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Solute carrier organic anion transporter family member 2A1 (Prostaglandin transporter) (PGT) (Solute carrier family 21 member 2)

 SO2A1_HUMAN             Reviewed;         643 AA.
Q92959; Q86V98; Q8IUN2;
15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
16-DEC-2008, sequence version 2.
12-SEP-2018, entry version 151.
RecName: Full=Solute carrier organic anion transporter family member 2A1;
AltName: Full=Prostaglandin transporter;
Short=PGT;
AltName: Full=Solute carrier family 21 member 2;
Name=SLCO2A1; Synonyms=OATP2A1, SLC21A2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT THR-396.
PubMed=8787677; DOI=10.1172/JCI118897;
Lu R., Kanai N., Bao Y., Schuster V.L.;
"Cloning, in vitro expression, and tissue distribution of a human
prostaglandin transporter cDNA(hPGT).";
J. Clin. Invest. 98:1142-1149(1996).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-396.
PubMed=9618293; DOI=10.1006/bbrc.1998.8715;
Lu R., Schuster V.L.;
"Molecular cloning of the gene for the human prostaglandin transporter
hPGT: gene organization, promoter activity, and chromosomal
localization.";
Biochem. Biophys. Res. Commun. 246:805-812(1998).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain, and Prostate;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
TISSUE SPECIFICITY, AND VARIANT PHOAR2 SER-557.
PubMed=22331663; DOI=10.1002/humu.22042;
Seifert W., Kuhnisch J., Tuysuz B., Specker C., Brouwers A., Horn D.;
"Mutations in the prostaglandin transporter encoding gene SLCO2A1
cause primary hypertrophic osteoarthropathy and isolated digital
clubbing.";
Hum. Mutat. 33:660-664(2012).
[6]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[7]
VARIANTS PHOAR2 ARG-222 AND GLU-255.
PubMed=22197487; DOI=10.1016/j.ajhg.2011.11.019;
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.;
"Exome sequencing identifies SLCO2A1 mutations as a cause of primary
hypertrophic osteoarthropathy.";
Am. J. Hum. Genet. 90:125-132(2012).
[8]
VARIANTS PHOAR2 PHE-85; HIS-97; ALA-181; ASP-181; LEU-204; ARG-222;
PHE-420 AND GLY-565, VARIANT CYS-445, AND CHARACTERIZATION OF VARIANT
PHOAR2 PHE-420.
PubMed=22553128; DOI=10.1002/humu.22111;
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.;
"Prostaglandin transporter mutations cause pachydermoperiostosis with
myelofibrosis.";
Hum. Mutat. 33:1175-1181(2012).
[9]
VARIANTS PHOAR2 ARG-255 AND HIS-556.
PubMed=22696055; DOI=10.1038/jid.2012.146;
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.;
"Mutations in the prostaglandin transporter SLCO2A1 cause primary
hypertrophic osteoarthropathy with digital clubbing.";
J. Invest. Dermatol. 132:2473-2476(2012).
-!- 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. {ECO:0000269|PubMed:22331663}.
-!- 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. {ECO:0000269|PubMed:22197487,
ECO:0000269|PubMed:22331663, ECO:0000269|PubMed:22553128,
ECO:0000269|PubMed:22696055}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the organo anion transporter (TC 2.A.60)
family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Solute carrier organic anion transporter
family, member 2A1 (SLCO2A1); Note=Leiden Open Variation Database
(LOVD);
URL="http://www.lovd.nl/SLCO2A1";
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EMBL; U70867; AAC09469.1; -; mRNA.
EMBL; AF056732; AAC62004.1; -; Genomic_DNA.
EMBL; AF056719; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056720; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056721; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056722; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056723; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056724; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056725; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056726; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056727; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056728; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056729; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056730; AAC62004.1; JOINED; Genomic_DNA.
EMBL; AF056731; AAC62004.1; JOINED; Genomic_DNA.
EMBL; CH471052; EAW79156.1; -; Genomic_DNA.
EMBL; BC041140; AAH41140.2; -; mRNA.
EMBL; BC051347; AAH51347.1; -; mRNA.
CCDS; CCDS3084.1; -.
RefSeq; NP_005621.2; NM_005630.2.
UniGene; Hs.518270; -.
PDB; 3MRR; X-ray; 1.60 A; P=178-187.
PDBsum; 3MRR; -.
ProteinModelPortal; Q92959; -.
SMR; Q92959; -.
IntAct; Q92959; 1.
STRING; 9606.ENSP00000311291; -.
BindingDB; Q92959; -.
ChEMBL; CHEMBL2073703; -.
DrugBank; DB00770; Alprostadil.
DrugBank; DB04557; Arachidonic Acid.
DrugBank; DB01160; Dinoprost Tromethamine.
DrugBank; DB00917; Dinoprostone.
DrugBank; DB00695; Furosemide.
DrugBank; DB03581; Glucose-6-Phosphate.
DrugBank; DB02263; Glyceraldehyde-3-Phosphate.
DrugBank; DB01088; Iloprost.
DrugBank; DB04398; Lactic Acid.
DrugBank; DB01174; Phenobarbital.
DrugBank; DB01819; Phosphoenolpyruvate.
DrugBank; DB00119; Pyruvic acid.
SwissLipids; SLP:000001646; -.
TCDB; 2.A.60.1.19; the organo anion transporter (oat) family.
iPTMnet; Q92959; -.
PhosphoSitePlus; Q92959; -.
BioMuta; SLCO2A1; -.
DMDM; 218511799; -.
EPD; Q92959; -.
PaxDb; Q92959; -.
PeptideAtlas; Q92959; -.
PRIDE; Q92959; -.
ProteomicsDB; 75631; -.
Ensembl; ENST00000310926; ENSP00000311291; ENSG00000174640.
GeneID; 6578; -.
KEGG; hsa:6578; -.
UCSC; uc003eqa.4; human.
CTD; 6578; -.
DisGeNET; 6578; -.
EuPathDB; HostDB:ENSG00000174640.12; -.
GeneCards; SLCO2A1; -.
H-InvDB; HIX0024333; -.
HGNC; HGNC:10955; SLCO2A1.
HPA; HPA013742; -.
MalaCards; SLCO2A1; -.
MIM; 601460; gene.
MIM; 614441; phenotype.
neXtProt; NX_Q92959; -.
OpenTargets; ENSG00000174640; -.
Orphanet; 2796; Pachydermoperiostosis.
PharmGKB; PA35840; -.
eggNOG; KOG3626; Eukaryota.
eggNOG; ENOG410XRSF; LUCA.
GeneTree; ENSGT00760000119014; -.
HOGENOM; HOG000231269; -.
HOVERGEN; HBG108345; -.
InParanoid; Q92959; -.
KO; K14345; -.
OMA; IYLNCSC; -.
OrthoDB; EOG091G08QD; -.
PhylomeDB; Q92959; -.
TreeFam; TF317540; -.
Reactome; R-HSA-5619095; Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2).
Reactome; R-HSA-879518; Transport of organic anions.
ChiTaRS; SLCO2A1; human.
EvolutionaryTrace; Q92959; -.
GeneWiki; SLCO2A1; -.
GenomeRNAi; 6578; -.
PRO; PR:Q92959; -.
Proteomes; UP000005640; Chromosome 3.
Bgee; ENSG00000174640; Expressed in 188 organ(s), highest expression level in right lung.
CleanEx; HS_SLCO2A1; -.
ExpressionAtlas; Q92959; baseline and differential.
Genevisible; Q92959; HS.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0016020; C:membrane; TAS:ProtInc.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0005319; F:lipid transporter activity; TAS:ProtInc.
GO; GO:0015132; F:prostaglandin transmembrane transporter activity; IBA:GO_Central.
GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IBA:GO_Central.
GO; GO:0006869; P:lipid transport; TAS:ProtInc.
GO; GO:0043252; P:sodium-independent organic anion transport; IBA:GO_Central.
CDD; cd06174; MFS; 1.
InterPro; IPR002350; Kazal_dom.
InterPro; IPR036058; Kazal_dom_sf.
InterPro; IPR020846; MFS_dom.
InterPro; IPR036259; MFS_trans_sf.
InterPro; IPR004156; OATP.
PANTHER; PTHR11388; PTHR11388; 1.
Pfam; PF07648; Kazal_2; 1.
Pfam; PF03137; OATP; 1.
SUPFAM; SSF100895; SSF100895; 1.
SUPFAM; SSF103473; SSF103473; 4.
TIGRFAMs; TIGR00805; oat; 1.
PROSITE; PS51465; KAZAL_2; 1.
PROSITE; PS50850; MFS; 1.
1: Evidence at protein level;
3D-structure; Cell membrane; Complete proteome; Disease mutation;
Disulfide bond; Glycoprotein; Membrane; Polymorphism;
Reference proteome; Transmembrane; Transmembrane helix; Transport.
CHAIN 1 643 Solute carrier organic anion transporter
family member 2A1.
/FTId=PRO_0000191058.
TOPO_DOM 1 32 Cytoplasmic. {ECO:0000255}.
TRANSMEM 33 52 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 53 71 Extracellular. {ECO:0000255}.
TRANSMEM 72 92 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 93 98 Cytoplasmic. {ECO:0000255}.
TRANSMEM 99 123 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 124 167 Extracellular. {ECO:0000255}.
TRANSMEM 168 196 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 197 215 Cytoplasmic. {ECO:0000255}.
TRANSMEM 216 236 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 237 254 Extracellular. {ECO:0000255}.
TRANSMEM 255 279 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 280 321 Cytoplasmic. {ECO:0000255}.
TRANSMEM 322 343 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 344 363 Extracellular. {ECO:0000255}.
TRANSMEM 364 387 Helical; Name=8. {ECO:0000255}.
TOPO_DOM 388 391 Cytoplasmic. {ECO:0000255}.
TRANSMEM 392 415 Helical; Name=9. {ECO:0000255}.
TOPO_DOM 416 518 Extracellular. {ECO:0000255}.
TRANSMEM 519 541 Helical; Name=10. {ECO:0000255}.
TOPO_DOM 542 550 Cytoplasmic. {ECO:0000255}.
TRANSMEM 551 576 Helical; Name=11. {ECO:0000255}.
TOPO_DOM 577 610 Extracellular. {ECO:0000255}.
TRANSMEM 611 629 Helical; Name=12. {ECO:0000255}.
TOPO_DOM 630 643 Cytoplasmic. {ECO:0000255}.
DOMAIN 438 496 Kazal-like. {ECO:0000255|PROSITE-
ProRule:PRU00798}.
CARBOHYD 134 134 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 478 478 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 491 491 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 444 470 {ECO:0000255|PROSITE-ProRule:PRU00798}.
DISULFID 448 459 {ECO:0000255|PROSITE-ProRule:PRU00798}.
DISULFID 450 474 {ECO:0000255|PROSITE-ProRule:PRU00798}.
VARIANT 85 85 I -> F (in PHOAR2; dbSNP:rs387907296).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068636.
VARIANT 97 97 R -> H (in PHOAR2).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068637.
VARIANT 181 181 G -> A (in PHOAR2).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068638.
VARIANT 181 181 G -> D (in PHOAR2).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068639.
VARIANT 204 204 S -> L (in PHOAR2; dbSNP:rs555934769).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068640.
VARIANT 222 222 G -> R (in PHOAR2; dbSNP:rs774795340).
{ECO:0000269|PubMed:22197487,
ECO:0000269|PubMed:22553128}.
/FTId=VAR_067598.
VARIANT 255 255 G -> E (in PHOAR2; dbSNP:rs387906806).
{ECO:0000269|PubMed:22197487}.
/FTId=VAR_067599.
VARIANT 255 255 G -> R (in PHOAR2).
{ECO:0000269|PubMed:22696055}.
/FTId=VAR_068641.
VARIANT 396 396 A -> T (in dbSNP:rs34550074).
{ECO:0000269|PubMed:8787677,
ECO:0000269|PubMed:9618293}.
/FTId=VAR_053674.
VARIANT 420 420 C -> F (in PHOAR2; reduced activity;
dbSNP:rs387907295).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068642.
VARIANT 445 445 R -> C (in dbSNP:rs146970901).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068643.
VARIANT 556 556 Q -> H (in PHOAR2).
{ECO:0000269|PubMed:22696055}.
/FTId=VAR_068644.
VARIANT 557 557 F -> S (in PHOAR2).
{ECO:0000269|PubMed:22331663}.
/FTId=VAR_068352.
VARIANT 565 565 W -> G (in PHOAR2).
{ECO:0000269|PubMed:22553128}.
/FTId=VAR_068645.
CONFLICT 9 9 A -> V (in Ref. 1; AAC09469 and 2;
AAC62004). {ECO:0000305}.
CONFLICT 228 228 V -> I (in Ref. 1; AAC09469 and 2;
AAC62004). {ECO:0000305}.
STRAND 181 183 {ECO:0000244|PDB:3MRR}.
SEQUENCE 643 AA; 70044 MW; A1FF933246480984 CRC64;
MGLLPKLGAS QGSDTSTSRA GRCARSVFGN IKVFVLCQGL LQLCQLLYSA YFKSSLTTIE
KRFGLSSSSS GLISSLNEIS NAILIIFVSY FGSRVHRPRL IGIGGLFLAA GAFILTLPHF
LSEPYQYTLA STGNNSRLQA ELCQKHWQDL PPSKCHSTTQ NPQKETSSMW GLMVVAQLLA
GIGTVPIQPF GISYVDDFSE PSNSPLYISI LFAISVFGPA FGYLLGSVML QIFVDYGRVN
TAAVNLVPGD PRWIGAWWLG LLISSALLVL TSFPFFFFPR AMPIGAKRAP ATADEARKLE
EAKSRGSLVD FIKRFPCIFL RLLMNSLFVL VVLAQCTFSS VIAGLSTFLN KFLEKQYGTS
AAYANFLIGA VNLPAAALGM LFGGILMKRF VFSLQAIPRI ATTIITISMI LCVPLFFMGC
STPTVAEVYP PSTSSSIHPQ SPACRRDCSC PDSIFHPVCG DNGIEYLSPC HAGCSNINMS
SATSKQLIYL NCSCVTGGSA SAKTGSCPVP CAHFLLPAIF LISFVSLIAC ISHNPLYMMV
LRVVNQEEKS FAIGVQFLLM RLLAWLPSPA LYGLTIDHSC IRWNSLCLGR RGACAYYDND
ALRDRYLGLQ MGYKALGMLL LCFISWRVKK NKEYNVQKAA GLI


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