S22A5_MOUSE
ID S22A5_MOUSE Reviewed; 557 AA.
AC Q9Z0E8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Solute carrier family 22 member 5;
DE AltName: Full=High-affinity sodium-dependent carnitine cotransporter;
DE AltName: Full=Organic cation/carnitine transporter 2;
GN Name=Slc22a5; Synonyms=Octn2;
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].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=9916797; DOI=10.1038/5030;
RA Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N.,
RA Nikaido H., Sai Y., Koizumi A., Shoji Y., Takada G., Matsuishi T.,
RA Yashino M., Kato H., Ohura T., Tsujimoto G., Hayakawa J., Shimane M.,
RA Tsuji A.;
RT "Primary systemic carnitine deficiency is caused by mutations in a gene
RT encoding sodium ion-dependent carnitine transporter.";
RL Nat. Genet. 21:91-94(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT JVS ARG-352.
RC STRAIN=C3H/HeJ;
RX PubMed=9837751; DOI=10.1006/bbrc.1998.9708;
RA Lu K., Nishimori H., Nakamura Y., Shima K., Kuwajima M.;
RT "A missense mutation of mouse OCTN2, a sodium-dependent carnitine
RT cotransporter, in the juvenile visceral steatosis mouse.";
RL Biochem. Biophys. Res. Commun. 252:590-594(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=10454528;
RA Wu X., Huang W., Prasad P.D., Seth P., Rajan D.P., Leibach F.H., Chen J.,
RA Conway S.J., Ganapathy V.;
RT "Functional characteristics and tissue distribution pattern of organic
RT cation transporter 2 (OCTN2), an organic cation/carnitine transporter.";
RL J. Pharmacol. Exp. Ther. 290:1482-1492(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=11010964; DOI=10.1074/jbc.m005340200;
RA Tamai I., Ohashi R., Nezu J., Sai Y., Kobayashi D., Oku A., Shimane M.,
RA Tsuji A.;
RT "Molecular and functional characterization of organic cation/carnitine
RT transporter family in mice.";
RL J. Biol. Chem. 275:40064-40072(2000).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PDZK1.
RX PubMed=15523054; DOI=10.1124/mol.104.002212;
RA Kato Y., Sai Y., Yoshida K., Watanabe C., Hirata T., Tsuji A.;
RT "PDZK1 directly regulates the function of organic cation/carnitine
RT transporter OCTN2.";
RL Mol. Pharmacol. 67:734-743(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-550, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and 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).
CC -!- FUNCTION: Sodium-ion dependent, high affinity carnitine transporter.
CC Involved in the active cellular uptake of carnitine. Transports one
CC sodium ion with one molecule of carnitine. Also transports organic
CC cations such as tetraethylammonium (TEA) without the involvement of
CC sodium. Also relative uptake activity ratio of carnitine to TEA is
CC 11.3.
CC -!- SUBUNIT: Interacts with PDZK1. {ECO:0000269|PubMed:15523054}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:15523054}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15523054}. Note=Colocalizes with PDZK1 on apical
CC membranes of kidney proximal tubules.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in kidney, liver and
CC testis. {ECO:0000269|PubMed:11010964}.
CC -!- DISEASE: Note=Defects in Slc22a5 are the cause of the juvenile visceral
CC steatosis (JVS) phenotype. JVS is an autosomal recessive animal model
CC of systemic carnitine deficiency.
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; AB015800; BAA36590.1; -; mRNA.
DR EMBL; AF111425; AAC99787.1; -; mRNA.
DR EMBL; AF110417; AAD54060.1; -; mRNA.
DR EMBL; BC031118; AAH31118.1; -; mRNA.
DR CCDS; CCDS24687.1; -.
DR RefSeq; NP_035526.1; NM_011396.3.
DR AlphaFoldDB; Q9Z0E8; -.
DR SMR; Q9Z0E8; -.
DR STRING; 10090.ENSMUSP00000019044; -.
DR ChEMBL; CHEMBL2073665; -.
DR GlyConnect; 2733; 2 N-Linked glycans (1 site).
DR GlyGen; Q9Z0E8; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9Z0E8; -.
DR PhosphoSitePlus; Q9Z0E8; -.
DR jPOST; Q9Z0E8; -.
DR MaxQB; Q9Z0E8; -.
DR PaxDb; Q9Z0E8; -.
DR PRIDE; Q9Z0E8; -.
DR ProteomicsDB; 260885; -.
DR DNASU; 20520; -.
DR Ensembl; ENSMUST00000019044; ENSMUSP00000019044; ENSMUSG00000018900.
DR GeneID; 20520; -.
DR KEGG; mmu:20520; -.
DR UCSC; uc007ixc.2; mouse.
DR CTD; 6584; -.
DR MGI; MGI:1329012; Slc22a5.
DR VEuPathDB; HostDB:ENSMUSG00000018900; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00940000154155; -.
DR HOGENOM; CLU_001265_33_4_1; -.
DR InParanoid; Q9Z0E8; -.
DR OMA; MSWWLVP; -.
DR OrthoDB; 396963at2759; -.
DR PhylomeDB; Q9Z0E8; -.
DR TreeFam; TF315847; -.
DR Reactome; R-MMU-200425; Carnitine metabolism.
DR Reactome; R-MMU-549127; Organic cation transport.
DR BioGRID-ORCS; 20520; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Slc22a5; mouse.
DR PRO; PR:Q9Z0E8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9Z0E8; protein.
DR Bgee; ENSMUSG00000018900; Expressed in right kidney and 124 other tissues.
DR ExpressionAtlas; Q9Z0E8; baseline and differential.
DR Genevisible; Q9Z0E8; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IC:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:1901235; F:(R)-carnitine transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015226; F:carnitine transmembrane transporter activity; IDA:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:MGI.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:1902270; P:(R)-carnitine transmembrane transport; IMP:ARUK-UCL.
DR GO; GO:0007512; P:adult heart development; IMP:MGI.
DR GO; GO:0009437; P:carnitine metabolic process; IMP:MGI.
DR GO; GO:0015879; P:carnitine transport; IDA:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:0060731; P:positive regulation of intestinal epithelial structure maintenance; ISO:MGI.
DR GO; GO:0015697; P:quaternary ammonium group transport; IDA:MGI.
DR GO; GO:0048608; P:reproductive structure development; IMP:MGI.
DR GO; GO:0009609; P:response to symbiotic bacterium; ISO:MGI.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0070715; P:sodium-dependent organic cation transport; ISO:MGI.
DR GO; GO:0150104; P:transport across blood-brain barrier; IMP:ARUK-UCL.
DR CDD; cd17376; MFS_SLC22A4_5_OCTN1_2; 1.
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; IPR045915; S22A4/5.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00898; 2A0119; 1.
DR PROSITE; PS50850; MFS; 1.
DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Disease variant; Glycoprotein; Ion transport;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Sodium;
KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..557
FT /note="Solute carrier family 22 member 5"
FT /id="PRO_0000220501"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 21..41
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 42..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..197
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..257
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..373
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 395..406
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 428..430
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..451
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 452..462
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 463..483
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 484..488
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 489..509
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 510..557
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 218..225
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 486
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O76082"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 550
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 352
FT /note="L -> R (in JVS)"
FT /evidence="ECO:0000269|PubMed:9837751"
SQ SEQUENCE 557 AA; 62780 MW; 6093F0EE9612B204 CRC64;
MRDYDEVTAF LGEWGPFQRL IFFLLSASII PNGFNGMSIV FLAGTPEHRC LVPHTVNLSS
AWRNHSIPLE TKDGRQVPQK CRRYRLATIA NFSELGLEPG RDVDLEQLEQ ESCLDGWEYD
KDVFLSTIVT EWDLVCKDDW KAPLTTSLFF VGVLMGSFIS GQLSDRFGRK NVLFLTMGMQ
TGFSFLQVFS VNFEMFTVLF VLVGMGQISN YVAAFVLGTE ILSKSIRIIF ATLGVCIFYA
FGFMVLPLFA YFIRDWRMLL LALTVPGVLC GALWWFIPES PRWLISQGRI KEAEVIIRKA
AKINGIVAPS TIFDPSELQD LNSTKPQLHH IYDLIRTRNI RVITIMSIIL WLTISVGYFG
LSLDTPNLHG DIYVNCFLLA AVEVPAYVLA WLLLQYLPRR YSISAALFLG GSVLLFMQLV
PSELFYLSTA LVMVGKFGIT SAYSMVYVYT AELYPTVVRN MGVGVSSTAS RLGSILSPYF
VYLGAYDRFL PYILMGSLTI LTAILTLFFP ESFGVPLPDT IDQMLRVKGI KQWQIQSQTR
MQKDGEESPT VLKSTAF
