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2.A.1.13.3
The thyroid hormone transporter, MCT8 (transports L- and D-isomers of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3) and 3,3'-diiodothyronine [Km values = 2-5 μM; Leu, Phe, Trp and Tyr were not transported]) (Friesema et al., 2003). Loss of function mutations in MCT8 leads to Allan-Herndon-Dudley syndrome, severe X-linked psychomotor retardation and elevated serum T3 levels (Jansen et al., 2008). Essential molecular determinants for thyroid hormone transport and their structural implications are presented by Kinne et al. (2010). Induced by retinoic acid (Kogai et al., 2010). Mediates energy-independent bidirectional transport. MCT8 is specific for L-iodothyronines and requires at least one iodine atom per aromatic ring. Thyronamines, decarboxylated metabolites of iodothyronines, triiodothyroacetic acid and tetraiodothyroacetic acid, TH derivatives lacking both chiral center and amino group, are not substrates (Kinne et al., 2010). A deficiency causes altered thyroid morphology and a persistent high triiodothyronine/thyroxine ratio after thyroidectomy (Wirth et al., 2011). Primary and secondary thyroid hormone transporters have been reviewed (Kinne et al., 2011).

Accession Number:O70324
Protein Name:MCT 8
Length:545
Molecular Weight:60025.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Thyroxine, 3,3',5-triiodothyronine, 3,3'5'-triiodothyronine, 3,3'-diiodothyronine

Cross database links:

Genevestigator: O70324
HEGENOM: HBG717340
RefSeq: NP_033223.2   
Entrez Gene ID: 20502   
Pfam: PF07690   
KEGG: mmu:20502   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0015293 F:symporter activity
GO:0055085 P:transmembrane transport

References (3)

[1] “Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene.”  Debrand E.et.al.   9545634
[2] “Comparative sequence analysis of the X-inactivation center region in mouse, human and bovine.”  Chureau C.et.al.   12045143
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MALPSPASEE AEGPCQEANQ EYQEPVCSPV PEPEPEPEPE PEPDPEPVPV PPPEPQPEPE 
61:	PQPLPDPAPL PELGFEAEPV QEPEPTPTVE TRGTARGFQP PEGGFGWIVV FAATWCNGSI 
121:	FGIHNSVGIL YSMLLEEEKE KNRQVEFQAA WVGALAMGMI FFCSPIVSIF TDRLGCRITA 
181:	TTGAAVAFIG LHTSSFTSSL SLRYFTYGIL FGCGCSFAFQ PSLVILGHYF QRRLGLANGV 
241:	VSAGSSIFSM SFPFLIKMLG DKIKLAQTFQ VLSTFMFVLT LLSLTYRPLL PSSQDTPSKR 
301:	GAHTLRQRFL VQFRKYFNMR VFRQRTYRIW AFGIAAAALG YFVPYVHLMK YVEDKFKEIK 
361:	ETWVLLVCIG ATSGLGRLVS GHISDSIPGL KKIYLQVLSF LLLGLMSMMI PLCRDFGGLI 
421:	VVCLFLGLCD GFFITIMAPI AFELVGPMQA SQAIGYLLGM MALPMIAGPP IAGLLRNCFG 
481:	DYHVAFYFAG VPPIIGAVIL FFVPLMHQRM FKKEQRDSSK DKMLSHDPDP NGELLPGSPT 
541:	PEEPI