Q96BI1 (S22AI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 22 member 18

Alternative name(s):
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
Short name=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
Short name=p45-BWR1A

Gene names

Name:	SLC22A18
Synonyms:	BWR1A, BWSCR1A, HET, IMPT1, ITM, ORCTL2, SLC22A1L, TSSC5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.8
Subunit structure	Interacts with RNF167. Ref.9
Subcellular location	Apical cell membrane; Multi-pass membrane protein Potential. Note: Localized at the apical membrane surface of renal proximal tubules. Ref.8
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. Ref.3 Ref.4 Ref.5 Ref.8
Involvement in 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. Note: The gene represented in this entry may be involved in disease pathogenesis. Rhabdomyosarcoma 1 (RMS1) [MIM:268210]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchimal 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.
Sequence similarities	Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]
Caution	It is uncertain whether Met-1 or Met-17 is the initiator.
Sequence caution	The sequence AAB82727.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA32779.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	excretion Non-traceable author statement Ref.8. Source: UniProtKB organic cation transport Non-traceable author statement Ref.8. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from direct assay Ref.8. Source: UniProtKB cytoplasmic part Inferred from direct assay Ref.9. Source: UniProtKB integral to membrane Non-traceable author statement Ref.4Ref.1. Source: UniProtKB nuclear envelope Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	drug transmembrane transporter activity Inferred from direct assay Ref.8. Source: UniProtKB symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 424	424	Solute carrier family 22 member 18		PRO_0000220509
Regions
	Transmembrane	26 – 46	21	Helical; Potential
	Transmembrane	59 – 79	21	Helical; Potential
	Transmembrane	90 – 110	21	Helical; Potential
	Transmembrane	156 – 176	21	Helical; Potential
	Transmembrane	184 – 204	21	Helical; Potential
	Transmembrane	243 – 263	21	Helical; Potential
	Transmembrane	276 – 296	21	Helical; Potential
	Transmembrane	312 – 332	21	Helical; Potential
	Transmembrane	334 – 354	21	Helical; Potential
	Transmembrane	391 – 411	21	Helical; Potential
Natural variations
	Natural variant	6	1	A → T. Ref.5 Corresponds to variant rs1048046 [ dbSNP | Ensembl ].		VAR_055406
	Natural variant	12	1	R → Q. Ref.3 Ref.5 Ref.6 Ref.7 Corresponds to variant rs1048047 [ dbSNP | Ensembl ].		VAR_055407
	Natural variant	86	1	R → C in a rhabdomyosarcoma sample. Ref.5		VAR_024061
	Natural variant	233	1	S → F in lung cancer; somatic mutation. Ref.1		VAR_024062
	Natural variant	309	1	R → Q. Ref.1		VAR_024063
	Natural variant	324	1	W → C. Corresponds to variant rs1129782 [ dbSNP | Ensembl ].		VAR_055408
Experimental info
	Sequence conflict	84	1	D → N in AAC17492. Ref.5
	Sequence conflict	227	1	D → E in AAB82727. Ref.4
	Sequence conflict	227	1	D → E in AAC23505. Ref.6
	Sequence conflict	230	1	A → G in AAB82727. Ref.4
	Sequence conflict	230	1	A → G in AAC23505. Ref.6
	Sequence conflict	242	1	R → K in AAB82727. Ref.4
	Sequence conflict	242	1	R → K in AAC23505. Ref.6
	Sequence conflict	275	1	Q → K in AAB82727. Ref.4
	Sequence conflict	275	1	Q → K in AAC23505. Ref.6
	Sequence conflict	307	1	L → M in AAC04787. Ref.3
	Sequence conflict	309	1	R → G in AAB82727. Ref.4
	Sequence conflict	309	1	R → G in AAC23505. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q96BI1 [UniParc]. Last modified May 26, 2009. Version 3. Checksum: 9EFD5F902A77A6E8	FASTA	424	44,846
	10 20 30 40 50 60 MQGARAPRDQ GRSPGRMSAL GRSSVILLTY VLAATELTCL FMQFSIVPYL SRKLGLDSIA 70 80 90 100 110 120 FGYLQTTFGV LQLLGGPVFG RFADQRGARA ALTLSFLAAL ALYLLLAAAS SPALPGVYLL 130 140 150 160 170 180 FASRLPGALM HTLPAAQMVI TDLSAPEERP AALGRLGLCF GVGVILGSLL GGTLVSAYGI 190 200 210 220 230 240 QCPAILAALA TLLGAVLSFT CIPASTKGAK TDAQAPLPGG PRASVFDLKA IASLLRLPDV 250 260 270 280 290 300 PRIFLVKVAS NCPTGLFMVM FSIISMDFFQ LEAAQAGYLM SFFGLLQMVT QGLVIGQLSS 310 320 330 340 350 360 HFSEEVLLRA SVLVFIVVGL AMAWMSSVFH FCLLVPGLVF SLCTLNVVTD SMLIKAVSTS 370 380 390 400 410 420 DTGTMLGLCA SVQPLLRTLG PTVGGLLYRS FGVPVFGHVQ VAINTLVLLV LWRKPMPQRK DKVR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5." 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. Cancer Res. 58:4155-4159(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-309, VARIANT LUNG CANCER PHE-233.
[2]	"A novel gene, ITM, located between p57KIP2 and IPL, is imprinted in mice." Morisaki H., Hatada I., Morisaki T., Mukai T. DNA Res. 5:235-240(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Divergently transcribed overlapping genes expressed in liver and kidney and located in the 11p15.5 imprinted domain." 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. Genomics 49:38-51(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT GLN-12.
[4]	"IMPT1, an imprinted gene similar to polyspecific transporter and multi-drug resistance genes." Dao D., Frank D., Qian N., O'Keefe D., Vosatka R.J., Walsh C.P., Tycko B. Hum. Mol. Genet. 7:597-608(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Placenta.
[5]	"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." 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. Proc. Natl. Acad. Sci. U.S.A. 95:3873-3878(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS THR-6 AND GLN-12; CYS-86, TISSUE SPECIFICITY.
[6]	"Monoallelic expression of the gene encoding a human efflux transporter like protein (HET), on chromosome 11p15.5." Chen P., Shen W., Karnik P. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-12.
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-12. Tissue: Placenta.
[8]	"Functional characterization of ORCTL2 -- an organic cation transporter expressed in the renal proximal tubules." Reece M., Prawitt D., Landers J., Kast C., Gros P., Housman D., Zabel B.U., Pelletier J. FEBS Lett. 433:245-250(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105." Yamada H.Y., Gorbsky G.J. Oncogene 25:1330-1339(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF167.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF059663 mRNA. Translation: AAC14725.1. AB012083 mRNA. Translation: BAA32779.1. Different initiation. AF037064 mRNA. Translation: AAC04787.1. AF028738 mRNA. Translation: AAB82727.1. Different initiation. AF030302 mRNA. Translation: AAC17492.1. AF070479 mRNA. Translation: AAC23505.1. BC015571 mRNA. Translation: AAH15571.1.
IPI	IPI00410347.
RefSeq	NP_002546.3. NM_002555.5. NP_899056.2. NM_183233.2.
UniGene	Hs.50868.
3D structure databases
ProteinModelPortal	Q96BI1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000307859.
PTM databases
PhosphoSite	Q96BI1.
Polymorphism databases
DMDM	238054368.
Proteomic databases
PaxDb	Q96BI1.
PRIDE	Q96BI1.
Protocols and materials databases
DNASU	5002.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312221; ENSP00000311139; ENSG00000110628. ENST00000347936; ENSP00000307859; ENSG00000110628. ENST00000380574; ENSP00000369948; ENSG00000110628.
GeneID	5002.
KEGG	hsa:5002.
UCSC	uc001lwx.3. human.
Organism-specific databases
CTD	5002.
GeneCards	GC11P002877.
H-InvDB	HIX0019391.
HGNC	HGNC:10964. SLC22A18.
MIM	114480. phenotype. 211980. phenotype. 268210. phenotype. 602631. gene.
neXtProt	NX_Q96BI1.
PharmGKB	PA35846.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0477.
HOVERGEN	HBG082086.
InParanoid	Q96BI1.
KO	K08214.
OMA	THSIAGM.
OrthoDB	EOG4QZ7M5.
PhylomeDB	Q96BI1.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q96BI1.
Bgee	Q96BI1.
CleanEx	HS_SLC22A18.
Genevestigator	Q96BI1.
GermOnline	ENSG00000110628. Homo sapiens.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR001958. Tet-R_TetA/multi-R_MdtG. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
PRINTS	PR01035. TCRTETA.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5002.
NextBio	19262.
SOURCE	Search...

Entry information

Entry name

S22AI_HUMAN

Accession

Primary (citable) accession number: Q96BI1
Secondary accession number(s): O14906 , O43562, O60485, O60680, Q7LDS5, Q7LGF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	May 26, 2009
Last modified:	May 1, 2013
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.