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 27-MAR-2024, entry version 174. DE RecName: Full=Solute carrier family 22 member 1 {ECO:0000303|PubMed:12176030}; DE AltName: Full=Organic cation transporter 1 {ECO:0000303|PubMed:12176030}; DE Short=mOCT1 {ECO:0000303|PubMed:12176030}; GN Name=Slc22a1 {ECO:0000312|MGI:MGI:108111}; GN Synonyms=Lx1 {ECO:0000303|PubMed:8854860}, 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], FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. 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], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MISCELLANEOUS. 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], AND MISCELLANEOUS. 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 FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=11463829; DOI=10.1128/mcb.21.16.5471-5477.2001; RA Jonker J.W., Wagenaar E., Mol C.A., Buitelaar M., Koepsell H., Smit J.W., RA Schinkel A.H.; RT "Reduced hepatic uptake and intestinal excretion of organic cations in mice RT with a targeted disruption of the organic cation transporter 1 (Oct1 RT [Slc22a1]) gene."; RL Mol. Cell. Biol. 21:5471-5477(2001). RN [7] 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 [8] 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 [9] 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). RN [10] RP FUNCTION, TRANSPORTER ACTIVITY, AND MISCELLANEOUS. RX PubMed=23458604; DOI=10.1021/mp400024d; RA Sala-Rabanal M., Li D.C., Dake G.R., Kurata H.T., Inyushin M., RA Skatchkov S.N., Nichols C.G.; RT "Polyamine transport by the polyspecific organic cation transporters OCT1, RT OCT2, and OCT3."; RL Mol. Pharm. 10:1450-1458(2013). RN [11] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=23680637; DOI=10.1124/mol.112.084517; RA Han T.K., Everett R.S., Proctor W.R., Ng C.M., Costales C.L., Brouwer K.L., RA Thakker D.R.; RT "Organic cation transporter 1 (OCT1/mOct1) is localized in the apical RT membrane of Caco-2 cell monolayers and enterocytes."; RL Mol. Pharmacol. 84:182-189(2013). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE RP SPECIFICITY, DISRUPTION PHENOTYPE, AND MISCELLANEOUS. RX PubMed=24961373; DOI=10.1073/pnas.1314939111; RA Chen L., Shu Y., Liang X., Chen E.C., Yee S.W., Zur A.A., Li S., Xu L., RA Keshari K.R., Lin M.J., Chien H.C., Zhang Y., Morrissey K.M., Liu J., RA Ostrem J., Younger N.S., Kurhanewicz J., Shokat K.M., Ashrafi K., RA Giacomini K.M.; RT "OCT1 is a high-capacity thiamine transporter that regulates hepatic RT steatosis and is a target of metformin."; RL Proc. Natl. Acad. Sci. U.S.A. 111:9983-9988(2014). RN [13] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND MISCELLANEOUS. RX PubMed=28942964; DOI=10.1016/j.ajhg.2017.08.008; RA Kim H.I., Raffler J., Lu W., Lee J.J., Abbey D., Saleheen D., RA Rabinowitz J.D., Bennett M.J., Hand N.J., Brown C., Rader D.J.; RT "Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in RT Acylcarnitine Transport."; RL Am. J. Hum. Genet. 101:489-502(2017). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=34040533; DOI=10.3389/fphar.2021.674559; RA Jensen O., Matthaei J., Klemp H.G., Meyer M.J., Brockmoeller J., RA Tzvetkov M.V.; RT "Isobutyrylcarnitine as a Biomarker of OCT1 Activity and Interspecies RT Differences in its Membrane Transport."; RL Front. Pharmacol. 12:674559-674559(2021). RN [15] RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND RP MUTAGENESIS OF LEU-32 AND TYR-36. RX PubMed=35469921; DOI=10.1016/j.jbc.2022.101974; RA Meyer M.J., Schreier P.C.F., Basaran M., Vlasova S., Seitz T., RA Brockmoeller J., Zdrazil B., Tzvetkov M.V.; RT "Amino acids in transmembrane helix 1 confer major functional differences RT between human and mouse orthologs of the polyspecific membrane transporter RT OCT1."; RL J. Biol. Chem. 298:101974-101974(2022). CC -!- FUNCTION: Electrogenic voltage-dependent transporter that mediates the CC transport of a variety of organic cations such as endogenous bioactive CC amines, cationic drugs and xenobiotics (PubMed:10216142, CC PubMed:12176030, PubMed:11463829, PubMed:23458604, PubMed:24961373). CC Functions as a pH- and Na(+)-independent, bidirectional transporter (By CC similarity). Cation cellular uptake or release is driven by the CC electrochemical potential (i.e. membrane potential and concentration CC gradient) and substrate selectivity (By similarity). Hydrophobicity is CC a major requirement for recognition in polyvalent substrates and CC inhibitors (PubMed:23458604). Primarily expressed in the basolateral CC membrane of hepatocytes and proximal tubules and involved in the uptake CC and disposition of cationic compounds from the blood by hepatic and CC renal clearance (By similarity). Most likely functions as an uptake CC carrier in enterocytes contributing to the intestinal elimination of CC organic cations from the systemic circulation (PubMed:11463829, CC PubMed:24961373). Transports endogenous monoamines such as N-1- CC methylnicotinamide (NMN), guanidine, neurotransmitters dopamine, CC serotonin, noradrenaline, adrenaline and histamine, and quaternary CC ammonium compound such as choline (PubMed:24961373, PubMed:35469921). CC Also transports natural polyamines such as spermidine, agmatine and CC putrescine at low affinity, but relatively high turnover CC (PubMed:23458604). Involved in the hepatic and intestinal uptake of the CC vitamin B1/thiamine, hence regulating hepatic lipid and energy CC metabolism (PubMed:24961373). Contributes to the influx and efflux of CC fatty acid carriers carnitines and acylcarnitines across the CC basolateral membrane of hepatocytes, from the liver to the systemic CC circulation and inversely and may be involved in regulating the CC systemic availability of hepatic acylcarnitines (PubMed:28942964, CC PubMed:34040533). Also capable of transporting non-amine endogenous CC compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha CC (PGF2-alpha) (By similarity). May contribute to the transport of CC cationic compounds in testes across the blood-testis-barrier (By CC similarity). Also mediates the uptake of xenobiotics CC tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N- CC methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), CC azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21- CC deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N- CC methylpyridinium (ASP) (PubMed:11463829). CC {ECO:0000250|UniProtKB:O15245, ECO:0000250|UniProtKB:Q63089, CC ECO:0000269|PubMed:10216142, ECO:0000269|PubMed:11463829, CC ECO:0000269|PubMed:12176030, ECO:0000269|PubMed:23458604, CC ECO:0000269|PubMed:24961373, ECO:0000269|PubMed:28942964, CC ECO:0000269|PubMed:34040533, ECO:0000269|PubMed:35469921}. CC -!- CATALYTIC ACTIVITY: CC Reaction=1-methylnicotinamide(out) = 1-methylnicotinamide(in); CC Xref=Rhea:RHEA:73859, ChEBI:CHEBI:16797; CC Evidence={ECO:0000250|UniProtKB:Q63089}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dopamine(out) = dopamine(in); Xref=Rhea:RHEA:73863, CC ChEBI:CHEBI:59905; Evidence={ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=serotonin(out) = serotonin(in); Xref=Rhea:RHEA:73867, CC ChEBI:CHEBI:350546; Evidence={ECO:0000269|PubMed:24961373, CC ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-adrenaline(out) = (R)-adrenaline(in); CC Xref=Rhea:RHEA:73875, ChEBI:CHEBI:71406; CC Evidence={ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-noradrenaline(out) = (R)-noradrenaline(in); CC Xref=Rhea:RHEA:73871, ChEBI:CHEBI:72587; CC Evidence={ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=histamine(out) = histamine(in); Xref=Rhea:RHEA:73879, CC ChEBI:CHEBI:58432; Evidence={ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=guanidine(out) = guanidine(in); Xref=Rhea:RHEA:73883, CC ChEBI:CHEBI:30087; Evidence={ECO:0000250|UniProtKB:Q63089}; CC -!- CATALYTIC ACTIVITY: CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751, CC ChEBI:CHEBI:15354; Evidence={ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetylcholine(in) = acetylcholine(out); Xref=Rhea:RHEA:74663, CC ChEBI:CHEBI:15355; Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=thiamine(in) = thiamine(out); Xref=Rhea:RHEA:34919, CC ChEBI:CHEBI:18385; Evidence={ECO:0000269|PubMed:24961373, CC ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=spermidine(in) = spermidine(out); Xref=Rhea:RHEA:35039, CC ChEBI:CHEBI:57834; Evidence={ECO:0000269|PubMed:23458604}; CC -!- CATALYTIC ACTIVITY: CC Reaction=agmatine(out) = agmatine(in); Xref=Rhea:RHEA:72131, CC ChEBI:CHEBI:58145; Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=putrescine(out) = putrescine(in); Xref=Rhea:RHEA:72135, CC ChEBI:CHEBI:326268; Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(in) = (R)-carnitine(out); Xref=Rhea:RHEA:34959, CC ChEBI:CHEBI:16347; Evidence={ECO:0000269|PubMed:28942964, CC ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-isobutanoyl-(R)-carnitine(in) = O-isobutanoyl-(R)- CC carnitine(out); Xref=Rhea:RHEA:74315, ChEBI:CHEBI:84838; CC Evidence={ECO:0000269|PubMed:28942964, ECO:0000269|PubMed:34040533, CC ECO:0000269|PubMed:35469921}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-acetyl-(R)-carnitine(in) = O-acetyl-(R)-carnitine(out); CC Xref=Rhea:RHEA:74319, ChEBI:CHEBI:57589; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-3-hydroxybutanoyl-(R)-carnitine(in) = O-3-hydroxybutanoyl- CC (R)-carnitine(out); Xref=Rhea:RHEA:74323, ChEBI:CHEBI:84842; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-propanoyl-(R)-carnitine(in) = O-propanoyl-(R)- CC carnitine(out); Xref=Rhea:RHEA:74327, ChEBI:CHEBI:53210; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-butanoyl-(R)-carnitine(in) = O-butanoyl-(R)-carnitine(out); CC Xref=Rhea:RHEA:74331, ChEBI:CHEBI:21949; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-2-methylbutanoyl-(R)-carnitine(in) = O-2-methylbutanoyl-(R)- CC carnitine(out); Xref=Rhea:RHEA:74335, ChEBI:CHEBI:84840; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-3-methylbutanoyl-(R)-carnitine(in) = O-3-methylbutanoyl-(R)- CC carnitine(out); Xref=Rhea:RHEA:74339, ChEBI:CHEBI:70819; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O-hexanoyl-(R)-carnitine(in) = O-hexanoyl-(R)-carnitine(out); CC Xref=Rhea:RHEA:74343, ChEBI:CHEBI:84834; CC Evidence={ECO:0000269|PubMed:34040533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L- CC proline diketopiperazine(out); Xref=Rhea:RHEA:74787, CC ChEBI:CHEBI:90039; Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-salsolinol(in) = (R)-salsolinol(out); CC Xref=Rhea:RHEA:74791, ChEBI:CHEBI:194082; CC Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin F2alpha(out) = prostaglandin F2alpha(in); CC Xref=Rhea:RHEA:50988, ChEBI:CHEBI:57404; CC Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin E2(out) = prostaglandin E2(in); CC Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564; CC Evidence={ECO:0000250|UniProtKB:O15245}; CC -!- ACTIVITY REGULATION: Phosphorylation of the transporter leads to CC changes in its substrate affinity, resulting in a regulation of the CC transport activity. In contrast with rat ortholog, ASP uptake is CC inhibited by protein kinase A (PKA) and C (PKC) activation. ASP uptake CC is also endogenously activated by calmodulin, the calmodulin-dependent CC kinase II and LCK tyrosine kinase (By similarity). Inhibited by cGMP, CC most likely through a cGMP-binding protein that interacts with OCT1 (By CC similarity). {ECO:0000250|UniProtKB:O15245, CC ECO:0000250|UniProtKB:Q63089}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=242 uM for adrenaline {ECO:0000269|PubMed:35469921}; CC KM=1286 uM for choline {ECO:0000269|PubMed:35469921}; CC KM=285 uM for dopamine {ECO:0000269|PubMed:35469921}; CC KM=497 uM for histamine {ECO:0000269|PubMed:35469921}; CC KM=1470 uM for O-isobutanoyl-(R)-carnitine CC {ECO:0000269|PubMed:34040533}; CC KM=1377 uM for O-isobutanoyl-(R)-carnitine CC {ECO:0000269|PubMed:35469921}; CC KM=409 uM for noradrenaline {ECO:0000269|PubMed:35469921}; CC KM=257 uM for serotonin {ECO:0000269|PubMed:35469921}; CC KM=143 uM for thiamine {ECO:0000269|PubMed:35469921}; CC KM=490 uM for thiamine {ECO:0000269|PubMed:24961373}; CC Vmax=7.547 nmol/min/mg enzyme with adrenaline as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=16.564 nmol/min/mg enzyme with choline as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=1.714 nmol/min/mg enzyme with dopamine as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=5.961 nmol/min/mg enzyme with histamine as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=8.5 nmol/min/mg enzyme with O-isobutanoyl-(R)-carnitine as CC substrate {ECO:0000269|PubMed:34040533}; CC Vmax=8.366 nmol/min/mg enzyme with O-isobutanoyl-(R)-carnitine as CC substrate {ECO:0000269|PubMed:35469921}; CC Vmax=6.068 nmol/min/mg enzyme with noradrenaline as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=16.162 nmol/min/mg enzyme with serotonin as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=3.715 nmol/min/mg enzyme with thiamine as substrate CC {ECO:0000269|PubMed:35469921}; CC Vmax=5.8 nmol/min/mg enzyme with thiamine as substrate CC {ECO:0000269|PubMed:24961373}; CC pH dependence: CC Optimum pH is 8.5 for TEA transport (PubMed:10216142). Optimum pH is CC 8.4 for MPP(+) transport (PubMed:12176030). CC {ECO:0000269|PubMed:10216142, ECO:0000269|PubMed:12176030}; CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane CC {ECO:0000269|PubMed:28942964}; Multi-pass membrane protein CC {ECO:0000305}. Apical cell membrane {ECO:0000269|PubMed:23680637}; CC Multi-pass membrane protein {ECO:0000305}. Lateral cell membrane CC {ECO:0000250|UniProtKB:O15245}; Multi-pass membrane protein CC {ECO:0000305}. Basal cell membrane {ECO:0000250|UniProtKB:O15245}; CC Multi-pass membrane protein {ECO:0000305}. Note=Localized to the CC sinusoidal/basolateral membrane of hepatocytes (PubMed:28942964). CC Mainly localized to the basolateral membrane of renal proximal tubular CC cells (By similarity). However, also identified at the apical side of CC proximal tubular cells (By similarity). Mainly expressed at the lateral CC membrane of enterocytes (By similarity). Also observed at the apical CC side of enterocytes (PubMed:23680637). Localized to the basal membrane CC of Sertoli cells (By similarity). {ECO:0000250|UniProtKB:O15245, CC ECO:0000250|UniProtKB:Q63089, ECO:0000269|PubMed:23680637, CC ECO:0000269|PubMed:28942964}. CC -!- TISSUE SPECIFICITY: Expressed in kidney (PubMed:8854860, CC PubMed:11463829, PubMed:16381671, PubMed:23680637, PubMed:28942964). CC Expressed in liver (PubMed:8854860, PubMed:11463829, PubMed:16381671, CC PubMed:24961373, PubMed:28942964). In liver, mainly expressed in the CC central vein (PubMed:24961373). Expressed in intestines CC (PubMed:11463829, PubMed:23680637, PubMed:28942964). Weakly expressed CC in adrenals and in lacting mammary glands (PubMed:8854860). CC {ECO:0000269|PubMed:11463829, ECO:0000269|PubMed:16381671, CC ECO:0000269|PubMed:23680637, ECO:0000269|PubMed:24961373, CC ECO:0000269|PubMed:28942964, 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 -!- DOMAIN: A large substrate binding region with partially overlapping CC binding domains for structurally different substrates is formed by CC several transmembrane helix domains (TMH) including TMH 2, 4, 10 and CC 11, and it is alternatingly exposed to the extracellular or CC intracellular side during substrate transport (By similarity). Amino CC acids in TMH 1 confer major functional differences between human and CC mouse orthologs (PubMed:35469921). {ECO:0000250|UniProtKB:Q63089, CC ECO:0000269|PubMed:35469921}. CC -!- DOMAIN: Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that CC is required for transport activity. {ECO:0000250|UniProtKB:O15245}. CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q63089}. CC -!- DISRUPTION PHENOTYPE: Knockout mice appeared to be viable, healthy and CC fertile, and displayed no obvious phenotypic abnormalities CC (PubMed:11463829). Showed slightly greater body weights after 16 weeks CC compared to wild-type mice (PubMed:24961373). Reduced hepatic uptake CC and intestinal excretion of organic cations (PubMed:11463829). Showed CC reduced thiamine and thiamine vitamers levels in liver and intestine CC and higher levels of thiamine and vitamers in plasma compared to wild- CC type mice (PubMed:24961373). Also showed increased ratio of AMP to ATP, CC activation of the energy sensor AMP-activated kinase (AMPK) and CC increased fatty acid oxidation in the liver, which contributes to CC reduced hepatic triglyceride (TG) levels (PubMed:24961373). Circulating CC triglyceride levels were not changed (PubMed:24961373). CC {ECO:0000269|PubMed:11463829, ECO:0000269|PubMed:24961373}. CC -!- MISCELLANEOUS: Involved in the uptake of clinically used drugs CC including diabete treatment medicine metformin, neurotoxins 1-methyl-4- CC phenylpyridinium (MPP(+)) and iobenguane and platinum-based drug CC cisplatin (PubMed:12176030, PubMed:11463829, PubMed:23458604, CC PubMed:24961373, PubMed:28942964). Metformin competitively inhibits CC OCT1-mediated thiamine uptake, leading to a decrease in hepatic CC steatosis (PubMed:24961373). Plays a role in the anticancer activity of CC cisplatin and may contribute to antitumor specificity (By similarity). CC {ECO:0000250|UniProtKB:O15245, ECO:0000269|PubMed:11463829, CC ECO:0000269|PubMed:12176030, ECO:0000269|PubMed:23458604, CC ECO:0000269|PubMed:24961373, ECO:0000269|PubMed:28942964}. 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 -!- CAUTION: Cellular localization of OCT1 in the intestine and the kidney CC remains to be finally defined. While most authors have deduced a CC localization at the basolateral side of enterocytes consistent with a CC physiological role in organic anions uptake from the blood flow and CC intestinal excretion (PubMed:11463829), other studies demonstrated an CC apical localization (PubMed:23680637), supporting a function in CC intestinal absorption of organic anions and drugs (PubMed:11463829, CC PubMed:23680637). Similarly, contradictory findings have shown a CC localization to the basolateral side (By similarity) or to the apical CC side (By similarity) of proximal tubules (By similarity). While CC carnitine efflux is Na(+)-independent, carnitine uptake is CC significantly reduced in the absence of Na(+) (PubMed:28942964). Not CC able to uptake and choline in the liver (PubMed:24961373). Affinity and CC capacity of the transporter for endogenous substrates vary among CC orthologs (PubMed:34040533, PubMed:35469921). For endogenous compounds CC such as dopamine, histamine, serotonin and thiamine, mouse ortholog CC display higher affinity and capacity compared with human OCT1 CC (PubMed:35469921). In contrast with human ortholog, not involved in CC metformin efflux transport (PubMed:34040533). CC {ECO:0000250|UniProtKB:O15245, ECO:0000250|UniProtKB:Q63089, CC ECO:0000269|PubMed:11463829, ECO:0000269|PubMed:23680637, CC ECO:0000269|PubMed:24961373, ECO:0000269|PubMed:28942964, CC ECO:0000269|PubMed:34040533, ECO:0000269|PubMed:35469921}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; O08966; 1 site, No reported glycans. DR GlyGen; O08966; 1 site. DR iPTMnet; O08966; -. DR PhosphoSitePlus; O08966; -. DR SwissPalm; O08966; -. DR jPOST; O08966; -. DR MaxQB; O08966; -. DR PaxDb; 10090-ENSMUSP00000024596; -. DR PeptideAtlas; O08966; -. DR ProteomicsDB; 260883; -. DR Antibodypedia; 33480; 338 antibodies from 33 providers. DR DNASU; 20517; -. DR Ensembl; ENSMUST00000024596.10; ENSMUSP00000024596.9; ENSMUSG00000023829.10. DR GeneID; 20517; -. DR KEGG; mmu:20517; -. DR UCSC; uc008akx.1; mouse. DR AGR; MGI:108111; -. 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; IMIFIPH; -. DR OrthoDB; 1474205at2759; -. 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 Reactome; R-MMU-9793528; Ciprofloxacin ADME. DR BioGRID-ORCS; 20517; 2 hits in 77 CRISPR screens. DR PRO; PR:O08966; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; O08966; Protein. DR Bgee; ENSMUSG00000023829; Expressed in right kidney and 56 other cell types or tissues. DR ExpressionAtlas; O08966; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:1901235; F:(R)-carnitine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; ISS:UniProtKB. 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; IDA:UniProtKB. DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; ISO:MGI. DR GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:MGI. DR GO; GO:0015132; F:prostaglandin transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015489; F:putrescine transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015214; F:pyrimidine nucleoside transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0008513; F:secondary active organic cation transmembrane transporter activity; ISO:MGI. DR GO; GO:0015606; F:spermidine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015234; F:thiamine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0019534; F:toxin transmembrane transporter activity; IMP:ARUK-UCL. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:1902270; P:(R)-carnitine transmembrane transport; IDA:UniProtKB. DR GO; GO:0015870; P:acetylcholine transport; ISS:UniProtKB. DR GO; GO:1902616; P:acyl carnitine transmembrane transport; IDA:UniProtKB. DR GO; GO:0015872; P:dopamine transport; IDA:UniProtKB. DR GO; GO:0090494; P:dopamine uptake; ISO:MGI. DR GO; GO:0048241; P:epinephrine transport; IDA:UniProtKB. DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; ISO:MGI. DR GO; GO:0072237; P:metanephric proximal tubule development; IEA:Ensembl. DR GO; GO:0015844; P:monoamine transport; IDA:UniProtKB. DR GO; GO:0098655; P:monoatomic cation transmembrane transport; ISO:MGI. DR GO; GO:0006812; P:monoatomic cation transport; IDA:MGI. DR GO; GO:0006836; P:neurotransmitter transport; ISO:MGI. DR GO; GO:0015874; P:norepinephrine transport; IDA:UniProtKB. DR GO; GO:0015695; P:organic cation transport; ISO:MGI. DR GO; GO:0015732; P:prostaglandin transport; ISS:UniProtKB. DR GO; GO:0015847; P:putrescine transport; ISS:UniProtKB. DR GO; GO:0015697; P:quaternary ammonium group transport; ISO:MGI. DR GO; GO:0006837; P:serotonin transport; IDA:UniProtKB. DR GO; GO:0051610; P:serotonin uptake; ISO:MGI. DR GO; GO:0015848; P:spermidine transport; IDA:UniProtKB. DR GO; GO:0071934; P:thiamine transmembrane transport; IDA:UniProtKB. DR GO; GO:0015888; P:thiamine transport; ISO:MGI. DR GO; GO:1901998; P:toxin transport; IMP:ARUK-UCL. DR GO; GO:0042908; P:xenobiotic transport; IDA:UniProtKB. DR GO; GO:1990962; P:xenobiotic transport across blood-brain barrier; NAS:ARUK-UCL. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 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 NCBIfam; TIGR00898; 2A0119; 1. DR PANTHER; PTHR24064; SOLUTE CARRIER FAMILY 22 MEMBER; 1. DR PANTHER; PTHR24064:SF291; SOLUTE CARRIER FAMILY 22 MEMBER 1; 1. DR Pfam; PF00083; Sugar_tr; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 1. DR Genevisible; O08966; MM. 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 MOTIF 284..288 FT /note="Proline-rich sequence" FT /evidence="ECO:0000250|UniProtKB:O15245" 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 MUTAGEN 32 FT /note="L->F: Increased trospium uptake. Increased trospium FT affinity. No change in fenoterol uptake." FT /evidence="ECO:0000269|PubMed:35469921" FT MUTAGEN 36 FT /note="Y->C: Decreased fenoterol uptake. Decreased FT fenoterol affinity. No change in trospium uptake. No change FT in terbutaline affinity." FT /evidence="ECO:0000269|PubMed:35469921" 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 //