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Family Report for: Thyroglobulin

Thyroglobulin



Relationship
Block C
Parent Family : Non-catalytic_C

Comment
Only the C-terminal part of thyroglobulin is a member of the alpha/beta hydrolase family, here starting with the first G in cholinesterase 2206 (aa numbering in human thyroglobulin). The N-terminal part of thyroglobulin is made of three domains, labeled I to III, that encompass 10 repeats of a ca. 65 amino acid residues known as the Tg type-1 repeat PF00086 PS00484 IPR011641 IPR000716 not included in ESTHER. Thyroglobulin is the glycoprotein precursor to the thyroid hormones T3 (triiodothyronine) and T4 (tetraiodothyronine). It has a molecular mass of 660 kD, with 2 identical subunits, yet its complete hydrolysis yields only 2 to 4 molecules of T3 and T4. The protein contains a 19-amino acid signal peptide followed by 2,748 residues. Van Ommen (1987) suggested that defects in the TG gene can cause either dominant or recessive disorders depending on the nature of the defect. When the gene is absent or at least when no thyroglobulin is synthesized, the disorder is likely to be recessive, whereas the presence of an abnormal subunit leads to a dominantly inherited disorder. The explanation for this is that in a dimeric protein such as thyroglobulin, 75% of the dimers in heterozygotes will contain 1 or more abnormal subunits. This should profoundly disturb thyroglobulin metabolism, since this protein fulfills a dual storage/catalytic role as a dimer, is present in bulk quantities (100 mg Tg/g thyroid mass), and needs to be exocytosed, iodinated, endocytosed, and degraded. EnsemblClone AF230666, EnsemblContig AC079020.2.132816.152274, AF235100_2 gene chromosome 8 clone PAC 98A24 map 8q24.3. there is a small gene with only a little bit of thyroglobuline just 3' of the real gene AC069434.7.189089.192039 ENST00000254617 ENSG00000132287. Three out of five iodination sites are in the cholinesterase homologous domain 2573 (In T4), 2587 (In T4),2766 (In T3)
1 Disease(s)


Database
Sequences
Interpro
|
IPR016324 (Thyroglobulin), IPR002018 (Carboxylesterase, type B)
PIRSF
|
Pdoc
|
PFam
|
PF00135 (COesterase)
Prints
|
Prosite
|
no EC number



Peptide in
|Fasta
Nucleotide in
|Fasta
Alignment with Multalin
|Text only/graphic display
Seed alignment with MAFFT
|No colour/coloured with Mview
Alignment with MAFFT
|No colour/coloured with Mview
Dendrogram
|Graphical display, obtained with the dnd file produced by Clustalw

References
28 more
    Title: Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin
    Marechal N, Serrano BP, Zhang X, Weitz CJ
    Ref: Nat Commun, 13:2380, 2022 : PubMed

            

    Title: The role of thyroglobulin in thyroid hormonogenesis
    Citterio CE, Targovnik HM, Arvan P
    Ref: Nat Rev Endocrinol, 15:323, 2019 : PubMed

            

    Title: Relationship between the dimerization of thyroglobulin and its ability to form triiodothyronine
    Citterio CE, Morishita Y, Dakka N, Veluswamy B, Arvan P
    Ref: Journal of Biological Chemistry, 293:4860, 2018 : PubMed

            

Other Papers


No structure scheme yet for this family

Structures in Thyroglobulin family (4)

Genes Proteins in Thyroglobulin family (68)

Fragments of genes in Thyroglobulin family (37)

No Substrate

No Inhibitor



Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
For technical information about these pages see:
ESTHER Home Page and ACEDB Home Page
AcePerl Lincoln Stein Home Page
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