Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P36021 (MOT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC16A2
Synonyms:MCT8, XPCT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length539 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.7

Subunit structure

Homodimer. Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Highly expressed in liver and heart.

Involvement in disease

Monocarboxylate transporter 8 deficiency (MCT8 deficiency) [MIM:300523]: Consists 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Miscellaneous

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

Sequence similarities

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

Sequence caution

The sequence AAB60374.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAB60375.1 differs from that shown. Reason: Erroneous gene model prediction.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 539538Monocarboxylate transporter 8
PRO_0000211401

Regions

Topological domain2 – 9695Cytoplasmic Potential
Transmembrane97 – 11721Helical; Potential
Topological domain118 – 14326Extracellular Potential
Transmembrane144 – 16421Helical; Potential
Topological domain165 – 1717Cytoplasmic Potential
Transmembrane172 – 19221Helical; Potential
Topological domain193 – 2008Extracellular Potential
Transmembrane201 – 22121Helical; Potential
Topological domain222 – 2298Cytoplasmic Potential
Transmembrane230 – 25021Helical; Potential
Topological domain251 – 2588Extracellular Potential
Transmembrane259 – 27921Helical; Potential
Topological domain280 – 32243Cytoplasmic Potential
Transmembrane323 – 34321Helical; Potential
Topological domain344 – 35613Extracellular Potential
Transmembrane357 – 37721Helical; Potential
Topological domain378 – 3869Cytoplasmic Potential
Transmembrane387 – 40721Helical; Potential
Topological domain408 – 4092Extracellular Potential
Transmembrane410 – 43021Helical; Potential
Topological domain431 – 44717Cytoplasmic Potential
Transmembrane448 – 46821Helical; Potential
Topological domain469 – 4779Extracellular Potential
Transmembrane478 – 49821Helical; Potential
Topological domain499 – 53941Cytoplasmic Potential

Amino acid modifications

Modified residue21N-acetylalanine Ref.4 Ref.6

Natural variations

Natural variant1201S → F in MCT8 deficiency. Ref.13
VAR_059054
Natural variant1501A → V in MCT8 deficiency. Ref.8 Ref.12
VAR_022348
Natural variant1561Missing in MCT8 deficiency. Ref.13
VAR_059055
Natural variant1611V → M in MCT8 deficiency. Ref.13
VAR_059056
Natural variant3231I → L.
Corresponds to variant rs12849411 [ dbSNP | Ensembl ].
VAR_057723
Natural variant3601L → W in MCT8 deficiency. Ref.13
VAR_059057
Natural variant3971L → P in MCT8 deficiency. Ref.12
VAR_022349
Natural variant4271Missing in MCT8 deficiency. Ref.14
VAR_059058
Natural variant4381L → P in MCT8 deficiency. Ref.9
VAR_022350
Natural variant4901G → R in MCT8 deficiency. Ref.14
VAR_059059
Natural variant4941L → P in MCT8 deficiency. Ref.13
VAR_059060

Experimental info

Mutagenesis1181H → A: Reduction of thyroid hormone (TH) transport. Ref.7
Mutagenesis1861H → A: No effect on thyroid hormone (TH) transport. Ref.7
Mutagenesis3761H → A: No effect on thyroid hormone (TH) transport. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P36021 [UniParc].

Last modified September 5, 2006. Version 2.
Checksum: E4DB873D59FA4DD6

FASTA53959,511
        10         20         30         40         50         60 
MALQSQASEE AKGPWQEADQ EQQEPVGSPE PESEPEPEPE PEPVPVPPPE PQPEPQPLPD 

        70         80         90        100        110        120 
PAPLPELEFE SERVHEPEPT PTVETRGTAR GFQPPEGGFG WVVVFAATWC NGSIFGIHNS 

       130        140        150        160        170        180 
VGILYSMLLE EEKEKNRQVE FQAAWVGALA MGMIFFCSPI VSIFTDRLGC RITATAGAAV 

       190        200        210        220        230        240 
AFIGLHTSSF TSSLSLRYFT YGILFGCGCS FAFQPSLVIL GHYFQRRLGL ANGVVSAGSS 

       250        260        270        280        290        300 
IFSMSFPFLI RMLGDKIKLA QTFQVLSTFM FVLMLLSLTY RPLLPSSQDT PSKRGVRTLH 

       310        320        330        340        350        360 
QRFLAQLRKY FNMRVFRQRT YRIWAFGIAA AALGYFVPYV HLMKYVEEEF SEIKETWVLL 

       370        380        390        400        410        420 
VCIGATSGLG RLVSGHISDS IPGLKKIYLQ VLSFLLLGLM SMMIPLCRDF GGLIVVCLFL 

       430        440        450        460        470        480 
GLCDGFFITI MAPIAFELVG PMQASQAIGY LLGMMALPMI AGPPIAGLLR NCFGDYHVAF 

       490        500        510        520        530 
YFAGVPPIIG AVILFFVPLM HQRMFKKEQR DSSKDKMLAP DPDPNGELLP GSPNPEEPI 

« Hide

References

« Hide 'large scale' references
[1]"A novel transmembrane transporter encoded by the XPCT gene in Xq13.2."
Lafreniere R.G., Carrel L., Willard H.F.
Hum. Mol. Genet. 3:1133-1140(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"X-linked PEST-containing transporter (XPCT) identified in the X-chromosome inactivation center is an acidic amino acid transporter which requires CD147 for its functional expression."
Kim D., Kanai Y., Choi H., Shin H., Kim J., Teraoka H., Shigeta Y., Chairoungdua A., Babu E., Anzai N., Iribe Y., Endou H.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[5]"Evidence for a homodimeric structure of human monocarboxylate transporter 8."
Visser W.E., Philp N.J., van Dijk T.B., Klootwijk W., Friesema E.C., Jansen J., Beesley P.W., Ianculescu A.G., Visser T.J.
Endocrinology 150:5163-5170(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[6]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Importance of His192 in the human thyroid hormone transporter MCT8 for substrate recognition."
Groeneweg S., Lima de Souza E.C., Visser W.E., Peeters R.P., Visser T.J.
Endocrinology 154:2525-2532(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF HIS-118; HIS-186 AND HIS-376.
[8]"Mutations in a thyroid hormone transporter in patients with severe psychomotor retardation and high serum T3 levels."
Friesema E., Grueters A., Halestrap A., Reeser M., Visser T.
Thyroid 13:672-672(2003)
Cited for: VARIANT MCT8 DEFICIENCY VAL-150.
[9]"A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene."
Dumitrescu A.M., Liao X.-H., Best T.B., Brockmann K., Refetoff S.
Am. J. Hum. Genet. 74:168-175(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MCT8 DEFICIENCY PRO-438.
[10]Erratum
Dumitrescu A.M., Liao X.-H., Best T.B., Brockmann K., Refetoff S.
Am. J. Hum. Genet. 74:598-598(2004)
[11]"MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression."
Frints S.G., Lenzner S., Bauters M., Jensen L.R., Van Esch H., des Portes V., Moog U., Macville M.V., van Roozendaal K., Schrander-Stumpel C.T., Tzschach A., Marynen P., Fryns J.P., Hamel B., van Bokhoven H., Chelly J., Beldjord C., Turner G. expand/collapse author list , Gecz J., Moraine C., Raynaud M., Ropers H.H., Froyen G., Kuss A.W.
Eur. J. Hum. Genet. 16:1029-1037(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF START CODON.
[12]"Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation."
Friesema E.C.H., Grueters A., Biebermann H., Krude H., von Moers A., Reeser M., Barrett T.G., Mancilla E.E., Svensson J., Kester M.H.A., Kuiper G.G.J.M., Balkassmi S., Uitterlinden A.G., Koehrle J., Rodien P., Halestrap A.P., Visser T.J.
Lancet 364:1435-1437(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCT8 DEFICIENCY VAL-150 AND PRO-397.
[13]"Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene."
Schwartz C.E., May M.M., Carpenter N.J., Rogers R.C., Martin J., Bialer M.G., Ward J., Sanabria J., Marsa S., Lewis J.A., Echeverri R., Lubs H.A., Voeller K., Simensen R.J., Stevenson R.E.
Am. J. Hum. Genet. 77:41-53(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCT8 DEFICIENCY PHE-120; PHE-156 DEL; MET-161; TRP-360 AND PRO-494.
[14]"Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations."
Visser W.E., Jansen J., Friesema E.C.H., Kester M.H.A., Mancilla E., Lundgren J., van der Knaap M.S., Lunsing R.J., Brouwer O.F., Visser T.J.
Hum. Mutat. 30:29-38(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCT8 DEFICIENCY PHE-427 DEL AND ARG-490, POSSIBLE PATHOGENIC MECHANISM OF BRAIN DEVELOPMENT.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U05321 expand/collapse EMBL AC list , 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.
PIRI39295.
RefSeqNP_006508.2. NM_006517.4.
UniGeneHs.75317.

3D structure databases

ProteinModelPortalP36021.
SMRP36021. Positions 221-254, 272-297, 349-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000276033.

Chemistry

DrugBankDB00119. Pyruvic acid.

Protein family/group databases

TCDB2.A.1.13.10. the major facilitator superfamily (mfs).

PTM databases

PhosphoSiteP36021.

Polymorphism databases

DMDM114152841.

Proteomic databases

PaxDbP36021.
PRIDEP36021.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000276033; ENSP00000276033; ENSG00000147100.
ENST00000587091; ENSP00000465734; ENSG00000147100.
GeneID6567.
KEGGhsa:6567.
UCSCuc031tjy.1. human.

Organism-specific databases

CTD6567.
GeneCardsGC0XP073640.
H-InvDBHIX0056105.
HGNCHGNC:10923. SLC16A2.
HPAHPA003353.
MIM300095. gene.
300523. phenotype.
neXtProtNX_P36021.
Orphanet59. Allan-Herndon-Dudley syndrome.
PharmGKBPA35814.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG321880.
HOVERGENHBG006387.
InParanoidP36021.
KOK08231.
OrthoDBEOG7KWSH8.
PhylomeDBP36021.
TreeFamTF313792.

Gene expression databases

BgeeP36021.
CleanExHS_SLC16A2.
GenevestigatorP36021.

Family and domain databases

InterProIPR011701. MFS.
IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
[Graphical view]
PfamPF07690. MFS_1. 1 hit.
[Graphical view]
SUPFAMSSF103473. SSF103473. 1 hit.
PROSITEPS50850. MFS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC16A2. human.
GeneWikiSLC16A2.
GenomeRNAi6567.
NextBio25551.
PROP36021.
SOURCESearch...

Entry information

Entry nameMOT8_HUMAN
AccessionPrimary (citable) accession number: P36021
Secondary accession number(s): Q7Z797
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: September 5, 2006
Last modified: April 16, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM