SLC16A2

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
Traceable author statementⁱ
- 9425115
symporter activity Source: UniProtKB-KW
thyroid hormone transmembrane transporter activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 26426690
transporter activity
Source: ProtInc
Traceable author statementⁱ
- 7981683

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

monocarboxylic acid transport
Source: ProtInc
Traceable author statementⁱ
- 9425115
sodium-independent organic anion transport Source: Reactome
thyroid hormone transport
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 26426690

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Symport, Transport

Biological process

Symport, Transport

Enzyme and pathway databases

Reactomeⁱ	R-HSA-879518 Transport of organic anions

Reactomeⁱ

R-HSA-879518 Transport of organic anions

Protein family/group databases

TCDBⁱ	2.A.1.13.10 the major facilitator superfamily (mfs)

TCDBⁱ

2.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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome X

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000147100.9
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10923 SLC16A2
MIMⁱ	300095 gene
neXtProtⁱ	NX_P36021

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	2 – 96	CytoplasmicSequence analysisAdd BLAST	95
Transmembraneⁱ	97 – 117	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	118 – 143	ExtracellularSequence analysisAdd BLAST	26
Transmembraneⁱ	144 – 164	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	165 – 171	CytoplasmicSequence analysis	7
Transmembraneⁱ	172 – 192	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	193 – 200	ExtracellularSequence analysis	8
Transmembraneⁱ	201 – 221	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	222 – 229	CytoplasmicSequence analysis	8
Transmembraneⁱ	230 – 250	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	251 – 258	ExtracellularSequence analysis	8
Transmembraneⁱ	259 – 279	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	280 – 322	CytoplasmicSequence analysisAdd BLAST	43
Transmembraneⁱ	323 – 343	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	344 – 356	ExtracellularSequence analysisAdd BLAST	13
Transmembraneⁱ	357 – 377	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	378 – 386	CytoplasmicSequence analysis	9
Transmembraneⁱ	387 – 407	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	408 – 409	ExtracellularSequence analysis	2
Transmembraneⁱ	410 – 430	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	431 – 447	CytoplasmicSequence analysisAdd BLAST	17
Transmembraneⁱ	448 – 468	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	469 – 477	ExtracellularSequence analysis	9
Transmembraneⁱ	478 – 498	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	499 – 539	CytoplasmicSequence analysisAdd BLAST	41

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.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	118	H → A: Reduction of thyroid hormone (TH) transport. 1 Publication	1
Mutagenesisⁱ	186	H → A: No effect on thyroid hormone (TH) transport. 1 Publication	1
Mutagenesisⁱ	216	S → A: No effect on thyroid hormone transport. No effect on protein abundance. No effect on protein localization to the plasma membrane. 1 Publication	1
Mutagenesisⁱ	376	H → A: No effect on thyroid hormone (TH) transport. 1 Publication	1
Mutagenesisⁱ	490	G → A: No effect on thyroid hormone (TH) transport. 1 Publication	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	6567
GeneReviewsⁱ	SLC16A2
MalaCards human disease database More...MalaCardsⁱ	SLC16A2
MIMⁱ	300523 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000147100
Orphanetⁱ	59 Allan-Herndon-Dudley syndrome
PharmGKBⁱ	PA35814

Chemistry databases

Drug and drug target database More...DrugBankⁱ	DB00149 L-Leucine DB00150 L-Tryptophan DB00135 L-Tyrosine DB00451 Levothyroxine DB01583 Liotrix DB00119 Pyruvic acid

DrugBankⁱ

DB00149 L-Leucine
DB00150 L-Tryptophan
DB00135 L-Tyrosine
DB00451 Levothyroxine
DB01583 Liotrix
DB00119 Pyruvic acid

Polymorphism and mutation databases

BioMutaⁱ	SLC16A2
DMDMⁱ	114152841

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		RemovedCombined sources
ChainⁱPRO_0000211401	2 – 539	Monocarboxylate transporter 8Add BLAST		538

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	2	N-acetylalanineCombined sources		1

Keywords - PTMⁱ

Acetylation

Proteomic databases

EPDⁱ	P36021
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P36021
PaxDbⁱ	P36021
PeptideAtlas More...PeptideAtlasⁱ	P36021
PRIDEⁱ	P36021
ProteomicsDBⁱ	55173

PTM databases

iPTMnetⁱ	P36021
PhosphoSitePlusⁱ	P36021

Expressionⁱ

Tissue specificityⁱ

Highly expressed in liver and heart.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000147100 Expressed in 148 organ(s), highest expression level in right adrenal gland
CleanExⁱ	HS_SLC16A2
ExpressionAtlasⁱ	P36021 baseline and differential
Genevisibleⁱ	P36021 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA072719

HPAⁱ

HPA072719

Interactionⁱ

Subunit structureⁱ

Homodimer.2 Publications

Protein-protein interaction databases

BioGridⁱ	112455, 4 interactors
STRINGⁱ	9606.ENSP00000276033

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P36021
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family. [View classification]Curated

Keywords - Domainⁱ

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG410IMVZ Eukaryota ENOG410Z4JM LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00910000144077
HOVERGENⁱ	HBG006387
InParanoidⁱ	P36021
KEGG Orthology (KO) More...KOⁱ	K08231
OMAⁱ	VRYFTYG
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0449
PhylomeDBⁱ	P36021
TreeFamⁱ	TF313792

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd06174 MFS, 1 hit
InterProⁱ	View protein in InterPro IPR030761 MCT8 IPR011701 MFS IPR020846 MFS_dom IPR036259 MFS_trans_sf
PANTHERⁱ	PTHR11360:SF123 PTHR11360:SF123, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07690 MFS_1, 1 hit
SUPFAMⁱ	SSF103473 SSF103473, 1 hit
PROSITEⁱ	View 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]FASTA Add 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.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	K7ELT4	K7ELT4_HUMAN		Monocarboxylate transporter 8 Monocarboxylate transporter 8	SLC16A2	229	Annotation score:
	A0A1B0GVB4	A0A1B0GVB4_HUMAN		Monocarboxylate transporter 8 Monocarboxylate transporter 8	SLC16A2	69	Annotation 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_059054	120	S → F in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs113994162EnsemblClinVar.	1
Natural variantⁱVAR_074572	147	G → R in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication	1
Natural variantⁱVAR_074573	150	A → T in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs373279555Ensembl.	1
Natural variantⁱVAR_022348	150	A → V in MCT8 deficiency; does not affect homodimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs104894936EnsemblClinVar.	1
Natural variantⁱVAR_059055	156	Missing in MCT8 deficiency; increased homodimerization activity. 2 Publications	1
Natural variantⁱVAR_059056	161	V → M in MCT8 deficiency; increased homodimerization activity. 2 Publications	1
Natural variantⁱVAR_074574	197	R → H in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs727504155EnsemblClinVar.	1
Natural variantⁱVAR_074575	208	G → C in MCT8 deficiency; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 1 Publication	1
Natural variantⁱVAR_075145	216	S → 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_078497	217	L → R in MCT8 deficiency; atypical form; characterized by developmental delay hypotonia and delayed myelination. 1 Publication	1
Natural variantⁱVAR_074576	247	P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication	1
Natural variantⁱVAR_057723	323	I → L. Corresponds to variant dbSNP:rs12849411Ensembl.	1
Natural variantⁱVAR_059057	360	L → W in MCT8 deficiency; impaired homodimerization. 2 PublicationsCorresponds to variant dbSNP:rs104894939EnsemblClinVar.	1
Natural variantⁱVAR_074577	371	R → C in MCT8 deficiency; impaired homodimerization. 1 PublicationCorresponds to variant dbSNP:rs587784384EnsemblClinVar.	1
Natural variantⁱVAR_074578	379	D → V in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication	1
Natural variantⁱVAR_022349	397	L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs122455132EnsemblClinVar.	1
Natural variantⁱVAR_059058	427	Missing in MCT8 deficiency. 1 Publication	1
Natural variantⁱVAR_022350	438	L → P in MCT8 deficiency; does not affect homodimerization activity. 2 PublicationsCorresponds to variant dbSNP:rs104894931EnsemblClinVar.	1
Natural variantⁱVAR_074579	463	P → L in MCT8 deficiency; impaired thyroid hormone transporter activity; does not affect localization to the cell membrane. 1 Publication	1
Natural variantⁱVAR_074580	484	G → D in MCT8 deficiency; does not affect homodimerization activity; impaired thyroid hormone transporter activity; impaired localization to the cell membrane. 2 Publications	1
Natural variantⁱVAR_078498	490	G → E in MCT8 deficiency; results in a mild clinical phenotype; retains some residual thyroid hormone transporter activity. 1 Publication	1
Natural variantⁱVAR_059059	490	G → R in MCT8 deficiency; loss of thyroid hormone transport. 2 PublicationsCorresponds to variant dbSNP:rs794727799EnsemblClinVar.	1
Natural variantⁱVAR_059060	494	L → 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 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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS14426.2
PIRⁱ	I39295
NCBI Reference Sequences More...RefSeqⁱ	NP_006508.2, NM_006517.4
UniGeneⁱ	Hs.75317

Genome annotation databases

Ensemblⁱ	ENST00000587091; ENSP00000465734; ENSG00000147100
GeneIDⁱ	6567
KEGGⁱ	hsa:6567
UCSC genome browser More...UCSCⁱ	uc031tjy.2 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P36021	Solute carrier family 16 member 2		ICTTR		543	UniRef90_P36021
monocarboxylate transporter 8		ERIEU		541
Monocarboxylate transporter 8		HETGA		539
Solute carrier family 16 member 2		MACFA		537
Solute carrier family 16 member 2		MACNE		537
+18

Protein	Similar proteins		Species	Score	Length	Source
P36021	Monocarboxylate transporter 8		MOUSE		545	UniRef50_P36021
Monocarboxylate transporter 8		RAT		545
Solute carrier family 16 member 2		ICTTR		543
monocarboxylate transporter 8		ERIEU		541
Monocarboxylate transporter 8		HETGA		539
+106

Entry informationⁱ

Entry nameⁱ	MOT8_HUMAN
Accessionⁱ	P36021Primary (citable) accession number: P36021 Secondary accession number(s): Q7Z797
Entry historyⁱ	Integrated 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 statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P36021 (MOT8_HUMAN)

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Monocarboxylate transporter 8

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Plasma Membrane

Topology

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Computationally mapped potential isoform sequencesⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ