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Solute carrier family 22 member 18 (Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene A protein) (Efflux transporter-like protein) (Imprinted multi-membrane-spanning polyspecific transporter-related protein 1) (Organic cation transporter-like protein 2) (ORCTL-2) (Solute carrier family 22 member 1-like) (Tumor-suppressing STF cDNA 5 protein) (Tumor-suppressing subchromosomal transferable fragment candidate gene 5 protein) (p45-Beckwith-Wiedemann region 1 A) (p45-BWR1A)

 S22AI_HUMAN             Reviewed;         424 AA.
Q96BI1; O14906; O43562; O60485; O60680; Q7LDS5; Q7LGF7;
06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
26-MAY-2009, sequence version 3.
27-SEP-2017, entry version 134.
RecName: Full=Solute carrier family 22 member 18;
AltName: Full=Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene A protein;
AltName: Full=Efflux transporter-like protein;
AltName: Full=Imprinted multi-membrane-spanning polyspecific transporter-related protein 1;
AltName: Full=Organic cation transporter-like protein 2;
Short=ORCTL-2;
AltName: Full=Solute carrier family 22 member 1-like;
AltName: Full=Tumor-suppressing STF cDNA 5 protein;
AltName: Full=Tumor-suppressing subchromosomal transferable fragment candidate gene 5 protein;
AltName: Full=p45-Beckwith-Wiedemann region 1 A;
Short=p45-BWR1A;
Name=SLC22A18;
Synonyms=BWR1A, BWSCR1A, HET, IMPT1, ITM, ORCTL2, SLC22A1L, TSSC5;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-309, AND VARIANT LUNG CANCER
PHE-233.
PubMed=9751628;
Lee M.P., Reeves C., Schmitt A., Su K., Connors T.D., Hu R.J.,
Brandenburg S., Lee M.J., Miller G., Feinberg A.P.;
"Somatic mutation of TSSC5, a novel imprinted gene from human
chromosome 11p15.5.";
Cancer Res. 58:4155-4159(1998).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=9802569; DOI=10.1093/dnares/5.4.235;
Morisaki H., Hatada I., Morisaki T., Mukai T.;
"A novel gene, ITM, located between p57KIP2 and IPL, is imprinted in
mice.";
DNA Res. 5:235-240(1998).
[3]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT GLN-12.
PubMed=9570947; DOI=10.1006/geno.1998.5221;
Cooper P.R., Smilinich N.J., Day C.D., Nowak N.J., Reid L.H.,
Pearsall R.S., Reece M., Prawitt D., Landers J., Housman D.E.,
Winterpacht A., Zabel B.U., Pelletier J., Weissman B.E., Shows T.B.,
Higgins M.J.;
"Divergently transcribed overlapping genes expressed in liver and
kidney and located in the 11p15.5 imprinted domain.";
Genomics 49:38-51(1998).
[4]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Placenta;
PubMed=9499412; DOI=10.1093/hmg/7.4.597;
Dao D., Frank D., Qian N., O'Keefe D., Vosatka R.J., Walsh C.P.,
Tycko B.;
"IMPT1, an imprinted gene similar to polyspecific transporter and
multi-drug resistance genes.";
Hum. Mol. Genet. 7:597-608(1998).
[5]
NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-6 AND GLN-12; CYS-86, AND
TISSUE SPECIFICITY.
PubMed=9520460; DOI=10.1073/pnas.95.7.3873;
Schwienbacher C., Sabbioni S., Campi M., Veronese A., Bernardi G.,
Menegatti A., Hatada I., Mukai T., Ohashi H., Barbanti-Brodano G.,
Croce C.M., Negrini M.;
"Transcriptional map of 170-kb region at chromosome 11p15.5:
identification and mutational analysis of the BWR1A gene reveals the
presence of mutations in tumor samples.";
Proc. Natl. Acad. Sci. U.S.A. 95:3873-3878(1998).
[6]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-12.
Chen P., Shen W., Karnik P.;
"Monoallelic expression of the gene encoding a human efflux
transporter like protein (HET), on chromosome 11p15.5.";
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-12.
TISSUE=Placenta;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=9744804; DOI=10.1016/S0014-5793(98)00907-7;
Reece M., Prawitt D., Landers J., Kast C., Gros P., Housman D.,
Zabel B.U., Pelletier J.;
"Functional characterization of ORCTL2 -- an organic cation
transporter expressed in the renal proximal tubules.";
FEBS Lett. 433:245-250(1998).
[9]
INTERACTION WITH RNF167.
PubMed=16314844; DOI=10.1038/sj.onc.1209167;
Yamada H.Y., Gorbsky G.J.;
"Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel
ubiquitin ligase RING105.";
Oncogene 25:1330-1339(2006).
-!- FUNCTION: May act as a transporter of organic cations based on a
proton efflux antiport mechanism. May play a role in the transport
of chloroquine and quinidine-related compounds in kidney.
{ECO:0000269|PubMed:9744804}.
-!- SUBUNIT: Interacts with RNF167. {ECO:0000269|PubMed:16314844}.
-!- INTERACTION:
Q99801:NKX3-1; NbExp=4; IntAct=EBI-11721845, EBI-1385894;
-!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000305}; Multi-
pass membrane protein {ECO:0000305}. Note=Localized at the apical
membrane surface of renal proximal tubules.
{ECO:0000269|PubMed:9744804}.
-!- TISSUE SPECIFICITY: Expressed at high levels in adult and fetal
kidney and liver, and adult colon. Expressed in fetal renal
proximal tubules (at protein level). Expressed at lower levels in
heart, brain and lung. {ECO:0000269|PubMed:9499412,
ECO:0000269|PubMed:9520460, ECO:0000269|PubMed:9570947,
ECO:0000269|PubMed:9744804}.
-!- DISEASE: Lung cancer (LNCR) [MIM:211980]: A common malignancy
affecting tissues of the lung. The most common form of lung cancer
is non-small cell lung cancer (NSCLC) that can be divided into 3
major histologic subtypes: squamous cell carcinoma,
adenocarcinoma, and large cell lung cancer. NSCLC is often
diagnosed at an advanced stage and has a poor prognosis.
{ECO:0000269|PubMed:9751628}. Note=The gene represented in this
entry may be involved in disease pathogenesis.
-!- DISEASE: Rhabdomyosarcoma, embryonal, 1 (RMSE1) [MIM:268210]: A
form of rhabdomyosarcoma, a highly malignant tumor of striated
muscle derived from primitive mesenchymal cells and exhibiting
differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is
one of the most frequently occurring soft tissue sarcomas and the
most common in children. It occurs in four forms: alveolar,
pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=The
disease may be caused by mutations affecting the gene represented
in this entry.
-!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1)
superfamily. Organic cation transporter (TC 2.A.1.19) family.
{ECO:0000305}.
-!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAB82727.1; Type=Erroneous initiation; Evidence={ECO:0000305};
Sequence=BAA32779.1; Type=Erroneous initiation; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; AF059663; AAC14725.1; -; mRNA.
EMBL; AB012083; BAA32779.1; ALT_INIT; mRNA.
EMBL; AF037064; AAC04787.1; -; mRNA.
EMBL; AF028738; AAB82727.1; ALT_INIT; mRNA.
EMBL; AF030302; AAC17492.1; -; mRNA.
EMBL; AF070479; AAC23505.1; -; mRNA.
EMBL; BC015571; AAH15571.1; -; mRNA.
CCDS; CCDS7740.1; -.
RefSeq; NP_001302430.1; NM_001315501.1.
RefSeq; NP_001302431.1; NM_001315502.1.
RefSeq; NP_002546.3; NM_002555.5.
RefSeq; NP_899056.2; NM_183233.2.
UniGene; Hs.50868; -.
ProteinModelPortal; Q96BI1; -.
BioGrid; 111044; 26.
IntAct; Q96BI1; 5.
STRING; 9606.ENSP00000307859; -.
TCDB; 2.A.1.2.53; the major facilitator superfamily (mfs).
iPTMnet; Q96BI1; -.
PhosphoSitePlus; Q96BI1; -.
BioMuta; SLC22A18; -.
DMDM; 238054368; -.
EPD; Q96BI1; -.
MaxQB; Q96BI1; -.
PaxDb; Q96BI1; -.
PeptideAtlas; Q96BI1; -.
PRIDE; Q96BI1; -.
DNASU; 5002; -.
Ensembl; ENST00000312221; ENSP00000311139; ENSG00000110628.
Ensembl; ENST00000347936; ENSP00000307859; ENSG00000110628.
Ensembl; ENST00000380574; ENSP00000369948; ENSG00000110628.
GeneID; 5002; -.
KEGG; hsa:5002; -.
UCSC; uc001lwx.3; human.
CTD; 5002; -.
DisGeNET; 5002; -.
EuPathDB; HostDB:ENSG00000110628.13; -.
GeneCards; SLC22A18; -.
H-InvDB; HIX0019391; -.
HGNC; HGNC:10964; SLC22A18.
HPA; HPA067812; -.
HPA; HPA071461; -.
MalaCards; SLC22A18; -.
MIM; 114480; phenotype.
MIM; 211980; phenotype.
MIM; 268210; phenotype.
MIM; 602631; gene.
neXtProt; NX_Q96BI1; -.
OpenTargets; ENSG00000110628; -.
PharmGKB; PA35846; -.
eggNOG; ENOG410IIP5; Eukaryota.
eggNOG; ENOG4111F2C; LUCA.
GeneTree; ENSGT00830000128359; -.
HOVERGEN; HBG082086; -.
InParanoid; Q96BI1; -.
KO; K08214; -.
OMA; GLFMVMF; -.
OrthoDB; EOG091G0H3E; -.
PhylomeDB; Q96BI1; -.
TreeFam; TF352510; -.
Reactome; R-HSA-549127; Organic cation transport.
GeneWiki; SLC22A18; -.
GenomeRNAi; 5002; -.
PRO; PR:Q96BI1; -.
Proteomes; UP000005640; Chromosome 11.
Bgee; ENSG00000110628; -.
CleanEx; HS_SLC22A18; -.
ExpressionAtlas; Q96BI1; baseline and differential.
Genevisible; Q96BI1; HS.
GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
GO; GO:0016020; C:membrane; IDA:UniProtKB.
GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0015238; F:drug transmembrane transporter activity; IDA:UniProtKB.
GO; GO:0015307; F:drug:proton antiporter activity; TAS:Reactome.
GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
GO; GO:0015893; P:drug transport; IDA:UniProtKB.
GO; GO:0007588; P:excretion; NAS:UniProtKB.
GO; GO:0015695; P:organic cation transport; NAS:UniProtKB.
CDD; cd06174; MFS; 1.
InterPro; IPR011701; MFS.
InterPro; IPR020846; MFS_dom.
InterPro; IPR001958; Tet-R_TetA/multi-R_MdtG.
Pfam; PF07690; MFS_1; 1.
PRINTS; PR01035; TCRTETA.
SUPFAM; SSF103473; SSF103473; 1.
PROSITE; PS50850; MFS; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Disease mutation; Ion transport;
Membrane; Polymorphism; Reference proteome; Symport; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 424 Solute carrier family 22 member 18.
/FTId=PRO_0000220509.
TRANSMEM 26 46 Helical. {ECO:0000255}.
TRANSMEM 59 79 Helical. {ECO:0000255}.
TRANSMEM 90 110 Helical. {ECO:0000255}.
TRANSMEM 156 176 Helical. {ECO:0000255}.
TRANSMEM 184 204 Helical. {ECO:0000255}.
TRANSMEM 243 263 Helical. {ECO:0000255}.
TRANSMEM 276 296 Helical. {ECO:0000255}.
TRANSMEM 312 332 Helical. {ECO:0000255}.
TRANSMEM 334 354 Helical. {ECO:0000255}.
TRANSMEM 391 411 Helical. {ECO:0000255}.
VARIANT 6 6 A -> T (in dbSNP:rs1048046).
{ECO:0000269|PubMed:9520460}.
/FTId=VAR_055406.
VARIANT 12 12 R -> Q (in dbSNP:rs1048047).
{ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:9520460,
ECO:0000269|PubMed:9570947,
ECO:0000269|Ref.6}.
/FTId=VAR_055407.
VARIANT 86 86 R -> C (in a rhabdomyosarcoma sample).
{ECO:0000269|PubMed:9520460}.
/FTId=VAR_024061.
VARIANT 233 233 S -> F (in lung cancer; somatic mutation;
dbSNP:rs121909071).
{ECO:0000269|PubMed:9751628}.
/FTId=VAR_024062.
VARIANT 309 309 R -> Q (in dbSNP:rs141165353).
{ECO:0000269|PubMed:9751628}.
/FTId=VAR_024063.
VARIANT 324 324 W -> C (in dbSNP:rs1129782).
/FTId=VAR_055408.
CONFLICT 84 84 D -> N (in Ref. 5; AAC17492).
{ECO:0000305}.
CONFLICT 227 227 D -> E (in Ref. 4; AAB82727 and 6;
AAC23505). {ECO:0000305}.
CONFLICT 230 230 A -> G (in Ref. 4; AAB82727 and 6;
AAC23505). {ECO:0000305}.
CONFLICT 242 242 R -> K (in Ref. 4; AAB82727 and 6;
AAC23505). {ECO:0000305}.
CONFLICT 275 275 Q -> K (in Ref. 4; AAB82727 and 6;
AAC23505). {ECO:0000305}.
CONFLICT 307 307 L -> M (in Ref. 3; AAC04787).
{ECO:0000305}.
CONFLICT 309 309 R -> G (in Ref. 4; AAB82727 and 6;
AAC23505). {ECO:0000305}.
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


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