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   27-MAR-2024, entry version 171.
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; 9606-ENSP00000321735; -.
DR   PeptideAtlas; O95907; -.
DR   ProteomicsDB; 51122; -.
DR   Antibodypedia; 12301; 171 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   AGR; HGNC:16270; -.
DR   CTD; 23539; -.
DR   DisGeNET; 23539; -.
DR   GeneCards; SLC16A8; -.
DR   HGNC; HGNC:16270; SLC16A8.
DR   HPA; ENSG00000100156; Tissue enhanced (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; TYFCIVS; -.
DR   OrthoDB; 2917104at2759; -.
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 1155 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 106 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
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; ISS:UniProtKB.
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   CDD; cd17430; MFS_MCT3_4; 1.
DR   Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1.
DR   InterPro; IPR004743; MCT.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   NCBIfam; TIGR00892; 2A0113; 1.
DR   PANTHER; PTHR11360; MONOCARBOXYLATE TRANSPORTER; 1.
DR   PANTHER; PTHR11360:SF26; MONOCARBOXYLATE TRANSPORTER 3; 1.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR   PROSITE; PS50850; MFS; 1.
DR   Genevisible; O95907; HS.
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
//