S22A2_MOUSE
ID S22A2_MOUSE Reviewed; 553 AA.
AC O70577; Q8BWF6; Q8K4X8;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Solute carrier family 22 member 2;
DE AltName: Full=Organic cation transporter 2;
GN Name=Slc22a2; Synonyms=Oct2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=129, and BALB/cJ; TISSUE=Kidney, and Liver;
RX PubMed=10051314; DOI=10.1007/s003359900976;
RA Mooslehner K.A., Allen N.D.;
RT "Cloning of the mouse organic cation transporter 2 gene, Slc22a2, from an
RT enhancer-trap transgene integration locus.";
RL Mamm. Genome 10:218-224(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 226-553.
RC STRAIN=129S6/SvEvTac;
RA Brathwaite M., Waeltz P., Qian Y., Dudekula D., Schlessinger D.,
RA Nagaraja R.;
RT "Genomic sequence analysis in the mouse T-complex region.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O70577-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O70577-2; Sequence=VSP_031775, VSP_031776;
CC -!- TISSUE SPECIFICITY: Expressed in kidney and ureter. To a lower extent,
CC also expressed in brain and embryo. {ECO:0000269|PubMed:10051314}.
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; AJ006036; CAA06827.1; -; mRNA.
DR EMBL; AK052658; BAC35086.1; -; mRNA.
DR EMBL; BC015250; AAH15250.1; -; mRNA.
DR EMBL; BC069911; AAH69911.1; -; mRNA.
DR EMBL; AF481054; AAM22158.1; -; Genomic_DNA.
DR CCDS; CCDS28392.1; -. [O70577-1]
DR CCDS; CCDS88992.1; -. [O70577-2]
DR RefSeq; NP_038695.1; NM_013667.2. [O70577-1]
DR RefSeq; XP_011244498.1; XM_011246196.1.
DR AlphaFoldDB; O70577; -.
DR SMR; O70577; -.
DR STRING; 10090.ENSMUSP00000041186; -.
DR BindingDB; O70577; -.
DR ChEMBL; CHEMBL2073662; -.
DR GlyGen; O70577; 1 site.
DR iPTMnet; O70577; -.
DR PhosphoSitePlus; O70577; -.
DR jPOST; O70577; -.
DR MaxQB; O70577; -.
DR PaxDb; O70577; -.
DR PRIDE; O70577; -.
DR ProteomicsDB; 260753; -. [O70577-1]
DR ProteomicsDB; 260754; -. [O70577-2]
DR Antibodypedia; 20032; 277 antibodies from 29 providers.
DR DNASU; 20518; -.
DR Ensembl; ENSMUST00000046959; ENSMUSP00000041186; ENSMUSG00000040966. [O70577-1]
DR Ensembl; ENSMUST00000233066; ENSMUSP00000156710; ENSMUSG00000040966. [O70577-2]
DR GeneID; 20518; -.
DR KEGG; mmu:20518; -.
DR UCSC; uc008akw.1; mouse. [O70577-1]
DR CTD; 6582; -.
DR MGI; MGI:1335072; Slc22a2.
DR VEuPathDB; HostDB:ENSMUSG00000040966; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000155089; -.
DR HOGENOM; CLU_001265_33_5_1; -.
DR InParanoid; O70577; -.
DR OMA; HIGEFHF; -.
DR OrthoDB; 326501at2759; -.
DR PhylomeDB; O70577; -.
DR TreeFam; TF315847; -.
DR Reactome; R-MMU-112311; Neurotransmitter clearance.
DR Reactome; R-MMU-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-MMU-2161517; Abacavir transmembrane transport.
DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-MMU-549127; Organic cation transport.
DR BioGRID-ORCS; 20518; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Slc22a2; mouse.
DR PRO; PR:O70577; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O70577; protein.
DR Bgee; ENSMUSG00000040966; Expressed in right kidney and 40 other tissues.
DR Genevisible; O70577; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005275; F:amine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015220; F:choline transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; ISO:MGI.
DR GO; GO:0061459; F:L-arginine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISO:MGI.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015214; F:pyrimidine nucleoside transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; ISO:MGI.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IMP: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; ISO:MGI.
DR GO; GO:0015837; P:amine transport; ISO:MGI.
DR GO; GO:0089718; P:amino acid import across plasma membrane; ISO:MGI.
DR GO; GO:0006812; P:cation transport; IDA:MGI.
DR GO; GO:0015871; P:choline transport; ISO:MGI.
DR GO; GO:0090494; P:dopamine uptake; ISO:MGI.
DR GO; GO:0140115; P:export across plasma membrane; ISO:MGI.
DR GO; GO:0051608; P:histamine transport; ISO:MGI.
DR GO; GO:0051615; P:histamine uptake; ISO:MGI.
DR GO; GO:1902475; P:L-alpha-amino acid transmembrane transport; ISO:MGI.
DR GO; GO:0097638; P:L-arginine import across plasma membrane; ISO:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:MGI.
DR GO; GO:0051620; P:norepinephrine uptake; ISO:MGI.
DR GO; GO:0015695; P:organic cation transport; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0015697; P:quaternary ammonium group transport; ISO:MGI.
DR GO; GO:0051610; P:serotonin uptake; ISO:MGI.
DR GO; GO:1901998; P:toxin transport; IMP:ARUK-UCL.
DR GO; GO:0042908; P:xenobiotic transport; IMP: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..553
FT /note="Solute carrier family 22 member 2"
FT /id="PRO_0000320958"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..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..210
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..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..404
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 405..425
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 426..432
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 433..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..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..553
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 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 534..544
FT /note="RPRKKKEKRIY -> SLGRLVQTVCH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031775"
FT VAR_SEQ 545..553
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031776"
SQ SEQUENCE 553 AA; 61831 MW; 1E9744F0D5415483 CRC64;
MPTVDDILEH IGEFHLFQKQ TFFLLALLSG AFTPIYVGIV FLGFTPNHHC RSPGVAELSQ
RCGWSPAEEL NYTVPGLGSA GEVSFLSQCM RYEVDWNQST LDCVDPLSSL AANRSHLPLS
PCEHGWVYDT PGSSIVTEFN LVCAHSWMLD LFQSLVNVGF FIGAVGIGYL ADRFGRKFCL
LVTILINAIS GVLMAISPNY AWMLVFRFLQ GLVSKAGWLI GYILITEFVG LGYRRTVGIC
YQIAFTVGLL ILAGVAYALP NWRWLQFAVT LPNFCFLLYF WCIPESPRWL ISQNKNAKAM
KIIKHIAKKN GKSVPVSLQS LTADEDTGMK LNPSFLDLVR TPQIRKHTLI LMYNWFTSSV
LYQGLIMHMG LAGDNIYLDF FYSALVEFPA AFIIILTIDR IGRRYPWAVS NMVAGAACLA
SVFIPDDLQW LKITVACLGR MGITIAYEMV CLVNAELYPT YIRNLAVLVC SSMCDIGGIV
TPFLVYRLTD IWLEFPLVVF AVVGLVAGGL VLLLPETKGK ALPETIEDAE KMQRPRKKKE
KRIYLQVKKA ELS
