S22A1_RAT
ID S22A1_RAT Reviewed; 556 AA.
AC Q63089; O35882; Q6AYW1;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Solute carrier family 22 member 1;
DE AltName: Full=Organic cation transporter 1;
DE Short=rOCT1;
GN Name=Slc22a1; Synonyms=Oct1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7990927; DOI=10.1038/372549a0;
RA Gruendemann D., Gorboulev V., Gambaryan S., Veyhl M., Koepsell H.;
RT "Drug excretion mediated by a new prototype of polyspecific transporter.";
RL Nature 372:549-552(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=9195965; DOI=10.1074/jbc.272.26.16548;
RA Zhang L., Dresser M.J., Chun J.K., Babbitt P.C., Giacomini K.M.;
RT "Cloning and functional characterization of a rat renal organic cation
RT transporter isoform (rOCT1A).";
RL J. Biol. Chem. 272:16548-16554(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC 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 FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8955087; DOI=10.1074/jbc.271.51.32599;
RA Busch A.E., Quester S., Ulzheimer J.C., Waldegger S., Gorboulev V.,
RA Arndt P., Lang F., Koepsell H.;
RT "Electrogenic properties and substrate specificity of the polyspecific rat
RT cation transporter rOCT1.";
RL J. Biol. Chem. 271:32599-32604(1996).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9703985; DOI=10.1006/bbrc.1998.9034;
RA Meyer-Wentrup F., Karbach U., Gorboulev V., Arndt P., Koepsell H.;
RT "Membrane localization of the electrogenic cation transporter rOCT1 in rat
RT liver.";
RL Biochem. Biophys. Res. Commun. 248:673-678(1998).
RN [6]
RP FUNCTION.
RX PubMed=9776363; DOI=10.1038/sj.bjp.0702065;
RA Breidert T., Spitzenberger F., Gruendemann D., Schoemig E.;
RT "Catecholamine transport by the organic cation transporter type 1 (OCT1).";
RL Br. J. Pharmacol. 125:218-224(1998).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9808712;
RA Urakami Y., Okuda M., Masuda S., Saito H., Inui K.;
RT "Functional characteristics and membrane localization of rat multispecific
RT organic cation transporters, OCT1 and OCT2, mediating tubular secretion of
RT cationic drugs.";
RL J. Pharmacol. Exp. Ther. 287:800-805(1998).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10997918; DOI=10.1152/ajprenal.2000.279.4.f679;
RA Karbach U., Kricke J., Meyer-Wentrup F., Gorboulev V., Volk C.,
RA Loffing-Cueni D., Kaissling B., Bachmann S., Koepsell H.;
RT "Localization of organic cation transporters OCT1 and OCT2 in rat kidney.";
RL Am. J. Physiol. 279:F679-F687(2000).
RN [9]
RP FUNCTION.
RX PubMed=11502595; DOI=10.1152/ajprenal.2001.281.3.f454;
RA Arndt P., Volk C., Gorboulev V., Budiman T., Popp C., Ulzheimer-Teuber I.,
RA Akhoundova A., Koppatz S., Bamberg E., Nagel G., Koepsell H.;
RT "Interaction of cations, anions, and weak base quinine with rat renal
RT cation transporter rOCT2 compared with rOCT1.";
RL Am. J. Physiol. 281:F454-F468(2001).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11792693; DOI=10.1124/dmd.30.2.212;
RA Slitt A.L., Cherrington N.J., Hartley D.P., Leazer T.M., Klaassen C.D.;
RT "Tissue distribution and renal developmental changes in rat organic cation
RT transporter mRNA levels.";
RL Drug Metab. Dispos. 30:212-219(2002).
RN [11]
RP INDUCTION.
RX PubMed=15122767; DOI=10.1002/hep.20176;
RA Denk G.U., Soroka C.J., Mennone A., Koepsell H., Beuers U., Boyer J.L.;
RT "Down-regulation of the organic cation transporter 1 of rat liver in
RT obstructive cholestasis.";
RL Hepatology 39:1382-1389(2004).
RN [12]
RP FUNCTION.
RX PubMed=16142924; DOI=10.1021/bi050676c;
RA Keller T., Elfeber M., Gorboulev V., Reilaender H., Koepsell H.;
RT "Purification and functional reconstitution of the rat organic cation
RT transporter OCT1.";
RL Biochemistry 44:12253-12263(2005).
RN [13]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15640376; DOI=10.1124/dmd.104.002519;
RA Ishiguro N., Saito A., Yokoyama K., Morikawa M., Igarashi T., Tamai I.;
RT "Transport of the dopamine D2 agonist pramipexole by rat organic cation
RT transporters OCT1 and OCT2 in kidney.";
RL Drug Metab. Dispos. 33:495-499(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 MUTAGENESIS OF SER-286; SER-292; THR-296; SER-328 AND THR-550, AND
RP PHOSPHORYLATION.
RX PubMed=15829703; DOI=10.1681/asn.2004040256;
RA Ciarimboli G., Koepsell H., Iordanova M., Gorboulev V., Durner B., Lang D.,
RA Edemir B., Schroter R., Van Le T., Schlatter E.;
RT "Individual PKC-phosphorylation sites in organic cation transporter 1
RT determine substrate selectivity and transport regulation.";
RL J. Am. Soc. Nephrol. 16:1562-1570(2005).
RN [16]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16581093; DOI=10.1016/j.neuropharm.2006.01.005;
RA Amphoux A., Vialou V., Drescher E., Bruess M., Mannoury La Cour C.,
RA Rochat C., Millan M.J., Giros B., Boenisch H., Gautron S.;
RT "Differential pharmacological in vitro properties of organic cation
RT transporters and regional distribution in rat brain.";
RL Neuropharmacology 50:941-952(2006).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF CYS-26; CYS-155; CYS-179; CYS-322; CYS-358;
RP CYS-418; CYS-437; CYS-451; CYS-470 AND CYS-474.
RX PubMed=17567940; DOI=10.1152/ajprenal.00106.2007;
RA Sturm A., Gorboulev V., Gorbunov D., Keller T., Volk C., Schmitt B.M.,
RA Schlachtbauer P., Ciarimboli G., Koepsell H.;
RT "Identification of cysteines in rat organic cation transporters rOCT1
RT (C322, C451) and rOCT2 (C451) critical for transport activity and substrate
RT affinity.";
RL Am. J. Physiol. 293:F767-F779(2007).
RN [18]
RP INDUCTION.
RX PubMed=17553914; DOI=10.1124/dmd.107.015842;
RA Maeda T., Oyabu M., Yotsumoto T., Higashi R., Nagata K., Yamazoe Y.,
RA Tamai I.;
RT "Effect of pregnane X receptor ligand on pharmacokinetics of substrates of
RT organic cation transporter Oct1 in rats.";
RL Drug Metab. Dispos. 35:1580-1586(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-334, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:11502595,
CC ECO:0000269|PubMed:15640376, ECO:0000269|PubMed:16142924,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:17567940, ECO:0000269|PubMed:7990927,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965,
CC ECO:0000269|PubMed:9776363, ECO:0000269|PubMed:9808712}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.73 mM for metformin {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=42 uM for TEA {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=9.6 uM for MPP {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=0.34 mM for NMN {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=1.1 mM for choline {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=49.5 uM for pramipexole {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=1.6 mM for dopamine {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=0.9 mM for serotonin {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=0.8 mM for norepinephrine {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC KM=1.1 mM for epinephrine {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC Vmax=145 pmol/min/mg enzyme uptake {ECO:0000269|PubMed:15640376,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:8955087, ECO:0000269|PubMed:9195965};
CC -!- INTERACTION:
CC Q63089; Q63089: Slc22a1; NbExp=4; IntAct=EBI-5261153, EBI-5261153;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:10997918, ECO:0000269|PubMed:7990927,
CC ECO:0000269|PubMed:9703985, ECO:0000269|PubMed:9808712}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10997918,
CC ECO:0000269|PubMed:7990927, ECO:0000269|PubMed:9703985,
CC ECO:0000269|PubMed:9808712}. Note=Within sinusoidal membrane of
CC hepatocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q63089-1; Sequence=Displayed;
CC Name=2; Synonyms=rOCT1A;
CC IsoId=Q63089-2; Sequence=VSP_033591, VSP_033592;
CC -!- TISSUE SPECIFICITY: Expressed in kidney, kidney cortex, kidney medulla,
CC liver, intestine and colon. Expressed in proximal tubules in kidney,
CC hepatocytes in liver and enterocytes of villi and crypts in
CC smallintestine. Expressed throughout the liver lobuli. Expressed in
CC hepatocytes surrounding the central veins (at protein level). Expressed
CC in S1, S2 segments of proximal tubules in kidney (at protein level).
CC Highly expressed in kidney and spleen, moderately in skin, and weakly
CC in the gastrointestinal tract, brain, lung, thymus, muscle, and
CC prostate. Weakly expressed in some white matter regions like the corpus
CC callosum and in the granular layer of the cerebellum.
CC {ECO:0000269|PubMed:10997918, ECO:0000269|PubMed:11792693,
CC ECO:0000269|PubMed:7990927, ECO:0000269|PubMed:9195965,
CC ECO:0000269|PubMed:9703985}.
CC -!- DEVELOPMENTAL STAGE: Renal level increases gradually from postnatal day
CC 1 through day 45 in both genders. {ECO:0000269|PubMed:11792693}.
CC -!- INDUCTION: Down-regulated in obstructive cholestasis. Up-regulated by
CC treatment with pregnenolone-16 alpha-carbonitrile (PCN) and by
CC overexpression of pregnane X receptor (PXR).
CC {ECO:0000269|PubMed:15122767, ECO:0000269|PubMed:17553914}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:15829703}.
CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily.
CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH78883.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X78855; CAA55411.1; -; mRNA.
DR EMBL; U76379; AAB67702.1; -; mRNA.
DR EMBL; BC078883; AAH78883.1; ALT_INIT; mRNA.
DR PIR; S50862; S50862.
DR RefSeq; NP_036829.1; NM_012697.1. [Q63089-1]
DR AlphaFoldDB; Q63089; -.
DR SMR; Q63089; -.
DR IntAct; Q63089; 1.
DR STRING; 10116.ENSRNOP00000022254; -.
DR BindingDB; Q63089; -.
DR ChEMBL; CHEMBL2073670; -.
DR TCDB; 2.A.1.19.1; the major facilitator superfamily (mfs).
DR GlyGen; Q63089; 1 site.
DR iPTMnet; Q63089; -.
DR PhosphoSitePlus; Q63089; -.
DR PaxDb; Q63089; -.
DR PRIDE; Q63089; -.
DR Ensembl; ENSRNOT00000022068; ENSRNOP00000022068; ENSRNOG00000016337. [Q63089-2]
DR Ensembl; ENSRNOT00000022254; ENSRNOP00000022254; ENSRNOG00000016337. [Q63089-1]
DR GeneID; 24904; -.
DR KEGG; rno:24904; -.
DR CTD; 6580; -.
DR RGD; 3224; Slc22a1.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162065; -.
DR HOGENOM; CLU_001265_33_5_1; -.
DR InParanoid; Q63089; -.
DR OMA; YLWFSCA; -.
DR OrthoDB; 704438at2759; -.
DR PhylomeDB; Q63089; -.
DR Reactome; R-RNO-112311; Neurotransmitter clearance.
DR Reactome; R-RNO-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-2161517; Abacavir transmembrane transport.
DR Reactome; R-RNO-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-RNO-549127; Organic cation transport.
DR PRO; PR:Q63089; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016337; Expressed in adult mammalian kidney and 13 other tissues.
DR Genevisible; Q63089; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; IDA:RGD.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IDA:RGD.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; IDA:RGD.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:RGD.
DR GO; GO:0015214; F:pyrimidine nucleoside transmembrane transporter activity; ISO:RGD.
DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:RGD.
DR GO; GO:0008513; F:secondary active organic cation transmembrane transporter activity; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0006812; P:cation transport; ISO:RGD.
DR GO; GO:0015872; P:dopamine transport; IDA:RGD.
DR GO; GO:0090494; P:dopamine uptake; ISO:RGD.
DR GO; GO:0048241; P:epinephrine transport; IDA:RGD.
DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; IDA:RGD.
DR GO; GO:0015844; P:monoamine transport; IDA:RGD.
DR GO; GO:0006836; P:neurotransmitter transport; ISO:RGD.
DR GO; GO:0015874; P:norepinephrine transport; IDA:RGD.
DR GO; GO:0015695; P:organic cation transport; IDA:RGD.
DR GO; GO:0015697; P:quaternary ammonium group transport; IDA:RGD.
DR GO; GO:0051610; P:serotonin uptake; ISO:RGD.
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 Alternative splicing; Cell membrane; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..556
FT /note="Solute carrier family 22 member 1"
FT /id="PRO_0000333879"
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 MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
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 VAR_SEQ 1..126
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9195965"
FT /id="VSP_033591"
FT VAR_SEQ 127..172
FT /note="VYDTPGSSIVTEFNLVCGDAWKVDLFQSCVNLGFFLGSLVVGYIAD -> MR
FT WTGTRAPLTVWTHCPAWLPTGVSCHWAPASMAGYTTLPAPPSSL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9195965"
FT /id="VSP_033592"
FT MUTAGEN 26
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-155; A-179; S-322; A-358; A-
FT 418; S-437; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 155
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-179; S-322; A-358; A-
FT 418; S-437; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 179
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; S-322; A-358; A-
FT 418; S-437; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 286
FT /note="S->A: No effect of PKC-induced stimulation on ASP
FT uptake. No effect of PKC-induced stimulation on ASP uptake;
FT when associated with A-292; A-296; A-328 and A-550. No
FT effect of PKA activation on ASP uptake. No effect of PKA
FT activation on ASP uptake; when associated with A-292; A-
FT 296; A-328 and A-550. Significant reduction of ASP uptake
FT by p56(lck) tyrosine kinase-induced inhibition. Significant
FT reduction of ASP uptake by p56(lck) tyrosine kinase-induced
FT inhibition; when associated with A-292; A-296; A-328 and A-
FT 550. No significant effect on trafficking from
FT intracellular pools to the cell membrane; when associated
FT with A-292; A-296; A-328 and A-550. suppresses
FT phosphorylation by PKC; when associated with A-292; A-296;
FT A-328 and A-550."
FT /evidence="ECO:0000269|PubMed:15829703"
FT MUTAGEN 292
FT /note="S->A: No effect of PKC-induced stimulation on ASP
FT uptake. No effect of PKC-induced stimulation on ASP uptake;
FT when associated with A-286; A-296; A-328 and A-550. No
FT effect of PKA activation on ASP uptake. No effect of PKA
FT activation on ASP uptake; when associated with A-286; A-
FT 296; A-328 and A-550. Significant reduction of ASP uptake
FT by p56(lck) tyrosine kinase-induced inhibition. Significant
FT reduction of ASP uptake by p56(lck) tyrosine kinase-induced
FT inhibition; when associated with A-286; A-296; A-328 and A-
FT 550. No significant effect on trafficking from
FT intracellular pools to the cell membrane; when associated
FT with A-286; A-296; A-328 and A-550. suppresses
FT phosphorylation by PKC; when associated with A-286; A-296;
FT A-328 and A-550."
FT /evidence="ECO:0000269|PubMed:15829703"
FT MUTAGEN 296
FT /note="T->A: No effect of PKC-induced stimulation on ASP
FT uptake. No effect of PKC-induced stimulation on ASP uptake;
FT when associated with A-286; A-292; A-328; A-550.
FT Significant increase of the ASP uptake by PKA activation.
FT No effect of PKA activation on ASP uptake; when associated
FT with A-286; A-292; A-328; A-550. Significant reduction of
FT ASP uptake by p56(lck) tyrosine kinase-induced inhibition.
FT Significant reduction of ASP uptake by p56(lck) tyrosine
FT kinase-induced inhibition; when associated with A-286; A-
FT 292; A-328; A-550. No significant effect on trafficking
FT from intracellular pools to the cell membrane; when
FT associated with A-286; A-292; A-328 and A-550. suppresses
FT phosphorylation by PKC; when associated with A-286; A-292;
FT A-328 and A-550."
FT /evidence="ECO:0000269|PubMed:15829703"
FT MUTAGEN 322
FT /note="C->S: Reduces the activation by MMTS. Abolishes the
FT activation by MMTs; when associated with M-451. Choline
FT affinity is increased fivefold by MMTS. Choline affinity is
FT increased fourfold by MMTS; when associated with A-26; A-
FT 155; A-179; A-358; A-418; S-437; A-470 and A-474. Choline
FT affinity is increased four- to fivefold; when associated
FT with M-451."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 328
FT /note="S->A: No effect of PKC-induced stimulation on ASP
FT uptake. No effect of PKC-induced stimulation on ASP uptake;
FT when associated with A-286; A-292; A-296 and A-550. No
FT effect of PKA activation on ASP uptake. No effect of PKA
FT activation on ASP uptake; when associated with A-286; A-
FT 292; A-296 and A-550. Significant reduction of ASP uptake
FT by p56(lck) tyrosine kinase-induced inhibition. Significant
FT reduction of ASP uptake by p56(lck) tyrosine kinase-induced
FT inhibition; when associated with A-286; A-292; A-296; A-
FT 550. No significant effect on trafficking from
FT intracellular pools to the cell membrane; when associated
FT with A-286; A-292; A-296 and A-550. suppresses
FT phosphorylation by PKC; when associated with A-286; A-292;
FT A-296 and A-550."
FT /evidence="ECO:0000269|PubMed:15829703"
FT MUTAGEN 358
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; A-179; S-322; A-
FT 418; S-437; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 418
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; A-179; S-322; A-
FT 358; S-437; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 437
FT /note="C->S: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; A-179; S-322; A-
FT 358; A-418; A-470 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 451
FT /note="C->M: Reduces the activation by MMTS. Abolishes the
FT activation by MMTs; when associated with S-322. Abolishes
FT the effect of MMTs on choline-induced currents. Choline
FT affinity is not influenced by MMTS. Choline affinity is
FT increased four- to fivefold; when associated with S-322."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 470
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; A-179; S-322; A-
FT 358; A-418; A-437 and A-474."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 474
FT /note="C->A: Choline affinity is increased fourfold by
FT MMTS; when associated with A-26; A-155; A-179; S-322; A-
FT 358; A-418; A-437 and A-470."
FT /evidence="ECO:0000269|PubMed:17567940"
FT MUTAGEN 550
FT /note="T->A: No effect of PKC-induced stimulation on ASP
FT uptake. No effect of PKC-induced stimulation on ASP uptake;
FT when associated with A-286; A-292; A-296; A-328.
FT Significant increase of the ASP uptake by PKA activation.
FT No effect of PKA activation on ASP uptake; when associated
FT with A-286; A-292; A-296 and A-328. Significant reduction
FT of ASP uptake by p56(lck) tyrosine kinase-induced
FT inhibition. Significant reduction of ASP uptake by p56(lck)
FT tyrosine kinase-induced inhibition; when associated with A-
FT 286; A-292; A-296; A-328. No significant effect on
FT trafficking from intracellular pools to the cell membrane;
FT when associated with A-286; A-292; A-296 and A-328.
FT suppresses phosphorylation by PKC; when associated with A-
FT 286; A-292; A-296 and A-328."
FT /evidence="ECO:0000269|PubMed:15829703"
SQ SEQUENCE 556 AA; 61541 MW; 9F42131CCCEC0920 CRC64;
MPTVDDVLEQ VGEFGWFQKQ AFLLLCLISA SLAPIYVGIV FLGFTPGHYC QNPGVAELSQ
RCGWSQAEEL NYTVPGLGPS DEASFLSQCM RYEVDWNQST LDCVDPLSSL VANRSQLPLG
PCEHGWVYDT PGSSIVTEFN LVCGDAWKVD LFQSCVNLGF FLGSLVVGYI ADRFGRKLCL
LVTTLVTSVS GVLTAVAPDY TSMLLFRLLQ GMVSKGSWVS GYTLITEFVG SGYRRTTAIL
YQMAFTVGLV GLAGVAYAIP DWRWLQLAVS LPTFLFLLYY WFVPESPRWL LSQKRTTRAV
RIMEQIAQKN GKVPPADLKM LCLEEDASEK RSPSFADLFR TPNLRKHTVI LMYLWFSCAV
LYQGLIMHVG ATGANLYLDF FYSSLVEFPA AFIILVTIDR IGRIYPIAAS NLVTGAACLL
MIFIPHELHW LNVTLACLGR MGATIVLQMV CLVNAELYPT FIRNLGMMVC SALCDLGGIF
TPFMVFRLME VWQALPLILF GVLGLTAGAM TLLLPETKGV ALPETIEEAE NLGRRKSKAK
ENTIYLQVQT GKSSST
