S22A3_HUMAN
ID S22A3_HUMAN Reviewed; 556 AA.
AC O75751; Q5SYN6; Q9UP02;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Solute carrier family 22 member 3;
DE AltName: Full=Extraneuronal monoamine transporter;
DE Short=EMT;
DE AltName: Full=Organic cation transporter 3;
GN Name=SLC22A3; Synonyms=EMTH, OCT3;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10196521; DOI=10.1038/1557;
RA Gruendemann D., Schechinger B., Rappold G.A., Schoemig E.;
RT "Molecular identification of the corticosterone-sensitive extraneuronal
RT catecholamine transporter.";
RL Nat. Neurosci. 1:349-351(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 513-556, AND TISSUE SPECIFICITY.
RX PubMed=9933568; DOI=10.1006/geno.1998.5639;
RA Verhaagh S., Schweifer N., Barlow D.P., Zwart R.;
RT "Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3)
RT identifies a conserved cluster of three organic cation transporters on
RT mouse chromosome 17 and human 6q26-q27.";
RL Genomics 55:209-218(1999).
RN [6] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10966924; DOI=10.1152/ajprenal.2000.279.3.f449;
RA Wu X., Huang W., Ganapathy M.E., Wang H., Kekuda R., Conway S.J.,
RA Leibach F.H., Ganapathy V.;
RT "Structure, function, and regional distribution of the organic cation
RT transporter OCT3 in the kidney.";
RL Am. J. Physiol. 279:F449-F458(2000).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Mediates potential-dependent transport of a variety of
CC organic cations. May play a significant role in the disposition of
CC cationic neurotoxins and neurotransmitters in the brain.
CC {ECO:0000269|PubMed:10196521, ECO:0000269|PubMed:10966924}.
CC -!- INTERACTION:
CC O75751; P00519: ABL1; NbExp=2; IntAct=EBI-1752674, EBI-375543;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in placenta, skeletal muscle, prostate,
CC aorta, liver, fetal lung, salivary gland, adrenal gland, kidney and
CC brain cortex. No expression detected in spleen.
CC {ECO:0000269|PubMed:10196521, ECO:0000269|PubMed:10966924,
CC ECO:0000269|PubMed:9933568}.
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; AJ001417; CAA04751.1; -; mRNA.
DR EMBL; AK314590; BAG37164.1; -; mRNA.
DR EMBL; AL591069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47599.1; -; Genomic_DNA.
DR EMBL; AF078749; AAD20977.1; -; mRNA.
DR CCDS; CCDS5277.1; -.
DR RefSeq; NP_068812.1; NM_021977.3.
DR AlphaFoldDB; O75751; -.
DR SMR; O75751; -.
DR BioGRID; 112468; 6.
DR IntAct; O75751; 2.
DR STRING; 9606.ENSP00000275300; -.
DR BindingDB; O75751; -.
DR ChEMBL; CHEMBL2073673; -.
DR DrugBank; DB00718; Adefovir dipivoxil.
DR DrugBank; DB08838; Agmatine.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB00122; Choline.
DR DrugBank; DB14006; Choline salicylate.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB00575; Clonidine.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB00988; Dopamine.
DR DrugBank; DB00783; Estradiol.
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; DB00536; Guanidine.
DR DrugBank; DB05381; Histamine.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB00709; Lamivudine.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB08882; Linagliptin.
DR DrugBank; DB01042; Melphalan.
DR DrugBank; DB01577; Metamfetamine.
DR DrugBank; DB00331; Metformin.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB00368; Norepinephrine.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB00925; Phenoxybenzamine.
DR DrugBank; DB00413; Pramipexole.
DR DrugBank; DB00457; Prazosin.
DR DrugBank; DB01035; Procainamide.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB00938; Salmeterol.
DR DrugBank; DB00391; Sulpiride.
DR DrugBank; DB13943; Testosterone cypionate.
DR DrugBank; DB13944; Testosterone enanthate.
DR DrugBank; DB08837; Tetraethylammonium.
DR DrugBank; DB08841; Tyramine.
DR DrugBank; DB00541; Vincristine.
DR DrugCentral; O75751; -.
DR GuidetoPHARMACOLOGY; 1021; -.
DR TCDB; 2.A.1.19.24; the major facilitator superfamily (mfs).
DR GlyGen; O75751; 4 sites.
DR iPTMnet; O75751; -.
DR PhosphoSitePlus; O75751; -.
DR BioMuta; SLC22A3; -.
DR jPOST; O75751; -.
DR MassIVE; O75751; -.
DR PaxDb; O75751; -.
DR PeptideAtlas; O75751; -.
DR PRIDE; O75751; -.
DR ProteomicsDB; 50179; -.
DR Antibodypedia; 20034; 213 antibodies from 34 providers.
DR DNASU; 6581; -.
DR Ensembl; ENST00000275300.3; ENSP00000275300.2; ENSG00000146477.6.
DR GeneID; 6581; -.
DR KEGG; hsa:6581; -.
DR MANE-Select; ENST00000275300.3; ENSP00000275300.2; NM_021977.4; NP_068812.1.
DR UCSC; uc003qti.5; human.
DR CTD; 6581; -.
DR DisGeNET; 6581; -.
DR GeneCards; SLC22A3; -.
DR HGNC; HGNC:10967; SLC22A3.
DR HPA; ENSG00000146477; Tissue enhanced (skeletal).
DR MIM; 604842; gene.
DR neXtProt; NX_O75751; -.
DR OpenTargets; ENSG00000146477; -.
DR PharmGKB; PA330; -.
DR VEuPathDB; HostDB:ENSG00000146477; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000160810; -.
DR HOGENOM; CLU_001265_33_5_1; -.
DR InParanoid; O75751; -.
DR OMA; QMRRNTL; -.
DR OrthoDB; 762280at2759; -.
DR PhylomeDB; O75751; -.
DR TreeFam; TF315847; -.
DR PathwayCommons; O75751; -.
DR Reactome; R-HSA-2161517; Abacavir transmembrane transport.
DR Reactome; R-HSA-549127; Organic cation transport.
DR SignaLink; O75751; -.
DR BioGRID-ORCS; 6581; 14 hits in 1068 CRISPR screens.
DR ChiTaRS; SLC22A3; human.
DR GeneWiki; SLC22A3; -.
DR GenomeRNAi; 6581; -.
DR Pharos; O75751; Tchem.
DR PRO; PR:O75751; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O75751; protein.
DR Bgee; ENSG00000146477; Expressed in thoracic aorta and 121 other tissues.
DR Genevisible; O75751; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
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:0008514; F:organic anion transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0090494; P:dopamine uptake; IDA:ARUK-UCL.
DR GO; GO:0051625; P:epinephrine uptake; IDA:ARUK-UCL.
DR GO; GO:0001692; P:histamine metabolic process; TAS:ARUK-UCL.
DR GO; GO:0051615; P:histamine uptake; IDA:ARUK-UCL.
DR GO; GO:0015844; P:monoamine transport; IMP:ARUK-UCL.
DR GO; GO:0015718; P:monocarboxylic acid transport; IEA:Ensembl.
DR GO; GO:0006836; P:neurotransmitter transport; IDA:ARUK-UCL.
DR GO; GO:0051620; P:norepinephrine uptake; IDA:ARUK-UCL.
DR GO; GO:0015711; P:organic anion transport; ISS: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:0032098; P:regulation of appetite; IEA:Ensembl.
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 Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR004749; Orgcat_transp/SVOP.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF07690; MFS_1; 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 Glycoprotein; Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..556
FT /note="Solute carrier family 22 member 3"
FT /id="PRO_0000220503"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 468..488
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 44
FT /note="T -> M (in dbSNP:rs8187715)"
FT /id="VAR_020351"
FT VARIANT 116
FT /note="A -> S (in dbSNP:rs8187717)"
FT /id="VAR_020352"
SQ SEQUENCE 556 AA; 61280 MW; C3CA2D77DD21C658 CRC64;
MPSFDEALQR VGEFGRFQRR VFLLLCLTGV TFAFLFVGVV FLGTQPDHYW CRGPSAAALA
ERCGWSPEEE WNRTAPASRG PEPPERRGRC QRYLLEAAND SASATSALSC ADPLAAFPNR
SAPLVPCRGG WRYAQAHSTI VSEFDLVCVN AWMLDLTQAI LNLGFLTGAF TLGYAADRYG
RIVIYLLSCL GVGVTGVVVA FAPNFPVFVI FRFLQGVFGK GTWMTCYVIV TEIVGSKQRR
IVGIVIQMFF TLGIIILPGI AYFIPNWQGI QLAITLPSFL FLLYYWVVPE SPRWLITRKK
GDKALQILRR IAKCNGKYLS SNYSEITVTD EEVSNPSFLD LVRTPQMRKC TLILMFAWFT
SAVVYQGLVM RLGIIGGNLY IDFFISGVVE LPGALLILLT IERLGRRLPF AASNIVAGVA
CLVTAFLPEG IAWLRTTVAT LGRLGITMAF EIVYLVNSEL YPTTLRNFGV SLCSGLCDFG
GIIAPFLLFR LAAVWLELPL IIFGILASIC GGLVMLLPET KGIALPETVD DVEKLGSPHS
CKCGRNKKTP VSRSHL
