S22A2_HUMAN
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 03-AUG-2022, entry version 181.
DE RecName: Full=Solute carrier family 22 member 2;
DE AltName: Full=Organic cation transporter 2;
DE Short=hOCT2;
GN Name=SLC22A2; 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), TISSUE SPECIFICITY, FUNCTION, AND
RP 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, BIOPHYSICOCHEMICAL
RP PROPERTIES, 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, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
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 BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11758759; DOI=10.1023/a:1013070128668;
RA Urakami Y., Okuda M., Masuda S., Akazawa M., Saito H., Inui K.;
RT "Distinct characteristics of organic cation transporters, OCT1 and OCT2, in
RT the basolateral membrane of renal tubules.";
RL Pharm. Res. 18:1528-1534(2001).
RN [10]
RP 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 [11]
RP FUNCTION, 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 [12]
RP FUNCTION.
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 [13]
RP FUNCTION, AND INDUCTION.
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 [14]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [15]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [16]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [17]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [18]
RP FUNCTION.
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 [19]
RP FUNCTION.
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 [20]
RP FUNCTION.
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 [21]
RP FUNCTION.
RX PubMed=17582384; DOI=10.1016/j.bcp.2007.03.004;
RA Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K.;
RT "Differential contribution of organic cation transporters, OCT2 and MATE1,
RT in platinum agent-induced nephrotoxicity.";
RL Biochem. Pharmacol. 74:477-487(2007).
RN [22]
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 [23]
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 [24]
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).
CC -!- FUNCTION: Mediates tubular uptake of organic compounds from
CC circulation. Mediates the influx of agmatine, dopamine, noradrenaline
CC (norepinephrine), serotonin, choline, famotidine, ranitidine,
CC histamine, creatinine, amantadine, memantine, acriflavine, 4-[4-
CC (dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin,
CC N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-
CC phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin.
CC Cisplatin may develop a nephrotoxic action. Transport of creatinine is
CC inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter
CC is a major determinant of the anticancer activity of oxaliplatin and
CC may contribute to antitumor specificity. {ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15496291,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16314463,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:16914559,
CC ECO:0000269|PubMed:16951202, ECO:0000269|PubMed:17072098,
CC ECO:0000269|PubMed:17582384, ECO:0000269|PubMed:9260930,
CC ECO:0000269|PubMed:9687576}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1 mM for agmatine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=95 uM for amiloride {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=24 uM for ASP {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=34 uM for memantine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=27 uM for amantadine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=1.38 mM for metformin {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=1.9 mM for noradrenaline {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=1.9 mM for norepinephrine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=1.3 mM for histamine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=0.39 mM for dopamine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=0.08 mM for serotonin {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=72.6 uM for cimetidine (at pH 7.4 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC KM=56.1 uM for famotidine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=65.2 uM for ranitidine {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=431 uM for TEA (isoform 1) {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC KM=63 uM for TEA (isoform 2) {ECO:0000269|PubMed:11758759,
CC ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
CC ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
CC ECO:0000269|PubMed:9687576};
CC Vmax=3770 pmol/min/mg enzyme for TEA uptake (isoform 1)
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC Vmax=314 pmol/min/mg enzyme for TEA uptake (isoform 2)
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC Vmax=11.9 nmol/min/mg enzyme for metformin uptake
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC Vmax=2170 pmol/min/mg enzyme for cimetidine uptake
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC Vmax=204 pmol/min/mg enzyme for famotidine uptake
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC Vmax=265 pmol/min/mg enzyme for ranitidine uptake
CC {ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
CC ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
CC ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
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. Localized at the
CC luminal membrane and basolateral membrane of kidney distal tubule and
CC proximal tubules. To a lower extent, expressed in neurons of the
CC cerebral cortex and in various subcortical nuclei (at protein levels).
CC Also detected in secretory phase endometrium; in scattered cells in the
CC stroma. {ECO:0000269|PubMed:11912245, ECO:0000269|PubMed:17393420,
CC ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9687576}.
CC -!- INDUCTION: May be down-regulated in diabetic patients.
CC {ECO:0000269|PubMed:16314463}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
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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 AlphaFoldDB; O15244; -.
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; 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; 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; 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; DB11837; Osilodrostat.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB01580; Oxprenolol.
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; 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 GlyGen; O15244; 1 site.
DR iPTMnet; O15244; -.
DR PhosphoSitePlus; O15244; -.
DR BioMuta; SLC22A2; -.
DR jPOST; O15244; -.
DR MassIVE; O15244; -.
DR PaxDb; O15244; -.
DR PeptideAtlas; O15244; -.
DR PRIDE; O15244; -.
DR ProteomicsDB; 48533; -. [O15244-1]
DR ProteomicsDB; 48534; -. [O15244-2]
DR ProteomicsDB; 48535; -. [O15244-3]
DR Antibodypedia; 20032; 277 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 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; HIGEFHF; -.
DR OrthoDB; 326501at2759; -.
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 SignaLink; O15244; -.
DR BioGRID-ORCS; 6582; 13 hits in 1066 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 75 other tissues.
DR ExpressionAtlas; O15244; baseline and differential.
DR Genevisible; O15244; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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: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:ARUK-UCL.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015214; F:pyrimidine nucleoside transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IMP:ARUK-UCL.
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:0090494; P:dopamine uptake; IDA:ARUK-UCL.
DR GO; GO:0140115; P:export across plasma membrane; IDA:ARUK-UCL.
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:0006836; P:neurotransmitter transport; IDA:ARUK-UCL.
DR GO; GO:0051620; P:norepinephrine uptake; IDA:ARUK-UCL.
DR GO; GO:0015695; P:organic cation transport; IDA:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0072530; P:purine-containing compound transmembrane transport; TAS:Reactome.
DR GO; GO:0051610; P:serotonin uptake; IDA:ARUK-UCL.
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 Gene3D; 1.20.1250.20; -; 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 Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00898; 2A0119; 1.
DR PROSITE; PS50850; MFS; 1.
DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Ion transport; Membrane;
KW Reference proteome; Transmembrane; 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 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"
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; dbSNP:rs8177507)"
FT /evidence="ECO:0000269|PubMed:12142729"
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 (increased Ki value for TBA inhibition of
FT MPP; 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: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; dbSNP:rs8177516)"
FT /evidence="ECO:0000269|PubMed:12142729"
FT /id="VAR_039327"
FT VARIANT 432
FT /note="K -> Q (lower Km value for MPP and reduced Ki value
FT for TBA inhibition of MPP; dbSNP:rs8177517)"
FT /evidence="ECO:0000269|PubMed:12142729"
FT /id="VAR_039328"
FT VARIANT 463
FT /note="R -> K (in dbSNP:rs3907239)"
FT /id="VAR_039329"
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
