MOT3_HUMAN
ID MOT3_HUMAN Reviewed; 504 AA.
AC O95907; Q9UBE2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Monocarboxylate transporter 3;
DE Short=MCT 3;
DE AltName: Full=Solute carrier family 16 member 8;
GN Name=SLC16A8 {ECO:0000312|HGNC:HGNC:16270}; Synonyms=MCT3;
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], VARIANTS TRP-235 AND ALA-405, AND TISSUE
RP SPECIFICITY.
RX PubMed=10493836; DOI=10.1006/geno.1999.5926;
RA Yoon H., Donoso L.A., Philp N.J.;
RT "Cloning of the human monocarboxylate transporter MCT3 gene: localization
RT to chromosome 22q12.3-q13.2.";
RL Genomics 60:366-370(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 465-PRO--VAL-469; GLU-471;
RP GLU-472; VAL-481 AND LEU-482.
RX PubMed=21199217; DOI=10.1111/j.1600-0854.2010.01155.x;
RA Castorino J.J., Deborde S., Deora A., Schreiner R., Gallagher-Colombo S.M.,
RA Rodriguez-Boulan E., Philp N.J.;
RT "Basolateral sorting signals regulating tissue-specific polarity of
RT heteromeric monocarboxylate transporters in epithelia.";
RL Traffic 12:483-498(2011).
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 a role
CC in pH and ion homeostasis of the outer retina (By similarity).
CC {ECO:0000250|UniProtKB:O35308, ECO:0000250|UniProtKB:Q90632}.
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:21199217}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Basolateral sorting signals (BLSS) in C-terminal
CC cytoplasmic tail ensure its basolateral expression (PubMed:21199217).
CC Colocalizes with BSG in basolateral cell membrane of the retinal
CC pigment epithelium (By similarity). {ECO:0000250|UniProtKB:O35308,
CC ECO:0000269|PubMed:21199217}.
CC -!- TISSUE SPECIFICITY: Retinal pigment epithelium.
CC {ECO:0000269|PubMed:10493836}.
CC -!- DOMAIN: The two basolateral sorting signals (BSS) are required to
CC direct SLC16A8 to the basolateral membrane.
CC {ECO:0000269|PubMed:21199217}.
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; AF132610; AAF03565.1; -; mRNA.
DR EMBL; AF132611; AAF03489.1; -; Genomic_DNA.
DR EMBL; AL031587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS13966.1; -.
DR RefSeq; NP_037488.2; NM_013356.2.
DR RefSeq; XP_016884174.1; XM_017028685.1.
DR AlphaFoldDB; O95907; -.
DR SMR; O95907; -.
DR BioGRID; 117083; 20.
DR IntAct; O95907; 2.
DR STRING; 9606.ENSP00000321735; -.
DR ChEMBL; CHEMBL3308921; -.
DR DrugBank; DB00119; Pyruvic acid.
DR TCDB; 2.A.1.13.9; the major facilitator superfamily (mfs).
DR iPTMnet; O95907; -.
DR PhosphoSitePlus; O95907; -.
DR BioMuta; SLC16A8; -.
DR jPOST; O95907; -.
DR MassIVE; O95907; -.
DR PaxDb; O95907; -.
DR PeptideAtlas; O95907; -.
DR PRIDE; O95907; -.
DR ProteomicsDB; 51122; -.
DR Antibodypedia; 12301; 157 antibodies from 22 providers.
DR DNASU; 23539; -.
DR Ensembl; ENST00000320521.10; ENSP00000321735.5; ENSG00000100156.12.
DR Ensembl; ENST00000681075.2; ENSP00000506669.1; ENSG00000100156.12.
DR GeneID; 23539; -.
DR KEGG; hsa:23539; -.
DR MANE-Select; ENST00000681075.2; ENSP00000506669.1; NM_013356.3; NP_037488.2.
DR UCSC; uc003auu.4; human.
DR CTD; 23539; -.
DR DisGeNET; 23539; -.
DR GeneCards; SLC16A8; -.
DR HGNC; HGNC:16270; SLC16A8.
DR HPA; ENSG00000100156; Tissue enriched (brain).
DR MIM; 610409; gene.
DR neXtProt; NX_O95907; -.
DR OpenTargets; ENSG00000100156; -.
DR PharmGKB; PA38106; -.
DR VEuPathDB; HostDB:ENSG00000100156; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000161934; -.
DR HOGENOM; CLU_001265_59_1_1; -.
DR InParanoid; O95907; -.
DR OMA; MKDFHVG; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; O95907; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; O95907; -.
DR Reactome; R-HSA-210991; Basigin interactions.
DR Reactome; R-HSA-433692; Proton-coupled monocarboxylate transport.
DR Reactome; R-HSA-70268; Pyruvate metabolism.
DR SignaLink; O95907; -.
DR BioGRID-ORCS; 23539; 21 hits in 1075 CRISPR screens.
DR ChiTaRS; SLC16A8; human.
DR GenomeRNAi; 23539; -.
DR Pharos; O95907; Tbio.
DR PRO; PR:O95907; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O95907; protein.
DR Bgee; ENSG00000100156; Expressed in pigmented layer of retina and 104 other tissues.
DR Genevisible; O95907; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
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:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015129; F:lactate transmembrane transporter activity; TAS:ProtInc.
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:0015727; P:lactate transport; TAS:ProtInc.
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; 1.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00892; 2A0113; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..504
FT /note="Monocarboxylate transporter 3"
FT /id="PRO_0000211390"
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..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..172
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..254
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 276..289
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 311..318
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 336..342
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..363
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 364..376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..410
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..504
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 196..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 441..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..484
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000269|PubMed:21199217"
FT REGION 485..504
FT /note="Basolateral sorting signal"
FT /evidence="ECO:0000269|PubMed:21199217"
FT COMPBIAS 487..504
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 235
FT /note="R -> W (in dbSNP:rs4289289)"
FT /evidence="ECO:0000269|PubMed:10493836"
FT /id="VAR_060107"
FT VARIANT 405
FT /note="V -> A (in dbSNP:rs2076371)"
FT /evidence="ECO:0000269|PubMed:10493836"
FT /id="VAR_053654"
FT MUTAGEN 465..469
FT /note="Missing: Affects subcellular localization leading to
FT apical localization."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 471
FT /note="E->A: Abolishes basolateral membrane localization;
FT when associated with A-472."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 472
FT /note="E->A: Abolishes basolateral membrane localization;
FT when associated with A-471."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 481
FT /note="V->A: Affects subcellular localization leading to
FT apical localization; when associated with A-482."
FT /evidence="ECO:0000269|PubMed:21199217"
FT MUTAGEN 482
FT /note="L->A: Affects subcellular localization leading to
FT apical localization; when associated with A-481."
FT /evidence="ECO:0000269|PubMed:21199217"
SQ SEQUENCE 504 AA; 52319 MW; E924D4FC31340398 CRC64;
MGAGGPRRGE GPPDGGWGWV VLGACFVVTG FAYGFPKAVS VFFRALMRDF DAGYSDTAWV
SSIMLAMLYG TGPVSSILVT RFGCRPVMLA GGLLASAGMI LASFATRLLE LYLTAGVLTG
LGLALNFQPS LIMLGLYFER RRPLANGLAA AGSPVFLSAL SPLGQQLLER FGWRGGFLLL
GGLLLHCCAC GAVMRPPPGP GPRPRRDSAG DRAGDAPGEA EADGAGLQLR EASPRVRPRR
RLLDLAVCTD RAFAVYAVTK FLMALGLFVP AILLVNYAKD AGVPDTDAAF LLSIVGFVDI
VARPACGALA GLARLRPHVP YLFSLALLAN GLTDLSSARA RSYGALVAFC VAFGLSYGMV
GALQFEVLMA AVGAPRFPSA LGLVLLVEAA AVLIGPPSAG RLVDVLKNYE IIFYLAGSEV
ALAGVFMAVA TNCCLRCAKA APSGPGTEGG ASDTEDAEAE GDSEPLPVVA EEPGNLEALE
VLSARGEPTE PEIEARPRLA AESV
