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Identification
HMDB Protein ID HMDBP04308
Secondary Accession Numbers
  • 9897
Name Solute carrier family 22 member 2
Synonyms
  1. Organic cation transporter 2
  2. hOCT2
Gene Name SLC22A2
Protein Type Transporter
Biological Properties
General Function Involved in ion transmembrane transporter activity
Specific Function Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity
Pathways
  • Amiloride Action Pathway
  • Bendroflumethiazide Action Pathway
  • Blue diaper syndrome
  • Bumetanide Action Pathway
  • Chlorothiazide Action Pathway
  • Chlorthalidone Action Pathway
  • Cyclothiazide Action Pathway
  • Cystinuria
  • Eplerenone Action Pathway
  • Ethacrynic Acid Action Pathway
  • Furosemide Action Pathway
  • Glucose Transporter Defect (SGLT2)
  • Glucose Transporter Defect (SGLT2)
  • Hartnup Disorder
  • Hydrochlorothiazide Action Pathway
  • Hydroflumethiazide Action Pathway
  • Iminoglycinuria
  • Indapamide Action Pathway
  • Kidney Function
  • Lamivudine Metabolism Pathway
  • Lysinuric Protein Intolerance
  • Lysinuric protein intolerance (LPI)
  • Methyclothiazide Action Pathway
  • Metolazone Action Pathway
  • Polythiazide Action Pathway
  • Quinethazone Action Pathway
  • Spironolactone Action Pathway
  • Torsemide Action Pathway
  • Triamterene Action Pathway
  • Trichlormethiazide Action Pathway
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
Process
establishment of localization
transport
transmembrane transport
ion transport
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein (Potential)
Gene Properties
Chromosome Location Chromosome:6
Locus 6q26
SNPs SLC22A2
Gene Sequence
>1668 bp
ATGCCCACCACCGTGGACGATGTCCTGGAGCATGGAGGGGAGTTTCACTTTTTCCAGAAG
CAAATGTTTTTCCTCTTGGCTCTGCTCTCGGCTACCTTCGCGCCCATCTACGTGGGCATC
GTCTTCCTGGGCTTCACCCCTGACCACCGCTGCCGGAGCCCCGGAGTGGCCGAGCTGAGT
CTGCGCTGCGGCTGGAGTCCTGCAGAGGAACTGAACTACACGGTGCCGGGCCCAGGACCT
GCGGGCGAAGCCTCCCCAAGACAGTGTAGGCGCTACGAGGTGGACTGGAACCAGAGCACC
TTTGACTGCGTGGACCCCCTGGCCAGCCTGGACACCAACAGGAGCCGCCTGCCACTGGGC
CCCTGCCGGGACGGCTGGGTGTACGAGACGCCTGGCTCGTCCATCGTCACCGAGTTTAAC
CTGGTATGTGCCAACTCCTGGATGTTGGACCTATTCCAGTCATCAGTGAATGTAGGATTC
TTTATTGGCTCTATGAGTATCGGCTACATAGCAGACAGGTTTGGCCGTAAGCTCTGCCTC
CTAACTACAGTCCTCATAAATGCTGCAGCTGGAGTTCTCATGGCCATTTCCCCAACCTAT
ACGTGGATGTTAATTTTTCGCTTAATCCAAGGACTGGTCAGCAAAGCAGGCTGGTTAATA
GGCTACATCCTGATTACAGAATTTGTTGGGCGGAGATATCGGAGAACAGTGGGGATTTTT
TACCAAGTTGCCTATACAGTTGGGCTCCTGGTGCTAGCTGGGGTGGCTTACGCACTTCCT
CACTGGAGGTGGTTGCAGTTCACAGTTGCTCTGCCCAACTTCTTCTTCTTGCTCTATTAC
TGGTGCATACCTGAGTCTCCCAGGTGGCTGATCTCCCAGAATAAGAATGCTGAAGCCATG
AGAATCATTAAGCACATCGCAAAGAAAAATGGAAAATCTCTACCCGCCTCCCTTCAGCGC
CTGAGACTTGAAGAGGAAACTGGCAAGAAATTGAACCCTTCATTTCTTGACTTGGTCAGA
ACTCCTCAGATAAGGAAACATACTATGATATTGATGTACAACTGGTTCACGAGCTCTGTG
CTCTACCAGGGCCTCATCATGCACATGGGCCTTGCAGGTGACAATATCTACCTGGATTTC
TTCTACTCTGCCCTGGTTGAATTCCCAGCTGCCTTCATGATCATCCTCACCATCGACCGC
ATCGGACGCCGTTACCCTTGGGCTGCATCAAATATGGTTGCAGGGGCAGCCTGTCTGGCC
TCAGTTTTTATACCTGGTGATCTACAATGGCTAAAAATTATTATCTCATGCTTGGGAAGA
ATGGGGATCACAATGGCCTATGAGATAGTCTGCCTGGTCAATGCTGAGCTGTACCCCACA
TTCATTAGGAATCTTGGCGTCCACATCTGTTCCTCAATGTGTGACATTGGTGGCATCATC
ACGCCATTCCTGGTCTACCGGCTCACTAACATCTGGCTTGAGCTCCCGCTGATGGTTTTC
GGCGTACTTGGCTTGGTTGCTGGAGGTCTGGTGCTGTTGCTTCCAGAAACTAAAGGGAAA
GCTTTGCCTGAGACCATCGAGGAAGCCGAAAATATGCAAAGACCAAGAAAAAATAAAGAA
AAGATGATTTACCTCCAAGTTCAGAAACTAGACATTCCATTGAACTAA
Protein Properties
Number of Residues 555
Molecular Weight 62564.0
Theoretical pI 8.45
Pfam Domain Function
Signals
  • None
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
Protein Sequence
>Solute carrier family 22 member 2
MPTTVDDVLEHGGEFHFFQKQMFFLLALLSATFAPIYVGIVFLGFTPDHRCRSPGVAELS
LRCGWSPAEELNYTVPGPGPAGEASPRQCRRYEVDWNQSTFDCVDPLASLDTNRSRLPLG
PCRDGWVYETPGSSIVTEFNLVCANSWMLDLFQSSVNVGFFIGSMSIGYIADRFGRKLCL
LTTVLINAAAGVLMAISPTYTWMLIFRLIQGLVSKAGWLIGYILITEFVGRRYRRTVGIF
YQVAYTVGLLVLAGVAYALPHWRWLQFTVALPNFFFLLYYWCIPESPRWLISQNKNAEAM
RIIKHIAKKNGKSLPASLQRLRLEEETGKKLNPSFLDLVRTPQIRKHTMILMYNWFTSSV
LYQGLIMHMGLAGDNIYLDFFYSALVEFPAAFMIILTIDRIGRRYPWAASNMVAGAACLA
SVFIPGDLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGGII
TPFLVYRLTNIWLELPLMVFGVLGLVAGGLVLLLPETKGKALPETIEEAENMQRPRKNKE
KMIYLQVQKLDIPLN
GenBank ID Protein 2281942
UniProtKB/Swiss-Prot ID O15244
UniProtKB/Swiss-Prot Entry Name S22A2_HUMAN
PDB IDs Not Available
GenBank Gene ID X98333
GeneCard ID SLC22A2
GenAtlas ID SLC22A2
HGNC ID HGNC:10966
References
General References
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  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. [PubMed:15489334 ]
  4. 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. [PubMed:9260930 ]
  5. 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. [PubMed:12089365 ]
  6. Grundemann D, Schomig E: Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. Hum Genet. 2000 Jun;106(6):627-35. [PubMed:10942111 ]
  7. 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. [PubMed:9687576 ]
  8. 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. [PubMed:11758759 ]
  9. 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. [PubMed:11912245 ]
  10. 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. [PubMed:12538837 ]
  11. 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. [PubMed:15496291 ]
  12. 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. [PubMed:16314463 ]
  13. 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. [PubMed:16272756 ]
  14. 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. [PubMed:16006492 ]
  15. Kimura N, Okuda M, Inui K: Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm Res. 2005 Feb;22(2):255-9. [PubMed:15783073 ]
  16. 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. [PubMed:16394027 ]
  17. 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. [PubMed:16951202 ]
  18. 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. [PubMed:17072098 ]
  19. 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. [PubMed:16914559 ]
  20. 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. [PubMed:17582384 ]
  21. Bottalico B, Noskova V, Pilka R, Larsson I, Domanski H, Casslen B, Hansson SR: The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11. [PubMed:17393420 ]
  22. Leabman MK, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, DeYoung J, Taylor T, Clark AG, Herskowitz I, Giacomini KM: Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics. 2002 Jul;12(5):395-405. [PubMed:12142729 ]
  23. Shikata E, Yamamoto R, Takane H, Shigemasa C, Ikeda T, Otsubo K, Ieiri I: Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. J Hum Genet. 2007;52(2):117-22. Epub 2006 Nov 17. [PubMed:17111267 ]