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Protein

Monocarboxylate transporter 8

Gene

SLC16A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Very active and specific thyroid hormone transporter. Stimulates cellular uptake of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine. Does not transport Leu, Phe, Trp or Tyr.2 Publications

Miscellaneous

Abnormal brain development associated with MCT8 deficiency may be the consequence of either decreased or increased intracellular T3 concentrations.1 Publication

GO - Molecular functioni

  • monocarboxylic acid transmembrane transporter activity Source: ProtInc
  • symporter activity Source: UniProtKB-KW
  • thyroid hormone transmembrane transporter activity Source: UniProtKB
  • transporter activity Source: ProtInc

GO - Biological processi

Keywordsi

Biological processSymport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-879518 Transport of organic anions

Protein family/group databases

TCDBi2.A.1.13.10 the major facilitator superfamily (mfs)

Names & Taxonomyi

Protein namesi
Recommended name:
Monocarboxylate transporter 8
Short name:
MCT 8
Alternative name(s):
Monocarboxylate transporter 7
Short name:
MCT 7
Solute carrier family 16 member 2
X-linked PEST-containing transporter
Gene namesi
Name:SLC16A2
Synonyms:MCT8, XPCT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000147100.9
HGNCiHGNC:10923 SLC16A2
MIMi300095 gene
neXtProtiNX_P36021

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 96CytoplasmicSequence analysisAdd BLAST95
Transmembranei97 – 117HelicalSequence analysisAdd BLAST21
Topological domaini118 – 143ExtracellularSequence analysisAdd BLAST26
Transmembranei144 – 164HelicalSequence analysisAdd BLAST21
Topological domaini165 – 171CytoplasmicSequence analysis7
Transmembranei172 – 192HelicalSequence analysisAdd BLAST21
Topological domaini193 – 200ExtracellularSequence analysis8
Transmembranei201 – 221HelicalSequence analysisAdd BLAST21
Topological domaini222 – 229CytoplasmicSequence analysis8
Transmembranei230 – 250HelicalSequence analysisAdd BLAST21
Topological domaini251 – 258ExtracellularSequence analysis8
Transmembranei259 – 279HelicalSequence analysisAdd BLAST21
Topological domaini280 – 322CytoplasmicSequence analysisAdd BLAST43
Transmembranei323 – 343HelicalSequence analysisAdd BLAST21
Topological domaini344 – 356ExtracellularSequence analysisAdd BLAST13
Transmembranei357 – 377HelicalSequence analysisAdd BLAST21
Topological domaini378 – 386CytoplasmicSequence analysis9
Transmembranei387 – 407HelicalSequence analysisAdd BLAST21
Topological domaini408 – 409ExtracellularSequence analysis2
Transmembranei410 – 430HelicalSequence analysisAdd BLAST21
Topological domaini431 – 447CytoplasmicSequence analysisAdd BLAST17
Transmembranei448 – 468HelicalSequence analysisAdd BLAST21
Topological domaini469 – 477ExtracellularSequence analysis9
Transmembranei478 – 498HelicalSequence analysisAdd BLAST21
Topological domaini499 – 539CytoplasmicSequence analysisAdd BLAST41

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Monocarboxylate transporter 8 deficiency (MCT8 deficiency)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionConsists of a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels. Thyroid hormone deficiency can be caused by defects of hormone synthesis and action, but it has also been linked to a defect in cellular hormone transport. Affected patients are males with abnormal relative concentrations of three circulating iodothyronines, as well as severe neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects.
See also OMIM:300523
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059054120S → F in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs113994162EnsemblClinVar.1
Natural variantiVAR_074572147G → R in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_074573150A → T in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs373279555Ensembl.1
Natural variantiVAR_022348150A → V in MCT8 deficiency; does not affect homodimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs104894936EnsemblClinVar.1
Natural variantiVAR_059055156Missing in MCT8 deficiency; increased homodimerization activity. 2 Publications1
Natural variantiVAR_059056161V → M in MCT8 deficiency; increased homodimerization activity. 2 Publications1
Natural variantiVAR_074574197R → H in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs727504155EnsemblClinVar.1
Natural variantiVAR_074575208G → C in MCT8 deficiency; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 1 Publication1
Natural variantiVAR_075145216S → F in MCT8 deficiency; decreased thyroid hormone transport; decreased protein abundance; decreased localization to the plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs398124232EnsemblClinVar.1
Natural variantiVAR_078497217L → R in MCT8 deficiency; atypical form; characterized by developmental delay hypotonia and delayed myelination. 1 Publication1
Natural variantiVAR_074576247P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_059057360L → W in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs104894939EnsemblClinVar.1
Natural variantiVAR_074577371R → C in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs587784384EnsemblClinVar.1
Natural variantiVAR_074578379D → V in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_022349397L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs122455132EnsemblClinVar.1
Natural variantiVAR_059058427Missing in MCT8 deficiency. 1 Publication1
Natural variantiVAR_022350438L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs104894931EnsemblClinVar.1
Natural variantiVAR_074579463P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_074580484G → D in MCT8 deficiency; does not affect homodimerization activity; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 2 Publications1
Natural variantiVAR_078498490G → E in MCT8 deficiency; results in a mild clinical phenotype; retains some residual thyroid hormone transporter activity. 1 Publication1
Natural variantiVAR_059059490G → R in MCT8 deficiency; loss of thyroid hormone transport. 2 PublicationsCorresponds to variant dbSNP:rs794727799EnsemblClinVar.1
Natural variantiVAR_059060494L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs104894938EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi118H → A: Reduction of thyroid hormone (TH) transport. 1 Publication1
Mutagenesisi186H → A: No effect on thyroid hormone (TH) transport. 1 Publication1
Mutagenesisi216S → A: No effect on thyroid hormone transport. No effect on protein abundance. No effect on protein localization to the plasma membrane. 1 Publication1
Mutagenesisi376H → A: No effect on thyroid hormone (TH) transport. 1 Publication1
Mutagenesisi490G → A: No effect on thyroid hormone (TH) transport. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6567
GeneReviewsiSLC16A2
MalaCardsiSLC16A2
MIMi300523 phenotype
OpenTargetsiENSG00000147100
Orphaneti59 Allan-Herndon-Dudley syndrome
PharmGKBiPA35814

Chemistry databases

DrugBankiDB00149 L-Leucine
DB00150 L-Tryptophan
DB00135 L-Tyrosine
DB00451 Levothyroxine
DB01583 Liotrix
DB00119 Pyruvic acid

Polymorphism and mutation databases

BioMutaiSLC16A2
DMDMi114152841

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002114012 – 539Monocarboxylate transporter 8Add BLAST538

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP36021
MaxQBiP36021
PaxDbiP36021
PeptideAtlasiP36021
PRIDEiP36021
ProteomicsDBi55173

PTM databases

iPTMnetiP36021
PhosphoSitePlusiP36021

Expressioni

Tissue specificityi

Highly expressed in liver and heart.1 Publication

Gene expression databases

BgeeiENSG00000147100 Expressed in 148 organ(s), highest expression level in right adrenal gland
CleanExiHS_SLC16A2
ExpressionAtlasiP36021 baseline and differential
GenevisibleiP36021 HS

Organism-specific databases

HPAiHPA072719

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi112455, 4 interactors
STRINGi9606.ENSP00000276033

Structurei

3D structure databases

ProteinModelPortaliP36021
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IMVZ Eukaryota
ENOG410Z4JM LUCA
GeneTreeiENSGT00910000144077
HOVERGENiHBG006387
InParanoidiP36021
KOiK08231
OMAiVRYFTYG
OrthoDBiEOG091G0449
PhylomeDBiP36021
TreeFamiTF313792

Family and domain databases

CDDicd06174 MFS, 1 hit
InterProiView protein in InterPro
IPR030761 MCT8
IPR011701 MFS
IPR020846 MFS_dom
IPR036259 MFS_trans_sf
PANTHERiPTHR11360:SF123 PTHR11360:SF123, 1 hit
PfamiView protein in Pfam
PF07690 MFS_1, 1 hit
SUPFAMiSSF103473 SSF103473, 1 hit
PROSITEiView protein in PROSITE
PS50850 MFS, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

P36021-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MALQSQASEE AKGPWQEADQ EQQEPVGSPE PESEPEPEPE PEPVPVPPPE
60 70 80 90 100
PQPEPQPLPD PAPLPELEFE SERVHEPEPT PTVETRGTAR GFQPPEGGFG
110 120 130 140 150
WVVVFAATWC NGSIFGIHNS VGILYSMLLE EEKEKNRQVE FQAAWVGALA
160 170 180 190 200
MGMIFFCSPI VSIFTDRLGC RITATAGAAV AFIGLHTSSF TSSLSLRYFT
210 220 230 240 250
YGILFGCGCS FAFQPSLVIL GHYFQRRLGL ANGVVSAGSS IFSMSFPFLI
260 270 280 290 300
RMLGDKIKLA QTFQVLSTFM FVLMLLSLTY RPLLPSSQDT PSKRGVRTLH
310 320 330 340 350
QRFLAQLRKY FNMRVFRQRT YRIWAFGIAA AALGYFVPYV HLMKYVEEEF
360 370 380 390 400
SEIKETWVLL VCIGATSGLG RLVSGHISDS IPGLKKIYLQ VLSFLLLGLM
410 420 430 440 450
SMMIPLCRDF GGLIVVCLFL GLCDGFFITI MAPIAFELVG PMQASQAIGY
460 470 480 490 500
LLGMMALPMI AGPPIAGLLR NCFGDYHVAF YFAGVPPIIG AVILFFVPLM
510 520 530
HQRMFKKEQR DSSKDKMLAP DPDPNGELLP GSPNPEEPI
Length:539
Mass (Da):59,511
Last modified:September 5, 2006 - v2
Checksum:iE4DB873D59FA4DD6
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ELT4K7ELT4_HUMAN
Monocarboxylate transporter 8
SLC16A2
229Annotation score:
A0A1B0GVB4A0A1B0GVB4_HUMAN
Monocarboxylate transporter 8
SLC16A2
69Annotation score:

Sequence cautioni

The sequence AAB60374 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAB60375 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059054120S → F in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs113994162EnsemblClinVar.1
Natural variantiVAR_074572147G → R in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_074573150A → T in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs373279555Ensembl.1
Natural variantiVAR_022348150A → V in MCT8 deficiency; does not affect homodimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs104894936EnsemblClinVar.1
Natural variantiVAR_059055156Missing in MCT8 deficiency; increased homodimerization activity. 2 Publications1
Natural variantiVAR_059056161V → M in MCT8 deficiency; increased homodimerization activity. 2 Publications1
Natural variantiVAR_074574197R → H in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs727504155EnsemblClinVar.1
Natural variantiVAR_074575208G → C in MCT8 deficiency; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 1 Publication1
Natural variantiVAR_075145216S → F in MCT8 deficiency; decreased thyroid hormone transport; decreased protein abundance; decreased localization to the plasma membrane. 1 PublicationCorresponds to variant dbSNP:rs398124232EnsemblClinVar.1
Natural variantiVAR_078497217L → R in MCT8 deficiency; atypical form; characterized by developmental delay hypotonia and delayed myelination. 1 Publication1
Natural variantiVAR_074576247P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_057723323I → L. Corresponds to variant dbSNP:rs12849411Ensembl.1
Natural variantiVAR_059057360L → W in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs104894939EnsemblClinVar.1
Natural variantiVAR_074577371R → C in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs587784384EnsemblClinVar.1
Natural variantiVAR_074578379D → V in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_022349397L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs122455132EnsemblClinVar.1
Natural variantiVAR_059058427Missing in MCT8 deficiency. 1 Publication1
Natural variantiVAR_022350438L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs104894931EnsemblClinVar.1
Natural variantiVAR_074579463P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication1
Natural variantiVAR_074580484G → D in MCT8 deficiency; does not affect homodimerization activity; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 2 Publications1
Natural variantiVAR_078498490G → E in MCT8 deficiency; results in a mild clinical phenotype; retains some residual thyroid hormone transporter activity. 1 Publication1
Natural variantiVAR_059059490G → R in MCT8 deficiency; loss of thyroid hormone transport. 2 PublicationsCorresponds to variant dbSNP:rs794727799EnsemblClinVar.1
Natural variantiVAR_059060494L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs104894938EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U05321
, U05316, U05317, U05318, U05319, U05320 Genomic DNA Translation: AAB60375.1 Sequence problems.
U05315 mRNA Translation: AAB60374.1 Different initiation.
AB085789 mRNA Translation: BAC76827.1
AC004073 Genomic DNA No translation available.
AL157934 Genomic DNA No translation available.
CCDSiCCDS14426.2
PIRiI39295
RefSeqiNP_006508.2, NM_006517.4
UniGeneiHs.75317

Genome annotation databases

EnsembliENST00000587091; ENSP00000465734; ENSG00000147100
GeneIDi6567
KEGGihsa:6567
UCSCiuc031tjy.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMOT8_HUMAN
AccessioniPrimary (citable) accession number: P36021
Secondary accession number(s): Q7Z797
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: September 5, 2006
Last modified: September 12, 2018
This is version 145 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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