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Solute carrier family 22 member 2 (Organic cation transporter 2) (hOCT2)

 S22A2_HUMAN             Reviewed;         555 AA.
O15244; Q5T7Q6; Q6PIQ8; Q8NG62; Q9NQB9;
26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
30-NOV-2010, sequence version 2.
25-OCT-2017, entry version 153.
RecName: Full=Solute carrier family 22 member 2;
AltName: Full=Organic cation transporter 2;
Short=hOCT2;
Name=SLC22A2; Synonyms=OCT2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION,
AND VARIANT ALA-270.
TISSUE=Kidney cortex;
PubMed=9260930; DOI=10.1089/dna.1997.16.871;
Gorboulev V., Ulzheimer J.C., Akhoundova A., Ulzheimer-Teuber I.,
Karbach U., Quester S., Baumann C., Lang F., Busch A.E., Koepsell H.;
"Cloning and characterization of two human polyspecific organic cation
transporters.";
DNA Cell Biol. 16:871-881(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, BIOPHYSICOCHEMICAL
PROPERTIES, AND VARIANT ALA-270.
TISSUE=Kidney;
PubMed=12089365; DOI=10.1097/01.ASN.0000019413.78751.46;
Urakami Y., Akazawa M., Saito H., Okuda M., Inui K.;
"cDNA cloning, functional characterization, and tissue distribution of
an alternatively spliced variant of organic cation transporter hOCT2
predominantly expressed in the human kidney.";
J. Am. Soc. Nephrol. 13:1703-1710(2002).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
ALA-270.
TISSUE=Kidney;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=14574404; DOI=10.1038/nature02055;
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
"The DNA sequence and analysis of human chromosome 6.";
Nature 425:805-811(2003).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
ALA-270.
TISSUE=Colon, and Kidney;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-138.
PubMed=10942111; DOI=10.1007/s004390000309;
Gruendemann D., Schoemig E.;
"Gene structures of the human non-neuronal monoamine transporters EMT
and OCT2.";
Hum. Genet. 106:627-635(2000).
[8]
FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
PubMed=9687576;
Busch A.E., Karbach U., Miska D., Gorboulev V., Akhoundova A.,
Volk C., Arndt P., Ulzheimer J.C., Sonders M.S., Baumann C.,
Waldegger S., Lang F., Koepsell H.;
"Human neurons express the polyspecific cation transporter hOCT2,
which translocates monoamine neurotransmitters, amantadine, and
memantine.";
Mol. Pharmacol. 54:342-352(1998).
[9]
BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=11758759; DOI=10.1023/A:1013070128668;
Urakami Y., Okuda M., Masuda S., Akazawa M., Saito H., Inui K.;
"Distinct characteristics of organic cation transporters, OCT1 and
OCT2, in the basolateral membrane of renal tubules.";
Pharm. Res. 18:1528-1534(2001).
[10]
TISSUE SPECIFICITY.
PubMed=11912245;
Motohashi H., Sakurai Y., Saito H., Masuda S., Urakami Y., Goto M.,
Fukatsu A., Ogawa O., Inui K.;
"Gene expression levels and immunolocalization of organic ion
transporters in the human kidney.";
J. Am. Soc. Nephrol. 13:866-874(2002).
[11]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=12538837; DOI=10.1124/jpet.102.044404;
Grundemann D., Hahne C., Berkels R., Schomig E.;
"Agmatine is efficiently transported by non-neuronal monoamine
transporters extraneuronal monoamine transporter (EMT) and organic
cation transporter 2 (OCT2).";
J. Pharmacol. Exp. Ther. 304:810-817(2003).
[12]
FUNCTION.
PubMed=15496291; DOI=10.1016/j.ejphar.2004.09.032;
Motohashi H., Uwai Y., Hiramoto K., Okuda M., Inui K.;
"Different transport properties between famotidine and cimetidine by
human renal organic ion transporters (SLC22A).";
Eur. J. Pharmacol. 503:25-30(2004).
[13]
FUNCTION, AND INDUCTION.
PubMed=16314463; DOI=10.1016/S0002-9440(10)61234-5;
Ciarimboli G., Ludwig T., Lang D., Pavenstaedt H., Koepsell H.,
Piechota H.J., Haier J., Jaehde U., Zisowsky J., Schlatter E.;
"Cisplatin nephrotoxicity is critically mediated via the human organic
cation transporter 2.";
Am. J. Pathol. 167:1477-1484(2005).
[14]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=16272756; DOI=10.2133/dmpk.20.379;
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. 20:379-386(2005).
[15]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=16006492; DOI=10.1124/jpet.105.088104;
Tahara H., Kusuhara H., Endou H., Koepsell H., Imaoka T., Fuse E.,
Sugiyama Y.;
"A species difference in the transport activities of H2 receptor
antagonists by rat and human renal organic anion and cation
transporters.";
J. Pharmacol. Exp. Ther. 315:337-345(2005).
[16]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=15783073; DOI=10.1007/s11095-004-1193-3;
Kimura N., Okuda M., Inui K.;
"Metformin transport by renal basolateral organic cation transporter
hOCT2.";
Pharm. Res. 22:255-259(2005).
[17]
FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=16394027; DOI=10.1152/ajpcell.00622.2005;
Biermann J., Lang D., Gorboulev V., Koepsell H., Sindic A.,
Schroter R., Zvirbliene A., Pavenstadt H., Schlatter E.,
Ciarimboli G.;
"Characterization of regulatory mechanisms and states of human organic
cation transporter 2.";
Am. J. Physiol. 290:C1521-C1531(2006).
[18]
FUNCTION.
PubMed=16951202; DOI=10.1158/0008-5472.CAN-06-0769;
Zhang S., Lovejoy K.S., Shima J.E., Lagpacan L.L., Shu Y., Lapuk A.,
Chen Y., Komori T., Gray J.W., Chen X., Lippard S.J., Giacomini K.M.;
"Organic cation transporters are determinants of oxaliplatin
cytotoxicity.";
Cancer Res. 66:8847-8857(2006).
[19]
FUNCTION.
PubMed=17072098; DOI=10.2133/dmpk.21.432;
Okuda M., Kimura N., Inui K.;
"Interactions of fluoroquinolone antibacterials, DX-619 and
levofloxacin, with creatinine transport by renal organic cation
transporter hOCT2.";
Drug Metab. Pharmacokinet. 21:432-436(2006).
[20]
FUNCTION.
PubMed=16914559; DOI=10.1124/jpet.106.110346;
Yonezawa A., Masuda S., Yokoo S., Katsura T., Inui K.;
"Cisplatin and oxaliplatin, but not carboplatin and nedaplatin, are
substrates for human organic cation transporters (SLC22A1-3 and
multidrug and toxin extrusion family).";
J. Pharmacol. Exp. Ther. 319:879-886(2006).
[21]
FUNCTION.
PubMed=17582384; DOI=10.1016/j.bcp.2007.03.004;
Yokoo S., Yonezawa A., Masuda S., Fukatsu A., Katsura T., Inui K.;
"Differential contribution of organic cation transporters, OCT2 and
MATE1, in platinum agent-induced nephrotoxicity.";
Biochem. Pharmacol. 74:477-487(2007).
[22]
TISSUE SPECIFICITY.
PubMed=17393420; DOI=10.1002/mrd.20697;
Bottalico B., Noskova V., Pilka R., Larsson I., Domanski H.,
Casslen B., Hansson S.R.;
"The organic cation transporters (OCT1, OCT2, EMT) and the plasma
membrane monoamine transporter (PMAT) show differential distribution
and cyclic expression pattern in human endometrium and early pregnancy
decidua.";
Mol. Reprod. Dev. 74:1303-1311(2007).
[23]
VARIANT SER-54, AND CHARACTERIZATION OF VARIANTS ILE-165; ALA-270;
CYS-400 AND GLN-432.
PubMed=12142729; DOI=10.1097/00008571-200207000-00007;
Leabman M.K., Huang C.C., Kawamoto M., Johns S.J., Stryke D.,
Ferrin T.E., DeYoung J., Taylor T., Clark A.G., Herskowitz I.,
Giacomini K.M.;
"Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit
altered function.";
Pharmacogenetics 12:395-405(2002).
[24]
VARIANTS MET-201 AND ALA-270.
PubMed=17111267; DOI=10.1007/s10038-006-0087-0;
Shikata E., Yamamoto R., Takane H., Shigemasa C., Ikeda T., Otsubo K.,
Ieiri I.;
"Human organic cation transporter (OCT1 and OCT2) gene polymorphisms
and therapeutic effects of metformin.";
J. Hum. Genet. 52:117-122(2007).
-!- FUNCTION: Mediates tubular uptake of organic compounds from
circulation. Mediates the influx of agmatine, dopamine,
noradrenaline (norepinephrine), serotonin, choline, famotidine,
ranitidine, histamin, creatinine, amantadine, memantine,
acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP,
amiloride, metformin, N-1-methylnicotinamide (NMN),
tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP),
cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a
nephrotoxic action. Transport of creatinine is inhibited by
fluoroquinolones such as DX-619 and LVFX. This transporter is a
major determinant of the anticancer activity of oxaliplatin and
may contribute to antitumor specificity.
{ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15496291, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16314463, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:16914559, ECO:0000269|PubMed:16951202,
ECO:0000269|PubMed:17072098, ECO:0000269|PubMed:17582384,
ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9687576}.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=1 mM for agmatine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=95 uM for amiloride {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=24 uM for ASP {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=34 uM for memantine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=27 uM for amantadine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=1.38 mM for metformin {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=1.9 mM for noradrenaline {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=1.9 mM for norepinephrine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=1.3 mM for histamine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=0.39 mM for dopamine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=0.08 mM for serotonin {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=72.6 uM for cimetidine (at pH 7.4 and 37 degrees Celsius)
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
KM=56.1 uM for famotidine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=65.2 uM for ranitidine {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=431 uM for TEA (isoform 1) {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
KM=63 uM for TEA (isoform 2) {ECO:0000269|PubMed:11758759,
ECO:0000269|PubMed:12089365, ECO:0000269|PubMed:12538837,
ECO:0000269|PubMed:15783073, ECO:0000269|PubMed:16006492,
ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16394027,
ECO:0000269|PubMed:9687576};
Vmax=3770 pmol/min/mg enzyme for TEA uptake (isoform 1)
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
Vmax=314 pmol/min/mg enzyme for TEA uptake (isoform 2)
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
Vmax=11.9 nmol/min/mg enzyme for metformin uptake
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
Vmax=2170 pmol/min/mg enzyme for cimetidine uptake
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
Vmax=204 pmol/min/mg enzyme for famotidine uptake
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
Vmax=265 pmol/min/mg enzyme for ranitidine uptake
{ECO:0000269|PubMed:11758759, ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12538837, ECO:0000269|PubMed:15783073,
ECO:0000269|PubMed:16006492, ECO:0000269|PubMed:16272756,
ECO:0000269|PubMed:16394027, ECO:0000269|PubMed:9687576};
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
protein {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=O15244-1; Sequence=Displayed;
Name=2; Synonyms=OCT2-A;
IsoId=O15244-2; Sequence=VSP_031773, VSP_031774;
Name=3;
IsoId=O15244-3; Sequence=VSP_031771, VSP_031772;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Mainly expressed in kidney. Localized at the
luminal membrane and basolateral membrane of kidney distal tubule
and proximal tubules. To a lower extent, expressed in neurons of
the cerebral cortex and in various subcortical nuclei (at protein
levels). Also detected in secretory phase endometrium; in
scattered cells in the stroma. {ECO:0000269|PubMed:11912245,
ECO:0000269|PubMed:17393420, ECO:0000269|PubMed:9260930,
ECO:0000269|PubMed:9687576}.
-!- INDUCTION: May be down-regulated in diabetic patients.
{ECO:0000269|PubMed:16314463}.
-!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1)
superfamily. Organic cation transporter (TC 2.A.1.19) family.
{ECO:0000305}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; X98333; CAA66978.1; -; mRNA.
EMBL; AB075951; BAC02720.1; -; mRNA.
EMBL; AK290787; BAF83476.1; -; mRNA.
EMBL; AL162582; CAI20003.1; -; Genomic_DNA.
EMBL; CH471051; EAW47602.1; -; Genomic_DNA.
EMBL; BC030978; AAH30978.1; -; mRNA.
EMBL; BC039899; AAH39899.1; -; mRNA.
EMBL; AJ251885; CAB96133.1; -; Genomic_DNA.
CCDS; CCDS5276.1; -. [O15244-1]
RefSeq; NP_003049.2; NM_003058.3. [O15244-1]
UniGene; Hs.436385; -.
ProteinModelPortal; O15244; -.
BioGrid; 112469; 42.
IntAct; O15244; 8.
STRING; 9606.ENSP00000355920; -.
BindingDB; O15244; -.
ChEMBL; CHEMBL1743122; -.
DrugBank; DB08838; Agmatine.
DrugBank; DB00915; Amantadine.
DrugBank; DB00594; Amiloride.
DrugBank; DB02533; Aminoguanidine.
DrugBank; DB00345; Aminohippuric acid.
DrugBank; DB01114; Chlorphenamine.
DrugBank; DB00122; Choline.
DrugBank; DB00501; Cimetidine.
DrugBank; DB00515; Cisplatin.
DrugBank; DB00242; Cladribine.
DrugBank; DB00907; Cocaine.
DrugBank; DB00987; Cytarabine.
DrugBank; DB00694; Daunorubicin.
DrugBank; DB01151; Desipramine.
DrugBank; DB09555; Dexchlorpheniramine maleate.
DrugBank; DB01160; Dinoprost Tromethamine.
DrugBank; DB00917; Dinoprostone.
DrugBank; DB01075; Diphenhydramine.
DrugBank; DB00280; Disopyramide.
DrugBank; DB00988; Dopamine.
DrugBank; DB00668; Epinephrine.
DrugBank; DB00783; Estradiol.
DrugBank; DB00927; Famotidine.
DrugBank; DB00690; Flurazepam.
DrugBank; DB00365; Grepafloxacin.
DrugBank; DB00536; Guanidine.
DrugBank; DB05381; Histamine.
DrugBank; DB00619; Imatinib.
DrugBank; DB00458; Imipramine.
DrugBank; DB00709; Lamivudine.
DrugBank; DB01137; Levofloxacin.
DrugBank; DB01043; Memantine.
DrugBank; DB00331; Metformin.
DrugBank; DB00264; Metoprolol.
DrugBank; DB00184; Nicotine.
DrugBank; DB00368; Norepinephrine.
DrugBank; DB00526; Oxaliplatin.
DrugBank; DB01580; Oxprenolol.
DrugBank; DB01337; Pancuronium.
DrugBank; DB00914; Phenformin.
DrugBank; DB00925; Phenoxybenzamine.
DrugBank; DB00413; Pramipexole.
DrugBank; DB00457; Prazosin.
DrugBank; DB01032; Probenecid.
DrugBank; DB01035; Procainamide.
DrugBank; DB00396; Progesterone.
DrugBank; DB00571; Propranolol.
DrugBank; DB01103; Quinacrine.
DrugBank; DB00908; Quinidine.
DrugBank; DB00468; Quinine.
DrugBank; DB00206; Reserpine.
DrugBank; DB08837; Tetraethylammonium.
DrugBank; DB00152; Thiamine.
DrugBank; DB01199; Tubocurarine.
DrugBank; DB00570; Vinblastine.
DrugBank; DB00495; Zidovudine.
GuidetoPHARMACOLOGY; 1020; -.
TCDB; 2.A.1.19.30; the major facilitator superfamily (mfs).
iPTMnet; O15244; -.
PhosphoSitePlus; O15244; -.
BioMuta; SLC22A2; -.
PaxDb; O15244; -.
PeptideAtlas; O15244; -.
PRIDE; O15244; -.
Ensembl; ENST00000366953; ENSP00000355920; ENSG00000112499. [O15244-1]
GeneID; 6582; -.
KEGG; hsa:6582; -.
UCSC; uc003qtf.4; human. [O15244-1]
CTD; 6582; -.
DisGeNET; 6582; -.
EuPathDB; HostDB:ENSG00000112499.12; -.
GeneCards; SLC22A2; -.
H-InvDB; HIX0025014; -.
HGNC; HGNC:10966; SLC22A2.
HPA; CAB068236; -.
HPA; CAB068237; -.
HPA; HPA008567; -.
MIM; 602608; gene.
neXtProt; NX_O15244; -.
OpenTargets; ENSG00000112499; -.
PharmGKB; PA331; -.
eggNOG; KOG0255; Eukaryota.
eggNOG; COG0477; LUCA.
GeneTree; ENSGT00760000118852; -.
HOGENOM; HOG000234568; -.
HOVERGEN; HBG061545; -.
InParanoid; O15244; -.
KO; K08199; -.
OMA; IYLDFFY; -.
OrthoDB; EOG091G05AC; -.
PhylomeDB; O15244; -.
TreeFam; TF315847; -.
Reactome; R-HSA-112311; Neurotransmitter clearance.
Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
Reactome; R-HSA-2161517; Abacavir transmembrane transport.
Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
Reactome; R-HSA-549127; Organic cation transport.
GeneWiki; SLC22A2; -.
GenomeRNAi; 6582; -.
PRO; PR:O15244; -.
Proteomes; UP000005640; Chromosome 6.
Bgee; ENSG00000112499; -.
CleanEx; HS_SLC22A2; -.
ExpressionAtlas; O15244; baseline and differential.
Genevisible; O15244; HS.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0016020; C:membrane; TAS:ProtInc.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0098793; C:presynapse; IEA:GOC.
GO; GO:0005277; F:acetylcholine transmembrane transporter activity; IBA:GO_Central.
GO; GO:0005329; F:dopamine transmembrane transporter activity; IBA:GO_Central.
GO; GO:0005326; F:neurotransmitter transporter activity; TAS:Reactome.
GO; GO:0005333; F:norepinephrine transmembrane transporter activity; IBA:GO_Central.
GO; GO:0008514; F:organic anion transmembrane transporter activity; IBA:GO_Central.
GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:MGI.
GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IBA:GO_Central.
GO; GO:0008513; F:secondary active organic cation transmembrane transporter activity; IBA:GO_Central.
GO; GO:0007589; P:body fluid secretion; TAS:ProtInc.
GO; GO:0015872; P:dopamine transport; IBA:GO_Central.
GO; GO:0006855; P:drug transmembrane transport; TAS:Reactome.
GO; GO:0042136; P:neurotransmitter biosynthetic process; TAS:Reactome.
GO; GO:0007269; P:neurotransmitter secretion; TAS:Reactome.
GO; GO:0006836; P:neurotransmitter transport; IBA:GO_Central.
GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
GO; GO:0015695; P:organic cation transport; IDA:MGI.
CDD; cd06174; MFS; 1.
InterPro; IPR020846; MFS_dom.
InterPro; IPR005828; MFS_sugar_transport-like.
InterPro; IPR036259; MFS_trans_sf.
InterPro; IPR004749; Orgcat_transp/SVOP.
InterPro; IPR005829; Sugar_transporter_CS.
Pfam; PF00083; Sugar_tr; 1.
SUPFAM; SSF103473; SSF103473; 1.
TIGRFAMs; TIGR00898; 2A0119; 1.
PROSITE; PS50850; MFS; 1.
PROSITE; PS00216; SUGAR_TRANSPORT_1; 2.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Glycoprotein; Ion transport;
Membrane; Polymorphism; Reference proteome; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 555 Solute carrier family 22 member 2.
/FTId=PRO_0000320957.
TOPO_DOM 1 22 Cytoplasmic. {ECO:0000255}.
TRANSMEM 23 43 Helical. {ECO:0000255}.
TOPO_DOM 44 150 Extracellular. {ECO:0000255}.
TRANSMEM 151 171 Helical. {ECO:0000255}.
TOPO_DOM 172 177 Cytoplasmic. {ECO:0000255}.
TRANSMEM 178 198 Helical. {ECO:0000255}.
TOPO_DOM 199 208 Extracellular. {ECO:0000255}.
TRANSMEM 209 229 Helical. {ECO:0000255}.
TOPO_DOM 230 238 Cytoplasmic. {ECO:0000255}.
TRANSMEM 239 259 Helical. {ECO:0000255}.
TOPO_DOM 260 263 Extracellular. {ECO:0000255}.
TRANSMEM 264 284 Helical. {ECO:0000255}.
TOPO_DOM 285 348 Cytoplasmic. {ECO:0000255}.
TRANSMEM 349 369 Helical. {ECO:0000255}.
TOPO_DOM 370 375 Extracellular. {ECO:0000255}.
TRANSMEM 376 396 Helical. {ECO:0000255}.
TOPO_DOM 397 414 Cytoplasmic. {ECO:0000255}.
TRANSMEM 415 435 Helical. {ECO:0000255}.
TOPO_DOM 436 441 Extracellular. {ECO:0000255}.
TRANSMEM 442 462 Helical. {ECO:0000255}.
TOPO_DOM 463 464 Cytoplasmic. {ECO:0000255}.
TRANSMEM 465 485 Helical. {ECO:0000255}.
TOPO_DOM 486 494 Extracellular. {ECO:0000255}.
TRANSMEM 495 515 Helical. {ECO:0000255}.
TOPO_DOM 516 555 Cytoplasmic. {ECO:0000255}.
SITE 451 451 Involved in recognition of organic
cations and participates in structural
changes that occur during translocation
of organic cations. {ECO:0000250}.
CARBOHYD 72 72 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 225 242 ITEFVGRRYRRTVGIFYQ -> SKNVCACNCENKATSLPK
(in isoform 3).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_031771.
VAR_SEQ 243 555 Missing (in isoform 3).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_031772.
VAR_SEQ 427 483 DLQWLKIIISCLGRMGITMAYEIVCLVNAELYPTFIRNLGV
HICSSMCDIGGIITPF -> GKFQVKLESYLQDPGERECHG
PLIGKPCNLSSKSIWKDKLEGSIWDPSEQIHMASLL (in
isoform 2).
{ECO:0000303|PubMed:12089365}.
/FTId=VSP_031773.
VAR_SEQ 484 555 Missing (in isoform 2).
{ECO:0000303|PubMed:12089365}.
/FTId=VSP_031774.
VARIANT 54 54 P -> S (in dbSNP:rs8177504).
{ECO:0000269|PubMed:12142729}.
/FTId=VAR_039322.
VARIANT 165 165 M -> I (lower Vmax; dbSNP:rs8177507).
{ECO:0000269|PubMed:12142729}.
/FTId=VAR_039323.
VARIANT 201 201 T -> M (in dbSNP:rs145450955).
{ECO:0000269|PubMed:17111267}.
/FTId=VAR_039324.
VARIANT 270 270 S -> A (increased Ki value for TBA
inhibition of MPP; dbSNP:rs316019).
{ECO:0000269|PubMed:12089365,
ECO:0000269|PubMed:12142729,
ECO:0000269|PubMed:14702039,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:17111267,
ECO:0000269|PubMed:9260930}.
/FTId=VAR_039325.
VARIANT 297 297 A -> G (in dbSNP:rs8177513).
/FTId=VAR_039326.
VARIANT 400 400 R -> C (lower Vmax and reduced Ki value
for TBA inhibition of MPP;
dbSNP:rs8177516).
{ECO:0000269|PubMed:12142729}.
/FTId=VAR_039327.
VARIANT 432 432 K -> Q (lower Km value for MPP and
reduced Ki value for TBA inhibition of
MPP; dbSNP:rs8177517).
{ECO:0000269|PubMed:12142729}.
/FTId=VAR_039328.
VARIANT 463 463 R -> K (in dbSNP:rs3907239).
/FTId=VAR_039329.
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


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