S22AI_HUMAN
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 03-AUG-2022, entry version 165.
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; 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 BioMuta; SLC22A18; -.
DR DMDM; 238054368; -.
DR EPD; Q96BI1; -.
DR jPOST; Q96BI1; -.
DR MassIVE; Q96BI1; -.
DR MaxQB; Q96BI1; -.
DR PaxDb; Q96BI1; -.
DR PeptideAtlas; Q96BI1; -.
DR PRIDE; Q96BI1; -.
DR ProteomicsDB; 76077; -.
DR Antibodypedia; 23193; 141 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 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; FAPFWGR; -.
DR OrthoDB; 1090653at2759; -.
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 BioGRID-ORCS; 5002; 10 hits in 1089 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 92 other 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:0016021; C:integral component of membrane; NAS: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:0015299; F:solute:proton antiporter activity; 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: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 Gene3D; 1.20.1250.20; -; 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.
DR Pfam; PF07690; MFS_1; 1.
DR PRINTS; PR01035; TCRTETA.
DR SUPFAM; SSF103473; SSF103473; 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
