ID S22A2_HUMAN Reviewed; 555 AA. AC O15244; Q5T7Q6; Q6PIQ8; Q8NG62; Q9NQB9; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 2. DT 27-MAR-2024, entry version 190. DE RecName: Full=Solute carrier family 22 member 2 {ECO:0000303|PubMed:12538837}; DE AltName: Full=Organic cation transporter 2 {ECO:0000303|PubMed:9260930}; DE Short=hOCT2 {ECO:0000303|PubMed:9260930}; GN Name=SLC22A2 {ECO:0000312|HGNC:HGNC:10966}; Synonyms=OCT2; 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 [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP MISCELLANEOUS, AND VARIANT ALA-270. RC TISSUE=Kidney cortex; RX PubMed=9260930; DOI=10.1089/dna.1997.16.871; RA Gorboulev V., Ulzheimer J.C., Akhoundova A., Ulzheimer-Teuber I., RA Karbach U., Quester S., Baumann C., Lang F., Busch A.E., Koepsell H.; RT "Cloning and characterization of two human polyspecific organic cation RT transporters."; RL DNA Cell Biol. 16:871-881(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TRANSPORTER ACTIVITY, RP TISSUE SPECIFICITY, MISCELLANEOUS, AND VARIANT ALA-270. RC TISSUE=Kidney; RX PubMed=12089365; DOI=10.1097/01.asn.0000019413.78751.46; RA Urakami Y., Akazawa M., Saito H., Okuda M., Inui K.; RT "cDNA cloning, functional characterization, and tissue distribution of an RT alternatively spliced variant of organic cation transporter hOCT2 RT predominantly expressed in the human kidney."; RL J. Am. Soc. Nephrol. 13:1703-1710(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-270. RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP ALA-270. RC TISSUE=Colon, and Kidney; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-138. RX PubMed=10942111; DOI=10.1007/s004390000309; RA Gruendemann D., Schoemig E.; RT "Gene structures of the human non-neuronal monoamine transporters EMT and RT OCT2."; RL Hum. Genet. 106:627-635(2000). RN [8] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE RP SPECIFICITY, AND MISCELLANEOUS. RX PubMed=9687576; DOI=10.1124/mol.54.2.342; RA Busch A.E., Karbach U., Miska D., Gorboulev V., Akhoundova A., Volk C., RA Arndt P., Ulzheimer J.C., Sonders M.S., Baumann C., Waldegger S., Lang F., RA Koepsell H.; RT "Human neurons express the polyspecific cation transporter hOCT2, which RT translocates monoamine neurotransmitters, amantadine, and memantine."; RL Mol. Pharmacol. 54:342-352(1998). RN [9] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11912245; DOI=10.1681/asn.v134866; RA Motohashi H., Sakurai Y., Saito H., Masuda S., Urakami Y., Goto M., RA Fukatsu A., Ogawa O., Inui K.; RT "Gene expression levels and immunolocalization of organic ion transporters RT in the human kidney."; RL J. Am. Soc. Nephrol. 13:866-874(2002). RN [10] RP ACTIVITY REGULATION. RX PubMed=12395288; DOI=10.1007/s00232-002-1023-7; RA Schlatter E., Moennich V., Cetinkaya I., Mehrens T., Ciarimboli G., RA Hirsch J.R., Popp C., Koepsell H.; RT "The organic cation transporters rOCT1 and hOCT2 are inhibited by cGMP."; RL J. Membr. Biol. 189:237-244(2002). RN [11] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11907186; DOI=10.1124/jpet.301.1.293; RA Kimura H., Takeda M., Narikawa S., Enomoto A., Ichida K., Endou H.; RT "Human organic anion transporters and human organic cation transporters RT mediate renal transport of prostaglandins."; RL J. Pharmacol. Exp. Ther. 301:293-298(2002). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=12538837; DOI=10.1124/jpet.102.044404; RA Grundemann D., Hahne C., Berkels R., Schomig E.; RT "Agmatine is efficiently transported by non-neuronal monoamine transporters RT extraneuronal monoamine transporter (EMT) and organic cation transporter 2 RT (OCT2)."; RL J. Pharmacol. Exp. Ther. 304:810-817(2003). RN [13] RP MISCELLANEOUS. RX PubMed=15496291; DOI=10.1016/j.ejphar.2004.09.032; RA Motohashi H., Uwai Y., Hiramoto K., Okuda M., Inui K.; RT "Different transport properties between famotidine and cimetidine by human RT renal organic ion transporters (SLC22A)."; RL Eur. J. Pharmacol. 503:25-30(2004). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=15212162; DOI=10.1023/b:pham.0000029286.45788.ad; RA Urakami Y., Kimura N., Okuda M., Inui K.; RT "Creatinine transport by basolateral organic cation transporter hOCT2 in RT the human kidney."; RL Pharm. Res. 21:976-981(2004). RN [15] RP INDUCTION, AND MISCELLANEOUS. RX PubMed=16314463; DOI=10.1016/s0002-9440(10)61234-5; RA Ciarimboli G., Ludwig T., Lang D., Pavenstaedt H., Koepsell H., RA Piechota H.J., Haier J., Jaehde U., Zisowsky J., Schlatter E.; RT "Cisplatin nephrotoxicity is critically mediated via the human organic RT cation transporter 2."; RL Am. J. Pathol. 167:1477-1484(2005). RN [16] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR RP LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15817714; DOI=10.1165/rcmb.2004-0363oc; RA Lips K.S., Volk C., Schmitt B.M., Pfeil U., Arndt P., Miska D., Ermert L., RA Kummer W., Koepsell H.; RT "Polyspecific cation transporters mediate luminal release of acetylcholine RT from bronchial epithelium."; RL Am. J. Respir. Cell Mol. Biol. 33:79-88(2005). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MISCELLANEOUS. RX PubMed=16263091; DOI=10.1016/j.bcp.2005.09.011; RA Mueller J., Lips K.S., Metzner L., Neubert R.H.H., Koepsell H., RA Brandsch M.; RT "Drug specificity and intestinal membrane localization of human organic RT cation transporters (OCT)."; RL Biochem. Pharmacol. 70:1851-1860(2005). RN [18] RP MISCELLANEOUS. RX PubMed=16272756; DOI=10.2133/dmpk.20.379; RA Kimura N., Masuda S., Tanihara Y., Ueo H., Okuda M., Katsura T., Inui K.; RT "Metformin is a superior substrate for renal organic cation transporter RT OCT2 rather than hepatic OCT1."; RL Drug Metab. Pharmacokinet. 20:379-386(2005). RN [19] RP MISCELLANEOUS. RX PubMed=16006492; DOI=10.1124/jpet.105.088104; RA Tahara H., Kusuhara H., Endou H., Koepsell H., Imaoka T., Fuse E., RA Sugiyama Y.; RT "A species difference in the transport activities of H2 receptor RT antagonists by rat and human renal organic anion and cation transporters."; RL J. Pharmacol. Exp. Ther. 315:337-345(2005). RN [20] RP MISCELLANEOUS. RX PubMed=15783073; DOI=10.1007/s11095-004-1193-3; RA Kimura N., Okuda M., Inui K.; RT "Metformin transport by renal basolateral organic cation transporter RT hOCT2."; RL Pharm. Res. 22:255-259(2005). RN [21] RP MISCELLANEOUS. RX PubMed=16394027; DOI=10.1152/ajpcell.00622.2005; RA Biermann J., Lang D., Gorboulev V., Koepsell H., Sindic A., Schroter R., RA Zvirbliene A., Pavenstadt H., Schlatter E., Ciarimboli G.; RT "Characterization of regulatory mechanisms and states of human organic RT cation transporter 2."; RL Am. J. Physiol. 290:C1521-C1531(2006). RN [22] RP MISCELLANEOUS. RX PubMed=16951202; DOI=10.1158/0008-5472.can-06-0769; RA Zhang S., Lovejoy K.S., Shima J.E., Lagpacan L.L., Shu Y., Lapuk A., RA Chen Y., Komori T., Gray J.W., Chen X., Lippard S.J., Giacomini K.M.; RT "Organic cation transporters are determinants of oxaliplatin RT cytotoxicity."; RL Cancer Res. 66:8847-8857(2006). RN [23] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=17072098; DOI=10.2133/dmpk.21.432; RA Okuda M., Kimura N., Inui K.; RT "Interactions of fluoroquinolone antibacterials, DX-619 and levofloxacin, RT with creatinine transport by renal organic cation transporter hOCT2."; RL Drug Metab. Pharmacokinet. 21:432-436(2006). RN [24] RP MISCELLANEOUS. RX PubMed=16914559; DOI=10.1124/jpet.106.110346; RA Yonezawa A., Masuda S., Yokoo S., Katsura T., Inui K.; RT "Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are RT substrates for human organic cation transporters (SLC22A1-3 and multidrug RT and toxin extrusion family)."; RL J. Pharmacol. Exp. Ther. 319:879-886(2006). RN [25] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MISCELLANEOUS. RX PubMed=16581093; DOI=10.1016/j.neuropharm.2006.01.005; RA Amphoux A., Vialou V., Drescher E., Bruess M., Mannoury La Cour C., RA Rochat C., Millan M.J., Giros B., Boenisch H., Gautron S.; RT "Differential pharmacological in vitro properties of organic cation RT transporters and regional distribution in rat brain."; RL Neuropharmacology 50:941-952(2006). RN [26] RP TISSUE SPECIFICITY. RX PubMed=17393420; DOI=10.1002/mrd.20697; RA Bottalico B., Noskova V., Pilka R., Larsson I., Domanski H., Casslen B., RA Hansson S.R.; RT "The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane RT monoamine transporter (PMAT) show differential distribution and cyclic RT expression pattern in human endometrium and early pregnancy decidua."; RL Mol. Reprod. Dev. 74:1303-1311(2007). RN [27] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=21128598; DOI=10.1021/mp100180a; RA Winter T.N., Elmquist W.F., Fairbanks C.A.; RT "OCT2 and MATE1 provide bidirectional agmatine transport."; RL Mol. Pharm. 8:133-142(2011). RN [28] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MISCELLANEOUS. RX PubMed=24961373; DOI=10.1073/pnas.1314939111; RA Chen L., Shu Y., Liang X., Chen E.C., Yee S.W., Zur A.A., Li S., Xu L., RA Keshari K.R., Lin M.J., Chien H.C., Zhang Y., Morrissey K.M., Liu J., RA Ostrem J., Younger N.S., Kurhanewicz J., Shokat K.M., Ashrafi K., RA Giacomini K.M.; RT "OCT1 is a high-capacity thiamine transporter that regulates hepatic RT steatosis and is a target of metformin."; RL Proc. Natl. Acad. Sci. U.S.A. 111:9983-9988(2014). RN [29] RP ACTIVITY REGULATION, PHOSPHORYLATION, DOMAIN, AND MUTAGENESIS OF TYR-73; RP TYR-92; TYR-128; TYR-169; TYR-241; TYR-257; TYR-279; TYR-280; PRO-284; RP SER-286; PRO-287; TYR-362; TYR-377; TYR-458 AND TYR-544. RX PubMed=26979622; DOI=10.1038/ncomms10880; RA Sprowl J.A., Ong S.S., Gibson A.A., Hu S., Du G., Lin W., Li L., RA Bharill S., Ness R.A., Stecula A., Offer S.M., Diasio R.B., Nies A.T., RA Schwab M., Cavaletti G., Schlatter E., Ciarimboli G., Schellens J.H.M., RA Isacoff E.Y., Sali A., Chen T., Baker S.D., Sparreboom A., Pabla N.; RT "A phosphotyrosine switch regulates organic cation transporters."; RL Nat. Commun. 7:10880-10880(2016). RN [30] 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 [31] RP VARIANT SER-54, AND CHARACTERIZATION OF VARIANTS ILE-165; ALA-270; CYS-400 RP AND GLN-432. RX PubMed=12142729; DOI=10.1097/00008571-200207000-00007; RA Leabman M.K., Huang C.C., Kawamoto M., Johns S.J., Stryke D., Ferrin T.E., RA DeYoung J., Taylor T., Clark A.G., Herskowitz I., Giacomini K.M.; RT "Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit RT altered function."; RL Pharmacogenetics 12:395-405(2002). RN [32] RP VARIANTS MET-201 AND ALA-270. RX PubMed=17111267; DOI=10.1007/s10038-006-0087-0; RA Shikata E., Yamamoto R., Takane H., Shigemasa C., Ikeda T., Otsubo K., RA Ieiri I.; RT "Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and RT therapeutic effects of metformin."; RL J. Hum. Genet. 52:117-122(2007). RN [33] RP VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432, CHARACTERIZATION OF RP VARIANTS ILE-165; ALA-270; CYS-400 AND GLN-432, FUNCTION, TRANSPORTER RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY. RX PubMed=17460754; DOI=10.1371/journal.pone.0000385; RA Taubert D., Grimberg G., Stenzel W., Schoemig E.; RT "Identification of the endogenous key substrates of the human organic RT cation transporter OCT2 and their implication in function of dopaminergic RT neurons."; RL PLoS ONE 2:e385-e385(2007). CC -!- FUNCTION: Electrogenic voltage-dependent transporter that mediates the CC transport of a variety of organic cations such as endogenous bioactive CC amines, cationic drugs and xenobiotics (PubMed:9260930, CC PubMed:9687576). Functions as a Na(+)-independent, bidirectional CC uniporter (PubMed:9687576, PubMed:21128598). Cation cellular uptake or CC release is driven by the electrochemical potential, i.e. membrane CC potential and concentration gradient (PubMed:9260930, PubMed:9687576, CC PubMed:15212162). However, may also engage electroneutral cation CC exchange when saturating concentrations of cation substrates are CC reached (By similarity). Predominantly expressed at the basolateral CC membrane of hepatocytes and proximal tubules and involved in the uptake CC and disposition of cationic compounds by hepatic and renal clearance CC from the blood flow (PubMed:15783073). Implicated in monoamine CC neurotransmitters uptake such as histamine, dopamine, CC adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and CC tyramine, thereby supporting a physiological role in the central CC nervous system by regulating interstitial concentrations of CC neurotransmitters (PubMed:9687576, PubMed:16581093, PubMed:17460754). CC Also capable of transporting dopaminergic neuromodulators cyclo(his- CC pro), salsolinol and N-methyl-salsolinol, thereby involved in the CC maintenance of dopaminergic cell integrity in the central nervous CC system (PubMed:17460754). Mediates the bidirectional transport of CC acetylcholine (ACh) at the apical membrane of ciliated cell in airway CC epithelium, thereby playing a role in luminal release of ACh from CC bronchial epithelium (PubMed:15817714). Also transports guanidine and CC endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1- CC methylnicotinamide (NMN) (PubMed:9260930, PubMed:12089365, CC PubMed:15212162, PubMed:17072098, PubMed:24961373). Mediates the uptake CC and efflux of quaternary ammonium compound choline (PubMed:9260930). CC Mediates the bidirectional transport of polyamine agmatine and the CC uptake of polyamines putrescine and spermidine (PubMed:12538837, CC PubMed:21128598). Able to transport non-amine endogenous compounds such CC as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) CC (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4- CC (dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, CC PubMed:16394027). May contribute to regulate the transport of organic CC compounds in testis across the blood-testis-barrier (Probable). CC {ECO:0000250|UniProtKB:Q9R0W2, ECO:0000269|PubMed:11907186, CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12395288, CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15212162, CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:15817714, CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:16581093, CC ECO:0000269|PubMed:17072098, ECO:0000269|PubMed:17460754, CC ECO:0000269|PubMed:21128598, ECO:0000269|PubMed:24961373, CC ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9687576, CC ECO:0000305|PubMed:35307651}. CC -!- FUNCTION: [Isoform 2]: In contrast with isoform 1, not able to CC transport guanidine, creatinine, cimetidine and metformin. CC {ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:15212162, CC ECO:0000269|PubMed:16272756}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-noradrenaline(out) = (R)-noradrenaline(in); CC Xref=Rhea:RHEA:73871, ChEBI:CHEBI:72587; CC Evidence={ECO:0000269|PubMed:16581093, ECO:0000269|PubMed:9687576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-adrenaline(out) = (R)-adrenaline(in); CC Xref=Rhea:RHEA:73875, ChEBI:CHEBI:71406; CC Evidence={ECO:0000269|PubMed:16581093}; CC -!- CATALYTIC ACTIVITY: CC Reaction=serotonin(out) = serotonin(in); Xref=Rhea:RHEA:73867, CC ChEBI:CHEBI:350546; Evidence={ECO:0000269|PubMed:16581093, CC ECO:0000269|PubMed:9687576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dopamine(out) = dopamine(in); Xref=Rhea:RHEA:73863, CC ChEBI:CHEBI:59905; Evidence={ECO:0000269|PubMed:16581093, CC ECO:0000269|PubMed:9687576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=histamine(out) = histamine(in); Xref=Rhea:RHEA:73879, CC ChEBI:CHEBI:58432; Evidence={ECO:0000269|PubMed:16581093, CC ECO:0000269|PubMed:17460754, ECO:0000269|PubMed:9687576}; CC -!- CATALYTIC ACTIVITY: CC Reaction=thiamine(in) = thiamine(out); Xref=Rhea:RHEA:34919, CC ChEBI:CHEBI:18385; Evidence={ECO:0000269|PubMed:24961373}; CC -!- CATALYTIC ACTIVITY: CC Reaction=creatinine(in) = creatinine(out); Xref=Rhea:RHEA:74539, CC ChEBI:CHEBI:16737; Evidence={ECO:0000269|PubMed:15212162, CC ECO:0000269|PubMed:17072098}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-methylnicotinamide(out) = 1-methylnicotinamide(in); CC Xref=Rhea:RHEA:73859, ChEBI:CHEBI:16797; CC Evidence={ECO:0000269|PubMed:9260930}; CC -!- CATALYTIC ACTIVITY: CC Reaction=guanidine(out) = guanidine(in); Xref=Rhea:RHEA:73883, CC ChEBI:CHEBI:30087; Evidence={ECO:0000269|PubMed:12089365}; CC -!- CATALYTIC ACTIVITY: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:9260930}; CC -!- CATALYTIC ACTIVITY: CC Reaction=agmatine(out) = agmatine(in); Xref=Rhea:RHEA:72131, CC ChEBI:CHEBI:58145; Evidence={ECO:0000269|PubMed:12538837, CC ECO:0000269|PubMed:21128598}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72132; CC Evidence={ECO:0000305|PubMed:21128598}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:72133; CC Evidence={ECO:0000305|PubMed:21128598}; CC -!- CATALYTIC ACTIVITY: CC Reaction=putrescine(out) = putrescine(in); Xref=Rhea:RHEA:72135, CC ChEBI:CHEBI:326268; Evidence={ECO:0000269|PubMed:21128598}; CC -!- CATALYTIC ACTIVITY: CC Reaction=spermidine(in) = spermidine(out); Xref=Rhea:RHEA:35039, CC ChEBI:CHEBI:57834; Evidence={ECO:0000250|UniProtKB:O70577}; CC -!- CATALYTIC ACTIVITY: CC Reaction=tyramine(in) = tyramine(out); Xref=Rhea:RHEA:74783, CC ChEBI:CHEBI:327995; Evidence={ECO:0000269|PubMed:17460754}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L- CC proline diketopiperazine(out); Xref=Rhea:RHEA:74787, CC ChEBI:CHEBI:90039; Evidence={ECO:0000269|PubMed:17460754}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-salsolinol(in) = (R)-salsolinol(out); CC Xref=Rhea:RHEA:74791, ChEBI:CHEBI:194082; CC Evidence={ECO:0000269|PubMed:17460754}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-methyl-(R)-salsolinol(in) = N-methyl-(R)-salsolinol(out); CC Xref=Rhea:RHEA:74795, ChEBI:CHEBI:194083; CC Evidence={ECO:0000269|PubMed:17460754}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetylcholine(in) = acetylcholine(out); Xref=Rhea:RHEA:74663, CC ChEBI:CHEBI:15355; Evidence={ECO:0000269|PubMed:15817714}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin F2alpha(out) = prostaglandin F2alpha(in); CC Xref=Rhea:RHEA:50988, ChEBI:CHEBI:57404; CC Evidence={ECO:0000269|PubMed:11907186}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin E2(out) = prostaglandin E2(in); CC Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564; CC Evidence={ECO:0000269|PubMed:11907186}; CC -!- ACTIVITY REGULATION: Tyrosine phosphorylation of the transporter leads CC to activation of the transport activity (PubMed:26979622). TEA uptake CC is activated by tyrosine phosphorylation (PubMed:26979622). Inhibited CC by cGMP, most likely through a cGMP-binding protein that interacts with CC OCT2 (PubMed:12395288). {ECO:0000269|PubMed:12395288, CC ECO:0000269|PubMed:26979622}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=74 uM for cyclo(his-pro) {ECO:0000269|PubMed:17460754}; CC KM=80 uM for serotonin {ECO:0000269|PubMed:9687576}; CC KM=290 uM for serotonin {ECO:0000269|PubMed:16581093}; CC KM=130 uM for salsolinol {ECO:0000269|PubMed:17460754}; CC KM=150 uM for acetylcholine {ECO:0000269|PubMed:15817714}; CC KM=210 uM for choline {ECO:0000269|PubMed:9260930}; CC KM=300 uM for NMN {ECO:0000269|PubMed:9260930}; CC KM=390 uM for dopamine {ECO:0000269|PubMed:9687576}; CC KM=420 uM for adrenaline {ECO:0000269|PubMed:16581093}; CC KM=750 uM for thiamine {ECO:0000269|PubMed:24961373}; CC KM=940 uM for histamine {ECO:0000269|PubMed:16581093}; CC KM=1300 uM for histamine {ECO:0000269|PubMed:9687576}; CC KM=1400 uM for dopamine {ECO:0000269|PubMed:16581093}; CC KM=1500 uM for noradrenaline {ECO:0000269|PubMed:16581093}; CC KM=1900 uM for noradrenaline {ECO:0000269|PubMed:9687576}; CC KM=4000 uM for creatinine {ECO:0000269|PubMed:15212162}; CC KM=19010 uM for agmatine (at pH 6.0) {ECO:0000269|PubMed:21128598}; CC KM=1400 uM for agmatine (at pH 7.4) {ECO:0000269|PubMed:12538837}; CC KM=1840 uM for agmatine (at pH 7.4) {ECO:0000269|PubMed:21128598}; CC KM=740 uM for agmatine (at pH 8.5) {ECO:0000269|PubMed:21128598}; CC KM=390 uM for agmatine (at pH 9.5) {ECO:0000269|PubMed:21128598}; CC KM=33450 uM for putrescine (at pH 6.0) {ECO:0000269|PubMed:21128598}; CC KM=11290 uM for putrescine (at pH 7.4) {ECO:0000269|PubMed:21128598}; CC KM=3600 uM for putrescine (at pH 8.5) {ECO:0000269|PubMed:21128598}; CC KM=1410 uM for putrescine (at pH 9.5) {ECO:0000269|PubMed:21128598}; CC KM=0.0289 uM for prostaglandin E2 {ECO:0000269|PubMed:11907186}; CC KM=0.334 uM for prostaglandin F2-alpha {ECO:0000269|PubMed:11907186}; CC KM=19 uM for MPP {ECO:0000269|PubMed:9260930}; CC KM=24 uM for ASP (at 8 degrees Celsius) CC {ECO:0000269|PubMed:16394027}; CC Vmax=3 nmol/min/mg enzyme for cyclo(his-pro) uptake CC {ECO:0000269|PubMed:17460754}; CC Vmax=2.7 nmol/min/mg enzyme for salsolinol uptake CC {ECO:0000269|PubMed:17460754}; CC Vmax=4.56 nmol/min/mg enzyme for thiamine uptake CC {ECO:0000269|PubMed:24961373}; CC Vmax=23.5 nmol/min/mg enzyme for creatinine uptake CC {ECO:0000269|PubMed:21128598}; CC Vmax=24.1 nmol/min/mg enzyme for agmatine uptake (at pH 6.0) CC {ECO:0000269|PubMed:21128598}; CC Vmax=11.5 nmol/min/mg enzyme for agmatine uptake (at pH 7.4) CC {ECO:0000269|PubMed:12538837}; CC Vmax=12.9 nmol/min/mg enzyme for agmatine uptake (at pH 7.4) CC {ECO:0000269|PubMed:21128598}; CC Vmax=13.9 nmol/min/mg enzyme for agmatine uptake (at pH 8.5) CC {ECO:0000269|PubMed:21128598}; CC Vmax=16 nmol/min/mg enzyme for agmatine uptake (at pH 9.5) CC {ECO:0000269|PubMed:21128598}; CC Vmax=24.9 nmol/min/mg enzyme for putrescine uptake (at pH 6.0) CC {ECO:0000269|PubMed:21128598}; CC Vmax=15.6 nmol/min/mg enzyme for putrescine uptake (at pH 7.4) CC {ECO:0000269|PubMed:21128598}; CC Vmax=38.9 nmol/min/mg enzyme for putrescine uptake (at pH 8.5) CC {ECO:0000269|PubMed:21128598}; CC Vmax=52.3 nmol/min/mg enzyme for putrescine uptake (at pH 9.5) CC {ECO:0000269|PubMed:21128598}; CC pH dependence: CC Optimum pH is 9 for agmatine and putrescine uptake. CC {ECO:0000269|PubMed:21128598}; CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane CC {ECO:0000250|UniProtKB:Q9R0W2}; Multi-pass membrane protein CC {ECO:0000305}. Basal cell membrane {ECO:0000269|PubMed:35307651}; CC Multi-pass membrane protein {ECO:0000305}. Apical cell membrane CC {ECO:0000269|PubMed:15817714, ECO:0000269|PubMed:9260930}; Multi-pass CC membrane protein {ECO:0000305}. Note=Localized to the basal membrane of CC Sertoli cells (PubMed:35307651). Localized to the basolateral membrane CC of proximal tubule (PubMed:11912245). Localized to the luminal/apical CC membrane of distal tubule (PubMed:9260930). Localized to the CC luminal/apical membrane of ciliated epithelial cells in bronchi CC (PubMed:15817714). {ECO:0000269|PubMed:11912245, CC ECO:0000269|PubMed:15817714, ECO:0000269|PubMed:35307651, CC ECO:0000269|PubMed:9260930}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O15244-1; Sequence=Displayed; CC Name=2; Synonyms=OCT2-A; CC IsoId=O15244-2; Sequence=VSP_031773, VSP_031774; CC Name=3; CC IsoId=O15244-3; Sequence=VSP_031771, VSP_031772; CC -!- TISSUE SPECIFICITY: Mainly expressed in kidney, in the cortex and CC medulla (PubMed:9260930, PubMed:12089365, PubMed:11912245). Localized CC in testis, mostly to peritubular myoid cells and Leydig cells and also CC detected along the basal membrane of Sertoli cells (PubMed:12089365, CC PubMed:35307651). Expressed in brain, in neurons of the cerebral cortex CC and in various subcortical nuclei (PubMed:9260930, PubMed:12089365, CC PubMed:9687576). In the brain, also detected in the dopaminergic CC regions of the substantia nigra (PubMed:17460754). Expressed in CC tracheal and bronchial ciliated epithelium in the respiratory tract CC (PubMed:15817714). Also detected in secretory phase endometrium, in CC scattered stromal cells (PubMed:17393420). Expressed in spleen, CC placenta, small intestine and spinal cord (PubMed:9260930, CC PubMed:12089365). Weakly expressed in prostate, uterus and lung CC (PubMed:12089365). {ECO:0000269|PubMed:11912245, CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:15817714, CC ECO:0000269|PubMed:17393420, ECO:0000269|PubMed:17460754, CC ECO:0000269|PubMed:35307651, ECO:0000269|PubMed:9260930, CC ECO:0000269|PubMed:9687576}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Mainly expressed in kidney, bone CC marrow and testis (PubMed:12089365). Expressed in colon, skeletal CC muscle, spinal cord, placenta and liver (PubMed:12089365). CC {ECO:0000269|PubMed:12089365}. CC -!- INDUCTION: May be down-regulated in diabetic patients. CC {ECO:0000269|PubMed:16314463}. CC -!- DOMAIN: Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that CC may be involved in tyrosine-protein kinase YES1 binding and is required CC for the activation of substrate transport. CC {ECO:0000269|PubMed:26979622}. CC -!- PTM: Tyrosine phosphorylated by tyrosine-protein kinase YES1. CC {ECO:0000269|PubMed:26979622}. CC -!- MISCELLANEOUS: Mediates the renal secretion of many clinically used CC cationic drugs (PubMed:12089365, PubMed:16272756). Transports drugs CC such as diabetes treatment medicine metformin, 1-methyl-4- CC phenylpyridinium (MPP(+)), famotidine, ranitidine, amantadine, CC acriflavine, amiloride, memantine, cimetidine, platinum-based drugs CC cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and CC tetraethylammonium (TEA) (PubMed:9260930, PubMed:12089365, CC PubMed:15496291, PubMed:16314463, PubMed:16272756, PubMed:16006492, CC PubMed:15783073, PubMed:16394027, PubMed:16951202, PubMed:16914559, CC PubMed:16581093, PubMed:24961373). Mediates the bidirectional transport CC of MPP(+) (PubMed:9260930, PubMed:12089365, PubMed:9687576). Metformin CC competitively inhibits OCT1-mediated thiamine uptake, leading to a CC decrease in hepatic steatosis (PubMed:24961373). Plays a predominant CC role in the anticancer activity of cisplatin and oxaliplatin and may CC contribute to antitumor specificity (PubMed:16951202, PubMed:16914559). CC Involved in cisplatin-induced nephrotoxicity (By similarity). CC {ECO:0000250|UniProtKB:Q9R0W2, ECO:0000269|PubMed:12089365, CC ECO:0000269|PubMed:15496291, ECO:0000269|PubMed:15783073, CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756, CC ECO:0000269|PubMed:16314463, ECO:0000269|PubMed:16394027, CC ECO:0000269|PubMed:16581093, ECO:0000269|PubMed:16914559, CC ECO:0000269|PubMed:16951202, ECO:0000269|PubMed:24961373, CC ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9687576, CC ECO:0000303|PubMed:12089365, ECO:0000303|PubMed:16272756}. CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily. CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}. CC -!- CAUTION: Most authors have deduced a localization at the basolateral CC membrane of proximal tubules (PubMed:11912245). Other studies CC demonstrated a localization to the luminal membrane in the distal CC tubule (PubMed:9260930). {ECO:0000269|PubMed:11912245, CC ECO:0000269|PubMed:9260930}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X98333; CAA66978.1; -; mRNA. DR EMBL; AB075951; BAC02720.1; -; mRNA. DR EMBL; AK290787; BAF83476.1; -; mRNA. DR EMBL; AL162582; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47602.1; -; Genomic_DNA. DR EMBL; BC030978; AAH30978.1; -; mRNA. DR EMBL; BC039899; AAH39899.1; -; mRNA. DR EMBL; AJ251885; CAB96133.1; -; Genomic_DNA. DR CCDS; CCDS5276.1; -. [O15244-1] DR RefSeq; NP_003049.2; NM_003058.3. [O15244-1] DR PDB; 8ET9; EM; 3.61 A; A=1-555. DR PDBsum; 8ET9; -. DR AlphaFoldDB; O15244; -. DR EMDB; EMD-28589; -. DR SMR; O15244; -. DR BioGRID; 112469; 101. DR IntAct; O15244; 8. DR STRING; 9606.ENSP00000355920; -. DR BindingDB; O15244; -. DR ChEMBL; CHEMBL1743122; -. DR DrugBank; DB12001; Abemaciclib. DR DrugBank; DB08838; Agmatine. DR DrugBank; DB00437; Allopurinol. DR DrugBank; DB00915; Amantadine. DR DrugBank; DB11640; Amifampridine. DR DrugBank; DB00594; Amiloride. DR DrugBank; DB00345; Aminohippuric acid. DR DrugBank; DB01118; Amiodarone. DR DrugBank; DB11901; Apalutamide. DR DrugBank; DB11817; Baricitinib. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB01114; Chlorpheniramine. DR DrugBank; DB00122; Choline. DR DrugBank; DB14006; Choline salicylate. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB08912; Dabrafenib. DR DrugBank; DB06637; Dalfampridine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB09555; Dexchlorpheniramine maleate. DR DrugBank; DB01160; Dinoprost tromethamine. DR DrugBank; DB00917; Dinoprostone. DR DrugBank; DB01075; Diphenhydramine. DR DrugBank; DB00280; Disopyramide. DR DrugBank; DB00204; Dofetilide. DR DrugBank; DB08930; Dolutegravir. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB04855; Dronedarone. DR DrugBank; DB13874; Enasidenib. DR DrugBank; DB00668; Epinephrine. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB00783; Estradiol. DR DrugBank; DB13952; Estradiol acetate. DR DrugBank; DB13953; Estradiol benzoate. DR DrugBank; DB13954; Estradiol cypionate. DR DrugBank; DB13955; Estradiol dienanthate. DR DrugBank; DB13956; Estradiol valerate. DR DrugBank; DB00927; Famotidine. DR DrugBank; DB12265; Fexinidazole. DR DrugBank; DB00690; Flurazepam. DR DrugBank; DB00798; Gentamicin. DR DrugBank; DB00986; Glycopyrronium. DR DrugBank; DB00365; Grepafloxacin. DR DrugBank; DB01018; Guanfacine. DR DrugBank; DB00536; Guanidine. DR DrugBank; DB05381; Histamine. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB11886; Infigratinib. DR DrugBank; DB11633; Isavuconazole. DR DrugBank; DB00709; Lamivudine. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00448; Lansoprazole. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB01137; Levofloxacin. DR DrugBank; DB05667; Levoketoconazole. DR DrugBank; DB08882; Linagliptin. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00331; Metformin. DR DrugBank; DB09241; Methylene blue. DR DrugBank; DB00264; Metoprolol. DR DrugBank; DB08893; Mirabegron. DR DrugBank; DB08840; N-methylnicotinamide. DR DrugBank; DB12598; Nafamostat. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB16267; Olutasidenib. DR DrugBank; DB11837; Osilodrostat. DR DrugBank; DB00526; Oxaliplatin. DR DrugBank; DB01580; Oxprenolol. DR DrugBank; DB11697; Pacritinib. DR DrugBank; DB01337; Pancuronium. DR DrugBank; DB15102; Pemigatinib. DR DrugBank; DB00914; Phenformin. DR DrugBank; DB00925; Phenoxybenzamine. DR DrugBank; DB05383; Pimagedine. DR DrugBank; DB00960; Pindolol. DR DrugBank; DB00413; Pramipexole. DR DrugBank; DB01032; Probenecid. DR DrugBank; DB01035; Procainamide. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB00571; Propranolol. DR DrugBank; DB01103; Quinacrine. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB00863; Ranitidine. DR DrugBank; DB00206; Reserpine. DR DrugBank; DB12457; Rimegepant. DR DrugBank; DB06176; Romidepsin. DR DrugBank; DB00938; Salmeterol. DR DrugBank; DB08839; Serotonin. DR DrugBank; DB14754; Solriamfetol. DR DrugBank; DB00391; Sulpiride. DR DrugBank; DB06608; Tafenoquine. DR DrugBank; DB15133; Tepotinib. DR DrugBank; DB00871; Terbutaline. DR DrugBank; DB13946; Testosterone undecanoate. DR DrugBank; DB08837; Tetraethylammonium. DR DrugBank; DB00152; Thiamine. DR DrugBank; DB09343; Tipiracil. DR DrugBank; DB06137; Tirbanibulin. DR DrugBank; DB15442; Trilaciclib. DR DrugBank; DB01199; Tubocurarine. DR DrugBank; DB11652; Tucatinib. DR DrugBank; DB15328; Ubrogepant. DR DrugBank; DB05294; Vandetanib. DR DrugBank; DB01273; Varenicline. DR DrugBank; DB00495; Zidovudine. DR DrugCentral; O15244; -. DR GuidetoPHARMACOLOGY; 1020; -. DR TCDB; 2.A.1.19.30; the major facilitator superfamily (mfs). DR GlyCosmos; O15244; 1 site, No reported glycans. DR GlyGen; O15244; 1 site. DR iPTMnet; O15244; -. DR PhosphoSitePlus; O15244; -. DR BioMuta; SLC22A2; -. DR jPOST; O15244; -. DR MassIVE; O15244; -. DR PaxDb; 9606-ENSP00000355920; -. DR PeptideAtlas; O15244; -. DR ProteomicsDB; 48533; -. [O15244-1] DR ProteomicsDB; 48534; -. [O15244-2] DR ProteomicsDB; 48535; -. [O15244-3] DR Antibodypedia; 20032; 303 antibodies from 29 providers. DR DNASU; 6582; -. DR Ensembl; ENST00000366953.8; ENSP00000355920.3; ENSG00000112499.13. [O15244-1] DR GeneID; 6582; -. DR KEGG; hsa:6582; -. DR MANE-Select; ENST00000366953.8; ENSP00000355920.3; NM_003058.4; NP_003049.2. DR UCSC; uc003qtf.4; human. [O15244-1] DR AGR; HGNC:10966; -. DR CTD; 6582; -. DR DisGeNET; 6582; -. DR GeneCards; SLC22A2; -. DR HGNC; HGNC:10966; SLC22A2. DR HPA; ENSG00000112499; Tissue enriched (kidney). DR MIM; 602608; gene. DR neXtProt; NX_O15244; -. DR OpenTargets; ENSG00000112499; -. DR PharmGKB; PA331; -. DR VEuPathDB; HostDB:ENSG00000112499; -. DR eggNOG; KOG0255; Eukaryota. DR GeneTree; ENSGT00940000155089; -. DR HOGENOM; CLU_001265_33_5_1; -. DR InParanoid; O15244; -. DR OMA; IGEFHFF; -. DR OrthoDB; 1474205at2759; -. DR PhylomeDB; O15244; -. DR TreeFam; TF315847; -. DR PathwayCommons; O15244; -. DR Reactome; R-HSA-112311; Neurotransmitter clearance. DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle. DR Reactome; R-HSA-2161517; Abacavir transmembrane transport. DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters. DR Reactome; R-HSA-549127; Organic cation transport. DR SABIO-RK; O15244; -. DR SignaLink; O15244; -. DR BioGRID-ORCS; 6582; 14 hits in 1146 CRISPR screens. DR GeneWiki; SLC22A2; -. DR GenomeRNAi; 6582; -. DR Pharos; O15244; Tchem. DR PRO; PR:O15244; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; O15244; Protein. DR Bgee; ENSG00000112499; Expressed in adult mammalian kidney and 76 other cell types or tissues. DR ExpressionAtlas; O15244; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005275; F:amine transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015220; F:choline transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0061459; F:L-arginine transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0008514; F:organic anion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015132; F:prostaglandin transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015489; F:putrescine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015214; F:pyrimidine nucleoside transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015606; F:spermidine transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015234; F:thiamine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0019534; F:toxin transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015870; P:acetylcholine transport; IDA:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:ARUK-UCL. DR GO; GO:0015837; P:amine transport; IDA:ARUK-UCL. DR GO; GO:0089718; P:amino acid import across plasma membrane; IMP:ARUK-UCL. DR GO; GO:0007589; P:body fluid secretion; TAS:ProtInc. DR GO; GO:0015871; P:choline transport; IDA:ARUK-UCL. DR GO; GO:0015872; P:dopamine transport; IDA:UniProtKB. DR GO; GO:0090494; P:dopamine uptake; IDA:ARUK-UCL. DR GO; GO:0048241; P:epinephrine transport; IDA:UniProtKB. DR GO; GO:0140115; P:export across plasma membrane; IDA:ARUK-UCL. DR GO; GO:0051608; P:histamine transport; IDA:UniProtKB. DR GO; GO:0051615; P:histamine uptake; IDA:ARUK-UCL. DR GO; GO:1902475; P:L-alpha-amino acid transmembrane transport; IMP:ARUK-UCL. DR GO; GO:0097638; P:L-arginine import across plasma membrane; IMP:ARUK-UCL. DR GO; GO:0006812; P:monoatomic cation transport; IEA:Ensembl. DR GO; GO:0006836; P:neurotransmitter transport; IDA:ARUK-UCL. DR GO; GO:0015874; P:norepinephrine transport; IDA:UniProtKB. DR GO; GO:0051620; P:norepinephrine uptake; IDA:ARUK-UCL. DR GO; GO:0015695; P:organic cation transport; IDA:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL. DR GO; GO:0015732; P:prostaglandin transport; IDA:UniProtKB. DR GO; GO:0072530; P:purine-containing compound transmembrane transport; TAS:Reactome. DR GO; GO:0015847; P:putrescine transport; IDA:UniProtKB. DR GO; GO:0006837; P:serotonin transport; IDA:UniProtKB. DR GO; GO:0051610; P:serotonin uptake; IDA:ARUK-UCL. DR GO; GO:0015848; P:spermidine transport; ISS:UniProtKB. DR GO; GO:0071934; P:thiamine transmembrane transport; IDA:UniProtKB. DR GO; GO:1901998; P:toxin transport; IDA:ARUK-UCL. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0042908; P:xenobiotic transport; IDA:ARUK-UCL. DR GO; GO:1990962; P:xenobiotic transport across blood-brain barrier; NAS:ARUK-UCL. DR CDD; cd17379; MFS_SLC22A1_2_3; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR005828; MFS_sugar_transport-like. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR004749; Orgcat_transp/SVOP. DR InterPro; IPR005829; Sugar_transporter_CS. DR NCBIfam; TIGR00898; 2A0119; 1. DR PANTHER; PTHR24064; SOLUTE CARRIER FAMILY 22 MEMBER; 1. DR PANTHER; PTHR24064:SF432; SOLUTE CARRIER FAMILY 22 MEMBER 2; 1. DR Pfam; PF00083; Sugar_tr; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 2. DR Genevisible; O15244; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Glycoprotein; KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..555 FT /note="Solute carrier family 22 member 2" FT /id="PRO_0000320957" FT TOPO_DOM 1..22 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 23..43 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 44..150 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 151..171 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 172..177 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 178..198 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 199..208 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 209..229 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 230..238 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 239..259 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 260..263 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 264..284 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 285..348 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 349..369 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 370..375 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 376..396 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 397..414 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 415..435 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 436..441 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 442..462 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 463..464 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 465..485 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 486..494 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 495..515 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 516..555 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOTIF 284..288 FT /note="Proline-rich sequence" FT /evidence="ECO:0000269|PubMed:26979622" FT SITE 451 FT /note="Involved in recognition of organic cations and FT participates in structural changes that occur during FT translocation of organic cations" FT /evidence="ECO:0000250|UniProtKB:Q9R0W2" FT CARBOHYD 72 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 225..242 FT /note="ITEFVGRRYRRTVGIFYQ -> SKNVCACNCENKATSLPK (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_031771" FT VAR_SEQ 243..555 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_031772" FT VAR_SEQ 427..483 FT /note="DLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGVHICSSMCDIGG FT IITPF -> GKFQVKLESYLQDPGERECHGPLIGKPCNLSSKSIWKDKLEGSIWDPSEQ FT IHMASLL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12089365" FT /id="VSP_031773" FT VAR_SEQ 484..555 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12089365" FT /id="VSP_031774" FT VARIANT 54 FT /note="P -> S (in dbSNP:rs8177504)" FT /evidence="ECO:0000269|PubMed:12142729" FT /id="VAR_039322" FT VARIANT 165 FT /note="M -> I (lower Vmax for MPP(+) transport; no change FT in transport efficiency (Vmax/Km) and clearance of FT cyclo(his-pro) and salsolinol; dbSNP:rs8177507)" FT /evidence="ECO:0000269|PubMed:12142729, FT ECO:0000269|PubMed:17460754" FT /id="VAR_039323" FT VARIANT 201 FT /note="T -> M (in dbSNP:rs145450955)" FT /evidence="ECO:0000269|PubMed:17111267" FT /id="VAR_039324" FT VARIANT 270 FT /note="S -> A (decreased Ki value for TBA inhibition of FT MPP(+); no change in transport efficiency (Vmax/Km) and FT clearance of cyclo(his-pro) and salsolinol; FT dbSNP:rs316019)" FT /evidence="ECO:0000269|PubMed:12089365, FT ECO:0000269|PubMed:12142729, ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17111267, FT ECO:0000269|PubMed:17460754, ECO:0000269|PubMed:9260930" FT /id="VAR_039325" FT VARIANT 297 FT /note="A -> G (in dbSNP:rs8177513)" FT /id="VAR_039326" FT VARIANT 400 FT /note="R -> C (lower Vmax and reduced Ki value for TBA FT inhibition of MPP(+); lower transport efficiency (Vmax/Km) FT and clearance of cyclo(his-pro); no change in transport FT efficiency (Vmax/Km) and clearance of salsolinol; FT dbSNP:rs8177516)" FT /evidence="ECO:0000269|PubMed:12142729, FT ECO:0000269|PubMed:17460754" FT /id="VAR_039327" FT VARIANT 432 FT /note="K -> Q (lower Km value for MPP(+) and reduced Ki FT value for TBA inhibition of MPP; no change in transport FT efficiency (Vmax/Km) and clearance of cyclo(his-pro) and FT salsolinol; dbSNP:rs8177517)" FT /evidence="ECO:0000269|PubMed:12142729, FT ECO:0000269|PubMed:17460754" FT /id="VAR_039328" FT VARIANT 463 FT /note="R -> K (in dbSNP:rs3907239)" FT /id="VAR_039329" FT MUTAGEN 73 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 92 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 128 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 169 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 241 FT /note="Y->F: Slight decrease in TEA uptake. No change in FT tyrosine phosphorylation. Strong decrease in TEA uptake; FT when associated with F-362. Strong decrease in TEA and FT metformin uptake and YES1-mediated tyrosine FT phosphorylation; when associated with F-362 and F-377." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 257 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 279 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 280 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 284 FT /note="P->A: Decreased TEA and metformin uptake. Decreased FT tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 286 FT /note="S->A: No change in TEA and metformin uptake. No FT change in tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 287 FT /note="P->A: Decreased TEA and metformin uptake. Decreased FT tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 362 FT /note="Y->F: Decreased TEA uptake and YES1-mediated FT tyrosine phosphorylation. Strong decrease in TEA uptake; FT when associated with F-241. Strong decrease in TEA uptake; FT when associated with F-377. Strong decrease in TEA and FT metformin uptake and YES1-mediated tyrosine FT phosphorylation; when associated with F-241 and F-377." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 377 FT /note="Y->F: Slight decrease in TEA uptake. No change in FT tyrosine phosphorylation. Strong decrease in TEA uptake; FT when associated with F-362. Strong decrease in TEA and FT metformin uptake and YES1-mediated tyrosine FT phosphorylation; when associated with F-241 and F-362." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 458 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" FT MUTAGEN 544 FT /note="Y->F: No change in TEA uptake." FT /evidence="ECO:0000269|PubMed:26979622" SQ SEQUENCE 555 AA; 62581 MW; 06528F9519CE211E CRC64; MPTTVDDVLE HGGEFHFFQK QMFFLLALLS ATFAPIYVGI VFLGFTPDHR CRSPGVAELS LRCGWSPAEE LNYTVPGPGP AGEASPRQCR RYEVDWNQST FDCVDPLASL DTNRSRLPLG PCRDGWVYET PGSSIVTEFN LVCANSWMLD LFQSSVNVGF FIGSMSIGYI ADRFGRKLCL LTTVLINAAA GVLMAISPTY TWMLIFRLIQ GLVSKAGWLI GYILITEFVG RRYRRTVGIF YQVAYTVGLL VLAGVAYALP HWRWLQFTVS LPNFFFLLYY WCIPESPRWL ISQNKNAEAM RIIKHIAKKN GKSLPASLQR LRLEEETGKK LNPSFLDLVR TPQIRKHTMI LMYNWFTSSV LYQGLIMHMG LAGDNIYLDF FYSALVEFPA AFMIILTIDR IGRRYPWAAS NMVAGAACLA SVFIPGDLQW LKIIISCLGR MGITMAYEIV CLVNAELYPT FIRNLGVHIC SSMCDIGGII TPFLVYRLTN IWLELPLMVF GVLGLVAGGL VLLLPETKGK ALPETIEEAE NMQRPRKNKE KMIYLQVQKL DIPLN //