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Q8TCC7 (S22A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 22 member 8
Alternative name(s):
Organic anion transporter 3
Short name=hOAT3
Gene names
Name:SLC22A8
Synonyms:OAT3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length542 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8 Ref.9 Ref.10 Ref.11

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.7

Tissue specificity

Expressed in kidney. Ref.7

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.

Alternative products

This entry describes 5 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 5 (identifier: Q8TCC7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-123: Missing.
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.
Isoform 4 (identifier: Q8TCC7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 542542Solute carrier family 22 member 8
PRO_0000273439

Regions

Topological domain1 – 99Cytoplasmic Potential
Transmembrane10 – 3021Helical; Potential
Topological domain31 – 12393Extracellular Potential
Transmembrane124 – 14421Helical; Potential
Topological domain145 – 15410Cytoplasmic Potential
Transmembrane155 – 17521Helical; Potential
Topological domain1761Extracellular Potential
Transmembrane177 – 19721Helical; Potential
Topological domain198 – 21215Cytoplasmic Potential
Transmembrane213 – 23321Helical; Potential
Topological domain234 – 2363Extracellular Potential
Transmembrane237 – 25721Helical; Potential
Topological domain258 – 32770Cytoplasmic Potential
Transmembrane328 – 34821Helical; Potential
Topological domain349 – 3546Extracellular Potential
Transmembrane355 – 37521Helical; Potential
Topological domain376 – 38611Cytoplasmic Potential
Transmembrane387 – 40721Helical; Potential
Topological domain408 – 4114Extracellular Potential
Transmembrane412 – 43221Helical; Potential
Topological domain433 – 47139Cytoplasmic Potential
Transmembrane472 – 49221Helical; Potential
Topological domain493 – 54250Extracellular Potential

Amino acid modifications

Glycosylation861N-linked (GlcNAc...) Potential
Glycosylation1021N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 345345Missing in isoform 3.
VSP_022562
Alternative sequence1 – 123123Missing in isoform 5.
VSP_045824
Alternative sequence1 – 9191Missing in isoform 4.
VSP_045272
Alternative sequence406 – 45550DLQTV…LWTRV → GERLGLPQNPLEEAARLGAR DFTAGSASKSLCYLEQVPAL SGAQGLSSRK in isoform 3.
VSP_022563
Alternative sequence456 – 54287Missing in isoform 3.
VSP_022564
Alternative sequence5101W → WSVTASGPPR in isoform 2.
VSP_022565
Natural variant1291F → L.
Corresponds to variant rs11568479 [ dbSNP | Ensembl ].
VAR_030146
Natural variant1491R → S Complete loss of function. Ref.13
Corresponds to variant rs45566039 [ dbSNP | Ensembl ].
VAR_030147
Natural variant2601I → R Complete loss of function. Ref.13
Corresponds to variant rs11568493 [ dbSNP | Ensembl ].
VAR_030148
Natural variant2771R → W Reduced function. Ref.13
Corresponds to variant rs11568492 [ dbSNP | Ensembl ].
VAR_030149
Natural variant2811V → A in 6% of African-Americans.
Corresponds to variant rs45438191 [ dbSNP | Ensembl ].
VAR_030150
Natural variant3051I → F in 3.5% of Asian-American; reduced function. Ref.13
Corresponds to variant rs11568482 [ dbSNP | Ensembl ].
VAR_030151
Natural variant3891A → V. Ref.12
VAR_030152
Natural variant4481V → I.
Corresponds to variant rs11568486 [ dbSNP | Ensembl ].
VAR_030153

Experimental info

Sequence conflict1501Missing in AAD19357. Ref.1
Sequence conflict1511P → T in AAD19357. Ref.1
Sequence conflict2711K → E in BAB47393. Ref.2
Sequence conflict2861Missing in AAD19357. Ref.1
Sequence conflict4111R → E in AAD19357. Ref.1
Sequence conflict478 – 4803YGI → FTGS in AAD19357. Ref.1
Sequence conflict5261A → T in BAG60589. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: 22799360D91B4CCF

FASTA54259,856
        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 »

FASTA55160,709
Isoform 5 [UniParc].

Checksum: 3BBFC757CEE06790
Show »

FASTA41946,120
Isoform 3 [UniParc].

Checksum: 0050E6499A6446CB
Show »

FASTA11011,502
Isoform 4 [UniParc].

Checksum: B1E5B7631D8BED48
Show »

FASTA45149,821

References

« Hide '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] [Europe PMC] [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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Kidney.
[4]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.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Tissue: Kidney.
[7]"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] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-389.
[13]"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] [Europe PMC] [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.
AK298341 mRNA. Translation: BAG60589.1.
AB209692 mRNA. Translation: BAD92929.1. Different initiation.
AP001858 Genomic DNA. No translation available.
BC022387 mRNA. Translation: AAH22387.1.
RefSeqNP_001171661.1. NM_001184732.1.
NP_001171662.1. NM_001184733.1.
NP_001171665.1. NM_001184736.1.
NP_004245.2. NM_004254.3.
UniGeneHs.266223.

3D structure databases

ProteinModelPortalQ8TCC7.
SMRQ8TCC7. Positions 130-279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8TCC7. 1 interaction.
STRING9606.ENSP00000337335.

Chemistry

ChEMBLCHEMBL1641348.

Protein family/group databases

TCDB2.A.1.19.34. the major facilitator superfamily (mfs).

Polymorphism databases

DMDM74730587.

Proteomic databases

PaxDbQ8TCC7.
PRIDEQ8TCC7.

Protocols and materials databases

DNASU9376.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000336232; ENSP00000337335; ENSG00000149452. [Q8TCC7-1]
ENST00000430500; ENSP00000398548; ENSG00000149452. [Q8TCC7-1]
ENST00000535878; ENSP00000443368; ENSG00000149452. [Q8TCC7-5]
ENST00000545207; ENSP00000441658; ENSG00000149452. [Q8TCC7-4]
GeneID9376.
KEGGhsa:9376.
UCSCuc001nwo.3. human. [Q8TCC7-1]

Organism-specific databases

CTD9376.
GeneCardsGC11M062760.
HGNCHGNC:10972. SLC22A8.
HPAHPA044174.
MIM607581. gene.
neXtProtNX_Q8TCC7.
PharmGKBPA389.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0477.
HOGENOMHOG000234569.
HOVERGENHBG108433.
KOK08205.
OMAGWVYNST.
OrthoDBEOG7C8GH9.
PhylomeDBQ8TCC7.
TreeFamTF315847.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ8TCC7.
BgeeQ8TCC7.
CleanExHS_SLC22A8.
GenevestigatorQ8TCC7.

Family and domain databases

InterProIPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR004749. Orgcat_transp.
IPR005828. Sub_transporter.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
TIGRFAMsTIGR00898. 2A0119. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC22A8.
GenomeRNAi9376.
NextBio35126.
PROQ8TCC7.
SOURCESearch...

Entry information

Entry nameS22A8_HUMAN
AccessionPrimary (citable) accession number: Q8TCC7
Secondary accession number(s): B4DPH7 expand/collapse secondary AC list , F5GWA8, F5H5J1, O95820, Q59EW9, Q96TC1
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2007
Last sequence update: June 1, 2002
Last modified: April 16, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

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