P46721 (SO1A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier organic anion transporter family member 1A2

Alternative name(s):
OATP-A
Organic anion-transporting polypeptide 1
Short name=OATP-1
Sodium-independent organic anion transporter
Solute carrier family 21 member 3

Gene names

Name:	SLCO1A2
Synonyms:	OATP, OATP1, OATP1A2, SLC21A3

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	670 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Mediates the Na+-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids By similarity. Selectively inhibited by the grapefruit juice component naringin. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the organo anion transporter (TC 2.A.60) family. [View classification] Contains 1 Kazal-like domain.

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid and bile salt transport Traceable author statement. Source: Reactome bile acid metabolic process Traceable author statement. Source: Reactome sodium-independent organic anion transport Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	organic anion transmembrane transporter activity Traceable author statement PubMed 9007731. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform OATP1a (identifier: P46721-1)

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 OATP1b (identifier: P46721-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MGETEKRIETHRIRCLSKL → MFLTKNCKQEQERVESA
     559-581: AGIPAPIYFGALMDSTCLHWGTL → GKNSYFFPHPIRTILLLLFFITL
     582-670: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 670	670	Solute carrier organic anion transporter family member 1A2		PRO_0000191042
Regions
	Topological domain	1 – 20	20	Cytoplasmic Potential
	Transmembrane	21 – 40	20	Helical; Name=1; Potential
	Topological domain	41 – 59	19	Extracellular Potential
	Transmembrane	60 – 80	21	Helical; Name=2; Potential
	Topological domain	81 – 86	6	Cytoplasmic Potential
	Transmembrane	87 – 111	25	Helical; Name=3; Potential
	Topological domain	112 – 155	44	Extracellular Potential
	Transmembrane	156 – 184	29	Helical; Name=4; Potential
	Topological domain	185 – 203	19	Cytoplasmic Potential
	Transmembrane	204 – 224	21	Helical; Name=5; Potential
	Topological domain	225 – 242	18	Extracellular Potential
	Transmembrane	243 – 267	25	Helical; Name=6; Potential
	Topological domain	268 – 311	44	Cytoplasmic Potential
	Transmembrane	312 – 333	22	Helical; Name=7; Potential
	Topological domain	334 – 353	20	Extracellular Potential
	Transmembrane	354 – 377	24	Helical; Name=8; Potential
	Topological domain	378 – 381	4	Cytoplasmic Potential
	Transmembrane	382 – 405	24	Helical; Name=9; Potential
	Topological domain	406 – 513	108	Extracellular Potential
	Transmembrane	514 – 536	23	Helical; Name=10; Potential
	Topological domain	537 – 545	9	Cytoplasmic Potential
	Transmembrane	546 – 571	26	Helical; Name=11; Potential
	Topological domain	572 – 605	34	Extracellular Potential
	Transmembrane	606 – 623	18	Helical; Name=12; Potential
	Topological domain	624 – 670	47	Cytoplasmic Potential
	Domain	433 – 488	56	Kazal-like
Amino acid modifications
	Glycosylation	124	1	N-linked (GlcNAc...) Potential
	Glycosylation	135	1	N-linked (GlcNAc...) Potential
	Glycosylation	412	1	N-linked (GlcNAc...) Potential
	Glycosylation	419	1	N-linked (GlcNAc...) Potential
	Disulfide bond	439 ↔ 465		By similarity
	Disulfide bond	443 ↔ 454		By similarity
	Disulfide bond	445 ↔ 469		By similarity
Natural variations
	Alternative sequence	1 – 19	19	MGETE…CLSKL → MFLTKNCKQEQERVESA in isoform OATP1b.		VSP_006130
	Alternative sequence	559 – 581	23	AGIPA…HWGTL → GKNSYFFPHPIRTILLLLFF ITL in isoform OATP1b.		VSP_006131
	Alternative sequence	582 – 670	89	Missing in isoform OATP1b.		VSP_006132
	Natural variant	13	1	I → T. Ref.7 Corresponds to variant rs10841795 [ dbSNP | Ensembl ].		VAR_024644
	Natural variant	128	1	N → Y. Ref.7 Corresponds to variant rs11568567 [ dbSNP | Ensembl ].		VAR_020289
	Natural variant	135	1	N → I. Ref.7 Corresponds to variant rs45502302 [ dbSNP | Ensembl ].		VAR_020290
	Natural variant	172	1	E → D. Ref.7 Corresponds to variant rs11568563 [ dbSNP | Ensembl ].		VAR_020291
	Natural variant	187	1	A → T. Ref.7		VAR_036823
	Natural variant	220	1	V → I in a colorectal cancer sample; somatic mutation. Ref.8		VAR_036409
	Natural variant	355	1	I → V. Corresponds to variant rs45628437 [ dbSNP | Ensembl ].		VAR_020292
	Natural variant	668	1	T → S. Ref.7 Corresponds to variant rs11568557 [ dbSNP | Ensembl ].		VAR_020293

Sequences

	Sequence		Length	Mass (Da)
	Isoform OATP1a [UniParc]. Last modified November 1, 1995. Version 1. Checksum: C3A740CEF1E6F129	FASTA	670	74,145
	10 20 30 40 50 60 MGETEKRIET HRIRCLSKLK MFLLAITCAF VSKTLSGSYM NSMLTQIERQ FNIPTSLVGF 70 80 90 100 110 120 INGSFEIGNL LLIIFVSYFG TKLHRPIMIG IGCVVMGLGC FLKSLPHFLM NQYEYESTVS 130 140 150 160 170 180 VSGNLSSNSF LCMENGTQIL RPTQDPSECT KEVKSLMWVY VLVGNIVRGM GETPILPLGI 190 200 210 220 230 240 SYIEDFAKFE NSPLYIGLVE TGAIIGPLIG LLLASFCANV YVDTGFVNTD DLIITPTDTR 250 260 270 280 290 300 WVGAWWFGFL ICAGVNVLTA IPFFFLPNTL PKEGLETNAD IIKNENEDKQ KEEVKKEKYG 310 320 330 340 350 360 ITKDFLPFMK SLSCNPIYML FILVSVIQFN AFVNMISFMP KYLEQQYGIS SSDAIFLMGI 370 380 390 400 410 420 YNLPPICIGY IIGGLIMKKF KITVKQAAHI GCWLSLLEYL LYFLSFLMTC ENSSVVGINT 430 440 450 460 470 480 SYEGIPQDLY VENDIFADCN VDCNCPSKIW DPVCGNNGLS YLSACLAGCE TSIGTGINMV 490 500 510 520 530 540 FQNCSCIQTS GNSSAVLGLC DKGPDCSLML QYFLILSAMS SFIYSLAAIP GYMVLLRCMK 550 560 570 580 590 600 SEEKSLGVGL HTFCTRVFAG IPAPIYFGAL MDSTCLHWGT LKCGESGACR IYDSTTFRYI 610 620 630 640 650 660 YLGLPAALRG SSFVPALIIL ILLRKCHLPG ENASSGTELI ETKVKGKENE CKDIYQKSTV 670 LKDDELKTKL
	Isoform OATP1b [UniParc]. Checksum: 6D80DBB0029DC66E	FASTA	579	64,369
	10 20 30 40 50 60 MFLTKNCKQE QERVESAKMF LLAITCAFVS KTLSGSYMNS MLTQIERQFN IPTSLVGFIN 70 80 90 100 110 120 GSFEIGNLLL IIFVSYFGTK LHRPIMIGIG CVVMGLGCFL KSLPHFLMNQ YEYESTVSVS 130 140 150 160 170 180 GNLSSNSFLC MENGTQILRP TQDPSECTKE VKSLMWVYVL VGNIVRGMGE TPILPLGISY 190 200 210 220 230 240 IEDFAKFENS PLYIGLVETG AIIGPLIGLL LASFCANVYV DTGFVNTDDL IITPTDTRWV 250 260 270 280 290 300 GAWWFGFLIC AGVNVLTAIP FFFLPNTLPK EGLETNADII KNENEDKQKE EVKKEKYGIT 310 320 330 340 350 360 KDFLPFMKSL SCNPIYMLFI LVSVIQFNAF VNMISFMPKY LEQQYGISSS DAIFLMGIYN 370 380 390 400 410 420 LPPICIGYII GGLIMKKFKI TVKQAAHIGC WLSLLEYLLY FLSFLMTCEN SSVVGINTSY 430 440 450 460 470 480 EGIPQDLYVE NDIFADCNVD CNCPSKIWDP VCGNNGLSYL SACLAGCETS IGTGINMVFQ 490 500 510 520 530 540 NCSCIQTSGN SSAVLGLCDK GPDCSLMLQY FLILSAMSSF IYSLAAIPGY MVLLRCMKSE 550 560 570 EKSLGVGLHT FCTRVFGKNS YFFPHPIRTI LLLLFFITL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver." Kullak-Ublick G.-A., Hagenbuch B., Stieger B., Schteingart C.D., Hofmann A.F., Wolkoff A.W., Meier P.J. Gastroenterology 109:1274-1282(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM OATP1A). Tissue: Liver.
[2]	"Isolation of human neural alternative form of organic anion transporter subtype." Abe T., Kakyo M., Yawo H. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE (ISOFORM OATP1B).
[3]	"Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide." Koenig J., Cui Y., Nies A.T., Keppler D. J. Biol. Chem. 275:23161-23168(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM OATP1A).
[4]	"Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes." Speek M. Mol. Cell. Biol. 21:1973-1985(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM OATP1A). Tissue: Teratocarcinoma.
[5]	"Upstream region of the human organic anion transporting polypeptide A (OATP-A) gene." Kullak-Ublick G.-A. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 1-20.
[6]	"Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice." Bailey D.G., Dresser G.K., Leake B.F., Kim R.B. Clin. Pharmacol. Ther. 81:495-502(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Polymorphisms in human organic anion-transporting polypeptide 1A2 (OATP1A2): implications for altered drug disposition and central nervous system drug entry." Lee W., Glaeser H., Smith L.H., Roberts R.L., Moeckel G.W., Gervasini G., Leake B.F., Kim R.B. J. Biol. Chem. 280:9610-9617(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-13; TYR-128; ILE-135; ASP-172; THR-187 AND SER-668.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-220.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U21943 mRNA. Translation: AAA87732.1. AF085224 mRNA. Translation: AAD52694.1. AJ400735 , AJ400736, AJ400737, AJ400738, AJ400739, AJ400740, AJ400741, AJ400742, AJ400743, AJ400744, AJ400745, AJ400746, AJ400747, AJ400748 Genomic DNA. Translation: CAB97006.1. AF279784 mRNA. Translation: AAG30037.1. Y08062 Genomic DNA. Translation: CAB64372.1.
IPI	IPI00008254. IPI00220618.
RefSeq	NP_066580.1. NM_021094.3. NP_602307.1. NM_134431.3.
UniGene	Hs.46440.
3D structure databases
ProteinModelPortal	P46721.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46721. 1 interaction.
STRING	9606.ENSP00000305974.
Protein family/group databases
TCDB	2.A.60.1.14. organo anion transporter (OAT) family.
PTM databases
PhosphoSite	P46721.
Polymorphism databases
DMDM	1171882.
Proteomic databases
PaxDb	P46721.
PRIDE	P46721.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307378; ENSP00000305974; ENSG00000084453. ENST00000390670; ENSP00000375088; ENSG00000084453. ENST00000452078; ENSP00000393973; ENSG00000084453.
GeneID	6579.
KEGG	hsa:6579.
UCSC	uc001rer.3. human. uc001ret.3. human.
Organism-specific databases
CTD	6579.
GeneCards	GC12M021417.
HGNC	HGNC:10956. SLCO1A2.
HPA	HPA027537.
MIM	602883. gene.
neXtProt	NX_P46721.
PharmGKB	PA328.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG256971.
HOGENOM	HOG000231269.
HOVERGEN	HBG063896.
InParanoid	P46721.
KO	K03460.
OMA	THRIRCL.
OrthoDB	EOG45B1F2.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P46721.
Bgee	P46721.
CleanEx	HS_SLCO1A2.
Genevestigator	P46721.
GermOnline	ENSG00000084453. Homo sapiens.
Family and domain databases
InterPro	IPR002350. Kazal_dom. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. IPR004156. OA_transporter. [Graphical view]
PANTHER	PTHR11388. PTHR11388. 1 hit.
Pfam	PF07648. Kazal_2. 1 hit. PF03137. OATP. 1 hit. [Graphical view]
SMART	SM00280. KAZAL. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
TIGRFAMs	TIGR00805. oat. 1 hit.
PROSITE	PS51465. KAZAL_2. 1 hit. PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1743123.
ChiTaRS	SLCO1A2. human.
GenomeRNAi	6579.
NextBio	25595.
SOURCE	Search...

Entry information

Entry name

SO1A2_HUMAN

Accession

Primary (citable) accession number: P46721
Secondary accession number(s): Q9UGP7, Q9UL38

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 118 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.