P36021 (MOT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SLC16A2
Synonyms:	MCT8, XPCT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	539 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Subunit structure	Homodimer. Ref.4
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. The sequence AAB60375.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to plasma membrane Traceable author statement PubMed 9425115. Source: ProtInc
Molecular_function	monocarboxylic acid transmembrane transporter activity Traceable author statement PubMed 9425115. Source: ProtInc symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 539	539	Monocarboxylate transporter 8		PRO_0000211401
Regions
	Topological domain	1 – 96	96	Cytoplasmic Potential
	Transmembrane	97 – 117	21	Helical; Potential
	Topological domain	118 – 143	26	Extracellular Potential
	Transmembrane	144 – 164	21	Helical; Potential
	Topological domain	165 – 171	7	Cytoplasmic Potential
	Transmembrane	172 – 192	21	Helical; Potential
	Topological domain	193 – 200	8	Extracellular Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Topological domain	222 – 229	8	Cytoplasmic Potential
	Transmembrane	230 – 250	21	Helical; Potential
	Topological domain	251 – 258	8	Extracellular Potential
	Transmembrane	259 – 279	21	Helical; Potential
	Topological domain	280 – 322	43	Cytoplasmic Potential
	Transmembrane	323 – 343	21	Helical; Potential
	Topological domain	344 – 356	13	Extracellular Potential
	Transmembrane	357 – 377	21	Helical; Potential
	Topological domain	378 – 386	9	Cytoplasmic Potential
	Transmembrane	387 – 407	21	Helical; Potential
	Topological domain	408 – 409	2	Extracellular Potential
	Transmembrane	410 – 430	21	Helical; Potential
	Topological domain	431 – 447	17	Cytoplasmic Potential
	Transmembrane	448 – 468	21	Helical; Potential
	Topological domain	469 – 477	9	Extracellular Potential
	Transmembrane	478 – 498	21	Helical; Potential
	Topological domain	499 – 539	41	Cytoplasmic Potential
Natural variations
	Natural variant	120	1	S → F in MCT8 deficiency. Ref.10		VAR_059054
	Natural variant	150	1	A → V in MCT8 deficiency. Ref.5 Ref.9		VAR_022348
	Natural variant	156	1	Missing in MCT8 deficiency. Ref.10		VAR_059055
	Natural variant	161	1	V → M in MCT8 deficiency. Ref.10		VAR_059056
	Natural variant	323	1	I → L. Corresponds to variant rs12849411 [ dbSNP | Ensembl ].		VAR_057723
	Natural variant	360	1	L → W in MCT8 deficiency. Ref.10		VAR_059057
	Natural variant	397	1	L → P in MCT8 deficiency. Ref.9		VAR_022349
	Natural variant	427	1	Missing in MCT8 deficiency. Ref.11		VAR_059058
	Natural variant	438	1	L → P in MCT8 deficiency. Ref.6		VAR_022350
	Natural variant	490	1	G → R in MCT8 deficiency. Ref.11		VAR_059059
	Natural variant	494	1	L → P in MCT8 deficiency. Ref.10		VAR_059060

Sequences

	Sequence		Length	Mass (Da)
	P36021 [UniParc]. Last modified September 5, 2006. Version 2. Checksum: E4DB873D59FA4DD6	FASTA	539	59,511
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[5]	"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.
[6]	"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.
[7]	Erratum Dumitrescu A.M., Liao X.-H., Best T.B., Brockmann K., Refetoff S. Am. J. Hum. Genet. 74:598-598(2004)
[8]	"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. , 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.
[9]	"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.
[10]	"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.
[11]	"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

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00000655.
PIR	I39295.
RefSeq	NP_006508.2. NM_006517.4.
UniGene	Hs.75317.
3D structure databases
ProteinModelPortal	P36021.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000276033.
PTM databases
PhosphoSite	P36021.
Polymorphism databases
DMDM	114152841.
Proteomic databases
PaxDb	P36021.
PRIDE	P36021.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000276033; ENSP00000276033; ENSG00000147100. ENST00000587091; ENSP00000465734; ENSG00000147100.
GeneID	6567.
KEGG	hsa:6567.
Organism-specific databases
CTD	6567.
GeneCards	GC0XP073640.
H-InvDB	HIX0056105.
HGNC	HGNC:10923. SLC16A2.
HPA	HPA003353.
MIM	300095. gene. 300523. phenotype.
neXtProt	NX_P36021.
Orphanet	59. Allan-Herndon-Dudley syndrome. 280296. Pelizaeus-Merzbacher-like due to SLC16A2 mutation.
PharmGKB	PA35814.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG321880.
HOVERGEN	HBG006387.
InParanoid	P36021.
KO	K08231.
OrthoDB	EOG4H72BN.
Gene expression databases
ArrayExpress	P36021.
Bgee	P36021.
CleanEx	HS_SLC16A2.
Genevestigator	P36021.
Family and domain databases
InterPro	IPR011701. MFS. IPR020846. MFS_dom. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
Pfam	PF07690. MFS_1. 1 hit. [Graphical view]
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
PROSITE	PS50850. MFS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SLC16A2. human.
DrugBank	DB00119. Pyruvic acid.
GenomeRNAi	6567.
NextBio	25551.
SOURCE	Search...

Entry information

Entry name

MOT8_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.