Solute carrier family 22 member 8 - Homo sapiens (Human)

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Q8TCC7 (S22A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 76. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Solute carrier family 22 member 8

Alternative name(s):
Organic anion transporter 3
Short name=hOAT3

Gene names

Name:	SLC22A8
Synonyms:	OAT3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	542 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA). Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein Potential. Note: Localizes on the brush border membrane of the choroid epithelial cells. Localizes to the basolateral membrane of the proximal tubular cells. Localizes on the abluminal and possibly, luminal membrane of the brain capillary endothelial cells (BCEC) By similarity. Ref.5
Tissue specificity	Expressed in kidney. Ref.5
Sequence similarities	Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family. [View classification]
Sequence caution	The sequence AAD19357.1 differs from that shown. Reason: Frameshift at several positions. The sequence BAD92929.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Detoxification Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	response to toxin Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	basolateral plasma membrane Inferred from direct assay. Source: UniProtKB integral to plasma membrane Traceable author statement. Source: ProtInc membrane fraction Traceable author statement. Source: ProtInc
Molecular function	inorganic anion exchanger activity Inferred from direct assay. Source: UniProtKB organic anion transmembrane transporter activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TCC7-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8TCC7-2) The sequence of this isoform differs from the canonical sequence as follows: 510-510: W → WSVTASGPPR
Note: No experimental confirmation available.

Isoform 3 (identifier: Q8TCC7-3) The sequence of this isoform differs from the canonical sequence as follows: 1-345: Missing. 406-455: DLQTVRTVLA...MGVSNLWTRV → GERLGLPQNP...SGAQGLSSRK 456-542: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 542

542

Solute carrier family 22 member 8

PRO_0000273439

Regions

Topological domain

1 – 9

Cytoplasmic Potential

Transmembrane

10 – 30

Helical; Potential

Topological domain

31 – 123

Extracellular Potential

Transmembrane

124 – 144

Helical; Potential

Topological domain

145 – 154

Cytoplasmic Potential

Transmembrane

155 – 175

Helical; Potential

Topological domain

176

Extracellular Potential

Transmembrane

177 – 197

Helical; Potential

Topological domain

198 – 212

Cytoplasmic Potential

Transmembrane

213 – 233

Helical; Potential

Topological domain

234 – 236

Extracellular Potential

Transmembrane

237 – 257

Helical; Potential

Topological domain

258 – 327

Cytoplasmic Potential

Transmembrane

328 – 348

Helical; Potential

Topological domain

349 – 354

Extracellular Potential

Transmembrane

355 – 375

Helical; Potential

Topological domain

376 – 386

Cytoplasmic Potential

Transmembrane

387 – 407

Helical; Potential

Topological domain

408 – 411

Extracellular Potential

Transmembrane

412 – 432

Helical; Potential

Topological domain

433 – 471

Cytoplasmic Potential

Transmembrane

472 – 492

Helical; Potential

Topological domain

493 – 542

Extracellular Potential

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

102

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 345

345

Missing in isoform 3.

VSP_022562

Alternative sequence

406 – 455

DLQTV…LWTRV → GERLGLPQNPLEEAARLGAR DFTAGSASKSLCYLEQVPAL SGAQGLSSRK in isoform 3.

VSP_022563

Alternative sequence

456 – 542

Missing in isoform 3.

VSP_022564

Alternative sequence

510

W → WSVTASGPPR in isoform 2.

VSP_022565

Natural variant

129

F → L.
Corresponds to variant rs11568479 [ dbSNP | Ensembl ].

VAR_030146

Natural variant

149

R → S Complete loss of function. Ref.11
Corresponds to variant rs45566039 [ dbSNP | Ensembl ].

VAR_030147

Natural variant

260

I → R Complete loss of function. Ref.11
Corresponds to variant rs11568493 [ dbSNP | Ensembl ].

VAR_030148

Natural variant

277

R → W Reduced function. Ref.11
Corresponds to variant rs11568492 [ dbSNP | Ensembl ].

VAR_030149

Natural variant

281

V → A in 6% of African-Americans.
Corresponds to variant rs45438191 [ dbSNP | Ensembl ].

VAR_030150

Natural variant

305

I → F in 3.5% of Asian-American; reduced function. Ref.11
Corresponds to variant rs11568482 [ dbSNP | Ensembl ].

VAR_030151

Natural variant

389

A → V. Ref.10

VAR_030152

Natural variant

448

V → I.
Corresponds to variant rs11568486 [ dbSNP | Ensembl ].

VAR_030153

Experimental info

Sequence conflict

150

Missing in AAD19357. Ref.1

Sequence conflict

151

P → T in AAD19357. Ref.1

Sequence conflict

271

K → E in BAB47393. Ref.2

Sequence conflict

286

Missing in AAD19357. Ref.1

Sequence conflict

411

R → E in AAD19357. Ref.1

Sequence conflict

478 – 480

YGI → FTGS in AAD19357. Ref.1

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 22799360D91B4CCF Show »	FASTA	542	59,856
10 20 30 40 50 60 MTFSEILDRV GSMGHFQFLH VAILGLPILN MANHNLLQIF TAATPVHHCR PPHNASTGPW 70 80 90 100 110 120 VLPMGPNGKP ERCLRFVHPP NASLPNDTQR AMEPCLDGWV YNSTKDSIVT EWDLVCNSNK 130 140 150 160 170 180 LKEMAQSIFM AGILIGGLVL GDLSDRFGRR PILTCSYLLL AASGSGAAFS PTFPIYMVFR 190 200 210 220 230 240 FLCGFGISGI TLSTVILNVE WVPTRMRAIM STALGYCYTF GQFILPGLAY AIPQWRWLQL 250 260 270 280 290 300 TVSIPFFVFF LSSWWTPESI RWLVLSGKSS KALKILRRVA VFNGKKEEGE RLSLEELKLN 310 320 330 340 350 360 LQKEISLAKA KYTASDLFRI PMLRRMTFCL SLAWFATGFA YYSLAMGVEE FGVNLYILQI 370 380 390 400 410 420 IFGGVDVPAK FITILSLSYL GRHTTQAAAL LLAGGAILAL TFVPLDLQTV RTVLAVFGKG 430 440 450 460 470 480 CLSSSFSCLF LYTSELYPTV IRQTGMGVSN LWTRVGSMVS PLVKITGEVQ PFIPNIIYGI 490 500 510 520 530 540 TALLGGSAAL FLPETLNQPL PETIEDLENW SLRAKKPKQE PEVEKASQRI PLQPHGPGLG SS « Hide
Isoform 2 [UniParc]. Checksum: 0F202C686929638A Show »	FASTA	551	60,709
10 20 30 40 50 60 MTFSEILDRV GSMGHFQFLH VAILGLPILN MANHNLLQIF TAATPVHHCR PPHNASTGPW 70 80 90 100 110 120 VLPMGPNGKP ERCLRFVHPP NASLPNDTQR AMEPCLDGWV YNSTKDSIVT EWDLVCNSNK 130 140 150 160 170 180 LKEMAQSIFM AGILIGGLVL GDLSDRFGRR PILTCSYLLL AASGSGAAFS PTFPIYMVFR 190 200 210 220 230 240 FLCGFGISGI TLSTVILNVE WVPTRMRAIM STALGYCYTF GQFILPGLAY AIPQWRWLQL 250 260 270 280 290 300 TVSIPFFVFF LSSWWTPESI RWLVLSGKSS KALKILRRVA VFNGKKEEGE RLSLEELKLN 310 320 330 340 350 360 LQKEISLAKA KYTASDLFRI PMLRRMTFCL SLAWFATGFA YYSLAMGVEE FGVNLYILQI 370 380 390 400 410 420 IFGGVDVPAK FITILSLSYL GRHTTQAAAL LLAGGAILAL TFVPLDLQTV RTVLAVFGKG 430 440 450 460 470 480 CLSSSFSCLF LYTSELYPTV IRQTGMGVSN LWTRVGSMVS PLVKITGEVQ PFIPNIIYGI 490 500 510 520 530 540 TALLGGSAAL FLPETLNQPL PETIEDLENW SVTASGPPRS LRAKKPKQEP EVEKASQRIP 550 LQPHGPGLGS S « Hide
Isoform 3 [UniParc]. Checksum: 0050E6499A6446CB Show »	FASTA	110	11,502
10 20 30 40 50 60 MGVEEFGVNL YILQIIFGGV DVPAKFITIL SLSYLGRHTT QAAALLLAGG AILALTFVPL 70 80 90 100 110 GERLGLPQNP LEEAARLGAR DFTAGSASKS LCYLEQVPAL SGAQGLSSRK « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3)." Race J.E., Grassl S.M., Williams W.J., Holtzman E.J. Biochem. Biophys. Res. Commun. 255:508-514(1999) [PubMed: 10049739] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Kidney.
[2]	"Molecular cloning and characterization of human organic anion transporter 3." Cha S., Sekine T., Kanai Y., Endou H. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[3]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney.
[5]	"Gene expression levels and immunolocalization of organic ion transporters in the human kidney." Motohashi H., Sakurai Y., Saito H., Masuda S., Urakami Y., Goto M., Fukatsu A., Ogawa O., Inui K. J. Am. Soc. Nephrol. 13:866-874(2002) [PubMed: 11912245] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"Human organic anion transporter 3 (hOAT3) can operate as an exchanger and mediate secretory urate flux." Bakhiya A., Bahn A., Burckhardt G., Wolff N. Cell. Physiol. Biochem. 13:249-256(2003) [PubMed: 14586168] [Abstract] Cited for: FUNCTION.
[7]	"Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8)." Srimaroeng C., Chatsudthipong V., Aslamkhan A.G., Pritchard J.B. J. Pharmacol. Exp. Ther. 313:621-628(2005) [PubMed: 15644426] [Abstract] Cited for: FUNCTION.
[8]	"Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus monkey kidney." Tahara H., Shono M., Kusuhara H., Kinoshita H., Fuse E., Takadate A., Otagiri M., Sugiyama Y. Pharm. Res. 22:647-660(2005) [PubMed: 15846473] [Abstract] Cited for: FUNCTION.
[9]	"Inhibition of oat3-mediated renal uptake as a mechanism for drug-drug interaction between fexofenadine and probenecid." Tahara H., Kusuhara H., Maeda K., Koepsell H., Fuse E., Sugiyama Y. Drug Metab. Dispos. 34:743-747(2006) [PubMed: 16455804] [Abstract] Cited for: FUNCTION.
[10]	"Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics." Nishizato Y., Ieiri I., Suzuki H., Kimura M., Kawabata K., Hirota T., Takane H., Irie S., Kusuhara H., Urasaki Y., Urae A., Higuchi S., Otsubo K., Sugiyama Y. Clin. Pharmacol. Ther. 73:554-565(2003) [PubMed: 12811365] [Abstract] Cited for: VARIANT VAL-389.
[11]	"The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and functional genomics." Erdman A.R., Mangravite L.M., Urban T.J., Lagpacan L.L., Castro R.A., de la Cruz M., Chan W., Huang C.C., Johns S.J., Kawamoto M., Stryke D., Taylor T.R., Carlson E.J., Ferrin T.E., Brett C.M., Burchard E.G., Giacomini K.M. Am. J. Physiol. 290:F905-F912(2006) [PubMed: 16291576] [Abstract] Cited for: VARIANTS SER-149; ARG-260; TRP-277 AND PHE-305, CHARACTERIZATION OF VARIANTS SER-149; ARG-260; TRP-277 AND PHE-305.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF097491 mRNA. Translation: AAD19357.1. Frameshift. AB042505 mRNA. Translation: BAB47393.1. AB209692 mRNA. Translation: BAD92929.1. Different initiation. BC022387 mRNA. Translation: AAH22387.1.
IPI	IPI00163456. IPI00827526. IPI00827863.
RefSeq	NP_001171661.1. NM_001184732.1. NP_001171662.1. NM_001184733.1. NP_001171665.1. NM_001184736.1. NP_004245.2. NM_004254.3.
UniGene	Hs.266223.
3D structure databases
ProteinModelPortal	Q8TCC7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8TCC7. 1 interaction.
STRING	Q8TCC7.
Polymorphism databases
DMDM	74730587.
Proteomic databases
PRIDE	Q8TCC7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336232; ENSP00000337335; ENSG00000149452.
GeneID	9376.
KEGG	hsa:9376.
UCSC	uc001nwo.1. human. uc001nwp.2. human.
Organism-specific databases
CTD	9376.
GeneCards	GC11M062760.
H-InvDB	HIX0009733.
HGNC	HGNC:10972. SLC22A8.
HPA	HPA044174.
MIM	607581. gene.
neXtProt	NX_Q8TCC7.
PharmGKB	PA389.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15961.
GeneTree	ENSGT00550000074177.
HOVERGEN	HBG108433.
OrthoDB	EOG418BPG.
PhylomeDB	Q8TCC7.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q8TCC7.
Bgee	Q8TCC7.
CleanEx	HS_SLC22A8.
Genevestigator	Q8TCC7.
Family and domain databases
InterPro	IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004749. Orgcat_transp. IPR005828. Sub_transporter. IPR005829. Sugar_transporter_CS. [Graphical view]
KO	K08205.
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00898. 2A0119. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	35126.
SOURCE	Search...

Entry information

Entry name

S22A8_HUMAN

Accession

Primary (citable) accession number: Q8TCC7
Secondary accession number(s): O95820, Q59EW9, Q96TC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2007
Last sequence update:	June 1, 2002
Last modified:	January 25, 2012
This is version 76 of the entry and version 1 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.

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Human chromosome 11: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents