S22A1_HUMAN
ID S22A1_HUMAN Reviewed; 554 AA.
AC O15245; A6NFF3; A8K1H2; C9JSU6; O15395; Q9NQD4;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Solute carrier family 22 member 1;
DE AltName: Full=Organic cation transporter 1;
DE Short=hOCT1;
GN Name=SLC22A1; Synonyms=OCT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP VARIANT PHE-160.
RC TISSUE=Liver;
RX PubMed=9260930; DOI=10.1089/dna.1997.16.871;
RA Gorboulev V., Ulzheimer J.C., Akhoundova A., Ulzheimer-Teuber I.,
RA Karbach U., Quester S., Baumann C., Lang F., Busch A.E., Koepsell H.;
RT "Cloning and characterization of two human polyspecific organic cation
RT transporters.";
RL DNA Cell Biol. 16:871-881(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=9187257; DOI=10.1124/mol.51.6.913;
RA Zhang L., Dresser M.J., Gray A.T., Yost S.C., Terashita S., Giacomini K.M.;
RT "Cloning and functional expression of a human liver organic cation
RT transporter.";
RL Mol. Pharmacol. 51:913-921(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, TISSUE
RP SPECIFICITY, AND ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=11388889; DOI=10.1017/s0003480099007770;
RA Hayer M., Boenisch H., Bruess M.;
RT "Molecular cloning, functional characterization and genomic organization of
RT four alternatively spliced isoforms of the human organic cation transporter
RT 1 (hOCT1/SLC22A1).";
RL Ann. Hum. Genet. 63:473-482(1999).
RN [4]
RP ERRATUM OF PUBMED:11388889, AND SEQUENCE REVISION.
RA Hayer M., Bonisch H., Bruss M.;
RL Ann. Hum. Genet. 64:267-267(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS PHE-160;
RP VAL-408; MET-420 DEL AND ARG-465.
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PHE-160.
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 [8]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9655880;
RA Zhang L., Schaner M.E., Giacomini K.M.;
RT "Functional characterization of an organic cation transporter (hOCT1) in a
RT transiently transfected human cell line (HeLa).";
RL J. Pharmacol. Exp. Ther. 286:354-361(1998).
RN [9]
RP FUNCTION.
RX PubMed=11408531;
RA van Montfoort J.E., Mueller M., Groothuis G.M.M., Meijer D.K.F.,
RA Koepsell H., Meier P.J.;
RT "Comparison of 'type I' and 'type II' organic cation transport by organic
RT cation transporters and organic anion-transporting polypeptides.";
RL J. Pharmacol. Exp. Ther. 298:110-115(2001).
RN [10]
RP FUNCTION.
RX PubMed=15389554; DOI=10.1002/jcp.20081;
RA Ciarimboli G., Struwe K., Arndt P., Gorboulev V., Koepsell H.,
RA Schlatter E., Hirsch J.R.;
RT "Regulation of the human organic cation transporter hOCT1.";
RL J. Cell. Physiol. 201:420-428(2004).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=16263091; DOI=10.1016/j.bcp.2005.09.011;
RA Mueller J., Lips K.S., Metzner L., Neubert R.H.H., Koepsell H.,
RA Brandsch M.;
RT "Drug specificity and intestinal membrane localization of human organic
RT cation transporters (OCT).";
RL Biochem. Pharmacol. 70:1851-1860(2005).
RN [12]
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 [13]
RP INDUCTION.
RX PubMed=16436500; DOI=10.1124/jpet.105.099929;
RA Saborowski M., Kullak-Ublick G.A., Eloranta J.J.;
RT "The human organic cation transporter-1 gene is transactivated by
RT hepatocyte nuclear factor-4alpha.";
RL J. Pharmacol. Exp. Ther. 317:778-785(2006).
RN [14]
RP FUNCTION.
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 [15]
RP INDUCTION.
RX PubMed=17635184; DOI=10.1111/j.1472-8206.2007.00517.x;
RA Dias V., Ribeiro V.;
RT "The expression of the solute carriers NTCP and OCT-1 is regulated by
RT cholesterol in HepG2 cells.";
RL Fundam. Clin. Pharmacol. 21:445-450(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-541, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP VARIANTS CYS-61; ARG-88; PHE-160; SER-401 AND MET-420 DEL, AND
RP CHARACTERIZATION OF VARIANTS CYS-61; ARG-88; PHE-160; SER-401 AND MET-420
RP DEL.
RX PubMed=12439218; DOI=10.1097/00008571-200211000-00002;
RA Kerb R., Brinkmann U., Chatskaia N., Gorbunov D., Gorboulev V.,
RA Mornhinweg E., Keil A., Eichelbaum M., Koepsell H.;
RT "Identification of genetic variations of the human organic cation
RT transporter hOCT1 and their functional consequences.";
RL Pharmacogenetics 12:591-595(2002).
RN [18]
RP VARIANTS PHE-14; CYS-61; PHE-85; PHE-160; LEU-189; VAL-220; LEU-341;
RP HIS-342; SER-401; VAL-408; MET-420 DEL; ILE-440; ILE-461; ARG-465 AND
RP MET-488, CHARACTERIZATION OF VARIANTS PHE-14; CYS-61; PHE-85; PHE-160;
RP LEU-189; VAL-220; LEU-341; HIS-342; SER-401; VAL-408; MET-420 DEL; ILE-440;
RP ILE-461; ARG-465 AND MET-488, AND MUTAGENESIS OF GLY-465.
RX PubMed=12719534; DOI=10.1073/pnas.0730858100;
RA Shu Y., Leabman M.K., Feng B., Mangravite L.M., Huang C.C., Stryke D.,
RA Kawamoto M., Johns S.J., DeYoung J., Carlson E., Ferrin T.E.,
RA Herskowitz I., Giacomini K.M.;
RT "Evolutionary conservation predicts function of variants of the human
RT organic cation transporter, OCT1.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5902-5907(2003).
RN [19]
RP VARIANTS PHE-160; LEU-283; GLY-287 AND LEU-341.
RX PubMed=14697261; DOI=10.1016/j.bbrc.2003.11.175;
RA Sakata T., Anzai N., Shin H.J., Noshiro R., Hirata T., Yokoyama H.,
RA Kanai Y., Endou H.;
RT "Novel single nucleotide polymorphisms of organic cation transporter 1
RT (SLC22A1) affecting transport functions.";
RL Biochem. Biophys. Res. Commun. 313:789-793(2004).
RN [20]
RP VARIANTS LEU-41; PHE-160; LEU-341 AND VAL-408.
RX PubMed=15499200; DOI=10.2133/dmpk.19.308;
RA Itoda M., Saito Y., Maekawa K., Hichiya H., Komamura K., Kamakura S.,
RA Kitakaze M., Tomoike H., Ueno K., Ozawa S., Sawada J.;
RT "Seven novel single nucleotide polymorphisms in the human SLC22A1 gene
RT encoding organic cation transporter 1 (OCT1).";
RL Drug Metab. Pharmacokinet. 19:308-312(2004).
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:11388889,
CC ECO:0000269|PubMed:11408531, ECO:0000269|PubMed:15389554,
CC ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093,
CC ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9260930,
CC ECO:0000269|PubMed:9655880}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.47 mM for metformin {ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9655880};
CC KM=229 uM for TEA {ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9655880};
CC KM=14.6 uM for MPP {ECO:0000269|PubMed:16272756,
CC ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9655880};
CC Vmax=396 pmol/min/mg enzyme for metformin uptake
CC {ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:9187257,
CC ECO:0000269|PubMed:9655880};
CC Vmax=2.89 nmol/min/mg enzyme for TEA uptake
CC {ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:9187257,
CC ECO:0000269|PubMed:9655880};
CC -!- INTERACTION:
CC O15245; Q96G23: CERS2; NbExp=3; IntAct=EBI-1172714, EBI-1057080;
CC O15245; Q9BZL3: SMIM3; NbExp=3; IntAct=EBI-1172714, EBI-741850;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:16263091}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16263091}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=hOCT1G/L554;
CC IsoId=O15245-1; Sequence=Displayed;
CC Name=2; Synonyms=hOCT1G/L506;
CC IsoId=O15245-2; Sequence=VSP_033589, VSP_033590;
CC Name=3; Synonyms=hOCT1G483;
CC IsoId=O15245-3; Sequence=VSP_033588;
CC Name=4; Synonyms=hOCT1G353;
CC IsoId=O15245-4; Sequence=VSP_033587;
CC -!- TISSUE SPECIFICITY: Widely expressed with high level in liver. Isoform
CC 1 and isoform 2 are expressed in liver. Isoform 1, isoform 2, isoform 3
CC and isoform 4 are expressed in glial cell lines.
CC {ECO:0000269|PubMed:11388889, ECO:0000269|PubMed:9187257,
CC ECO:0000269|PubMed:9260930}.
CC -!- INDUCTION: In the liver activated by HNF4A and suppressed by bile acids
CC via NR0B2. Increased by cholesterol treatment in hepatocyte cells.
CC {ECO:0000269|PubMed:16436500, ECO:0000269|PubMed:17635184}.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 4]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
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; X98332; CAA66977.1; -; mRNA.
DR EMBL; U77086; AAB67703.1; -; mRNA.
DR EMBL; AJ243995; CAB95971.1; -; Genomic_DNA.
DR EMBL; AJ243996; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ243998; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ243999; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ244000; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ245460; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ276051; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ276052; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AJ276053; CAB95971.1; JOINED; Genomic_DNA.
DR EMBL; AK289887; BAF82576.1; -; mRNA.
DR EMBL; AL353625; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126364; AAI26365.1; -; mRNA.
DR CCDS; CCDS5274.1; -. [O15245-1]
DR CCDS; CCDS5275.1; -. [O15245-2]
DR RefSeq; NP_003048.1; NM_003057.2. [O15245-1]
DR RefSeq; NP_694857.1; NM_153187.1. [O15245-2]
DR RefSeq; XP_006715615.1; XM_006715552.1. [O15245-3]
DR AlphaFoldDB; O15245; -.
DR SMR; O15245; -.
DR BioGRID; 112467; 93.
DR IntAct; O15245; 2.
DR STRING; 9606.ENSP00000355930; -.
DR BindingDB; O15245; -.
DR ChEMBL; CHEMBL5685; -.
DR DrugBank; DB03128; Acetylcholine.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB08838; Agmatine.
DR DrugBank; DB00915; Amantadine.
DR DrugBank; DB06288; Amisulpride.
DR DrugBank; DB12597; Asciminib.
DR DrugBank; DB16098; Atogepant.
DR DrugBank; DB12267; Brigatinib.
DR DrugBank; DB04830; Buformin.
DR DrugBank; DB00520; Caspofungin.
DR DrugBank; DB01114; Chlorpheniramine.
DR DrugBank; DB00122; Choline.
DR DrugBank; DB14006; Choline salicylate.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB00758; Clopidogrel.
DR DrugBank; DB00318; Codeine.
DR DrugBank; DB00434; Cyproheptadine.
DR DrugBank; DB11963; Dacomitinib.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB09555; Dexchlorpheniramine maleate.
DR DrugBank; DB00280; Disopyramide.
DR DrugBank; DB00988; Dopamine.
DR DrugBank; DB00590; Doxazosin.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB00668; Epinephrine.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB01004; Ganciclovir.
DR DrugBank; DB00406; Gentian violet cation.
DR DrugBank; DB12141; Gilteritinib.
DR DrugBank; DB01018; Guanfacine.
DR DrugBank; DB00536; Guanidine.
DR DrugBank; DB05381; Histamine.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB11732; Lasmiditan.
DR DrugBank; DB01137; Levofloxacin.
DR DrugBank; DB08882; Linagliptin.
DR DrugBank; DB12674; Lurbinectedin.
DR DrugBank; DB00331; Metformin.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB12598; Nafamostat.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB00238; Nevirapine.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00368; Norepinephrine.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB09073; Palbociclib.
DR DrugBank; DB01337; Pancuronium.
DR DrugBank; DB00914; Phenformin.
DR DrugBank; DB00925; Phenoxybenzamine.
DR DrugBank; DB01621; Pipotiazine.
DR DrugBank; DB11642; Pitolisant.
DR DrugBank; DB00413; Pramipexole.
DR DrugBank; DB00457; Prazosin.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB01035; Procainamide.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB00863; Ranitidine.
DR DrugBank; DB00206; Reserpine.
DR DrugBank; DB00728; Rocuronium.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB00938; Salmeterol.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB03566; Spermidine.
DR DrugBank; DB00127; Spermine.
DR DrugBank; DB00391; Sulpiride.
DR DrugBank; DB08837; Tetraethylammonium.
DR DrugBank; DB00152; Thiamine.
DR DrugBank; DB01623; Thiothixene.
DR DrugBank; DB06137; Tirbanibulin.
DR DrugBank; DB01199; Tubocurarine.
DR DrugBank; DB00661; Verapamil.
DR DrugCentral; O15245; -.
DR GuidetoPHARMACOLOGY; 1019; -.
DR TCDB; 2.A.1.19.29; the major facilitator superfamily (mfs).
DR GlyGen; O15245; 1 site.
DR iPTMnet; O15245; -.
DR PhosphoSitePlus; O15245; -.
DR BioMuta; SLC22A1; -.
DR MassIVE; O15245; -.
DR PaxDb; O15245; -.
DR PeptideAtlas; O15245; -.
DR PRIDE; O15245; -.
DR ProteomicsDB; 48536; -. [O15245-1]
DR ProteomicsDB; 48537; -. [O15245-2]
DR ProteomicsDB; 48538; -. [O15245-3]
DR ProteomicsDB; 48539; -. [O15245-4]
DR Antibodypedia; 33480; 303 antibodies from 33 providers.
DR DNASU; 6580; -.
DR Ensembl; ENST00000324965.8; ENSP00000318103.4; ENSG00000175003.15. [O15245-2]
DR Ensembl; ENST00000366963.9; ENSP00000355930.4; ENSG00000175003.15. [O15245-1]
DR Ensembl; ENST00000457470.6; ENSP00000409557.2; ENSG00000175003.15. [O15245-3]
DR Ensembl; ENST00000460902.2; ENSP00000439274.1; ENSG00000175003.15. [O15245-4]
DR GeneID; 6580; -.
DR KEGG; hsa:6580; -.
DR MANE-Select; ENST00000366963.9; ENSP00000355930.4; NM_003057.3; NP_003048.1.
DR UCSC; uc003qtc.4; human. [O15245-1]
DR CTD; 6580; -.
DR DisGeNET; 6580; -.
DR GeneCards; SLC22A1; -.
DR HGNC; HGNC:10963; SLC22A1.
DR HPA; ENSG00000175003; Tissue enriched (liver).
DR MIM; 602607; gene.
DR neXtProt; NX_O15245; -.
DR OpenTargets; ENSG00000175003; -.
DR PharmGKB; PA329; -.
DR VEuPathDB; HostDB:ENSG00000175003; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000162065; -.
DR HOGENOM; CLU_001265_33_5_1; -.
DR InParanoid; O15245; -.
DR OMA; YLWFSCA; -.
DR OrthoDB; 704438at2759; -.
DR PhylomeDB; O15245; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; O15245; -.
DR Reactome; R-HSA-112311; Neurotransmitter clearance.
DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-2161517; Abacavir transmembrane transport.
DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-HSA-549127; Organic cation transport.
DR SignaLink; O15245; -.
DR BioGRID-ORCS; 6580; 10 hits in 1068 CRISPR screens.
DR GeneWiki; SLC22A1; -.
DR GenomeRNAi; 6580; -.
DR Pharos; O15245; Tchem.
DR PRO; PR:O15245; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O15245; protein.
DR Bgee; ENSG00000175003; Expressed in right lobe of liver and 98 other tissues.
DR ExpressionAtlas; O15245; baseline and differential.
DR Genevisible; O15245; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; IEA:Ensembl.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:ARUK-UCL.
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:ARUK-UCL.
DR GO; GO:0008513; F:secondary active organic cation transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0090494; P:dopamine uptake; IDA:ARUK-UCL.
DR GO; GO:0048241; P:epinephrine transport; IEA:Ensembl.
DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; IEA:Ensembl.
DR GO; GO:0006836; P:neurotransmitter transport; IDA:ARUK-UCL.
DR GO; GO:0015874; P:norepinephrine transport; IDA:ARUK-UCL.
DR GO; GO:0015695; P:organic cation transport; IDA:ARUK-UCL.
DR GO; GO:0072530; P:purine-containing compound transmembrane transport; TAS:Reactome.
DR GO; GO:0015697; P:quaternary ammonium group transport; IDA:ARUK-UCL.
DR GO; GO:0051610; P:serotonin uptake; IDA:ARUK-UCL.
DR GO; GO:1901998; P:toxin transport; IDA:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0042908; P:xenobiotic transport; IDA: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; 2.
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..554
FT /note="Solute carrier family 22 member 1"
FT /id="PRO_0000333875"
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..149
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 171..176
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 177..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..206
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..262
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..347
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 369..376
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..431
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..464
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 486..492
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 493..513
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 514..554
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT SITE 450
FT /note="Involved in affinity and selectivity of cations as
FT well as in translocation"
FT /evidence="ECO:0000250"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08966"
FT MOD_RES 541
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 354..554
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_033587"
FT VAR_SEQ 462..532
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_033588"
FT VAR_SEQ 462..506
FT /note="RNLGVMVCSSLCDIGGIITPFIVFRLREVWQALPLILFAVLGLLA -> SGV
FT GPACRGSDATSSRDQGGRFARDHEGRREPWEKSKAQRKHDLP (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_033589"
FT VAR_SEQ 507..554
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_033590"
FT VARIANT 14
FT /note="S -> F (exclusively found in the African American
FT population; increase of the MPP uptake when associated with
FT V-408; dbSNP:rs34447885)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043319"
FT VARIANT 41
FT /note="F -> L (in dbSNP:rs2297373)"
FT /evidence="ECO:0000269|PubMed:15499200"
FT /id="VAR_043320"
FT VARIANT 61
FT /note="R -> C (affects transporter activity; reduction of
FT the MPP uptake when associated with V-408;
FT dbSNP:rs12208357)"
FT /evidence="ECO:0000269|PubMed:12439218,
FT ECO:0000269|PubMed:12719534"
FT /id="VAR_043321"
FT VARIANT 85
FT /note="L -> F (no changes in the MPP uptake when associated
FT with V-408; dbSNP:rs35546288)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043322"
FT VARIANT 88
FT /note="C -> R (in dbSNP:rs55918055)"
FT /evidence="ECO:0000269|PubMed:12439218"
FT /id="VAR_043323"
FT VARIANT 160
FT /note="L -> F (no changes in both TEA and MPP uptake;
FT abolishes MPP uptake when associated with S-401; largely
FT localized to the plasma membrane; dbSNP:rs683369)"
FT /evidence="ECO:0000269|PubMed:12439218,
FT ECO:0000269|PubMed:12719534, ECO:0000269|PubMed:14697261,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15499200, ECO:0000269|PubMed:9260930"
FT /id="VAR_043324"
FT VARIANT 189
FT /note="S -> L (no changes in the MPP uptake;
FT dbSNP:rs34104736)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043325"
FT VARIANT 220
FT /note="G -> V (affects MPP uptake; reduction of the MPP
FT uptake when associated with V-408; dbSNP:rs36103319)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043326"
FT VARIANT 283
FT /note="P -> L (in dbSNP:rs4646277)"
FT /evidence="ECO:0000269|PubMed:14697261"
FT /id="VAR_043327"
FT VARIANT 287
FT /note="R -> G (in dbSNP:rs4646278)"
FT /evidence="ECO:0000269|PubMed:14697261"
FT /id="VAR_043328"
FT VARIANT 341
FT /note="P -> L (affects transporter activity; reduction of
FT the TEA uptake; reduction of the MPP uptake when associated
FT with V-408; largely localized to the plasma membrane;
FT dbSNP:rs2282143)"
FT /evidence="ECO:0000269|PubMed:12719534,
FT ECO:0000269|PubMed:14697261, ECO:0000269|PubMed:15499200"
FT /id="VAR_043329"
FT VARIANT 342
FT /note="R -> H (no changes in the MPP uptake when associated
FT with V-408; dbSNP:rs34205214)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043330"
FT VARIANT 401
FT /note="G -> S (affects transporter activity; reduction of
FT the serotonin uptake; no MPP uptake when associated with L-
FT 160; dbSNP:rs34130495)"
FT /evidence="ECO:0000269|PubMed:12439218,
FT ECO:0000269|PubMed:12719534"
FT /id="VAR_043331"
FT VARIANT 408
FT /note="M -> V (does not affect transporter activity; no
FT changes in the MPP uptake when associated with F-14; no
FT changes in the MPP uptake when associated with F-85; no
FT changes in the MPP uptake when associated with L-189; no
FT changes in the MPP uptake when associated with His-342; no
FT changes in the MPP uptake when associated with M-420 del;
FT no changes in the MPP uptake when associated with I-440; no
FT changes in the MPP uptake when associated with I-461; no
FT changes in the MPP uptake when associated with M-488;
FT reduction of the MPP uptake when associated with C-61; no
FT MPP uptake when associated with V-220; reduction of the MPP
FT uptake when associated with L-341; no MPP uptake when
FT associated with S-401; no MPP uptake when associated with
FT R-465; dbSNP:rs628031)"
FT /evidence="ECO:0000269|PubMed:12719534,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15499200"
FT /id="VAR_043332"
FT VARIANT 420
FT /note="Missing (no changes in the MPP uptake when
FT associated with V-408; dbSNP:rs72552763)"
FT /evidence="ECO:0000269|PubMed:12439218,
FT ECO:0000269|PubMed:12719534, ECO:0000269|PubMed:14702039"
FT /id="VAR_043333"
FT VARIANT 440
FT /note="M -> I (in dbSNP:rs35956182)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043334"
FT VARIANT 461
FT /note="V -> I (no changes in the MPP uptake when associated
FT with V-408; dbSNP:rs34295611)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043335"
FT VARIANT 465
FT /note="G -> R (reduction of the localization to the
FT basolateral membrane; no MPP uptake when associated with V-
FT 408; dbSNP:rs34059508)"
FT /evidence="ECO:0000269|PubMed:12719534,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_043336"
FT VARIANT 488
FT /note="R -> M (no changes in the MPP uptake when associated
FT with V-408; dbSNP:rs35270274)"
FT /evidence="ECO:0000269|PubMed:12719534"
FT /id="VAR_043337"
FT MUTAGEN 465
FT /note="G->A: No changes in the MPP uptake."
FT /evidence="ECO:0000269|PubMed:12719534"
SQ SEQUENCE 554 AA; 61154 MW; 55206B897DE32202 CRC64;
MPTVDDILEQ VGESGWFQKQ AFLILCLLSA AFAPICVGIV FLGFTPDHHC QSPGVAELSQ
RCGWSPAEEL NYTVPGLGPA GEAFLGQCRR YEVDWNQSAL SCVDPLASLA TNRSHLPLGP
CQDGWVYDTP GSSIVTEFNL VCADSWKLDL FQSCLNAGFL FGSLGVGYFA DRFGRKLCLL
GTVLVNAVSG VLMAFSPNYM SMLLFRLLQG LVSKGNWMAG YTLITEFVGS GSRRTVAIMY
QMAFTVGLVA LTGLAYALPH WRWLQLAVSL PTFLFLLYYW CVPESPRWLL SQKRNTEAIK
IMDHIAQKNG KLPPADLKML SLEEDVTEKL SPSFADLFRT PRLRKRTFIL MYLWFTDSVL
YQGLILHMGA TSGNLYLDFL YSALVEIPGA FIALITIDRV GRIYPMAMSN LLAGAACLVM
IFISPDLHWL NIIIMCVGRM GITIAIQMIC LVNAELYPTF VRNLGVMVCS SLCDIGGIIT
PFIVFRLREV WQALPLILFA VLGLLAAGVT LLLPETKGVA LPETMKDAEN LGRKAKPKEN
TIYLKVQTSE PSGT
