MOT3_MOUSE
ID MOT3_MOUSE Reviewed; 492 AA.
AC O35308;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Monocarboxylate transporter 3;
DE Short=MCT 3;
DE AltName: Full=Proton-coupled monocarboxylate transporter 3;
DE AltName: Full=Solute carrier family 16 member 8;
GN Name=Slc16a8; Synonyms=Mct3;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=129/Sv, and C3H/HeJ;
RX PubMed=11287345; DOI=10.1152/ajpcell.2001.280.5.c1319;
RA Philp N.J., Yoon H., Lombardi L.;
RT "Mouse MCT3 gene is expressed preferentially in retinal pigment and choroid
RT plexus epithelia.";
RL Am. J. Physiol. 280:C1319-C1326(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=12601063; DOI=10.1167/iovs.02-0552;
RA Philp N.J., Ochrietor J.D., Rudoy C., Muramatsu T., Linser P.J.;
RT "Loss of MCT1, MCT3, and MCT4 expression in the retinal pigment epithelium
RT and neural retina of the 5A11/basigin-null mouse.";
RL Invest. Ophthalmol. Vis. Sci. 44:1305-1311(2003).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18524945; DOI=10.1152/ajpcell.00124.2008;
RA Daniele L.L., Sauer B., Gallagher S.M., Pugh E.N. Jr., Philp N.J.;
RT "Altered visual function in monocarboxylate transporter 3 (Slc16a8)
RT knockout mice.";
RL Am. J. Physiol. 295:C451-C457(2008).
CC -!- FUNCTION: Probable retinal pigment epithelium (RPE)-specific proton-
CC coupled L-lactate transporter (By similarity). May facilitate transport
CC of lactate and H(+) out of the retina and could therefore play an
CC essential role in maintenance of metabolic and ionic homeostasis of the
CC outer retina (PubMed:18524945). {ECO:0000250|UniProtKB:Q90632,
CC ECO:0000269|PubMed:18524945}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate(in) + H(+)(in) = (S)-lactate(out) + H(+)(out);
CC Xref=Rhea:RHEA:29415, ChEBI:CHEBI:15378, ChEBI:CHEBI:16651;
CC Evidence={ECO:0000250|UniProtKB:Q90632};
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:11287345, ECO:0000269|PubMed:12601063}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Basolateral sorting signals (BLSS)
CC in C-terminal cytoplasmic tail ensure its basolateral expression (By
CC similarity). Colocalizes with BSG in basolateral cell membrane of the
CC retinal pigment epithelium (PubMed:18524945).
CC {ECO:0000250|UniProtKB:O95907, ECO:0000269|PubMed:18524945}.
CC -!- TISSUE SPECIFICITY: Expressed exclusively in retinal pigment epithelium
CC and choroid plexus epithelium. {ECO:0000269|PubMed:11287345}.
CC -!- DOMAIN: The two basolateral sorting signals (BLSS) in C-terminal
CC cytoplasmic tails direct SLC16A8 to the basolateral membrane.
CC {ECO:0000250|UniProtKB:O95907}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit significant differences in
CC lactate concentration and pH in the retina and display reduced visual
CC function. {ECO:0000269|PubMed:18524945}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
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DR EMBL; AF019111; AAB70582.2; -; mRNA.
DR EMBL; AF178956; AAF45042.1; -; Genomic_DNA.
DR EMBL; BC018216; AAH18216.1; -; mRNA.
DR CCDS; CCDS27636.1; -.
DR RefSeq; NP_065262.1; NM_020516.2.
DR RefSeq; XP_017172202.1; XM_017316713.1.
DR AlphaFoldDB; O35308; -.
DR SMR; O35308; -.
DR STRING; 10090.ENSMUSP00000040522; -.
DR iPTMnet; O35308; -.
DR PhosphoSitePlus; O35308; -.
DR PaxDb; O35308; -.
DR PRIDE; O35308; -.
DR ProteomicsDB; 291385; -.
DR Antibodypedia; 12301; 157 antibodies from 22 providers.
DR DNASU; 57274; -.
DR Ensembl; ENSMUST00000039752; ENSMUSP00000040522; ENSMUSG00000032988.
DR GeneID; 57274; -.
DR KEGG; mmu:57274; -.
DR UCSC; uc007wta.1; mouse.
DR CTD; 23539; -.
DR MGI; MGI:1929519; Slc16a8.
DR VEuPathDB; HostDB:ENSMUSG00000032988; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000161934; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; O35308; -.
DR OMA; MKDFHVG; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; O35308; -.
DR TreeFam; TF313792; -.
DR Reactome; R-MMU-210991; Basigin interactions.
DR Reactome; R-MMU-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-MMU-70268; Pyruvate metabolism.
DR BioGRID-ORCS; 57274; 0 hits in 71 CRISPR screens.
DR PRO; PR:O35308; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O35308; protein.
DR Bgee; ENSMUSG00000032988; Expressed in pigmented layer of retina and 35 other tissues.
DR ExpressionAtlas; O35308; baseline and differential.
DR Genevisible; O35308; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015718; P:monocarboxylic acid transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR004743; MCT.
DR InterPro; IPR030759; MCT3.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11360:SF26; PTHR11360:SF26; 2.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00892; 2A0113; 1.
DR PROSITE; PS50850; MFS; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Membrane; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..492
FT /note="Monocarboxylate transporter 3"
FT /id="PRO_0000211391"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..58
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..79
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 86..106
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 107..115
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..172
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..257
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..293
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..318
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..352
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 353..373
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 374..386
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..492
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 419..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 426..460
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O95907"
FT REGION 461..482
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000250|UniProtKB:O95907"
FT COMPBIAS 427..443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 476..492
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 492 AA; 51556 MW; 2B19E362B96D9ACC CRC64;
MGAGGPRRGA GPPDGGWGWV VLGACFVVTG FAYGFPKAVS VFFRELKRDF GAGYSDTAWV
SSIMLAMLYG TGPLSSILVT RFGCRPVMLA GGLLASAGMI LASFASRLVE LYLTAGVLTG
LGLALNFQPS LIMLGLYFER RRPLANGLAA AGSPVFLSML SPLGQLLGER FGWRGGFLLF
GGLLLHCCAC GAVMRPPPGP PPRRDPSPHG GPARRRRLLD VAVCTDRAFV VYVVTKFLMA
LGLFVPAILL VNYAKDAGVP DAEAAFLLSI VGFVDIVARP ACGALAGLGR LRPHVPYLFS
LALLANGLTD LISARARSYG TLVAFCIAFG LSYGMVGALQ FEVLMATVGA PRFPSALGLV
LLVEAVAVLI GPPSAGRLVD ALKNYEIIFY LAGSEVALAG VFMAVTTYCC LRCSKNISSG
RSAEGGASDP EDVEAERDSE PMPASTEEPG SLEALEVLSP RAGSPEQEPE EEAVPELDHE
SIGGHEARGQ KA
