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";
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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 Genevisible; Q92959; HS.
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.
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
//
