Solute carrier family 22 member 1

Details

Name
Solute carrier family 22 member 1
Synonyms
  • hOCT1
  • OCT1
  • Organic cation transporter 1
Gene Name
SLC22A1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037862|Solute carrier family 22 member 1
MPTVDDILEQVGESGWFQKQAFLILCLLSAAFAPICVGIVFLGFTPDHHCQSPGVAELSQ
RCGWSPAEELNYTVPGLGPAGEAFLGQCRRYEVDWNQSALSCVDPLASLATNRSHLPLGP
CQDGWVYDTPGSSIVTEFNLVCADSWKLDLFQSCLNAGFLFGSLGVGYFADRFGRKLCLL
GTVLVNAVSGVLMAFSPNYMSMLLFRLLQGLVSKGNWMAGYTLITEFVGSGSRRTVAIMY
QMAFTVGLVALTGLAYALPHWRWLQLAVSLPTFLFLLYYWCVPESPRWLLSQKRNTEAIK
IMDHIAQKNGKLPPADLKMLSLEEDVTEKLSPSFADLFRTPRLRKRTFILMYLWFTDSVL
YQGLILHMGATSGNLYLDFLYSALVEIPGAFIALITIDRVGRIYPMAMSNLLAGAACLVM
IFISPDLHWLNIIIMCVGRMGITIAIQMICLVNAELYPTFVRNLGVMVCSSLCDIGGIIT
PFIVFRLREVWQALPLILFAVLGLLAAGVTLLLPETKGVALPETMKDAENLGRKAKPKEN
TIYLKVQTSEPSGT
Number of residues
554
Molecular Weight
61153.345
Theoretical pI
6.81
GO Classification
Functions
acetylcholine transmembrane transporter activity / dopamine transmembrane transporter activity / norepinephrine transmembrane transporter activity / organic cation transmembrane transporter activity / quaternary ammonium group transmembrane transporter activity / secondary active organic cation transmembrane transporter activity
Processes
ammonium transmembrane transport / dopamine transport / drug transmembrane transport / epinephrine transport / establishment or maintenance of transmembrane electrochemical gradient / neurotransmitter transport / norepinephrine transport / organic cation transport / protein homooligomerization / quaternary ammonium group transport / small molecule metabolic process / transmembrane transport
Components
basolateral plasma membrane / integral component of plasma membrane / membrane / plasma membrane
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Pfam Domain Function
Transmembrane Regions
22-42 150-170 177-197 207-229 236-256 263-283 348-368 377-397 403-423 432-452 465-485 493-513
Cellular Location
Basolateral cell membrane
Gene sequence
>lcl|BSEQ0017170|Solute carrier family 22 member 1 (SLC22A1)
ATGCCCACCGTGGATGACATTCTGGAGCAGGTTGGGGAGTCTGGCTGGTTCCAGAAGCAA
GCCTTCCTCATCTTATGCCTGCTGTCGGCTGCCTTTGCGCCCATCTGTGTGGGCATCGTC
TTCCTGGGTTTCACACCTGACCACCACTGCCAGAGTCCTGGGGTGGCTGAGCTGAGCCAG
CGCTGTGGCTGGAGCCCTGCGGAGGAGCTGAACTATACAGTGCCAGGCCTGGGGCCCGCG
GGCGAGGCCTTCCTTGGCCAGTGCAGGCGCTATGAAGTGGACTGGAACCAGAGCGCCCTC
AGCTGTGTAGACCCCCTGGCTAGCCTGGCCACCAACAGGAGCCACCTGCCGCTGGGTCCC
TGCCAGGATGGCTGGGTGTATGACACGCCCGGCTCTTCCATCGTCACTGAGTTCAACCTG
GTGTGTGCTGACTCCTGGAAGCTGGACCTCTTTCAGTCCTGTTTGAATGCGGGCTTCTTG
TTTGGCTCTCTCGGTGTTGGCTACTTTGCAGACAGGTTTGGCCGTAAGCTGTGTCTCCTG
GGAACTGTGCTGGTCAACGCGGTGTCGGGCGTGCTCATGGCCTTCTCGCCCAACTACATG
TCCATGCTGCTCTTCCGCCTGCTGCAGGGCCTGGTCAGCAAGGGCAACTGGATGGCTGGC
TACACCCTAATCACAGAATTTGTTGGCTCGGGCTCCAGAAGAACGGTGGCGATCATGTAC
CAGATGGCCTTCACGGTGGGGCTGGTGGCGCTTACCGGGCTGGCCTACGCCCTGCCTCAC
TGGCGCTGGCTGCAGCTGGCAGTCTCCCTGCCCACCTTCCTCTTCCTGCTCTACTACTGG
TGTGTGCCGGAGTCCCCTCGGTGGCTGTTATCACAAAAAAGAAACACTGAAGCAATAAAG
ATAATGGACCACATCGCTCAAAAGAATGGGAAGTTGCCTCCTGCTGATTTAAAGATGCTT
TCCCTCGAAGAGGATGTCACCGAAAAGCTGAGCCCTTCATTTGCAGACCTGTTCCGCACG
CCGCGCCTGAGGAAGCGCACCTTCATCCTGATGTACCTGTGGTTCACGGACTCTGTGCTC
TATCAGGGGCTCATCCTGCACATGGGCGCCACCAGCGGGAACCTCTACCTGGATTTCCTT
TACTCCGCTCTGGTCGAAATCCCGGGGGCCTTCATAGCCCTCATCACCATTGACCGCGTG
GGCCGCATCTACCCCATGGCCATGTCAAATTTGTTGGCGGGGGCAGCCTGCCTCGTCATG
ATTTTTATCTCACCTGACCTGCACTGGTTAAACATCATAATCATGTGTGTTGGCCGAATG
GGAATCACCATTGCAATACAAATGATCTGCCTGGTGAATGCTGAGCTGTACCCCACATTC
GTCAGGAACCTCGGAGTGATGGTGTGTTCCTCCCTGTGTGACATAGGTGGGATAATCACC
CCCTTCATAGTCTTCAGGCTGAGGGAGGTCTGGCAAGCCTTGCCCCTCATTTTGTTTGCG
GTGTTGGGCCTGCTTGCCGCGGGAGTGACGCTACTTCTTCCAGAGACCAAGGGGGTCGCT
TTGCCAGAGACCATGAAGGACGCCGAGAACCTTGGGAGAAAAGCAAAGCCCAAAGAAAAC
ACGATTTACCTTAAGGTCCAAACCTCAGAACCCTCGGGCACCTGA
Chromosome Location
6
Locus
6q26
External Identifiers
ResourceLink
UniProtKB IDO15245
UniProtKB Entry NameS22A1_HUMAN
GenBank Protein ID2511670
GenBank Gene IDX98332
HGNC IDHGNC:10963
General References
  1. 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]
  2. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [PubMed:9187257]
  3. Hayer M, Bonisch H, Bruss M: Molecular cloning, functional characterization and genomic organization of four alternatively spliced isoforms of the human organic cation transporter 1 (hOCT1/SLC22A1). Ann Hum Genet. 1999 Nov;63(Pt 6):473-82. [PubMed:11388889]
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  5. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed:14574404]
  6. 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]
  7. Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [PubMed:9655880]
  8. van Montfoort JE, Muller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ: Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides. J Pharmacol Exp Ther. 2001 Jul;298(1):110-5. [PubMed:11408531]
  9. Ciarimboli G, Struwe K, Arndt P, Gorboulev V, Koepsell H, Schlatter E, Hirsch JR: Regulation of the human organic cation transporter hOCT1. J Cell Physiol. 2004 Dec;201(3):420-8. [PubMed:15389554]
  10. Muller J, Lips KS, Metzner L, Neubert RH, Koepsell H, Brandsch M: Drug specificity and intestinal membrane localization of human organic cation transporters (OCT). Biochem Pharmacol. 2005 Dec 5;70(12):1851-60. Epub 2005 Nov 2. [PubMed:16263091]
  11. 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]
  12. Saborowski M, Kullak-Ublick GA, Eloranta JJ: The human organic cation transporter-1 gene is transactivated by hepatocyte nuclear factor-4alpha. J Pharmacol Exp Ther. 2006 May;317(2):778-85. Epub 2006 Jan 25. [PubMed:16436500]
  13. Amphoux A, Vialou V, Drescher E, Bruss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bonisch H, Gautron S: Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology. 2006 Jun;50(8):941-52. Epub 2006 Mar 31. [PubMed:16581093]
  14. Dias V, Ribeiro V: The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells. Fundam Clin Pharmacol. 2007 Aug;21(4):445-50. [PubMed:17635184]
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  16. Kerb R, Brinkmann U, Chatskaia N, Gorbunov D, Gorboulev V, Mornhinweg E, Keil A, Eichelbaum M, Koepsell H: Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. Pharmacogenetics. 2002 Nov;12(8):591-5. [PubMed:12439218]
  17. Shu Y, Leabman MK, Feng B, Mangravite LM, Huang CC, Stryke D, Kawamoto M, Johns SJ, DeYoung J, Carlson E, Ferrin TE, Herskowitz I, Giacomini KM: Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proc Natl Acad Sci U S A. 2003 May 13;100(10):5902-7. Epub 2003 Apr 28. [PubMed:12719534]
  18. Sakata T, Anzai N, Shin HJ, Noshiro R, Hirata T, Yokoyama H, Kanai Y, Endou H: Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Biochem Biophys Res Commun. 2004 Jan 16;313(3):789-93. [PubMed:14697261]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00728RocuroniumapprovedunknownsubstrateDetails
DB00908Quinidineapproved, investigationalunknowninhibitorDetails
DB01004Ganciclovirapproved, investigationalunknownsubstrateinhibitorDetails
DB00787AcyclovirapprovedunknownsubstrateinhibitorDetails
DB00396Progesteroneapproved, vet_approvedunknowninhibitorDetails
DB00457PrazosinapprovedunknownsubstrateinhibitorDetails
DB00925PhenoxybenzamineapprovedunknowninhibitorDetails
DB00783Estradiolapproved, investigational, vet_approvedunknowninhibitorDetails
DB00914Phenforminapproved, investigational, withdrawnunknownsubstrateDetails
DB00331MetforminapprovedunknownsubstrateDetails
DB00152Thiamineapproved, investigational, nutraceutical, vet_approvedunknownsubstrateDetails
DB00863RanitidineapprovedunknownsubstrateDetails
DB01035ProcainamideapprovedunknowninhibitorDetails
DB00184NicotineapprovedunknowninhibitorDetails
DB05381Histamineapproved, investigationalunknownDetails
DB00988DopamineapprovedunknownsubstrateDetails
DB00406Gentian violet cationapprovedunknownDetails
DB00122Cholineapproved, nutraceuticalunknownsubstrateinhibitorDetails
DB00915AmantadineapprovedunknownsubstrateinhibitorDetails
DB00661VerapamilapprovedunknownsubstrateinhibitorDetails
DB00468QuinineapprovedunknownsubstrateinhibitorDetails
DB01337PancuroniumapprovedunknownsubstrateDetails
DB00501Cimetidineapproved, investigationalunknownsubstrateinhibitorDetails
DB00280DisopyramideapprovedunknowninhibitorDetails
DB01151Desipramineapproved, investigationalunknowninhibitorDetails
DB00520CaspofunginapprovedunknownDetails
DB00536GuanidineapprovedunknowninhibitorDetails
DB01032Probenecidapproved, investigationalunknowninhibitorDetails
DB01232Saquinavirapproved, investigationalunknowninhibitorDetails
DB00220NelfinavirapprovedunknowninhibitorDetails
DB01114ChlorphenamineapprovedunknowninhibitorDetails
DB00668Epinephrineapproved, vet_approvedunknownsubstrateDetails
DB00224IndinavirapprovedunknowninhibitorDetails
DB00206Reserpineapproved, investigationalunknowninhibitorDetails
DB00619ImatinibapprovedunknownsubstrateDetails
DB00368NorepinephrineapprovedunknownsubstrateDetails
DB03128Acetylcholineapproved, investigationalunknownsubstrateDetails
DB00127Spermineexperimental, nutraceuticalunknownsubstrateDetails
DB03566SpermidineexperimentalunknownsubstrateDetails
DB01199TubocurarineapprovedunknownsubstrateDetails
DB04830Buformininvestigational, withdrawnunknownsubstrateDetails
DB00987Cytarabineapproved, investigationalunknownsubstrateDetails
DB00413Pramipexoleapproved, investigationalunknownsubstrateDetails
DB01621Pipotiazineapproved, investigationalunknownDetails
DB01623ThiothixeneapprovedunknownDetails
DB08837Tetraethylammoniumexperimental, investigationalunknownDetails
DB00654Latanoprostapproved, investigationalunknownDetails
DB08838Agmatineexperimental, investigationalunknownsubstrateDetails
DB00318Codeineapproved, illicitunknownsubstrateinhibitorDetails
DB00709Lamivudineapproved, investigationalunknownsubstrateDetails
DB09555Dexchlorpheniramine maleateapprovedunknownsubstrateinhibitorDetails
DB12598NafamostatinvestigationalunknownsubstrateDetails
DB12267Brigatinibapproved, investigationalnoDetails
DB12332Rucaparibapproved, investigationalunknowninhibitorDetails
DB13952Estradiol acetateapproved, investigational, vet_approvedunknowninhibitorDetails
DB13953Estradiol benzoateapproved, investigational, vet_approvedunknowninhibitorDetails
DB13954Estradiol cypionateapproved, investigational, vet_approvedunknowninhibitorDetails
DB13955Estradiol dienanthateapproved, investigational, vet_approvedunknowninhibitorDetails
DB13956Estradiol valerateapproved, investigational, vet_approvedunknowninhibitorDetails
DB11642Pitolisantapproved, investigationalunknowninhibitorDetails
DB14006Choline salicylateapproved, nutraceuticalunknownsubstrateinhibitorDetails
DB00758ClopidogrelapprovedunknowninhibitorDetails
DB00590DoxazosinapprovednoinhibitorDetails
DB00625Efavirenzapproved, investigationalunknowninhibitorDetails
DB00238NevirapineapprovedunknowninhibitorDetails
DB11963Dacomitinibapproved, investigationalnoinhibitorDetails
DB12141Gilteritinibapproved, investigationalnoinhibitorDetails
DB09073Palbociclibapproved, investigationalnoinhibitorDetails
DB08882LinagliptinapprovedunknowninhibitorDetails
DB00448Lansoprazoleapproved, investigationalunknownDetails