Solute carrier family 22 member 2
Details
- Name
- Solute carrier family 22 member 2
- Synonyms
- hOCT2
- OCT2
- Organic cation transporter 2
- Gene Name
- SLC22A2
- UniProtKB Entry
- O15244Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0037250|Solute carrier family 22 member 2 MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHRCRSPGVAELS LRCGWSPAEELNYTVPGPGPAGEASPRQCRRYEVDWNQSTFDCVDPLASLDTNRSRLPLG PCRDGWVYETPGSSIVTEFNLVCANSWMLDLFQSSVNVGFFIGSMSIGYIADRFGRKLCL LTTVLINAAAGVLMAISPTYTWMLIFRLIQGLVSKAGWLIGYILITEFVGRRYRRTVGIF YQVAYTVGLLVLAGVAYALPHWRWLQFTVSLPNFFFLLYYWCIPESPRWLISQNKNAEAM RIIKHIAKKNGKSLPASLQRLRLEEETGKKLNPSFLDLVRTPQIRKHTMILMYNWFTSSV LYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFMIILTIDRIGRRYPWAASNMVAGAACLA SVFIPGDLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGGII TPFLVYRLTNIWLELPLMVFGVLGLVAGGLVLLLPETKGKALPETIEEAENMQRPRKNKE KMIYLQVQKLDIPLN
- Number of residues
- 555
- Molecular Weight
- 62579.99
- Theoretical pI
- 8.45
- GO Classification
- Functionsacetylcholine transmembrane transporter activity / amine transmembrane transporter activity / efflux transmembrane transporter activity / L-amino acid transmembrane transporter activity / L-arginine transmembrane transporter activity / monoamine transmembrane transporter activity / neurotransmitter transmembrane transporter activity / organic anion transmembrane transporter activity / prostaglandin transmembrane transporter activity / putrescine transmembrane transporter activity / pyrimidine nucleoside transmembrane transporter activity / spermidine transmembrane transporter activity / thiamine transmembrane transporter activity / toxin transmembrane transporter activity / xenobiotic transmembrane transporter activityProcessesacetylcholine transport / activation of cysteine-type endopeptidase activity involved in apoptotic process / amine transport / amino acid import across plasma membrane / cellular detoxification / dopamine uptake / epinephrine transport / export across plasma membrane / histamine transport / histamine uptake / L-alpha-amino acid transmembrane transport / L-arginine import across plasma membrane / monoatomic cation transport / neurotransmitter transport / norepinephrine transport / norepinephrine uptake / positive regulation of gene expression / prostaglandin transport / purine-containing compound transmembrane transport / putrescine transport / serotonin transport / serotonin uptake / spermidine transport / thiamine transmembrane transport / transport across blood-brain barrier / xenobiotic transport / xenobiotic transport across blood-brain barrierComponentsapical plasma membrane / basal plasma membrane / basolateral plasma membrane / presynapse
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Acetylcholine transmembrane transporter activity
- Pfam Domain Function
- Sugar_tr (PF00083)
- Signal Regions
- Not Available
- Transmembrane Regions
- 23-43 151-171 178-198 209-229 239-259 264-284 349-369 376-396 415-435 442-462 465-485 495-515
- Cellular Location
- Basolateral cell membrane
- Gene sequence
>lcl|BSEQ0012536|Solute carrier family 22 member 2 (SLC22A2) ATGCCCACCACCGTGGACGATGTCCTGGAGCATGGAGGGGAGTTTCACTTTTTCCAGAAG CAAATGTTTTTCCTCTTGGCTCTGCTCTCGGCTACCTTCGCGCCCATCTACGTGGGCATC GTCTTCCTGGGCTTCACCCCTGACCACCGCTGCCGGAGCCCCGGAGTGGCCGAGCTGAGT CTGCGCTGCGGCTGGAGTCCTGCAGAGGAACTGAACTACACGGTGCCGGGCCCAGGACCT GCGGGCGAAGCCTCCCCAAGACAGTGTAGGCGCTACGAGGTGGACTGGAACCAGAGCACC TTCGACTGCGTGGACCCCCTGGCCAGCCTGGACACCAACAGGAGCCGCCTGCCACTGGGC CCCTGCCGGGACGGCTGGGTGTACGAGACGCCTGGCTCGTCCATCGTCACCGAGTTTAAC CTGGTATGTGCCAACTCCTGGATGTTGGACCTATTCCAGTCATCAGTGAATGTAGGATTC TTTATTGGCTCTATGAGTATCGGCTACATAGCAGACAGGTTTGGCCGTAAGCTCTGCCTC CTAACTACAGTCCTCATAAATGCTGCAGCTGGAGTTCTCATGGCCATTTCCCCAACCTAT ACGTGGATGTTAATTTTTCGCTTAATCCAAGGACTGGTCAGCAAAGCAGGCTGGTTAATA GGCTACATCCTGATTACAGAATTTGTTGGGCGGAGATATCGGAGAACAGTGGGGATTTTT TACCAAGTTGCCTATACAGTTGGGCTCCTGGTGCTAGCTGGGGTGGCTTACGCACTTCCT CACTGGAGGTGGTTGCAGTTCACAGTTTCTCTGCCCAACTTCTTCTTCTTGCTCTATTAC TGGTGCATACCTGAGTCTCCCAGGTGGCTGATCTCCCAGAATAAGAATGCTGAAGCCATG AGAATCATTAAGCACATCGCAAAGAAAAATGGAAAATCTCTACCCGCCTCCCTTCAGCGC CTGAGACTTGAAGAGGAAACTGGCAAGAAATTGAACCCTTCATTTCTTGACTTGGTCAGA ACTCCTCAGATAAGGAAACATACTATGATATTGATGTACAACTGGTTCACGAGCTCTGTG CTCTACCAGGGCCTCATCATGCACATGGGCCTTGCAGGTGACAATATCTACCTGGATTTC TTCTACTCTGCCCTGGTTGAATTCCCAGCTGCCTTCATGATCATCCTCACCATCGACCGC ATCGGACGCCGTTACCCTTGGGCTGCATCAAATATGGTTGCAGGGGCAGCCTGTCTGGCC TCAGTTTTTATACCTGGTGATCTACAATGGCTAAAAATTATTATCTCATGCTTGGGAAGA ATGGGGATCACAATGGCCTATGAGATAGTCTGCCTGGTCAATGCTGAGCTGTACCCCACA TTCATTAGGAATCTTGGCGTCCACATCTGTTCCTCAATGTGTGACATTGGTGGCATCATC ACGCCATTCCTGGTCTACCGGCTCACTAACATCTGGCTTGAGCTCCCGCTGATGGTTTTC GGCGTGCTTGGCTTGGTTGCTGGAGGTCTGGTGCTGTTGCTTCCAGAAACTAAAGGGAAA GCTTTGCCTGAGACCATCGAGGAAGCCGAAAATATGCAAAGACCAAGAAAAAATAAAGAA AAGATGATTTACCTCCAAGTTCAGAAACTAGACATTCCATTGAACTAA
- Chromosome Location
- 6
- Locus
- 6q25.3
- External Identifiers
Resource Link UniProtKB ID O15244 UniProtKB Entry Name S22A2_HUMAN GenBank Protein ID 2281942 GenBank Gene ID X98333 GeneCard ID SLC22A2 HGNC ID HGNC:10966 PDB ID(s) 8ET9 KEGG ID hsa:6582 IUPHAR/Guide To Pharmacology ID 1020 NCBI Gene ID 6582 - General References
- Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [Article]
- Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. [Article]
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- Grundemann D, Schomig E: Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. Hum Genet. 2000 Jun;106(6):627-35. [Article]
- Busch AE, Karbach U, Miska D, Gorboulev V, Akhoundova A, Volk C, Arndt P, Ulzheimer JC, Sonders MS, Baumann C, Waldegger S, Lang F, Koepsell H: Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol. 1998 Aug;54(2):342-52. [Article]
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
- Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui K: Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol. 2002 Apr;13(4):866-74. [Article]
- Grundemann D, Hahne C, Berkels R, Schomig E: Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther. 2003 Feb;304(2):810-7. [Article]
- Motohashi H, Uwai Y, Hiramoto K, Okuda M, Inui K: Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol. 2004 Oct 25;503(1-3):25-30. [Article]
- Ciarimboli G, Ludwig T, Lang D, Pavenstadt H, Koepsell H, Piechota HJ, Haier J, Jaehde U, Zisowsky J, Schlatter E: Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005 Dec;167(6):1477-84. [Article]
- Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, Inui K: Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86. [Article]
- Tahara H, Kusuhara H, Endou H, Koepsell H, Imaoka T, Fuse E, Sugiyama Y: A species difference in the transport activities of H2 receptor antagonists by rat and human renal organic anion and cation transporters. J Pharmacol Exp Ther. 2005 Oct;315(1):337-45. Epub 2005 Jul 8. [Article]
- Kimura N, Okuda M, Inui K: Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm Res. 2005 Feb;22(2):255-9. [Article]
- Biermann J, Lang D, Gorboulev V, Koepsell H, Sindic A, Schroter R, Zvirbliene A, Pavenstadt H, Schlatter E, Ciarimboli G: Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31. Epub 2006 Jan 4. [Article]
- Zhang S, Lovejoy KS, Shima JE, Lagpacan LL, Shu Y, Lapuk A, Chen Y, Komori T, Gray JW, Chen X, Lippard SJ, Giacomini KM: Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57. doi: 10.1158/0008-5472.CAN-06-0769. [Article]
- Okuda M, Kimura N, Inui K: Interactions of fluoroquinolone antibacterials, DX-619 and levofloxacin, with creatinine transport by renal organic cation transporter hOCT2. Drug Metab Pharmacokinet. 2006 Oct;21(5):432-6. [Article]
- Yonezawa A, Masuda S, Yokoo S, Katsura T, Inui K: Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are substrates for human organic cation transporters (SLC22A1-3 and multidrug and toxin extrusion family). J Pharmacol Exp Ther. 2006 Nov;319(2):879-86. Epub 2006 Aug 16. [Article]
- Yokoo S, Yonezawa A, Masuda S, Fukatsu A, Katsura T, Inui K: Differential contribution of organic cation transporters, OCT2 and MATE1, in platinum agent-induced nephrotoxicity. Biochem Pharmacol. 2007 Aug 1;74(3):477-87. Epub 2007 Mar 12. [Article]
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Associated Data
- Bio-Entities
Bio-Entity Type Solute carrier family 22 member 2 (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Propranolol approved, investigational unknown transporter inhibitor Details Oxprenolol approved unknown transporter inhibitor Details Metoprolol approved, investigational unknown transporter inhibitor Details Quinine approved unknown transporter inhibitor Details Choline approved, nutraceutical unknown transporter substrateinhibitor Details Dinoprostone approved unknown transporter inhibitor Details Thiamine approved, investigational, nutraceutical, vet_approved unknown transporter inhibitor Details Quinidine approved, investigational unknown transporter inhibitor Details Procainamide approved unknown transporter inhibitor Details Norepinephrine approved unknown transporter substrateinhibitor Details Nicotine approved unknown transporter inhibitor Details Levofloxacin approved, investigational unknown transporter inhibitor Details Imipramine approved unknown transporter inhibitor Details Histamine approved, investigational unknown transporter substrateinhibitor Details Guanidine approved unknown transporter inhibitor Details Grepafloxacin approved, investigational, withdrawn unknown transporter inhibitor Details Dopamine approved unknown transporter substrateinhibitor Details Cimetidine approved, investigational unknown transporter substrateinhibitor Details Amantadine approved unknown transporter substrateinhibitor Details Progesterone approved, vet_approved unknown transporter inhibitor Details Phenoxybenzamine approved unknown transporter inhibitor Details Estradiol approved, investigational, vet_approved unknown transporter inhibitordownregulator Details Phenformin approved, investigational, withdrawn unknown transporter inhibitor Details Metformin approved unknown transporter substrateinhibitor Details Desipramine approved, investigational unknown transporter inhibitor Details Famotidine approved no transporter inhibitor Details Probenecid approved, investigational unknown transporter inhibitor Details Aminohippuric acid approved, investigational unknown transporter inhibitor Details Cocaine approved, illicit unknown transporter inhibitor Details Cisplatin approved unknown transporter substrateinhibitor Details Quinacrine investigational unknown transporter inhibitor Details Chlorpheniramine approved unknown transporter inhibitor Details Amiloride approved unknown transporter inhibitor Details Epinephrine approved, vet_approved unknown transporter substrate Details Disopyramide approved unknown transporter inhibitor Details Diphenhydramine approved, investigational unknown transporter inhibitor Details Imatinib approved no transporter inhibitor Details Pimagedine investigational unknown transporter inhibitor Details Memantine approved, investigational unknown transporter substrate Details Pramipexole approved, investigational unknown transporter substrate Details Reserpine approved, investigational, withdrawn unknown transporter substrate Details Oxaliplatin approved, investigational no transporter substrate Details Tetraethylammonium experimental, investigational unknown transporter substrate Details Serotonin investigational, nutraceutical unknown transporter Details N-methylnicotinamide experimental unknown transporter Details Zidovudine approved unknown transporter Details Agmatine experimental unknown transporter substrate Details Tubocurarine approved unknown transporter Details Pancuronium approved unknown transporter Details Dinoprost tromethamine approved, vet_approved unknown transporter Details Flurazepam approved, illicit, investigational unknown transporter inhibitor Details Lamivudine approved, investigational unknown transporter substrate Details Dexchlorpheniramine maleate approved unknown carrier inhibitor Details Nafamostat investigational unknown transporter substrate Details Enasidenib approved, investigational unknown transporter inhibitor Details Dolutegravir approved no transporter inhibitor Details Baricitinib approved, investigational unknown transporter inhibitor Details Estradiol acetate approved, investigational, vet_approved unknown transporter inhibitor Details Estradiol benzoate approved, investigational, vet_approved unknown transporter inhibitor Details Estradiol cypionate approved, investigational, vet_approved unknown transporter inhibitor Details Estradiol dienanthate approved, investigational, vet_approved unknown transporter inhibitor Details Estradiol valerate approved, investigational, vet_approved unknown transporter inhibitor Details Apalutamide approved, investigational no transporter inhibitor Details Isavuconazole approved, investigational unknown transporter inhibitor Details Choline salicylate approved, nutraceutical unknown transporter substrateinhibitor Details Ranitidine approved, withdrawn unknown transporter substrate Details Tafenoquine approved, investigational no transporter inhibitor Details Lenvatinib approved, investigational unknown transporter inhibitor Details Varenicline approved, investigational unknown transporter substrateinhibitor Details Bupropion approved unknown transporter inhibitor Details Dalfampridine approved unknown transporter substrate Details Amiodarone approved, investigational unknown transporter inhibitor Details Clopidogrel approved no transporter inhibitor Details Tipiracil approved, investigational unknown transporter substrate Details Dofetilide approved, investigational no transporter substrate Details Lamotrigine approved, investigational no transporter inhibitor Details Vandetanib approved no transporter inhibitor Details Allopurinol approved unknown transporter Details Solriamfetol approved unknown transporter Details Testosterone undecanoate approved, investigational unknown transporter inducer Details Linagliptin approved unknown transporter substrateinhibitor Details Erdafitinib approved, investigational no transporter inhibitor Details Lansoprazole approved, investigational unknown transporter Details Dronedarone approved no transporter inhibitor Details Abemaciclib approved, investigational unknown transporter inhibitor Details Ubrogepant approved, investigational unknown transporter inhibitor Details Guanfacine approved, investigational unknown transporter substrate Details Salmeterol approved unknown transporter inhibitor Details Rimegepant approved, investigational unknown transporter inhibitor Details Osilodrostat approved, investigational unknown transporter inhibitor Details Methylene blue approved, investigational unknown transporter inhibitor Details Tucatinib approved, investigational unknown transporter inhibitor Details Pemigatinib approved, investigational no transporter inhibitor Details Tirbanibulin approved, investigational no transporter inhibitor Details Trilaciclib approved, investigational unknown transporter inhibitor Details Sulpiride approved, investigational unknown transporter substrate Details Terbutaline approved unknown transporter substrate Details Pindolol approved, investigational unknown transporter substrate Details Mirabegron approved no transporter substrate Details Glycopyrronium approved, investigational, vet_approved unknown transporter substrate Details Gentamicin approved, vet_approved no transporter substrate Details Infigratinib approved, investigational no transporter inhibitor Details Fexinidazole approved, investigational unknown transporter inhibitor Details Romidepsin approved, investigational no transporter inhibitor Details Levoketoconazole approved, investigational no transporter inhibitor Details Pacritinib approved, investigational no transporter inhibitor Details Dabrafenib approved, investigational no transporter inhibitor Details Tepotinib approved, investigational no transporter inhibitor Details Amifampridine approved, investigational no transporter inhibitor Details Olutasidenib approved, investigational no transporter inhibitor Details Clozapine approved no transporter Details Tezacaftor approved, investigational no transporter inhibitor Details Umeclidinium approved no transporter substrate Details Encorafenib approved, investigational no transporter inhibitor Details Capivasertib approved, investigational no transporter inhibitor Details Isavuconazonium approved, investigational no transporter inhibitor Details Givinostat approved, investigational no transporter inhibitor Details Mavorixafor approved, investigational unknown transporter inhibitor Details Sofpironium approved, investigational no transporter inhibitor Details