Solute carrier organic anion transporter family member 2A1

Details

Name
Solute carrier organic anion transporter family member 2A1
Kind
protein
Synonyms
  • OATP2A1
  • PGT
  • PHOAR2
  • Prostaglandin transporter
  • SLC21A2
  • SLCO2A1
  • Solute carrier family 21 member 2
Gene Name
SLCO2A1
UniProtKB Entry
Q92959Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0012541|Solute carrier organic anion transporter family member 2A1
MGLLPKLGASQGSDTSTSRAGRCARSVFGNIKVFVLCQGLLQLCQLLYSAYFKSSLTTIE
KRFGLSSSSSGLISSLNEISNAILIIFVSYFGSRVHRPRLIGIGGLFLAAGAFILTLPHF
LSEPYQYTLASTGNNSRLQAELCQKHWQDLPPSKCHSTTQNPQKETSSMWGLMVVAQLLA
GIGTVPIQPFGISYVDDFSEPSNSPLYISILFAISVFGPAFGYLLGSVMLQIFVDYGRVN
TAAVNLVPGDPRWIGAWWLGLLISSALLVLTSFPFFFFPRAMPIGAKRAPATADEARKLE
EAKSRGSLVDFIKRFPCIFLRLLMNSLFVLVVLAQCTFSSVIAGLSTFLNKFLEKQYGTS
AAYANFLIGAVNLPAAALGMLFGGILMKRFVFSLQAIPRIATTIITISMILCVPLFFMGC
STPTVAEVYPPSTSSSIHPQSPACRRDCSCPDSIFHPVCGDNGIEYLSPCHAGCSNINMS
SATSKQLIYLNCSCVTGGSASAKTGSCPVPCAHFLLPAIFLISFVSLIACISHNPLYMMV
LRVVNQEEKSFAIGVQFLLMRLLAWLPSPALYGLTIDHSCIRWNSLCLGRRGACAYYDND
ALRDRYLGLQMGYKALGMLLLCFISWRVKKNKEYNVQKAAGLI
Number of residues
643
Molecular Weight
70043.33
Theoretical pI
8.95
GO Classification
Components
basal plasma membrane / basolateral plasma membrane / lysosome
General Function
Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane (PubMed:11997326, PubMed:26692285, PubMed:8787677). PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever (PubMed:15044627). Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination (PubMed:8787677). PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions (PubMed:29204966). Uses lactate, generated by glycolysis, as a counter-substrate to mediate PGE2 influx and efflux (PubMed:11997326). Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates (PubMed:11997326). Although the mechanism is not clear, this transporter can function in bidirectional mode (PubMed:29204966). When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion (By similarity). In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption) (By similarity). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells (PubMed:16339169). Involved in critical events for ovulation (PubMed:27169804). Regulates extracellular PGE2 concentration for follicular development in the ovaries (By similarity). Expressed intracellularly, may contribute to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized (By similarity). Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes (By similarity). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
lipid transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
33-52 72-92 99-123 168-196 216-236 255-279 322-343 364-387 392-415 519-541 551-576 611-629
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0012542|Solute carrier organic anion transporter family member 2A1 (SLCO2A1)
ATGGGGCTCCTGCCCAAGCTCGGCGCGTCCCAGGGCAGCGACACCTCTACTAGCCGAGCC
GGCCGCTGTGCCCGCTCGGTCTTCGGCAACATTAAGGTGTTTGTGCTCTGCCAAGGCCTC
CTGCAGCTCTGCCAACTCCTGTACAGCGCCTACTTCAAGAGCAGCCTCACCACCATTGAG
AAGCGCTTTGGGCTCTCCAGTTCTTCATCGGGTCTCATTTCCAGCTTGAATGAGATCAGC
AATGCCATCCTCATCATCTTTGTCAGCTACTTTGGCAGCCGGGTGCACCGTCCACGTCTG
ATTGGCATCGGAGGTCTCTTCCTGGCTGCAGGTGCCTTCATCCTCACCCTCCCACACTTC
CTCTCCGAGCCCTACCAGTACACCTTGGCCAGCACTGGGAACAACAGCCGCTTGCAGGCC
GAGCTCTGCCAGAAGCATTGGCAGGACCTGCCTCCCAGTAAGTGCCACAGCACCACCCAG
AACCCCCAGAAGGAGACCAGCAGCATGTGGGGCCTGATGGTGGTTGCCCAGCTGCTGGCT
GGCATCGGGACAGTGCCTATTCAGCCATTTGGGATCTCCTATGTGGATGACTTCTCAGAG
CCCAGCAACTCGCCCCTGTACATCTCCATCTTATTTGCCATCTCTGTATTTGGACCGGCT
TTCGGGTACCTGCTGGGCTCTGTCATGCTGCAGATCTTTGTGGACTATGGCAGGGTCAAC
ACAGCTGCAGTTAACTTGGTCCCGGGTGACCCCCGATGGATTGGAGCCTGGTGGCTAGGC
CTGCTCATTTCTTCAGCTTTATTGGTTCTCACCTCTTTCCCCTTTTTTTTCTTCCCTCGA
GCAATGCCCATAGGAGCAAAGAGGGCTCCTGCCACAGCAGATGAAGCAAGGAAGTTGGAG
GAGGCCAAGTCAAGAGGCTCCCTGGTGGATTTCATTAAACGGTTTCCATGCATCTTTCTG
AGGCTCCTGATGAACTCACTCTTCGTCCTGGTGGTCCTGGCCCAGTGCACCTTCTCCTCC
GTCATTGCTGGCCTCTCCACCTTCCTCAACAAGTTCCTGGAGAAGCAGTATGGCACCTCA
GCAGCCTATGCCAACTTCCTCATTGGTGCTGTGAACCTCCCTGCTGCAGCCTTGGGGATG
CTGTTTGGAGGAATCCTCATGAAGCGCTTTGTTTTCTCTCTACAAGCCATTCCCCGCATA
GCTACCACCATCATCACCATCTCCATGATCCTTTGTGTTCCTTTGTTCTTCATGGGATGC
TCCACCCCAACTGTGGCCGAAGTCTACCCCCCTAGCACATCAAGTTCTATACATCCGCAG
TCTCCTGCCTGCCGCAGGGACTGCTCGTGCCCAGATTCTATCTTCCACCCGGTCTGTGGA
GACAATGGAATCGAGTACCTCTCCCCTTGCCATGCCGGCTGCAGCAACATCAACATGAGC
TCTGCAACCTCCAAGCAACTGATCTATTTGAACTGCAGCTGTGTGACCGGGGGATCCGCT
TCAGCAAAGACAGGATCGTGCCCTGTCCCCTGTGCCCACTTCCTGCTCCCGGCCATCTTC
CTCATCTCCTTCGTGTCCCTGATAGCCTGCATCTCCCACAACCCCCTCTACATGATGGTT
CTGCGTGTGGTGAACCAGGAGGAAAAGTCATTTGCCATCGGGGTGCAGTTCTTGTTGATG
CGCTTGCTGGCCTGGCTGCCATCTCCAGCCCTCTATGGCCTCACCATTGACCACTCCTGC
ATCCGGTGGAACTCGCTGTGCTTGGGGAGGCGAGGGGCCTGCGCCTACTATGACAACGAT
GCTCTCCGAGACAGGTACCTGGGCCTGCAGATGGGCTACAAGGCGCTGGGCATGCTGCTG
CTTTGCTTCATCAGCTGGAGGGTGAAGAAGAACAAGGAGTACAACGTGCAGAAGGCGGCA
GGCCTCATCTGA
Chromosome Location
3
Locus
3q22.1-q22.2
External Identifiers
ResourceLink
UniProtKB IDQ92959
UniProtKB Entry NameSO2A1_HUMAN
GenBank Protein ID1617590
GenBank Gene IDU70867
GeneCard IDSLCO2A1
HGNC IDHGNC:10955
PDB ID(s)3MRR
KEGG IDhsa:6578
NCBI Gene ID6578
General References
  1. Lu R, Kanai N, Bao Y, Schuster VL: Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9. [Article]
  2. Lu R, Schuster VL: Molecular cloning of the gene for the human prostaglandin transporter hPGT: gene organization, promoter activity, and chromosomal localization. Biochem Biophys Res Commun. 1998 May 29;246(3):805-12. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. 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. 2012 Apr;33(4):660-4. doi: 10.1002/humu.22042. Epub 2012 Feb 24. [Article]
  5. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, 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. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  6. 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. 2012 Jan 13;90(1):125-32. doi: 10.1016/j.ajhg.2011.11.019. Epub 2011 Dec 22. [Article]
  7. Diggle CP, Parry DA, Logan CV, Laissue P, Rivera C, Restrepo CM, Fonseca DJ, Morgan JE, 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 PJ, Lichtenbelt KD, Aubry-Rozier B, Superti-Furga A, Dallapiccola B, Accadia M, Brancati F, Sheridan EG, Taylor GR, Carr IM, Johnson CA, Markham AF, Bonthron DT: Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. Hum Mutat. 2012 Aug;33(8):1175-81. doi: 10.1002/humu.22111. Epub 2012 May 29. [Article]
  8. Busch J, Frank V, Bachmann N, Otsuka A, Oji V, Metze D, Shah K, Danda S, Watzer B, Traupe H, Bolz HJ, Kabashima K, Bergmann C: Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing. J Invest Dermatol. 2012 Oct;132(10):2473-6. doi: 10.1038/jid.2012.146. Epub 2012 Jun 14. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Phenobarbitalapproved, investigationalunknowntransporterinducerDetails
Pyruvic acidapproved, investigational, nutraceuticalunknowntransporterinhibitorDetails
PhosphoenolpyruvateexperimentalunknowntransporterinhibitorDetails
Lactic acidapproved, vet_approvedunknowntransporterinhibitorDetails
D-glyceraldehyde 3-phosphateexperimentalunknowntransporterinhibitorDetails
Glucose-6-PhosphateexperimentalunknowntransporterinhibitorDetails
beta-D-fructofuranose 1,6-bisphosphateexperimentalunknowntransporterinhibitorDetails
Furosemideapproved, vet_approvedunknowntransporterinhibitorDetails
Latanoprostapproved, investigationalunknowntransportersubstrateDetails
DinoprostoneapprovedunknowntransportersubstrateDetails
Alprostadilapproved, investigationalunknowntransportersubstrateDetails
Iloprostapproved, investigationalunknowntransportersubstrateDetails
Arachidonic AcidexperimentalunknowntransportersubstrateDetails
Prostaglandin D2investigationalunknowntransporterDetails
Dinoprost tromethamineapproved, vet_approvedunknowntransporterDetails
Rifamycinapproved, investigationalnotransporterinhibitorDetails