ID   MOT8_MOUSE              Reviewed;         545 AA.
AC   O70324; Q8K3S9;
DT   27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 2.
DT   24-JAN-2024, entry version 168.
DE   RecName: Full=Monocarboxylate transporter 8;
DE            Short=MCT 8;
DE   AltName: Full=Solute carrier family 16 member 2;
DE   AltName: Full=X-linked PEST-containing transporter;
GN   Name=Slc16a2; Synonyms=Mct8, Xpct;
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=BALB/cJ; TISSUE=Liver;
RX   PubMed=9545634; DOI=10.1006/geno.1997.5173;
RA   Debrand E., Heard E., Avner P.;
RT   "Cloning and localization of the murine Xpct gene: evidence for complex
RT   rearrangements during the evolution of the region around the Xist gene.";
RL   Genomics 48:296-303(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/Sv;
RX   PubMed=12045143; DOI=10.1101/gr.152902;
RA   Chureau C., Prissette M., Bourdet A., Barbe V., Cattolico L., Jones L.,
RA   Eggen A., Avner P., Duret L.;
RT   "Comparative sequence analysis of the X-inactivation center region in
RT   mouse, human and bovine.";
RL   Genome Res. 12:894-908(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Olfactory epithelium;
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   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-540, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=18687783; DOI=10.1210/en.2008-0378;
RA   Roberts L.M., Woodford K., Zhou M., Black D.S., Haggerty J.E., Tate E.H.,
RA   Grindstaff K.K., Mengesha W., Raman C., Zerangue N.;
RT   "Expression of the thyroid hormone transporters monocarboxylate
RT   transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the
RT   blood-brain barrier.";
RL   Endocrinology 149:6251-6261(2008).
RN   [6]
RP   FUNCTION.
RX   PubMed=19147674; DOI=10.1210/en.2008-1616;
RA   Ceballos A., Belinchon M.M., Sanchez-Mendoza E., Grijota-Martinez C.,
RA   Dumitrescu A.M., Refetoff S., Morte B., Bernal J.;
RT   "Importance of monocarboxylate transporter 8 for the blood-brain barrier-
RT   dependent availability of 3,5,3'-triiodo-L-thyronine.";
RL   Endocrinology 150:2491-2496(2009).
RN   [7]
RP   DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=19641107; DOI=10.1523/jneurosci.6055-08.2009;
RA   Wirth E.K., Roth S., Blechschmidt C., Hoelter S.M., Becker L., Racz I.,
RA   Zimmer A., Klopstock T., Gailus-Durner V., Fuchs H., Wurst W., Naumann T.,
RA   Braeuer A., de Angelis M.H., Koehrle J., Grueters A., Schweizer U.;
RT   "Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of
RT   mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-
RT   Herndon-Dudley syndrome.";
RL   J. Neurosci. 29:9439-9449(2009).
RN   [8]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=32143555; DOI=10.1089/thy.2019.0544;
RA   Wilpert N.M., Krueger M., Opitz R., Sebinger D., Paisdzior S., Mages B.,
RA   Schulz A., Spranger J., Wirth E.K., Stachelscheid H., Mergenthaler P.,
RA   Vajkoczy P., Krude H., Kuehnen P., Bechmann I., Biebermann H.;
RT   "Spatiotemporal changes of cerebral monocarboxylate transporter 8
RT   expression.";
RL   Thyroid 30:1366-1383(2020).
RN   [9]
RP   FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=31436139; DOI=10.1089/thy.2019.0009;
RA   Groeneweg S., Kersseboom S., van den Berge A., Dolcetta-Capuzzo A.,
RA   van Geest F.S., van Heerebeek R.E.A., Arjona F.J., Meima M.E.,
RA   Peeters R.P., Visser W.E., Visser T.J.;
RT   "In Vitro Characterization of Human, Mouse, and Zebrafish MCT8
RT   Orthologues.";
RL   Thyroid 29:1499-1510(2019).
CC   -!- FUNCTION: Specific thyroid hormone transmembrane transporter, that
CC       mediates both uptake and efflux of thyroid hormones across the cell
CC       membrane independently of pH or a Na(+) gradient (PubMed:31436139).
CC       Major substrates are the iodothyronines T3 and T4 and to a lesser
CC       extent rT3 and 3,3-diiodothyronine (3,3'-T2). Acts as an important
CC       mediator of thyroid hormone transport, especially T3, through the
CC       blood-brain barrier (PubMed:19147674). {ECO:0000269|PubMed:19147674,
CC       ECO:0000269|PubMed:31436139}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3',5-triiodo-L-thyronine(out) = 3,3',5-triiodo-L-
CC         thyronine(in); Xref=Rhea:RHEA:71811, ChEBI:CHEBI:533015;
CC         Evidence={ECO:0000269|PubMed:31436139};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71812;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71813;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3',5'-triiodo-L-thyronine(out) = 3,3',5'-triiodo-L-
CC         thyronine(in); Xref=Rhea:RHEA:71815, ChEBI:CHEBI:57261;
CC         Evidence={ECO:0000269|PubMed:31436139};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71816;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71817;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-thyroxine(out) = L-thyroxine(in); Xref=Rhea:RHEA:71819,
CC         ChEBI:CHEBI:58448; Evidence={ECO:0000269|PubMed:31436139};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71820;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71821;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3'-diiodo-L-thyronine(out) = 3,3'-diiodo-L-thyronine(in);
CC         Xref=Rhea:RHEA:71823, ChEBI:CHEBI:176514;
CC         Evidence={ECO:0000269|PubMed:31436139};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71824;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71825;
CC         Evidence={ECO:0000305|PubMed:31436139};
CC   -!- SUBUNIT: Monomer (By similarity). Homodimer (By similarity).
CC       Homooligomer (By similarity). {ECO:0000250|UniProtKB:P36021}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18687783};
CC       Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC       {ECO:0000269|PubMed:18687783}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in cerebral microvessels.
CC       {ECO:0000269|PubMed:18687783}.
CC   -!- DEVELOPMENTAL STAGE: Strong expression in the brain barriers and many
CC       subpopulations of neurons, including cortical and cerebellar neurons at
CC       postnatal day 6. Decrease expression in neurons upon aging, whereas
CC       expression in the blood-brain barrier and blood-cerebrospinal fluid
CC       barrier do not change upon aging (at protein level).
CC       {ECO:0000269|PubMed:32143555}.
CC   -!- DISRUPTION PHENOTYPE: Deficient mice display abnormal thyroid hormone
CC       metabolism with no apparent neurological phenotype.
CC       {ECO:0000269|PubMed:19641107}.
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; AF045692; AAC40078.1; -; mRNA.
DR   EMBL; AJ421478; CAD33931.1; -; Genomic_DNA.
DR   EMBL; BC080678; AAH80678.1; -; mRNA.
DR   CCDS; CCDS30330.1; -.
DR   RefSeq; NP_033223.2; NM_009197.2.
DR   AlphaFoldDB; O70324; -.
DR   SMR; O70324; -.
DR   STRING; 10090.ENSMUSP00000037629; -.
DR   TCDB; 2.A.1.13.3; the major facilitator superfamily (mfs).
DR   iPTMnet; O70324; -.
DR   PhosphoSitePlus; O70324; -.
DR   SwissPalm; O70324; -.
DR   jPOST; O70324; -.
DR   PaxDb; 10090-ENSMUSP00000037629; -.
DR   PeptideAtlas; O70324; -.
DR   ProteomicsDB; 291388; -.
DR   Antibodypedia; 522; 227 antibodies from 30 providers.
DR   DNASU; 20502; -.
DR   Ensembl; ENSMUST00000042664.10; ENSMUSP00000037629.6; ENSMUSG00000033965.11.
DR   GeneID; 20502; -.
DR   KEGG; mmu:20502; -.
DR   UCSC; uc009tzy.1; mouse.
DR   AGR; MGI:1203732; -.
DR   CTD; 6567; -.
DR   MGI; MGI:1203732; Slc16a2.
DR   VEuPathDB; HostDB:ENSMUSG00000033965; -.
DR   eggNOG; KOG2504; Eukaryota.
DR   GeneTree; ENSGT00940000159450; -.
DR   HOGENOM; CLU_001265_59_5_1; -.
DR   InParanoid; O70324; -.
DR   OMA; AWCNGSI; -.
DR   OrthoDB; 2548871at2759; -.
DR   PhylomeDB; O70324; -.
DR   TreeFam; TF313792; -.
DR   Reactome; R-MMU-879518; Transport of organic anions.
DR   BioGRID-ORCS; 20502; 5 hits in 78 CRISPR screens.
DR   ChiTaRS; Slc16a2; mouse.
DR   PRO; PR:O70324; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; O70324; Protein.
DR   Bgee; ENSMUSG00000033965; Expressed in choroid plexus of fourth ventricle and 225 other cell types or tissues.
DR   ExpressionAtlas; O70324; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0015171; F:amino acid transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0008028; F:monocarboxylic acid transmembrane transporter activity; IBA:GO_Central.
DR   GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0089718; P:amino acid import across plasma membrane; ISO:MGI.
DR   GO; GO:0006520; P:amino acid metabolic process; ISO:MGI.
DR   GO; GO:0009914; P:hormone transport; ISO:MGI.
DR   GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; ISO:MGI.
DR   GO; GO:0006590; P:thyroid hormone generation; IMP:MGI.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; ISO:MGI.
DR   GO; GO:0070327; P:thyroid hormone transport; IDA:UniProtKB.
DR   GO; GO:0070460; P:thyroid-stimulating hormone secretion; IMP:MGI.
DR   GO; GO:0150104; P:transport across blood-brain barrier; ISO:MGI.
DR   CDD; cd17420; MFS_MCT8_10; 1.
DR   Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 2.
DR   InterPro; IPR011701; MFS.
DR   InterPro; IPR020846; MFS_dom.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   PANTHER; PTHR11360; MONOCARBOXYLATE TRANSPORTER; 1.
DR   PANTHER; PTHR11360:SF123; MONOCARBOXYLATE TRANSPORTER 8; 1.
DR   Pfam; PF07690; MFS_1; 1.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
DR   PROSITE; PS50850; MFS; 1.
DR   Genevisible; O70324; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cell membrane; Membrane; Phosphoprotein; Reference proteome;
KW   Repeat; Transmembrane; Transmembrane helix; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P36021"
FT   CHAIN           2..545
FT                   /note="Monocarboxylate transporter 8"
FT                   /id="PRO_0000211402"
FT   TOPO_DOM        2..102
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        103..123
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        124..149
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        150..170
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        171..177
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        178..198
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        199..206
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        207..227
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        228..235
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        236..256
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        257..264
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        265..285
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        286..328
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        329..349
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        350..362
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        363..383
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        384..392
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        393..413
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        414..415
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        416..436
FT                   /note="Helical; Name=10"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        437..453
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        454..474
FT                   /note="Helical; Name=11"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        475..483
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        484..504
FT                   /note="Helical; Name=12"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        505..545
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          29..50
FT                   /note="1"
FT   REPEAT          51..72
FT                   /note="2"
FT   REGION          1..98
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          29..72
FT                   /note="2 X 22 AA approximate tandem repeats"
FT   REGION          514..545
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        44..72
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        514..528
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P36021"
FT   MOD_RES         540
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CONFLICT        62
FT                   /note="Q -> QPLPDPAPLPELGFEAEPEPQ (in Ref. 1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        227
FT                   /note="G -> D (in Ref. 1; AAC40078)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   545 AA;  60025 MW;  ACCC7EC6B902A6DE CRC64;
     MALPSPASEE AEGPCQEANQ EYQEPVCSPV PEPEPEPEPE PEPDPEPVPV PPPEPQPEPE
     PQPLPDPAPL PELGFEAEPV QEPEPTPTVE TRGTARGFQP PEGGFGWIVV FAATWCNGSI
     FGIHNSVGIL YSMLLEEEKE KNRQVEFQAA WVGALAMGMI FFCSPIVSIF TDRLGCRITA
     TTGAAVAFIG LHTSSFTSSL SLRYFTYGIL FGCGCSFAFQ PSLVILGHYF QRRLGLANGV
     VSAGSSIFSM SFPFLIKMLG DKIKLAQTFQ VLSTFMFVLT LLSLTYRPLL PSSQDTPSKR
     GAHTLRQRFL VQFRKYFNMR VFRQRTYRIW AFGIAAAALG YFVPYVHLMK YVEDKFKEIK
     ETWVLLVCIG ATSGLGRLVS GHISDSIPGL KKIYLQVLSF LLLGLMSMMI PLCRDFGGLI
     VVCLFLGLCD GFFITIMAPI AFELVGPMQA SQAIGYLLGM MALPMIAGPP IAGLLRNCFG
     DYHVAFYFAG VPPIIGAVIL FFVPLMHQRM FKKEQRDSSK DKMLSHDPDP NGELLPGSPT
     PEEPI
//