Q92959 (SO2A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier organic anion transporter family member 2A1

Alternative name(s):
Prostaglandin transporter
Short name=PGT
Solute carrier family 21 member 2

Gene names

Name:	SLCO2A1
Synonyms:	OATP2A1, SLC21A2

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	643 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitous. Significant expression observed in ling, kidney, spleen, and heart. Ref.5
Involvement in disease	Hypertrophic osteoarthropathy, primary, autosomal recessive, 2 (PHOAR2) [MIM:614441]: A disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6 Ref.7 Ref.8
Sequence similarities	Belongs to the organo anion transporter (TC 2.A.60) family. [View classification] Contains 1 Kazal-like domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	sodium-independent organic anion transport Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	lipid transporter activity Traceable author statement Ref.1. Source: ProtInc prostaglandin transmembrane transporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	1	EBI-1760532,EBI-401755

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 643

643

Solute carrier organic anion transporter family member 2A1

PRO_0000191058

Regions

Topological domain

1 – 32

32

Cytoplasmic Potential

Transmembrane

33 – 52

20

Helical; Name=1; Potential

Topological domain

53 – 71

19

Extracellular Potential

Transmembrane

72 – 92

21

Helical; Name=2; Potential

Topological domain

93 – 98

6

Cytoplasmic Potential

Transmembrane

99 – 123

25

Helical; Name=3; Potential

Topological domain

124 – 167

44

Extracellular Potential

Transmembrane

168 – 196

29

Helical; Name=4; Potential

Topological domain

197 – 215

19

Cytoplasmic Potential

Transmembrane

216 – 236

21

Helical; Name=5; Potential

Topological domain

237 – 254

18

Extracellular Potential

Transmembrane

255 – 279

25

Helical; Name=6; Potential

Topological domain

280 – 321

42

Cytoplasmic Potential

Transmembrane

322 – 343

22

Helical; Name=7; Potential

Topological domain

344 – 363

20

Extracellular Potential

Transmembrane

364 – 387

24

Helical; Name=8; Potential

Topological domain

388 – 391

4

Cytoplasmic Potential

Transmembrane

392 – 415

24

Helical; Name=9; Potential

Topological domain

416 – 518

103

Extracellular Potential

Transmembrane

519 – 541

23

Helical; Name=10; Potential

Topological domain

542 – 550

9

Cytoplasmic Potential

Transmembrane

551 – 576

26

Helical; Name=11; Potential

Topological domain

577 – 610

34

Extracellular Potential

Transmembrane

611 – 629

19

Helical; Name=12; Potential

Topological domain

630 – 643

14

Cytoplasmic Potential

Domain

438 – 496

59

Kazal-like

Amino acid modifications

Glycosylation

134

1

N-linked (GlcNAc...) Potential

Glycosylation

478

1

N-linked (GlcNAc...) Potential

Glycosylation

491

1

N-linked (GlcNAc...) Potential

Disulfide bond

444 ↔ 470

By similarity

Disulfide bond

448 ↔ 459

By similarity

Disulfide bond

450 ↔ 474

By similarity

Natural variations

Natural variant

85

1

I → F in PHOAR2. Ref.7

VAR_068636

Natural variant

97

1

R → H in PHOAR2. Ref.7

VAR_068637

Natural variant

181

1

G → A in PHOAR2. Ref.7

VAR_068638

Natural variant

181

1

G → D in PHOAR2. Ref.7

VAR_068639

Natural variant

204

1

S → L in PHOAR2. Ref.7

VAR_068640

Natural variant

222

1

G → R in PHOAR2. Ref.6 Ref.7

VAR_067598

Natural variant

255

1

G → E in PHOAR2. Ref.6

VAR_067599

Natural variant

255

1

G → R in PHOAR2. Ref.8

VAR_068641

Natural variant

396

1

A → T. Ref.1 Ref.2
Corresponds to variant rs34550074 [ dbSNP | Ensembl ].

VAR_053674

Natural variant

420

1

C → F in PHOAR2; reduced activity. Ref.7

VAR_068642

Natural variant

445

1

R → C. Ref.7

VAR_068643

Natural variant

556

1

Q → H in PHOAR2. Ref.8

VAR_068644

Natural variant

557

1

F → S in PHOAR2. Ref.5

VAR_068352

Natural variant

565

1

W → G in PHOAR2. Ref.7

VAR_068645

Experimental info

Sequence conflict

9

1

A → V in AAC09469. Ref.1

Sequence conflict

9

1

A → V in AAC62004. Ref.2

Sequence conflict

228

1

V → I in AAC09469. Ref.1

Sequence conflict

228

1

V → I in AAC62004. Ref.2

Secondary structure

1

.

.

.

643

Helix Strand Turn

Details...

Beta strand

181 – 183

3

Sequences

	Sequence		Length	Mass (Da)
	Q92959 [UniParc]. Last modified December 16, 2008. Version 2. Checksum: A1FF933246480984	FASTA	643	70,044
	10 20 30 40 50 60 MGLLPKLGAS QGSDTSTSRA GRCARSVFGN IKVFVLCQGL LQLCQLLYSA YFKSSLTTIE 70 80 90 100 110 120 KRFGLSSSSS GLISSLNEIS NAILIIFVSY FGSRVHRPRL IGIGGLFLAA GAFILTLPHF 130 140 150 160 170 180 LSEPYQYTLA STGNNSRLQA ELCQKHWQDL PPSKCHSTTQ NPQKETSSMW GLMVVAQLLA 190 200 210 220 230 240 GIGTVPIQPF GISYVDDFSE PSNSPLYISI LFAISVFGPA FGYLLGSVML QIFVDYGRVN 250 260 270 280 290 300 TAAVNLVPGD PRWIGAWWLG LLISSALLVL TSFPFFFFPR AMPIGAKRAP ATADEARKLE 310 320 330 340 350 360 EAKSRGSLVD FIKRFPCIFL RLLMNSLFVL VVLAQCTFSS VIAGLSTFLN KFLEKQYGTS 370 380 390 400 410 420 AAYANFLIGA VNLPAAALGM LFGGILMKRF VFSLQAIPRI ATTIITISMI LCVPLFFMGC 430 440 450 460 470 480 STPTVAEVYP PSTSSSIHPQ SPACRRDCSC PDSIFHPVCG DNGIEYLSPC HAGCSNINMS 490 500 510 520 530 540 SATSKQLIYL NCSCVTGGSA SAKTGSCPVP CAHFLLPAIF LISFVSLIAC ISHNPLYMMV 550 560 570 580 590 600 LRVVNQEEKS FAIGVQFLLM RLLAWLPSPA LYGLTIDHSC IRWNSLCLGR RGACAYYDND 610 620 630 640 ALRDRYLGLQ MGYKALGMLL LCFISWRVKK NKEYNVQKAA GLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT)." Lu R., Kanai N., Bao Y., Schuster V.L. J. Clin. Invest. 98:1142-1149(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT THR-396.
[2]	"Molecular cloning of the gene for the human prostaglandin transporter hPGT: gene organization, promoter activity, and chromosomal localization." Lu R., Schuster V.L. Biochem. Biophys. Res. Commun. 246:805-812(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-396.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Prostate.
[5]	"Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing." Seifert W., Kuhnisch J., Tuysuz B., Specker C., Brouwers A., Horn D. Hum. Mutat. 33:660-664(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANT PHOAR2 SER-557.
[6]	"Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy." Zhang Z., Xia W., He J., Zhang Z., Ke Y., Yue H., Wang C., Zhang H., Gu J., Hu W., Fu W., Hu Y., Li M., Liu Y. Am. J. Hum. Genet. 90:125-132(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHOAR2 ARG-222 AND GLU-255.
[7]	"Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis." Diggle C.P., Parry D.A., Logan C.V., Laissue P., Rivera C., Restrepo C.M., Fonseca D.J., Morgan J.E., Allanore Y., Fontenay M., Wipff J., Varret M., Gibault L., Dalantaeva N., Korbonits M., Zhou B., Yuan G., Harifi G. , Cefle K., Palanduz S., Akoglu H., Zwijnenburg P.J., Lichtenbelt K.D., Aubry-Rozier B., Superti-Furga A., Dallapiccola B., Accadia M., Brancati F., Sheridan E.G., Taylor G.R., Carr I.M., Johnson C.A., Markham A.F., Bonthron D.T. Hum. Mutat. 33:1175-1181(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHOAR2 PHE-85; HIS-97; ALA-181; ASP-181; LEU-204; ARG-222; PHE-420 AND GLY-565, VARIANT CYS-445, CHARACTERIZATION OF VARIANT PHOAR2 PHE-420.
[8]	"Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing." Busch J., Frank V., Bachmann N., Otsuka A., Oji V., Metze D., Shah K., Danda S., Watzer B., Traupe H., Bolz H.J., Kabashima K., Bergmann C. J. Invest. Dermatol. 132:2473-2476(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHOAR2 ARG-255 AND HIS-556.
+	Additional computationally mapped references.

Web resources

Solute carrier organic anion transporter family, member 2A1 (SLCO2A1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U70867 mRNA. Translation: AAC09469.1.
AF056732 , AF056719, AF056720, AF056721, AF056722, AF056723, AF056724, AF056725, AF056726, AF056727, AF056728, AF056729, AF056730, AF056731 Genomic DNA. Translation: AAC62004.1.
CH471052 Genomic DNA. Translation: EAW79156.1.
BC041140 mRNA. Translation: AAH41140.2.
BC051347 mRNA. Translation: AAH51347.1.

IPI

IPI00295132.

RefSeq

NP_005621.2. NM_005630.2.

UniGene

Hs.518270.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MRR	X-ray	1.60	P	178-187	[»]

ProteinModelPortal

Q92959.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q92959. 1 interaction.

STRING

9606.ENSP00000311291.

Protein family/group databases

MEROPS

I01.972.

PTM databases

PhosphoSite

Q92959.

Polymorphism databases

DMDM

218511799.

Proteomic databases

PaxDb

Q92959.

PRIDE

Q92959.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310926; ENSP00000311291; ENSG00000174640.

GeneID

6578.

KEGG

hsa:6578.

UCSC

uc003eqa.4. human.

Organism-specific databases

CTD

6578.

GeneCards

GC03M133651.

H-InvDB

HIX0024333.

HGNC

HGNC:10955. SLCO2A1.

HPA

HPA013742.

MIM

601460. gene.
614441. phenotype.

neXtProt

NX_Q92959.

Orphanet

2796. Pachydermoperiostosis.

PharmGKB

PA35840.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG271773.

HOGENOM

HOG000231269.

HOVERGEN

HBG108345.

InParanoid

Q92959.

KO

K14345.

OMA

GYKALGM.

OrthoDB

EOG45QHCV.

PhylomeDB

Q92959.

Enzyme and pathway databases

Reactome

REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

Q92959.

Bgee

Q92959.

CleanEx

HS_SLCO2A1.

Genevestigator

Q92959.

GermOnline

ENSG00000174640. 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

BindingDB

Q92959.

ChiTaRS

SLCO2A1. human.

EvolutionaryTrace

Q92959.

GenomeRNAi

6578.

NextBio

25591.

SOURCE

Search...

Entry information

Entry name

SO2A1_HUMAN

Accession

Primary (citable) accession number: Q92959
Secondary accession number(s): Q86V98, Q8IUN2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	December 16, 2008
Last modified:	May 1, 2013
This is version 106 of the entry and version 2 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.