ID S22A2_PIG Reviewed; 554 AA.
AC O02713;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 24-JAN-2024, entry version 128.
DE RecName: Full=Solute carrier family 22 member 2 {ECO:0000250|UniProtKB:O15244};
DE AltName: Full=Apical organic cation transporter {ECO:0000250|UniProtKB:O15244};
DE AltName: Full=Organic cation transporter 2 {ECO:0000250|UniProtKB:O15244};
GN Name=SLC22A2; Synonyms=OCT2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=9099681; DOI=10.1074/jbc.272.16.10408;
RA Grundemann D., Babin-Ebell J., Martel F., Ording N., Schmidt A.,
RA Schoemig E.;
RT "Primary structure and functional expression of the apical organic cation
RT transporter from kidney epithelial LLC-PK1 cells.";
RL J. Biol. Chem. 272:10408-10413(1997).
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. Functions as a Na(+)-
CC independent, bidirectional uniporter. Cation cellular uptake or release
CC is driven by the electrochemical potential, i.e. membrane potential and
CC concentration gradient (By similarity). However, may also engage
CC electroneutral cation exchange when saturating concentrations of cation
CC substrates are reached (By similarity). Predominantly expressed at the
CC basolateral membrane of hepatocytes and proximal tubules and involved
CC in the uptake and disposition of cationic compounds by hepatic and
CC renal clearance from the blood flow. Implicated in monoamine
CC neurotransmitters uptake such as histamine, dopamine,
CC adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and
CC tyramine, thereby supporting a physiological role in the central
CC nervous system by regulating interstitial concentrations of
CC neurotransmitters. Also capable of transporting dopaminergic
CC neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol,
CC thereby involved in the maintenance of dopaminergic cell integrity in
CC the central nervous system. Mediates the bidirectional transport of
CC acetylcholine (ACh) at the apical membrane of ciliated cell in airway
CC epithelium, thereby playing a role in luminal release of ACh from
CC bronchial epithelium. Also transports guanidine and endogenous
CC monoamines such as vitamin B1/thiamine, creatinine and N-1-
CC methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary
CC ammonium compound choline. Mediates the bidirectional transport of
CC polyamine agmatine and the uptake of polyamines putrescine and
CC spermidine. Able to transport non-amine endogenous compounds such as
CC prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also
CC involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-
CC methylpyridinium (ASP). May contribute to regulate the transport of
CC organic compounds in testis across the blood-testis-barrier (By
CC similarity). {ECO:0000250|UniProtKB:O15244,
CC ECO:0000250|UniProtKB:Q9R0W2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-noradrenaline(out) = (R)-noradrenaline(in);
CC Xref=Rhea:RHEA:73871, ChEBI:CHEBI:72587;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-adrenaline(out) = (R)-adrenaline(in);
CC Xref=Rhea:RHEA:73875, ChEBI:CHEBI:71406;
CC Evidence={ECO:0000250|UniProtKB:Q9R0W2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=serotonin(out) = serotonin(in); Xref=Rhea:RHEA:73867,
CC ChEBI:CHEBI:350546; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dopamine(out) = dopamine(in); Xref=Rhea:RHEA:73863,
CC ChEBI:CHEBI:59905; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=histamine(out) = histamine(in); Xref=Rhea:RHEA:73879,
CC ChEBI:CHEBI:58432; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=thiamine(in) = thiamine(out); Xref=Rhea:RHEA:34919,
CC ChEBI:CHEBI:18385; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=creatinine(in) = creatinine(out); Xref=Rhea:RHEA:74539,
CC ChEBI:CHEBI:16737; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-methylnicotinamide(out) = 1-methylnicotinamide(in);
CC Xref=Rhea:RHEA:73859, ChEBI:CHEBI:16797;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanidine(out) = guanidine(in); Xref=Rhea:RHEA:73883,
CC ChEBI:CHEBI:30087; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=choline(out) = choline(in); Xref=Rhea:RHEA:32751,
CC ChEBI:CHEBI:15354; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=agmatine(out) = agmatine(in); Xref=Rhea:RHEA:72131,
CC ChEBI:CHEBI:58145; Evidence={ECO:0000250|UniProtKB:O15244};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72132;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:72133;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=putrescine(out) = putrescine(in); Xref=Rhea:RHEA:72135,
CC ChEBI:CHEBI:326268; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=spermidine(in) = spermidine(out); Xref=Rhea:RHEA:35039,
CC ChEBI:CHEBI:57834; Evidence={ECO:0000250|UniProtKB:O70577};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tyramine(in) = tyramine(out); Xref=Rhea:RHEA:74783,
CC ChEBI:CHEBI:327995; Evidence={ECO:0000250|UniProtKB:O15244};
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:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-salsolinol(in) = (R)-salsolinol(out);
CC Xref=Rhea:RHEA:74791, ChEBI:CHEBI:194082;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-methyl-(R)-salsolinol(in) = N-methyl-(R)-salsolinol(out);
CC Xref=Rhea:RHEA:74795, ChEBI:CHEBI:194083;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetylcholine(in) = acetylcholine(out); Xref=Rhea:RHEA:74663,
CC ChEBI:CHEBI:15355; Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin F2alpha(out) = prostaglandin F2alpha(in);
CC Xref=Rhea:RHEA:50988, ChEBI:CHEBI:57404;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin E2(out) = prostaglandin E2(in);
CC Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564;
CC Evidence={ECO:0000250|UniProtKB:O15244};
CC -!- ACTIVITY REGULATION: Tyrosine phosphorylation of the transporter leads
CC to activation of the transport activity. Inhibited by cGMP, most likely
CC through a cGMP-binding protein that interacts with OCT2.
CC {ECO:0000250|UniProtKB:O15244}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q9R0W2}; Multi-pass membrane protein
CC {ECO:0000305}. Basal cell membrane {ECO:0000250|UniProtKB:O15244};
CC Multi-pass membrane protein {ECO:0000305}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O15244}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- DOMAIN: Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that
CC may be involved in tyrosine-protein kinase YES1 binding and is required
CC for the activation of substrate transport.
CC {ECO:0000250|UniProtKB:O15244}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000250|UniProtKB:O15244}.
CC -!- MISCELLANEOUS: Mediates the renal secretion of many clinically used
CC cationic drugs. Transports drugs such as diabetes treatment medicine
CC metformin and neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)),
CC famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine,
CC cimetidine, cisplatin, oxaliplatin, platinum-based drugs cisplatin and
CC oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium
CC (TEA). Mediates the bidirectional transport of MPP(+). Metformin
CC competitively inhibits OCT1-mediated thiamine uptake, leading to a
CC decrease in hepatic steatosis. Plays a predominant role in the
CC anticancer activity of cisplatin and oxaliplatin and may contribute to
CC antitumor specificity (By similarity). Involved in cisplatin-induced
CC nephrotoxicity (By similarity). {ECO:0000250|UniProtKB:O15244,
CC ECO:0000250|UniProtKB:Q9R0W2}.
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: While most authors have deduced a localization at the
CC basolateral membrane of proximal tubules, other studies demonstrated a
CC localization to the luminal membrane in the distal tubule.
CC {ECO:0000250|UniProtKB:O15244}.
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DR EMBL; Y09400; CAA70567.1; -; mRNA.
DR RefSeq; NP_999067.1; NM_213902.1.
DR AlphaFoldDB; O02713; -.
DR SMR; O02713; -.
DR STRING; 9823.ENSSSCP00000004366; -.
DR TCDB; 2.A.1.19.5; the major facilitator superfamily (mfs).
DR GlyCosmos; O02713; 1 site, No reported glycans.
DR PaxDb; 9823-ENSSSCP00000004366; -.
DR Ensembl; ENSSSCT00035082011.1; ENSSSCP00035033991.1; ENSSSCG00035061058.1.
DR Ensembl; ENSSSCT00040020681.1; ENSSSCP00040008685.1; ENSSSCG00040015330.1.
DR Ensembl; ENSSSCT00045028737.1; ENSSSCP00045019883.1; ENSSSCG00045016889.1.
DR Ensembl; ENSSSCT00055022315.1; ENSSSCP00055017684.1; ENSSSCG00055011340.1.
DR Ensembl; ENSSSCT00065065075.1; ENSSSCP00065028203.1; ENSSSCG00065047562.1.
DR Ensembl; ENSSSCT00070054098.1; ENSSSCP00070045864.1; ENSSSCG00070026975.1.
DR GeneID; 396936; -.
DR KEGG; ssc:396936; -.
DR CTD; 6582; -.
DR eggNOG; KOG0255; Eukaryota.
DR InParanoid; O02713; -.
DR OrthoDB; 1474205at2759; -.
DR Reactome; R-SSC-112311; Neurotransmitter clearance.
DR Reactome; R-SSC-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-SSC-2161517; Abacavir transmembrane transport.
DR Reactome; R-SSC-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-SSC-549127; Organic cation transport.
DR ChiTaRS; SLC22A2; pig.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 1.
DR Proteomes; UP000694570; Unplaced.
DR Proteomes; UP000694571; Unplaced.
DR Proteomes; UP000694720; Unplaced.
DR Proteomes; UP000694722; Unplaced.
DR Proteomes; UP000694723; Unplaced.
DR Proteomes; UP000694724; Unplaced.
DR Proteomes; UP000694725; Unplaced.
DR Proteomes; UP000694726; Unplaced.
DR Proteomes; UP000694727; Unplaced.
DR Proteomes; UP000694728; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; ISS:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005277; F:acetylcholine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0008514; F:organic anion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; ISS:UniProtKB.
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:0015651; F:quaternary ammonium group transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015606; F:spermidine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015234; F:thiamine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015870; P:acetylcholine transport; ISS:UniProtKB.
DR GO; GO:0015872; P:dopamine transport; ISS:UniProtKB.
DR GO; GO:0048241; P:epinephrine transport; ISS:UniProtKB.
DR GO; GO:0051608; P:histamine transport; ISS:UniProtKB.
DR GO; GO:0006811; P:monoatomic ion transport; IEA:UniProtKB-KW.
DR GO; GO:0015874; P:norepinephrine transport; ISS:UniProtKB.
DR GO; GO:0015695; P:organic cation transport; IBA:GO_Central.
DR GO; GO:0015732; P:prostaglandin transport; ISS:UniProtKB.
DR GO; GO:0015847; P:putrescine transport; ISS:UniProtKB.
DR GO; GO:0006837; P:serotonin transport; ISS:UniProtKB.
DR GO; GO:0015848; P:spermidine transport; ISS:UniProtKB.
DR GO; GO:0071934; P:thiamine transmembrane transport; ISS:UniProtKB.
DR CDD; cd17379; MFS_SLC22A1_2_3; 1.
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:SF432; SOLUTE CARRIER FAMILY 22 MEMBER 2; 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; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Ion transport; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..554
FT /note="Solute carrier family 22 member 2"
FT /id="PRO_0000320959"
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..209
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..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..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 404..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..431
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 453..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 464..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..493
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 515..554
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 283..287
FT /note="Proline-rich sequence"
FT /evidence="ECO:0000250|UniProtKB:O15244"
FT SITE 450
FT /note="Involved in recognition of organic cations and
FT participates in structural changes that occur during
FT translocation of organic cations"
FT /evidence="ECO:0000250|UniProtKB:Q9R0W2"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 554 AA; 61990 MW; E14B5565600C553B CRC64;
MLTVDDILEH TGEFNFFQKQ TFFLLALLSA AFTPIYVGIV FLGFIPDHRC RSPGVAELSQ
RCGWSLAEEL NYTVPGPGPA GQAFPRQCRR YEVDWNQSTL GCVDPLAGLA ANSSHLPLGP
CRYGWVYDTP GSSIVTEFDL VCANSWLLDL FQSAVNVGFF IGSVGIGYIA DRFGRKLCLL
LTILINAVSG VLMAISPTYT WMLVFRLIQG LVSKAGWMIG YILITEFVGL SYRRTVGIFY
QVAFTFGLLV LAGVAYALPH WRWLQFTVTL PNFCFLFYYW CVPESPRWLI SQNKNAKAMS
IIKHIAKKNG KSLPASLQSL RPDEEVGEKL KPSFLDLVRT PQIRKHTLIL MYNWFTSAVL
YQGLVMHMGL AGSNLYLDFF YSALVEFPAA LLILLTIDRL GRRHPWAASN VVAGAACLAS
VFIPEDPHWL RITVLCLGRM GITMAYEMVC LVNAELYPTF IRNLGVLVCS SMCDIGGIIT
PFLVYRLTDI WHELPLVVFA VVGLIAGGLV LLLPETKGKT LPETIEEAET MRRPRKNKEK
IIYLQVKKLD IPPN
//
