; BAA32779.1; ALT_INIT; mRNA. DR EMBL; AF037064; AAC04787.1; -; mRNA. DR EMBL; AF028738; AAB82727.1; ALT_INIT; mRNA. DR EMBL; AF030302; AAC17492.1; -; mRNA. DR EMBL; AF070479; AAC23505.1; -; mRNA. DR EMBL; BC015571; AAH15571.1; -; mRNA. DR CCDS; CCDS7740.1; -. DR RefSeq; NP_001302430.1; NM_001315501.1. DR RefSeq; NP_001302431.1; NM_001315502.1. DR RefSeq; NP_002546.3; NM_002555.5. DR RefSeq; NP_899056.2; NM_183233.2. DR AlphaFoldDB; Q96BI1; -. DR SMR; Q96BI1; -. DR BioGRID; 111044; 98. DR IntAct; Q96BI1; 34. DR MINT; Q96BI1; -. DR STRING; 9606.ENSP00000369948; -. DR TCDB; 2.A.1.2.53; the major facilitator superfamily (mfs). DR iPTMnet; Q96BI1; -. DR PhosphoSitePlus; Q96BI1; -. DR SwissPalm; Q96BI1; -. DR BioMuta; SLC22A18; -. DR DMDM; 238054368; -. DR EPD; Q96BI1; -. DR jPOST; Q96BI1; -. DR MassIVE; Q96BI1; -. DR MaxQB; Q96BI1; -. DR PaxDb; 9606-ENSP00000369948; -. DR PeptideAtlas; Q96BI1; -. DR ProteomicsDB; 76077; -. DR Pumba; Q96BI1; -. DR Antibodypedia; 23193; 158 antibodies from 27 providers. DR DNASU; 5002; -. DR Ensembl; ENST00000347936.6; ENSP00000307859.2; ENSG00000110628.16. DR Ensembl; ENST00000380574.5; ENSP00000369948.1; ENSG00000110628.16. DR Ensembl; ENST00000649076.2; ENSP00000497561.1; ENSG00000110628.16. DR GeneID; 5002; -. DR KEGG; hsa:5002; -. DR MANE-Select; ENST00000649076.2; ENSP00000497561.1; NM_002555.6; NP_002546.3. DR UCSC; uc001lwx.3; human. DR AGR; HGNC:10964; -. DR CTD; 5002; -. DR DisGeNET; 5002; -. DR GeneCards; SLC22A18; -. DR HGNC; HGNC:10964; SLC22A18. DR HPA; ENSG00000110628; Tissue enhanced (intestine, liver). DR MalaCards; SLC22A18; -. DR MIM; 114480; phenotype. DR MIM; 211980; phenotype. DR MIM; 268210; phenotype. DR MIM; 602631; gene. DR neXtProt; NX_Q96BI1; -. DR OpenTargets; ENSG00000110628; -. DR Orphanet; 99757; Embryonal rhabdomyosarcoma. DR Orphanet; 227535; Hereditary breast cancer. DR PharmGKB; PA35846; -. DR VEuPathDB; HostDB:ENSG00000110628; -. DR eggNOG; ENOG502QT94; Eukaryota. DR GeneTree; ENSGT00940000160333; -. DR HOGENOM; CLU_001265_10_1_1; -. DR InParanoid; Q96BI1; -. DR OMA; RLMKYPR; -. DR OrthoDB; 5320116at2759; -. DR PhylomeDB; Q96BI1; -. DR TreeFam; TF352510; -. DR PathwayCommons; Q96BI1; -. DR Reactome; R-HSA-549127; Organic cation transport. DR Reactome; R-HSA-5619066; Defective SLC22A18 causes lung cancer (LNCR) and embryonal rhabdomyosarcoma 1 (RMSE1). DR SignaLink; Q96BI1; -. DR SIGNOR; Q96BI1; -. DR BioGRID-ORCS; 5002; 10 hits in 1169 CRISPR screens. DR GeneWiki; SLC22A18; -. DR GenomeRNAi; 5002; -. DR Pharos; Q96BI1; Tbio. DR PRO; PR:Q96BI1; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96BI1; Protein. DR Bgee; ENSG00000110628; Expressed in mucosa of transverse colon and 94 other cell types or tissues. DR ExpressionAtlas; Q96BI1; baseline and differential. DR Genevisible; Q96BI1; HS. DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; TAS:Reactome. DR GO; GO:0006811; P:monoatomic ion transport; IEA:UniProtKB-KW. DR GO; GO:0015695; P:organic cation transport; NAS:UniProtKB. DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IDA:UniProtKB. DR GO; GO:0042908; P:xenobiotic transport; IDA:UniProtKB. DR CDD; cd17331; MFS_SLC22A18; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR011701; MFS. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR001958; Tet-R_TetA/multi-R_MdtG-like. DR PANTHER; PTHR24002; SOLUTE CARRIER FAMILY 22 MEMBER 18; 1. DR PANTHER; PTHR24002:SF3; SOLUTE CARRIER FAMILY 22 MEMBER 18; 1. DR Pfam; PF07690; MFS_1; 1. DR PRINTS; PR01035; TCRTETA. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. PE 1: Evidence at protein level; KW Cell membrane; Disease variant; Ion transport; Membrane; KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..424 FT /note="Solute carrier family 22 member 18" FT /id="PRO_0000220509" FT TRANSMEM 26..46 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 59..79 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 90..110 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 156..176 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 184..204 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 243..263 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 276..296 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 312..332 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 334..354 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 391..411 FT /note="Helical" FT /evidence="ECO:0000255" FT VARIANT 6 FT /note="A -> T (in dbSNP:rs1048046)" FT /evidence="ECO:0000269|PubMed:9520460" FT /id="VAR_055406" FT VARIANT 12 FT /note="R -> Q (in dbSNP:rs1048047)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9520460, ECO:0000269|PubMed:9570947, FT ECO:0000269|Ref.6" FT /id="VAR_055407" FT VARIANT 86 FT /note="R -> C (in a rhabdomyosarcoma sample)" FT /evidence="ECO:0000269|PubMed:9520460" FT /id="VAR_024061" FT VARIANT 233 FT /note="S -> F (in lung cancer; somatic mutation; FT dbSNP:rs121909071)" FT /evidence="ECO:0000269|PubMed:9751628" FT /id="VAR_024062" FT VARIANT 309 FT /note="R -> Q (in dbSNP:rs141165353)" FT /evidence="ECO:0000269|PubMed:9751628" FT /id="VAR_024063" FT VARIANT 324 FT /note="W -> C (in dbSNP:rs1129782)" FT /id="VAR_055408" FT CONFLICT 84 FT /note="D -> N (in Ref. 5; AAC17492)" FT /evidence="ECO:0000305" FT CONFLICT 227 FT /note="D -> E (in Ref. 4; AAB82727 and 6; AAC23505)" FT /evidence="ECO:0000305" FT CONFLICT 230 FT /note="A -> G (in Ref. 4; AAB82727 and 6; AAC23505)" FT /evidence="ECO:0000305" FT CONFLICT 242 FT /note="R -> K (in Ref. 4; AAB82727 and 6; AAC23505)" FT /evidence="ECO:0000305" FT CONFLICT 275 FT /note="Q -> K (in Ref. 4; AAB82727 and 6; AAC23505)" FT /evidence="ECO:0000305" FT CONFLICT 307 FT /note="L -> M (in Ref. 3; AAC04787)" FT /evidence="ECO:0000305" FT CONFLICT 309 FT /note="R -> G (in Ref. 4; AAB82727 and 6; AAC23505)" FT /evidence="ECO:0000305" SQ SEQUENCE 424 AA; 44846 MW; 9EFD5F902A77A6E8 CRC64; MQGARAPRDQ GRSPGRMSAL GRSSVILLTY VLAATELTCL FMQFSIVPYL SRKLGLDSIA FGYLQTTFGV LQLLGGPVFG RFADQRGARA ALTLSFLAAL ALYLLLAAAS SPALPGVYLL FASRLPGALM HTLPAAQMVI TDLSAPEERP AALGRLGLCF GVGVILGSLL GGTLVSAYGI QCPAILAALA TLLGAVLSFT CIPASTKGAK TDAQAPLPGG PRASVFDLKA IASLLRLPDV PRIFLVKVAS NCPTGLFMVM FSIISMDFFQ LEAAQAGYLM SFFGLLQMVT QGLVIGQLSS HFSEEVLLRA SVLVFIVVGL AMAWMSSVFH FCLLVPGLVF SLCTLNVVTD SMLIKAVSTS DTGTMLGLCA SVQPLLRTLG PTVGGLLYRS FGVPVFGHVQ VAINTLVLLV LWRKPMPQRK DKVR //