MOT8_HUMAN
ID MOT8_HUMAN Reviewed; 539 AA.
AC P36021; Q7Z797;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Monocarboxylate transporter 8;
DE Short=MCT 8;
DE AltName: Full=Monocarboxylate transporter 7;
DE Short=MCT 7;
DE AltName: Full=Solute carrier family 16 member 2;
DE AltName: Full=X-linked PEST-containing transporter;
GN Name=SLC16A2; Synonyms=MCT8, XPCT;
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 [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7981683; DOI=10.1093/hmg/3.7.1133;
RA Lafreniere R.G., Carrel L., Willard H.F.;
RT "A novel transmembrane transporter encoded by the XPCT gene in Xq13.2.";
RL Hum. Mol. Genet. 3:1133-1140(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kim D., Kanai Y., Choi H., Shin H., Kim J., Teraoka H., Shigeta Y.,
RA Chairoungdua A., Babu E., Anzai N., Iribe Y., Endou H.;
RT "X-linked PEST-containing transporter (XPCT) identified in the X-chromosome
RT inactivation center is an acidic amino acid transporter which requires
RT CD147 for its functional expression.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [5]
RP SUBUNIT.
RX PubMed=19797118; DOI=10.1210/en.2009-0699;
RA Visser W.E., Philp N.J., van Dijk T.B., Klootwijk W., Friesema E.C.,
RA Jansen J., Beesley P.W., Ianculescu A.G., Visser T.J.;
RT "Evidence for a homodimeric structure of human monocarboxylate transporter
RT 8.";
RL Endocrinology 150:5163-5170(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF HIS-118; HIS-186 AND HIS-376.
RX PubMed=23610131; DOI=10.1210/en.2012-2225;
RA Groeneweg S., Lima de Souza E.C., Visser W.E., Peeters R.P., Visser T.J.;
RT "Importance of His192 in the human thyroid hormone transporter MCT8 for
RT substrate recognition.";
RL Endocrinology 154:2525-2532(2013).
RN [8]
RP VARIANT MCT8 DEFICIENCY VAL-150.
RA Friesema E., Grueters A., Halestrap A., Reeser M., Visser T.;
RT "Mutations in a thyroid hormone transporter in patients with severe
RT psychomotor retardation and high serum T3 levels.";
RL Thyroid 13:672-672(2003).
RN [9]
RP VARIANT MCT8 DEFICIENCY PRO-438.
RX PubMed=14661163; DOI=10.1086/380999;
RA Dumitrescu A.M., Liao X.-H., Best T.B., Brockmann K., Refetoff S.;
RT "A novel syndrome combining thyroid and neurological abnormalities is
RT associated with mutations in a monocarboxylate transporter gene.";
RL Am. J. Hum. Genet. 74:168-175(2004).
RN [10]
RP ERRATUM OF PUBMED:14661163.
RA Dumitrescu A.M., Liao X.-H., Best T.B., Brockmann K., Refetoff S.;
RL Am. J. Hum. Genet. 74:598-598(2004).
RN [11]
RP IDENTIFICATION OF START CODON.
RX PubMed=18398436; DOI=10.1038/ejhg.2008.66;
RA Frints S.G., Lenzner S., Bauters M., Jensen L.R., Van Esch H.,
RA des Portes V., Moog U., Macville M.V., van Roozendaal K.,
RA Schrander-Stumpel C.T., Tzschach A., Marynen P., Fryns J.P., Hamel B.,
RA van Bokhoven H., Chelly J., Beldjord C., Turner G., Gecz J., Moraine C.,
RA Raynaud M., Ropers H.H., Froyen G., Kuss A.W.;
RT "MCT8 mutation analysis and identification of the first female with Allan-
RT Herndon-Dudley syndrome due to loss of MCT8 expression.";
RL Eur. J. Hum. Genet. 16:1029-1037(2008).
RN [12]
RP VARIANTS MCT8 DEFICIENCY VAL-150 AND PRO-397.
RX PubMed=15488219; DOI=10.1016/s0140-6736(04)17226-7;
RA Friesema E.C.H., Grueters A., Biebermann H., Krude H., von Moers A.,
RA Reeser M., Barrett T.G., Mancilla E.E., Svensson J., Kester M.H.A.,
RA Kuiper G.G.J.M., Balkassmi S., Uitterlinden A.G., Koehrle J., Rodien P.,
RA Halestrap A.P., Visser T.J.;
RT "Association between mutations in a thyroid hormone transporter and severe
RT X-linked psychomotor retardation.";
RL Lancet 364:1435-1437(2004).
RN [13]
RP VARIANTS MCT8 DEFICIENCY PHE-120; PHE-156 DEL; MET-161; TRP-360 AND
RP PRO-494.
RX PubMed=15889350; DOI=10.1086/431313;
RA Schwartz C.E., May M.M., Carpenter N.J., Rogers R.C., Martin J.,
RA Bialer M.G., Ward J., Sanabria J., Marsa S., Lewis J.A., Echeverri R.,
RA Lubs H.A., Voeller K., Simensen R.J., Stevenson R.E.;
RT "Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8)
RT gene.";
RL Am. J. Hum. Genet. 77:41-53(2005).
RN [14]
RP VARIANTS MCT8 DEFICIENCY PHE-427 DEL AND ARG-490, AND POSSIBLE PATHOGENIC
RP MECHANISM OF BRAIN DEVELOPMENT.
RX PubMed=18636565; DOI=10.1002/humu.20808;
RA Visser W.E., Jansen J., Friesema E.C.H., Kester M.H.A., Mancilla E.,
RA Lundgren J., van der Knaap M.S., Lunsing R.J., Brouwer O.F., Visser T.J.;
RT "Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2)
RT mutations.";
RL Hum. Mutat. 30:29-38(2009).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANTS MCT8 DEFICIENCY ARG-147; CYS-208;
RP LEU-247; VAL-379; LEU-463 AND ASP-484, AND CHARACTERIZATION OF VARIANTS
RP MCT8 DEFICIENCY ARG-147; CYS-208; LEU-247; VAL-379; LEU-463 AND ASP-484.
RX PubMed=23550058; DOI=10.1210/me.2012-1356;
RA Kersseboom S., Kremers G.J., Friesema E.C., Visser W.E., Klootwijk W.,
RA Peeters R.P., Visser T.J.;
RT "Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting
RT its cellular distribution.";
RL Mol. Endocrinol. 27:801-813(2013).
RN [16]
RP INVOLVEMENT IN MCT8 DEFICIENCY, AND VARIANT MCT8 DEFICIENCY ARG-217.
RX PubMed=25380603; DOI=10.1177/0883073814555189;
RA La Piana R., Vanasse M., Brais B., Bernard G.;
RT "Myelination delay and Allan-Herndon-Dudley syndrome caused by a novel
RT mutation in the SLC16A2 gene.";
RL J. Child Neurol. 30:1371-1374(2015).
RN [17]
RP FUNCTION, VARIANT MCT8 DEFICIENCY PHE-216, CHARACTERIZATION OF VARIANT MCT8
RP DEFICIENCY PHE-216, MUTAGENESIS OF SER-216, AND SUBCELLULAR LOCATION.
RX PubMed=26426690; DOI=10.1371/journal.pone.0139343;
RA Armour C.M., Kersseboom S., Yoon G., Visser T.J.;
RT "Further insights into the Allan-Herndon-Dudley syndrome: clinical and
RT functional characterization of a novel MCT8 mutation.";
RL PLoS ONE 10:E0139343-E0139343(2015).
RN [18]
RP VARIANTS MCT8 DEFICIENCY THR-150; HIS-197; CYS-371 AND ASP-484,
RP CHARACTERIZATION OF VARIANTS MCT8 DEFICIENCY PHE-120; THR-150; VAL-150;
RP PHE-156 DEL; MET-161; HIS-197; TRP-360; CYS-371 PRO-397; PRO-438; ASP-484
RP AND PRO-494, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=25527620; DOI=10.1530/jme-14-0272;
RA Fischer J., Kleinau G., Mueller A., Kuehnen P., Zwanziger D., Kinne A.,
RA Rehders M., Moeller L.C., Fuehrer D., Grueters A., Krude H., Brix K.,
RA Biebermann H.;
RT "Modulation of monocarboxylate transporter 8 oligomerization by specific
RT pathogenic mutations.";
RL J. Mol. Endocrinol. 54:39-50(2015).
RN [19]
RP VARIANTS MCT8 DEFICIENCY HIS-197; ARG-490 AND GLU-490, CHARACTERIZATION OF
RP VARIANTS MCT8 DEFICIENCY ARG-490 AND GLU-490, AND MUTAGENESIS OF GLY-490.
RX PubMed=27805744; DOI=10.1002/humu.23140;
RA Novara F., Groeneweg S., Freri E., Estienne M., Reho P., Matricardi S.,
RA Castellotti B., Visser W.E., Zuffardi O., Visser T.J.;
RT "Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in
RT Three Families with the Allan-Herndon-Dudley Syndrome.";
RL Hum. Mutat. 38:260-264(2017).
CC -!- FUNCTION: Very active and specific thyroid hormone transporter.
CC Stimulates cellular uptake of thyroxine (T4), triiodothyronine (T3),
CC reverse triiodothyronine (rT3) and diidothyronine. Does not transport
CC Leu, Phe, Trp or Tyr. {ECO:0000269|PubMed:23550058,
CC ECO:0000269|PubMed:26426690}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19797118,
CC ECO:0000269|PubMed:25527620}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23550058,
CC ECO:0000269|PubMed:25527620, ECO:0000269|PubMed:26426690}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:23550058,
CC ECO:0000269|PubMed:25527620}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and heart.
CC {ECO:0000269|PubMed:7981683}.
CC -!- DISEASE: Monocarboxylate transporter 8 deficiency (MCT8 deficiency)
CC [MIM:300523]: Consists of a severe form of X-linked psychomotor
CC retardation combined with abnormal thyroid hormone (TH) levels. Thyroid
CC hormone deficiency can be caused by defects of hormone synthesis and
CC action, but it has also been linked to a defect in cellular hormone
CC transport. Affected patients are males with abnormal relative
CC concentrations of three circulating iodothyronines, as well as severe
CC neurological abnormalities, including global developmental delay,
CC central hypotonia, spastic quadriplegia, dystonic movements, rotary
CC nystagmus, and impaired gaze and hearing. Heterozygous females had a
CC milder thyroid phenotype and no neurological defects.
CC {ECO:0000269|PubMed:14661163, ECO:0000269|PubMed:15488219,
CC ECO:0000269|PubMed:15889350, ECO:0000269|PubMed:18636565,
CC ECO:0000269|PubMed:23550058, ECO:0000269|PubMed:25380603,
CC ECO:0000269|PubMed:25527620, ECO:0000269|PubMed:26426690,
CC ECO:0000269|PubMed:27805744, ECO:0000269|Ref.8}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Abnormal brain development associated with MCT8
CC deficiency may be the consequence of either decreased or increased
CC intracellular T3 concentrations. {ECO:0000269|PubMed:18636565}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC Monocarboxylate porter (TC 2.A.1.13) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB60374.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB60375.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; U05321; AAB60375.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U05316; AAB60375.1; JOINED; Genomic_DNA.
DR EMBL; U05317; AAB60375.1; JOINED; Genomic_DNA.
DR EMBL; U05318; AAB60375.1; JOINED; Genomic_DNA.
DR EMBL; U05319; AAB60375.1; JOINED; Genomic_DNA.
DR EMBL; U05320; AAB60375.1; JOINED; Genomic_DNA.
DR EMBL; U05315; AAB60374.1; ALT_INIT; mRNA.
DR EMBL; AB085789; BAC76827.1; -; mRNA.
DR EMBL; AC004073; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS14426.2; -.
DR PIR; I39295; I39295.
DR RefSeq; NP_006508.2; NM_006517.4.
DR AlphaFoldDB; P36021; -.
DR SMR; P36021; -.
DR BioGRID; 112455; 48.
DR IntAct; P36021; 3.
DR STRING; 9606.ENSP00000465734; -.
DR DrugBank; DB00149; Leucine.
DR DrugBank; DB00451; Levothyroxine.
DR DrugBank; DB01583; Liotrix.
DR DrugBank; DB00119; Pyruvic acid.
DR DrugBank; DB09100; Thyroid, porcine.
DR DrugBank; DB00150; Tryptophan.
DR DrugBank; DB00135; Tyrosine.
DR TCDB; 2.A.1.13.10; the major facilitator superfamily (mfs).
DR iPTMnet; P36021; -.
DR PhosphoSitePlus; P36021; -.
DR BioMuta; SLC16A2; -.
DR DMDM; 114152841; -.
DR EPD; P36021; -.
DR jPOST; P36021; -.
DR MassIVE; P36021; -.
DR MaxQB; P36021; -.
DR PaxDb; P36021; -.
DR PeptideAtlas; P36021; -.
DR PRIDE; P36021; -.
DR ProteomicsDB; 55173; -.
DR Antibodypedia; 522; 185 antibodies from 30 providers.
DR DNASU; 6567; -.
DR Ensembl; ENST00000587091.6; ENSP00000465734.1; ENSG00000147100.11.
DR GeneID; 6567; -.
DR KEGG; hsa:6567; -.
DR MANE-Select; ENST00000587091.6; ENSP00000465734.1; NM_006517.5; NP_006508.2.
DR UCSC; uc031tjy.2; human.
DR CTD; 6567; -.
DR DisGeNET; 6567; -.
DR GeneCards; SLC16A2; -.
DR GeneReviews; SLC16A2; -.
DR HGNC; HGNC:10923; SLC16A2.
DR HPA; ENSG00000147100; Tissue enhanced (liver).
DR MalaCards; SLC16A2; -.
DR MIM; 300095; gene.
DR MIM; 300523; phenotype.
DR neXtProt; NX_P36021; -.
DR OpenTargets; ENSG00000147100; -.
DR Orphanet; 59; Allan-Herndon-Dudley syndrome.
DR PharmGKB; PA35814; -.
DR VEuPathDB; HostDB:ENSG00000147100; -.
DR eggNOG; KOG2504; Eukaryota.
DR GeneTree; ENSGT00940000159450; -.
DR HOGENOM; CLU_001265_59_5_1; -.
DR InParanoid; P36021; -.
DR OMA; EFKTAWV; -.
DR OrthoDB; 916876at2759; -.
DR PhylomeDB; P36021; -.
DR TreeFam; TF313792; -.
DR PathwayCommons; P36021; -.
DR Reactome; R-HSA-879518; Transport of organic anions.
DR SignaLink; P36021; -.
DR SIGNOR; P36021; -.
DR BioGRID-ORCS; 6567; 11 hits in 692 CRISPR screens.
DR ChiTaRS; SLC16A2; human.
DR GeneWiki; SLC16A2; -.
DR GenomeRNAi; 6567; -.
DR Pharos; P36021; Tbio.
DR PRO; PR:P36021; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P36021; protein.
DR Bgee; ENSG00000147100; Expressed in right adrenal gland and 115 other tissues.
DR ExpressionAtlas; P36021; baseline and differential.
DR Genevisible; P36021; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0089718; P:amino acid import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IGI:ARUK-UCL.
DR GO; GO:0015718; P:monocarboxylic acid transport; TAS:ProtInc.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0006590; P:thyroid hormone generation; IEA:Ensembl.
DR GO; GO:0042403; P:thyroid hormone metabolic process; IGI:ARUK-UCL.
DR GO; GO:0070327; P:thyroid hormone transport; IDA:ARUK-UCL.
DR GO; GO:0070460; P:thyroid-stimulating hormone secretion; IEA:Ensembl.
DR GO; GO:0150104; P:transport across blood-brain barrier; IMP:ARUK-UCL.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR030761; MCT8.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR11360:SF123; PTHR11360:SF123; 1.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Disease variant; Membrane; Reference proteome;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..539
FT /note="Monocarboxylate transporter 8"
FT /id="PRO_0000211401"
FT TOPO_DOM 2..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..143
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..258
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..322
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..356
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 378..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 408..409
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 448..468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 469..477
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..539
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..64
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT VARIANT 120
FT /note="S -> F (in MCT8 deficiency; impaired
FT homodimerization; dbSNP:rs113994162)"
FT /evidence="ECO:0000269|PubMed:15889350,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_059054"
FT VARIANT 147
FT /note="G -> R (in MCT8 deficiency; impaired thyroid hormone
FT transporter activity; does not affect localization to the
FT cell membrane; dbSNP:rs1602140936)"
FT /evidence="ECO:0000269|PubMed:23550058"
FT /id="VAR_074572"
FT VARIANT 150
FT /note="A -> T (in MCT8 deficiency; impaired
FT homodimerization; dbSNP:rs373279555)"
FT /evidence="ECO:0000269|PubMed:25527620"
FT /id="VAR_074573"
FT VARIANT 150
FT /note="A -> V (in MCT8 deficiency; does not affect
FT homodimerization activity; dbSNP:rs104894936)"
FT /evidence="ECO:0000269|PubMed:15488219,
FT ECO:0000269|PubMed:25527620, ECO:0000269|Ref.8"
FT /id="VAR_022348"
FT VARIANT 156
FT /note="Missing (in MCT8 deficiency; increased
FT homodimerization activity)"
FT /evidence="ECO:0000269|PubMed:15889350,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_059055"
FT VARIANT 161
FT /note="V -> M (in MCT8 deficiency; increased
FT homodimerization activity)"
FT /evidence="ECO:0000269|PubMed:15889350,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_059056"
FT VARIANT 197
FT /note="R -> H (in MCT8 deficiency; does not affect
FT homodimerization activity; dbSNP:rs727504155)"
FT /evidence="ECO:0000269|PubMed:25527620,
FT ECO:0000269|PubMed:27805744"
FT /id="VAR_074574"
FT VARIANT 208
FT /note="G -> C (in MCT8 deficiency; impaired thyroid hormone
FT transporter activity; impaired localization to the cell
FT membrane)"
FT /evidence="ECO:0000269|PubMed:23550058"
FT /id="VAR_074575"
FT VARIANT 216
FT /note="S -> F (in MCT8 deficiency; decreased thyroid
FT hormone transport; decreased protein abundance; decreased
FT localization to the plasma membrane; dbSNP:rs398124232)"
FT /evidence="ECO:0000269|PubMed:26426690"
FT /id="VAR_075145"
FT VARIANT 217
FT /note="L -> R (in MCT8 deficiency; atypical form;
FT characterized by developmental delay hypotonia and delayed
FT myelination)"
FT /evidence="ECO:0000269|PubMed:25380603"
FT /id="VAR_078497"
FT VARIANT 247
FT /note="P -> L (in MCT8 deficiency; impaired thyroid hormone
FT transporter activity; does not affect localization to the
FT cell membrane)"
FT /evidence="ECO:0000269|PubMed:23550058"
FT /id="VAR_074576"
FT VARIANT 323
FT /note="I -> L (in dbSNP:rs12849411)"
FT /id="VAR_057723"
FT VARIANT 360
FT /note="L -> W (in MCT8 deficiency; impaired
FT homodimerization; dbSNP:rs104894939)"
FT /evidence="ECO:0000269|PubMed:15889350,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_059057"
FT VARIANT 371
FT /note="R -> C (in MCT8 deficiency; impaired
FT homodimerization; dbSNP:rs587784384)"
FT /evidence="ECO:0000269|PubMed:25527620"
FT /id="VAR_074577"
FT VARIANT 379
FT /note="D -> V (in MCT8 deficiency; impaired thyroid hormone
FT transporter activity; does not affect localization to the
FT cell membrane)"
FT /evidence="ECO:0000269|PubMed:23550058"
FT /id="VAR_074578"
FT VARIANT 397
FT /note="L -> P (in MCT8 deficiency; does not affect
FT homodimerization activity; dbSNP:rs122455132)"
FT /evidence="ECO:0000269|PubMed:15488219,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_022349"
FT VARIANT 427
FT /note="Missing (in MCT8 deficiency; dbSNP:rs113994164)"
FT /evidence="ECO:0000269|PubMed:18636565"
FT /id="VAR_059058"
FT VARIANT 438
FT /note="L -> P (in MCT8 deficiency; does not affect
FT homodimerization activity; dbSNP:rs104894931)"
FT /evidence="ECO:0000269|PubMed:14661163,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_022350"
FT VARIANT 463
FT /note="P -> L (in MCT8 deficiency; impaired thyroid hormone
FT transporter activity; does not affect localization to the
FT cell membrane)"
FT /evidence="ECO:0000269|PubMed:23550058"
FT /id="VAR_074579"
FT VARIANT 484
FT /note="G -> D (in MCT8 deficiency; does not affect
FT homodimerization activity; impaired thyroid hormone
FT transporter activity; impaired localization to the cell
FT membrane)"
FT /evidence="ECO:0000269|PubMed:23550058,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_074580"
FT VARIANT 490
FT /note="G -> E (in MCT8 deficiency; results in a mild
FT clinical phenotype; retains some residual thyroid hormone
FT transporter activity)"
FT /evidence="ECO:0000269|PubMed:27805744"
FT /id="VAR_078498"
FT VARIANT 490
FT /note="G -> R (in MCT8 deficiency; loss of thyroid hormone
FT transport; dbSNP:rs794727799)"
FT /evidence="ECO:0000269|PubMed:18636565,
FT ECO:0000269|PubMed:27805744"
FT /id="VAR_059059"
FT VARIANT 494
FT /note="L -> P (in MCT8 deficiency; does not affect
FT homodimerization activity; dbSNP:rs104894938)"
FT /evidence="ECO:0000269|PubMed:15889350,
FT ECO:0000269|PubMed:25527620"
FT /id="VAR_059060"
FT MUTAGEN 118
FT /note="H->A: Reduction of thyroid hormone (TH) transport."
FT /evidence="ECO:0000269|PubMed:23610131"
FT MUTAGEN 186
FT /note="H->A: No effect on thyroid hormone (TH) transport."
FT /evidence="ECO:0000269|PubMed:23610131"
FT MUTAGEN 216
FT /note="S->A: No effect on thyroid hormone transport. No
FT effect on protein abundance. No effect on protein
FT localization to the plasma membrane."
FT /evidence="ECO:0000269|PubMed:26426690"
FT MUTAGEN 376
FT /note="H->A: No effect on thyroid hormone (TH) transport."
FT /evidence="ECO:0000269|PubMed:23610131"
FT MUTAGEN 490
FT /note="G->A: No effect on thyroid hormone (TH) transport."
FT /evidence="ECO:0000269|PubMed:27805744"
SQ SEQUENCE 539 AA; 59511 MW; E4DB873D59FA4DD6 CRC64;
MALQSQASEE AKGPWQEADQ EQQEPVGSPE PESEPEPEPE PEPVPVPPPE PQPEPQPLPD
PAPLPELEFE SERVHEPEPT PTVETRGTAR GFQPPEGGFG WVVVFAATWC NGSIFGIHNS
VGILYSMLLE EEKEKNRQVE FQAAWVGALA MGMIFFCSPI VSIFTDRLGC RITATAGAAV
AFIGLHTSSF TSSLSLRYFT YGILFGCGCS FAFQPSLVIL GHYFQRRLGL ANGVVSAGSS
IFSMSFPFLI RMLGDKIKLA QTFQVLSTFM FVLMLLSLTY RPLLPSSQDT PSKRGVRTLH
QRFLAQLRKY FNMRVFRQRT YRIWAFGIAA AALGYFVPYV HLMKYVEEEF SEIKETWVLL
VCIGATSGLG RLVSGHISDS IPGLKKIYLQ VLSFLLLGLM SMMIPLCRDF GGLIVVCLFL
GLCDGFFITI MAPIAFELVG PMQASQAIGY LLGMMALPMI AGPPIAGLLR NCFGDYHVAF
YFAGVPPIIG AVILFFVPLM HQRMFKKEQR DSSKDKMLAP DPDPNGELLP GSPNPEEPI
