S22A1_MOUSE
ID S22A1_MOUSE Reviewed; 556 AA.
AC O08966; Q9R1Q4;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Solute carrier family 22 member 1;
DE AltName: Full=Organic cation transporter 1;
DE Short=mOCT1;
GN Name=Slc22a1; Synonyms=Lx1, Oct1;
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], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=8854860; DOI=10.1007/s003359900223;
RA Schweifer N., Barlow D.P.;
RT "The Lx1 gene maps to mouse chromosome 17 and codes for a protein that is
RT homologous to glucose and polyspecific transmembrane transporters.";
RL Mamm. Genome 7:735-740(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=C57BL/6 X CBA;
RX PubMed=10216142; DOI=10.1002/hep.510290530;
RA Green R.M., Lo K., Sterritt C., Beier D.R.;
RT "Cloning and functional expression of a mouse liver organic cation
RT transporter.";
RL Hepatology 29:1556-1562(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=ddY; TISSUE=Kidney;
RX PubMed=12176030; DOI=10.1016/s0006-291x(02)00926-9;
RA Kakehi M., Koyabu N., Nakamura T., Uchiumi T., Kuwano M., Ohtani H.,
RA Sawada Y.;
RT "Functional characterization of mouse cation transporter mOCT2 compared
RT with mOCT1.";
RL Biochem. Biophys. Res. Commun. 296:644-650(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [6]
RP INDUCTION.
RX PubMed=15458920; DOI=10.1152/ajpgi.00057.2004;
RA Nie W., Sweetser S., Rinella M., Green R.M.;
RT "Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome
RT proliferator agonist receptor-alpha and -gamma.";
RL Am. J. Physiol. 288:G207-G212(2005).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16381671; DOI=10.1124/dmd.105.006932;
RA Alnouti Y., Petrick J.S., Klaassen C.D.;
RT "Tissue distribution and ontogeny of organic cation transporters in mice.";
RL Drug Metab. Dispos. 34:477-482(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334, AND IDENTIFICATION BY
RP 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: Translocates a broad array of organic cations with various
CC structures and molecular weights including the model compounds 1-
CC methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-
CC methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-
CC methylpyridinium (ASP), the endogenous compounds choline, guanidine,
CC histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the
CC drugs quinine, and metformin. The transport of organic cations is
CC inhibited by a broad array of compounds like tetramethylammonium (TMA),
CC cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin,
CC cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide,
CC quinine, tetrabutylammonium, and tetrapentylammonium. Translocates
CC organic cations in an electrogenic and pH-independent manner.
CC Translocates organic cations across the plasma membrane in both
CC directions. Transports the polyamines spermine and spermidine.
CC Transports pramipexole across the basolateral membrane of the proximal
CC tubular epithelial cells. The choline transport is activated by MMTS.
CC Regulated by various intracellular signaling pathways including
CC inhibition by protein kinase A activation, and endogenously activation
CC by the calmodulin complex, the calmodulin-dependent kinase II and LCK
CC tyrosine kinase. {ECO:0000269|PubMed:10216142,
CC ECO:0000269|PubMed:12176030}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane; Multi-pass membrane
CC protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver, kidney and intestine.
CC Weakly expressed in adrenals and in lacting mammary glands.
CC {ECO:0000269|PubMed:16381671, ECO:0000269|PubMed:8854860}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed 2 days before birth, but
CC gradually increased during the first 3 weeks of age, reaching a plateau
CC around day 22 in both kidney and liver. At 45 days of age, renal and
CC hepatic levels is 4 to 6 times higher than the level immediately after
CC birth. {ECO:0000269|PubMed:16381671}.
CC -!- INDUCTION: Increased by PPARA and PPARG treatment in both liver and H35
CC cells. {ECO:0000269|PubMed:15458920}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
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; U38652; AAB19097.1; -; mRNA.
DR EMBL; AF010259; AAC98884.1; -; mRNA.
DR EMBL; AF481054; AAM22157.1; -; Genomic_DNA.
DR EMBL; BC021651; AAH21651.1; -; mRNA.
DR CCDS; CCDS28393.1; -.
DR RefSeq; NP_033228.2; NM_009202.5.
DR AlphaFoldDB; O08966; -.
DR SMR; O08966; -.
DR BioGRID; 203296; 24.
DR STRING; 10090.ENSMUSP00000024596; -.
DR BindingDB; O08966; -.
DR ChEMBL; CHEMBL2073664; -.
DR DrugCentral; O08966; -.
DR GlyGen; O08966; 1 site.
DR iPTMnet; O08966; -.
DR PhosphoSitePlus; O08966; -.
DR jPOST; O08966; -.
DR MaxQB; O08966; -.
DR PaxDb; O08966; -.
DR PeptideAtlas; O08966; -.
DR PRIDE; O08966; -.
DR ProteomicsDB; 260883; -.
DR Antibodypedia; 33480; 303 antibodies from 33 providers.
DR DNASU; 20517; -.
DR Ensembl; ENSMUST00000024596; ENSMUSP00000024596; ENSMUSG00000023829.
DR GeneID; 20517; -.
DR KEGG; mmu:20517; -.
DR UCSC; uc008akx.1; mouse.
DR CTD; 6580; -.
DR MGI; MGI:108111; Slc22a1.
DR VEuPathDB; HostDB:ENSMUSG00000023829; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162065; -.
DR HOGENOM; CLU_001265_33_5_1; -.
DR InParanoid; O08966; -.
DR OMA; YLWFSCA; -.
DR OrthoDB; 704438at2759; -.
DR PhylomeDB; O08966; -.
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; 20517; 2 hits in 72 CRISPR screens.
DR PRO; PR:O08966; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O08966; protein.
DR Bgee; ENSMUSG00000023829; Expressed in right kidney and 55 other tissues.
DR ExpressionAtlas; O08966; baseline and differential.
DR Genevisible; O08966; 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:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; ISO:MGI.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; 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:0005334; F:norepinephrine:sodium symporter 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:0008513; F:secondary active organic cation transmembrane transporter activity; 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:0098655; P:cation transmembrane transport; ISO:MGI.
DR GO; GO:0006812; P:cation transport; IDA:MGI.
DR GO; GO:0015872; P:dopamine transport; ISO:MGI.
DR GO; GO:0090494; P:dopamine uptake; ISO:MGI.
DR GO; GO:0048241; P:epinephrine transport; ISO:MGI.
DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; ISO:MGI.
DR GO; GO:0015844; P:monoamine transport; ISO:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:MGI.
DR GO; GO:0015874; P:norepinephrine transport; ISO:MGI.
DR GO; GO:0015695; P:organic cation transport; 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; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..556
FT /note="Solute carrier family 22 member 1"
FT /id="PRO_0000333876"
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..211
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..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..377
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..465
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 466..486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 487..493
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 515..556
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 451
FT /note="Involved in affinity and selectivity of cations as
FT well as in translocation"
FT /evidence="ECO:0000250"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 543
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15245"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 26
FT /note="C -> Y (in Ref. 1; AAB19097)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="G -> V (in Ref. 1; AAB19097)"
FT /evidence="ECO:0000305"
FT CONFLICT 506
FT /note="S -> T (in Ref. 1; AAB19097)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 556 AA; 61521 MW; 0230EF5A2B1E2723 CRC64;
MPTVDDVLEH VGEFGWFQKQ AFLLLCLISA SLAPIYVGIV FLGFTPDHHC RSPGVAELSQ
RCGWSPAEEL NYTVPGLGSA GEASFLSQCM KYEVDWNQST LDCVDPLSSL AANRSHLPLS
PCEHGWVYDT PGSSIVTEFN LVCGDAWKVD LFQSCVNLGF FLGSLVVGYI ADRFGRKLCL
LVTTLVTSLS GVLTAVAPDY TSMLLFRLLQ GMVSKGSWVS GYTLITEFVG SGYRRTTAIL
YQVAFTVGLV GLAGVAYAIP DWRWLQLAVS LPTFLFLLYY WFVPESPRWL LSQKRTTQAV
RIMEQIAQKN RKVPPADLKM MCLEEDASER RSPSFADLFR TPSLRKHTLI LMYLWFSCAV
LYQGLIMHVG ATGANLYLDF FYSSLVEFPA AFIILVTIDR IGRIYPIAAS NLVAGAACLL
MIFIPHELHW LNVTLACLGR MGATIVLQMV CLVNAELYPT FIRNLGMMVC SALCDLGGIF
TPFMVFRLME VWQALPLILF GVLGLSAGAV TLLLPETKGV ALPETIEEAE NLGRRKSKAK
ENTIYLQVQT GKSPHT
