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   02-OCT-2024, entry version 176.
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};
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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; 46.
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   jPOST; Q96BI1; -.
DR   MassIVE; Q96BI1; -.
DR   PaxDb; 9606-ENSP00000369948; -.
DR   PeptideAtlas; Q96BI1; -.
DR   ProteomicsDB; 76077; -.
DR   Pumba; Q96BI1; -.
DR   Antibodypedia; 23193; 160 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   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   Proteomics identification; Reference proteome; Symport; Transmembrane;
KW   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
//