ID SO2A1_HUMAN Reviewed; 643 AA. AC Q92959; Q86V98; Q8IUN2; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 16-DEC-2008, sequence version 2. DT 24-JAN-2024, entry version 181. DE RecName: Full=Solute carrier organic anion transporter family member 2A1 {ECO:0000303|PubMed:29204966}; DE Short=SLCO2A1 {ECO:0000303|PubMed:26692285, ECO:0000303|PubMed:27169804, ECO:0000303|PubMed:29204966}; DE AltName: Full=OATP2A1 {ECO:0000303|PubMed:26692285, ECO:0000303|PubMed:29204966}; DE AltName: Full=PHOAR2; DE AltName: Full=Prostaglandin transporter {ECO:0000303|PubMed:11997326, ECO:0000303|PubMed:27169804, ECO:0000303|PubMed:8787677}; DE Short=PGT {ECO:0000303|PubMed:11997326, ECO:0000303|PubMed:27169804, ECO:0000303|PubMed:8787677}; DE AltName: Full=Solute carrier family 21 member 2; DE Short=SLC21A2; GN Name=SLCO2A1 {ECO:0000312|HGNC:HGNC:10955}; Synonyms=OATP2A1, SLC21A2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT THR-396, TRANSPORTER RP ACTIVITY, FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=8787677; DOI=10.1172/jci118897; RA Lu R., Kanai N., Bao Y., Schuster V.L.; RT "Cloning, in vitro expression, and tissue distribution of a human RT prostaglandin transporter cDNA(hPGT)."; RL J. Clin. Invest. 98:1142-1149(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-396. RX PubMed=9618293; DOI=10.1006/bbrc.1998.8715; RA Lu R., Schuster V.L.; RT "Molecular cloning of the gene for the human prostaglandin transporter RT hPGT: gene organization, promoter activity, and chromosomal localization."; RL Biochem. Biophys. Res. Commun. 246:805-812(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TRANSPORTER ACTIVITY. RC TISSUE=Lung; RX PubMed=10484490; DOI=10.1152/ajpregu.1999.277.3.r734; RA Pucci M.L., Bao Y., Chan B., Itoh S., Lu R., Copeland N.G., Gilbert D.J., RA Jenkins N.A., Schuster V.L.; RT "Cloning of mouse prostaglandin transporter PGT cDNA: species-specific RT substrate affinities."; RL Am. J. Physiol. 277:R734-R741(1999). RN [6] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=11997326; DOI=10.1152/ajprenal.00151.2001; RA Chan B.S., Endo S., Kanai N., Schuster V.L.; RT "Identification of lactate as a driving force for prostanoid transport by RT prostaglandin transporter PGT."; RL Am. J. Physiol. 282:F1097-F1102(2002). RN [7] RP FUNCTION. RX PubMed=15044627; DOI=10.1124/mol.65.4.973; RA Nomura T., Lu R., Pucci M.L., Schuster V.L.; RT "The two-step model of prostaglandin signal termination: in vitro RT reconstitution with the prostaglandin transporter and prostaglandin 15 RT dehydrogenase."; RL Mol. Pharmacol. 65:973-978(2004). RN [8] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=15657371; DOI=10.1210/jc.2004-1482; RA Kang J., Chapdelaine P., Parent J., Madore E., Laberge P.Y., Fortier M.A.; RT "Expression of human prostaglandin transporter in the human endometrium RT across the menstrual cycle."; RL J. Clin. Endocrinol. Metab. 90:2308-2313(2005). RN [9] RP FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RX PubMed=16339169; DOI=10.1093/humrep/dei400; RA Kang J., Chapdelaine P., Laberge P.Y., Fortier M.A.; RT "Functional characterization of prostaglandin transporter and terminal RT prostaglandin synthases during decidualization of human endometrial stromal RT cells."; RL Hum. Reprod. 21:592-599(2006). RN [10] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=26692285; DOI=10.1016/j.prostaglandins.2015.12.003; RA Gose T., Nakanishi T., Kamo S., Shimada H., Otake K., Tamai I.; RT "Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local RT disposition of eicosapentaenoic acid-derived PGE3."; RL Prostaglandins Other Lipid Mediat. 122:10-17(2016). RN [11] RP FUNCTION, TRANSPORTER ACTIVITY, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, RP AND ACTIVITY REGULATION. RX PubMed=27169804; DOI=10.1126/scitranslmed.aad2709; RA Yerushalmi G.M., Markman S., Yung Y., Maman E., Aviel-Ronen S., Orvieto R., RA Adashi E.Y., Hourvitz A.; RT "The prostaglandin transporter (PGT) as a potential mediator of RT ovulation."; RL Sci. Transl. Med. 8:338ra68-338ra68(2016). RN [12] RP FUNCTION. RX PubMed=29204966; DOI=10.1208/s12248-017-0163-8; RA Nakanishi T., Tamai I.; RT "Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in RT Regulating the Pathophysiological Actions of Prostaglandins."; RL AAPS J. 20:13-13(2017). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=35307651; DOI=10.1124/dmd.121.000748; RA Hau R.K., Klein R.R., Wright S.H., Cherrington N.J.; RT "Localization of Xenobiotic Transporters Expressed at the Human Blood- RT Testis Barrier."; RL Drug Metab. Dispos. 50:770-780(2022). RN [15] RP VARIANTS PHOAR2 ARG-222 AND GLU-255. RX PubMed=22197487; DOI=10.1016/j.ajhg.2011.11.019; RA Zhang Z., Xia W., He J., Zhang Z., Ke Y., Yue H., Wang C., Zhang H., Gu J., RA Hu W., Fu W., Hu Y., Li M., Liu Y.; RT "Exome sequencing identifies SLCO2A1 mutations as a cause of primary RT hypertrophic osteoarthropathy."; RL Am. J. Hum. Genet. 90:125-132(2012). RN [16] RP TISSUE SPECIFICITY, AND VARIANT PHOAR2 SER-557. RX PubMed=22331663; DOI=10.1002/humu.22042; RA Seifert W., Kuhnisch J., Tuysuz B., Specker C., Brouwers A., Horn D.; RT "Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause RT primary hypertrophic osteoarthropathy and isolated digital clubbing."; RL Hum. Mutat. 33:660-664(2012). RN [17] RP VARIANTS PHOAR2 PHE-85; HIS-97; ALA-181; ASP-181; LEU-204; ARG-222; PHE-420 RP AND GLY-565, VARIANT CYS-445, AND CHARACTERIZATION OF VARIANT PHOAR2 RP PHE-420. RX PubMed=22553128; DOI=10.1002/humu.22111; RA Diggle C.P., Parry D.A., Logan C.V., Laissue P., Rivera C., Restrepo C.M., RA Fonseca D.J., Morgan J.E., Allanore Y., Fontenay M., Wipff J., Varret M., RA Gibault L., Dalantaeva N., Korbonits M., Zhou B., Yuan G., Harifi G., RA Cefle K., Palanduz S., Akoglu H., Zwijnenburg P.J., Lichtenbelt K.D., RA Aubry-Rozier B., Superti-Furga A., Dallapiccola B., Accadia M., RA Brancati F., Sheridan E.G., Taylor G.R., Carr I.M., Johnson C.A., RA Markham A.F., Bonthron D.T.; RT "Prostaglandin transporter mutations cause pachydermoperiostosis with RT myelofibrosis."; RL Hum. Mutat. 33:1175-1181(2012). RN [18] RP VARIANTS PHOAR2 ARG-255 AND HIS-556. RX PubMed=22696055; DOI=10.1038/jid.2012.146; RA Busch J., Frank V., Bachmann N., Otsuka A., Oji V., Metze D., Shah K., RA Danda S., Watzer B., Traupe H., Bolz H.J., Kabashima K., Bergmann C.; RT "Mutations in the prostaglandin transporter SLCO2A1 cause primary RT hypertrophic osteoarthropathy with digital clubbing."; RL J. Invest. Dermatol. 132:2473-2476(2012). RN [19] RP VARIANTS PHOAR2 165-GLU--ILE-643 DEL; ARG-222; ASP-369; GLU-379 AND RP LYS-465, AND INVOLVEMENT IN PHOAD. RX PubMed=23509104; DOI=10.1210/jc.2012-3568; RA Zhang Z., He J.W., Fu W.Z., Zhang C.Q., Zhang Z.L.; RT "Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a RT clinical and biochemical characterization."; RL J. Clin. Endocrinol. Metab. 98:E923-E933(2013). RN [20] RP VARIANTS PHOAR2 ARG-181; 207-TYR--ILE-643 DEL; ARG-255; SER-328 AND RP LEU-374, VARIANTS PHOAD ARG-222; ASP-369; ARG-554 AND 603-ARG--ILE-643 DEL, RP AND INVOLVEMENT IN PHOAD. RX PubMed=33852188; DOI=10.1002/jbmr.4310; RA Xu Y., Zhang Z., Yue H., Li S., Zhang Z.; RT "Monoallelic mutations in SLCO2A1 cause autosomal dominant primary RT hypertrophic osteoarthropathy."; RL J. Bone Miner. Res. 36:1459-1468(2021). CC -!- FUNCTION: Mediates the transport of prostaglandins (PGs, mainly PGE2, CC PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) CC across the cell membrane (PubMed:8787677, PubMed:11997326, CC PubMed:26692285). PGs and thromboxanes play fundamental roles in CC diverse functions such as intraocular pressure, gastric acid secretion, CC renal salt and water transport, vascular tone, and fever CC (PubMed:15044627). Plays a role in the clearance of PGs from the CC circulation through cellular uptake, which allows cytoplasmic oxidation CC and PG signal termination (PubMed:8787677). PG uptake is dependent upon CC membrane potential and involves exchange of a monovalent anionic CC substrate (PGs exist physiologically as an anionic monovalent form) CC with a stoichiometry of 1:1 for divalent anions or of 1:2 for CC monovalent anions (PubMed:29204966). Uses lactate, generated by CC glycolysis, as a counter-substrate to mediate PGE2 influx and efflux CC (PubMed:11997326). Under nonglycolytic conditions, metabolites other CC than lactate might serve as counter-substrates (PubMed:11997326). CC Although the mechanism is not clear, this transporter can function in CC bidirectional mode (PubMed:29204966). When apically expressed in CC epithelial cells, it facilitates transcellular transport (also called CC vectorial release), extracting PG from the apical medium and CC facilitating transport across the cell toward the basolateral side, CC whereupon the PG exits the cell by simple diffusion (By similarity). In CC the renal collecting duct, regulates renal Na+ balance by removing PGE2 CC from apical medium (PGE2 EP4 receptor is likely localized to the CC luminal/apical membrane and stimulates Na+ resorption) and transporting CC it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors CC inhibit Na+ resorption) (By similarity). Plays a role in endometrium CC during decidualization, increasing uptake of PGs by decidual cells CC (PubMed:16339169). Involved in critical events for ovulation CC (PubMed:27169804). Regulates extracellular PGE2 concentration for CC follicular development in the ovaries (By similarity). Expressed CC intracellularly, may contribute to vesicular uptake of newly CC synthesized intracellular PGs, thereby facilitating exocytotic CC secretion of PGs without being metabolized (By similarity). Essential CC core component of the major type of large-conductance anion channel, CC Maxi-Cl, which plays essential roles in inorganic anion transport, cell CC volume regulation and release of ATP and glutamate not only in CC physiological processes but also in pathological processes (By CC similarity). May contribute to regulate the transport of organic CC compounds in testis across the blood-testis-barrier (Probable). CC {ECO:0000250|UniProtKB:Q00910, ECO:0000250|UniProtKB:Q9EPT5, CC ECO:0000269|PubMed:11997326, ECO:0000269|PubMed:16339169, CC ECO:0000269|PubMed:26692285, ECO:0000269|PubMed:27169804, CC ECO:0000269|PubMed:8787677, ECO:0000303|PubMed:11997326, CC ECO:0000303|PubMed:15044627, ECO:0000303|PubMed:29204966, CC ECO:0000305|PubMed:35307651}. CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin E2(out) = prostaglandin E2(in); CC Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564; CC Evidence={ECO:0000250|UniProtKB:Q9EPT5}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin E2(out) = 2 (S)-lactate(out) CC + prostaglandin E2(in); Xref=Rhea:RHEA:74383, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:10484490, CC ECO:0000269|PubMed:11997326, ECO:0000269|PubMed:26692285, CC ECO:0000305|PubMed:27169804, ECO:0000305|PubMed:8787677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin E1(out) = 2 (S)-lactate(out) CC + prostaglandin E1(in); Xref=Rhea:RHEA:74395, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:57397; Evidence={ECO:0000305|PubMed:8787677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin F2alpha(out) = 2 (S)- CC lactate(out) + prostaglandin F2alpha(in); Xref=Rhea:RHEA:74399, CC ChEBI:CHEBI:16651, ChEBI:CHEBI:57404; CC Evidence={ECO:0000305|PubMed:10484490, ECO:0000305|PubMed:8787677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin D2(out) = 2 (S)-lactate(out) CC + prostaglandin D2(in); Xref=Rhea:RHEA:74403, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:57406; Evidence={ECO:0000305|PubMed:10484490, CC ECO:0000305|PubMed:8787677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + thromboxane B2(out) = 2 (S)-lactate(out) + CC thromboxane B2(in); Xref=Rhea:RHEA:74407, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:90696; Evidence={ECO:0000305|PubMed:8787677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin E3(out) = 2 (S)-lactate(out) CC + prostaglandin E3(in); Xref=Rhea:RHEA:74351, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:133132; Evidence={ECO:0000269|PubMed:26692285}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 (S)-lactate(in) + prostaglandin H2(out) = 2 (S)-lactate(out) CC + prostaglandin H2(in); Xref=Rhea:RHEA:74379, ChEBI:CHEBI:16651, CC ChEBI:CHEBI:57405; Evidence={ECO:0000250|UniProtKB:Q00910}; CC -!- ACTIVITY REGULATION: Chorionic gonadotropin stimulates expression in CC the ovaries. {ECO:0000269|PubMed:27169804}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.331 uM for PGE2 {ECO:0000269|PubMed:26692285}; CC KM=7.202 uM for PGE3 {ECO:0000269|PubMed:26692285}; CC Vmax=0.721 pmol/sec/mg protein with PGE2 CC {ECO:0000269|PubMed:26692285}; CC Vmax=2.682 pmol/sec/mg protein with PGE3 CC {ECO:0000269|PubMed:26692285}; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:8787677}; CC Multi-pass membrane protein {ECO:0000255}. Basal cell membrane CC {ECO:0000269|PubMed:35307651}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q9EPT5}. Lysosome CC {ECO:0000250|UniProtKB:Q9EPT5}. Note=Localized to the basal membrane of CC Sertoli cells. {ECO:0000269|PubMed:35307651}. CC -!- TISSUE SPECIFICITY: Ubiquitous (PubMed:8787677, PubMed:22331663). CC Significant expression observed in lung, kidney, spleen, and heart CC (PubMed:22331663). Expressed in the endometrium (at both mRNA and CC protein levels) (PubMed:15657371, PubMed:16339169). Expressed in the CC ovaries (at mRNA and protein levels) (PubMed:27169804). In testis, CC primarily localized to the basal membrane of Sertoli cells and weakly CC expressed within the tubules (PubMed:35307651). CC {ECO:0000269|PubMed:15657371, ECO:0000269|PubMed:16339169, CC ECO:0000269|PubMed:22331663, ECO:0000269|PubMed:27169804, CC ECO:0000269|PubMed:35307651, ECO:0000269|PubMed:8787677}. CC -!- DEVELOPMENTAL STAGE: Expression in the uterus changes during the CC menstrual cycle (PubMed:15657371, PubMed:16339169). In endometrium, CC expression is higher in the menstrual, proliferative, and early CC secretory phases than in the mid-late secretory phase (PubMed:15657371, CC PubMed:16339169). In the ovaries, expression is ovulation-dependent, CC levels are negligible in preovulatory follicles, and increase in CC postovulatory follicles and in the corpus luteum (PubMed:27169804). CC {ECO:0000269|PubMed:15657371, ECO:0000269|PubMed:16339169, CC ECO:0000269|PubMed:27169804}. CC -!- DISEASE: Hypertrophic osteoarthropathy, primary, autosomal recessive, 2 CC (PHOAR2) [MIM:614441]: A disease characterized by digital clubbing, CC periostosis, acroosteolysis, painful joint enlargement, and variable CC features of pachydermia that include thickened facial skin and a CC thickened scalp. Other developmental anomalies include delayed closure CC of the cranial sutures and congenital heart disease. CC {ECO:0000269|PubMed:22197487, ECO:0000269|PubMed:22331663, CC ECO:0000269|PubMed:22553128, ECO:0000269|PubMed:22696055, CC ECO:0000269|PubMed:23509104, ECO:0000269|PubMed:33852188}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hypertrophic osteoarthropathy, primary, autosomal dominant CC (PHOAD) [MIM:167100]: A form of primary hypertrophic osteoarthropathy, CC a disease characterized by digital clubbing, periostosis, CC acroosteolysis, painful joint enlargement, and variable features of CC pachydermia that include thickened facial skin and a thickened scalp. CC PHOAD patients may also experience joint swelling and pain, and some CC have reported gastrointestinal symptoms, including watery diarrhea. CC Males are more commonly affected, and more severely affected, than CC females. {ECO:0000269|PubMed:23509104, ECO:0000269|PubMed:33852188}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the organo anion transporter (TC 2.A.60) family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Solute carrier organic anion transporter family, CC member 2A1 (SLCO2A1); Note=Leiden Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/SLCO2A1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U70867; AAC09469.1; -; mRNA. DR EMBL; AF056732; AAC62004.1; -; Genomic_DNA. DR EMBL; AF056719; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056720; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056721; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056722; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056723; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056724; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056725; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056726; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056727; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056728; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056729; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056730; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; AF056731; AAC62004.1; JOINED; Genomic_DNA. DR EMBL; CH471052; EAW79156.1; -; Genomic_DNA. DR EMBL; BC041140; AAH41140.2; -; mRNA. DR EMBL; BC051347; AAH51347.1; -; mRNA. DR CCDS; CCDS3084.1; -. DR RefSeq; NP_005621.2; NM_005630.2. DR PDB; 3MRR; X-ray; 1.60 A; P=178-187. DR PDBsum; 3MRR; -. DR AlphaFoldDB; Q92959; -. DR SMR; Q92959; -. DR IntAct; Q92959; 1. DR STRING; 9606.ENSP00000311291; -. DR BindingDB; Q92959; -. DR ChEMBL; CHEMBL2073703; -. DR DrugBank; DB00770; Alprostadil. DR DrugBank; DB04557; Arachidonic Acid. DR DrugBank; DB04551; beta-D-fructofuranose 1,6-bisphosphate. DR DrugBank; DB02263; D-glyceraldehyde 3-phosphate. DR DrugBank; DB01160; Dinoprost tromethamine. DR DrugBank; DB00917; Dinoprostone. DR DrugBank; DB00695; Furosemide. DR DrugBank; DB03581; Glucose-6-Phosphate. DR DrugBank; DB01088; Iloprost. DR DrugBank; DB04398; Lactic acid. DR DrugBank; DB00654; Latanoprost. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB01819; Phosphoenolpyruvate. DR DrugBank; DB02056; Prostaglandin D2. DR DrugBank; DB00119; Pyruvic acid. DR DrugBank; DB11753; Rifamycin. DR SwissLipids; SLP:000001646; -. DR TCDB; 2.A.60.1.19; the organo anion transporter (oat) family. DR GlyCosmos; Q92959; 3 sites, No reported glycans. DR GlyGen; Q92959; 3 sites. DR iPTMnet; Q92959; -. DR PhosphoSitePlus; Q92959; -. DR BioMuta; SLCO2A1; -. DR DMDM; 218511799; -. DR EPD; Q92959; -. DR jPOST; Q92959; -. DR MassIVE; Q92959; -. DR PaxDb; 9606-ENSP00000311291; -. DR PeptideAtlas; Q92959; -. DR ProteomicsDB; 75631; -. DR Pumba; Q92959; -. DR Antibodypedia; 33384; 103 antibodies from 16 providers. DR DNASU; 6578; -. DR Ensembl; ENST00000310926.11; ENSP00000311291.4; ENSG00000174640.15. DR GeneID; 6578; -. DR KEGG; hsa:6578; -. DR MANE-Select; ENST00000310926.11; ENSP00000311291.4; NM_005630.3; NP_005621.2. DR UCSC; uc003eqa.4; human. DR AGR; HGNC:10955; -. DR CTD; 6578; -. DR DisGeNET; 6578; -. DR GeneCards; SLCO2A1; -. DR HGNC; HGNC:10955; SLCO2A1. DR HPA; ENSG00000174640; Tissue enhanced (lung). DR MalaCards; SLCO2A1; -. DR MIM; 167100; phenotype. DR MIM; 601460; gene. DR MIM; 614441; phenotype. DR neXtProt; NX_Q92959; -. DR OpenTargets; ENSG00000174640; -. DR Orphanet; 468641; Chronic enteropathy associated with SLCO2A1 gene. DR Orphanet; 2796; Pachydermoperiostosis. DR PharmGKB; PA35840; -. DR VEuPathDB; HostDB:ENSG00000174640; -. DR eggNOG; KOG3626; Eukaryota. DR GeneTree; ENSGT01080000257336; -. DR InParanoid; Q92959; -. DR OMA; MMVLRCV; -. DR OrthoDB; 2874223at2759; -. DR PhylomeDB; Q92959; -. DR TreeFam; TF317540; -. DR PathwayCommons; Q92959; -. DR Reactome; R-HSA-5619095; Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2). DR Reactome; R-HSA-879518; Transport of organic anions. DR SignaLink; Q92959; -. DR BioGRID-ORCS; 6578; 10 hits in 1156 CRISPR screens. DR ChiTaRS; SLCO2A1; human. DR EvolutionaryTrace; Q92959; -. DR GeneWiki; SLCO2A1; -. DR GenomeRNAi; 6578; -. DR Pharos; Q92959; Tchem. DR PRO; PR:Q92959; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q92959; Protein. DR Bgee; ENSG00000174640; Expressed in right lung and 169 other cell types or tissues. DR ExpressionAtlas; Q92959; baseline and differential. DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005319; F:lipid transporter activity; TAS:ProtInc. DR GO; GO:0015132; F:prostaglandin transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0015347; F:sodium-independent organic anion transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0006869; P:lipid transport; TAS:ProtInc. DR GO; GO:0015732; P:prostaglandin transport; IBA:GO_Central. DR GO; GO:0043252; P:sodium-independent organic anion transport; IBA:GO_Central. DR CDD; cd17461; MFS_SLCO2A_OATP2A; 1. DR Gene3D; 3.30.60.30; -; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR002350; Kazal_dom. DR InterPro; IPR036058; Kazal_dom_sf. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR004156; OATP. DR NCBIfam; TIGR00805; oat; 1. DR PANTHER; PTHR11388; ORGANIC ANION TRANSPORTER; 1. DR PANTHER; PTHR11388:SF14; SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY MEMBER 2A1; 1. DR Pfam; PF07648; Kazal_2; 1. DR Pfam; PF03137; OATP; 1. DR SUPFAM; SSF100895; Kazal-type serine protease inhibitors; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS51465; KAZAL_2; 1. DR PROSITE; PS50850; MFS; 1. DR Genevisible; Q92959; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cytoplasm; Disease variant; Disulfide bond; KW Glycoprotein; Lipid transport; Lysosome; Membrane; Reference proteome; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..643 FT /note="Solute carrier organic anion transporter family FT member 2A1" FT /id="PRO_0000191058" FT TOPO_DOM 1..32 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 33..52 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 53..71 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 72..92 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 93..98 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 99..123 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 124..167 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 168..196 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 197..215 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 216..236 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 237..254 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 255..279 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 280..321 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 322..343 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 344..363 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 364..387 FT /note="Helical; Name=8" FT /evidence="ECO:0000255" FT TOPO_DOM 388..391 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 392..415 FT /note="Helical; Name=9" FT /evidence="ECO:0000255" FT TOPO_DOM 416..518 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 519..541 FT /note="Helical; Name=10" FT /evidence="ECO:0000255" FT TOPO_DOM 542..550 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 551..576 FT /note="Helical; Name=11" FT /evidence="ECO:0000255" FT TOPO_DOM 577..610 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 611..629 FT /note="Helical; Name=12" FT /evidence="ECO:0000255" FT TOPO_DOM 630..643 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 438..496 FT /note="Kazal-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 478 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 491 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 444..474 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 450..470 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT DISULFID 459..494 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00798" FT VARIANT 85 FT /note="I -> F (in PHOAR2; dbSNP:rs387907296)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068636" FT VARIANT 97 FT /note="R -> H (in PHOAR2; dbSNP:rs1376989560)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068637" FT VARIANT 165..643 FT /note="Missing (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:23509104" FT /id="VAR_085955" FT VARIANT 181 FT /note="G -> A (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068638" FT VARIANT 181 FT /note="G -> D (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068639" FT VARIANT 181 FT /note="G -> R (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085956" FT VARIANT 204 FT /note="S -> L (in PHOAR2; dbSNP:rs555934769)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068640" FT VARIANT 207..643 FT /note="Missing (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085957" FT VARIANT 222 FT /note="G -> R (in PHOAR2 and PHOAD; dbSNP:rs774795340)" FT /evidence="ECO:0000269|PubMed:22197487, FT ECO:0000269|PubMed:22553128, ECO:0000269|PubMed:23509104, FT ECO:0000269|PubMed:33852188" FT /id="VAR_067598" FT VARIANT 255 FT /note="G -> E (in PHOAR2; dbSNP:rs387906806)" FT /evidence="ECO:0000269|PubMed:22197487" FT /id="VAR_067599" FT VARIANT 255 FT /note="G -> R (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22696055, FT ECO:0000269|PubMed:33852188" FT /id="VAR_068641" FT VARIANT 328 FT /note="F -> S (in PHOAR2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085958" FT VARIANT 369 FT /note="G -> D (in PHOAR2 and PHOAD; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:23509104, FT ECO:0000269|PubMed:33852188" FT /id="VAR_085959" FT VARIANT 374 FT /note="P -> L (in PHOAR2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085960" FT VARIANT 379 FT /note="G -> E (in PHOAR2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:23509104" FT /id="VAR_085961" FT VARIANT 396 FT /note="A -> T (in dbSNP:rs34550074)" FT /evidence="ECO:0000269|PubMed:8787677, FT ECO:0000269|PubMed:9618293" FT /id="VAR_053674" FT VARIANT 420 FT /note="C -> F (in PHOAR2; reduced activity; FT dbSNP:rs387907295)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068642" FT VARIANT 445 FT /note="R -> C (in dbSNP:rs146970901)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068643" FT VARIANT 465 FT /note="E -> K (in PHOAR2; uncertain significance; FT dbSNP:rs779203269)" FT /evidence="ECO:0000269|PubMed:23509104" FT /id="VAR_085962" FT VARIANT 554 FT /note="G -> R (in PHOAD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085963" FT VARIANT 556 FT /note="Q -> H (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22696055" FT /id="VAR_068644" FT VARIANT 557 FT /note="F -> S (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22331663" FT /id="VAR_068352" FT VARIANT 565 FT /note="W -> G (in PHOAR2)" FT /evidence="ECO:0000269|PubMed:22553128" FT /id="VAR_068645" FT VARIANT 603..643 FT /note="Missing (in PHOAD; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33852188" FT /id="VAR_085964" FT CONFLICT 9 FT /note="A -> V (in Ref. 1; AAC09469 and 2; AAC62004)" FT /evidence="ECO:0000305" FT CONFLICT 228 FT /note="V -> I (in Ref. 1; AAC09469 and 2; AAC62004)" FT /evidence="ECO:0000305" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:3MRR" SQ 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 //