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Gene_locus Report for: human-TG

Homo sapiens (Human) Thyroglobulin TG Tg

Comment
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. Only the C-terminal part is homologous to alph/beta hydrolase. 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) only c-term Pfam A COesterase 2186 2718 here only homologous region starting with first G in cholinesterase 2206


Relationship
Family|Thyroglobulin
Block| C
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E


Molecular evidence
Database
96 mutations: Table (e.g. : A1727HfsX26_human-TG, A1773D_human-TG, A2215D ... more)
2 structures: 6SCJ, 7B75
No kinetic

Disease: Goiter, familial with hypothyroidism, autosomal recessive -



No Substrate
No inhibitor
>3 Genbank links 25 more: BC140933, BC127887, X05615
>3 UniProt links 6 more: P01266, Q59GF0, A1L1A0
>3 Ncbi-nid links 1 more: 37173, 10444520, 11079646
>3 Ncbi-pid links 2 more: NP_003226, 10444520, 5787968
2 Structure : 7B75, 6SCJ
>3 UniProt links 7 more: Q59GF0, A1L1A0, B2RU26
>3 Interpro links 7 more: Q59GF0, A1L1A0, B2RU26
>3 Prodom links 7 more: Q59GF0, A1L1A0, B2RU26
>3 Pfam links 7 more: Q59GF0, A1L1A0, B2RU26
>3 PIRSF links 7 more: Q59GF0, A1L1A0, B2RU26
>3 SUPERFAM links 7 more: Q59GF0, A1L1A0, B2RU26
1 EntrezGene : 7038
1 SNP : 7038
1 UniGene : 654591
1 HUGO HGNC : 11764
2 OMIM : 188450, 274700
1 Ensembl : ENSG00000042832
Sequence
Graphical view for this peptide sequence: human-TG
Colored MSA for Thyroglobulin (raw)
HGRLLGRSQAIQVGTSWKQVDQFLGVPYAAPPLAERRFQAPEPLNWTGSW
DASKPRASCWQPGTRTSTSPGVSEDCLYLNVFIPQNVAPNASVLVFFHNT
MDREESEGWPAIDGSFLAAVGNLIVVTASYRVGVFGFLSSGSGEVSGNWG
LLDQVAALTWVQTHIRGFGGDPRRVSLAADRGGADVASIHLLTARATNSQ
LFRRAVLMGGSALSPAAVISHERAQQQAIALAKEVSCPMSSSQEVVSCLR
QKPANVLNDAQTKLLAVSGPFHYWGPVIDGHFLREPPARALKRSLWVEVD
LLIGSSQDDGLINRAKAVKQFEESRGRTSSKTAFYQALQNSLGGEDSDAR
VEAAATWYYSLEHSTDDYASFSRALENATRDYFIICPIIDMASAWAKRAR
GNVFMYHAPENYGHGSLELLADVQFALGLPFYPAYEGQFSLEEKSLSLKI
MQYFSHFIRSGNPNYPYEFSRKVPTFATPWPDFVPRAGGENYKEFSELLP
NRQGLKKADCSFWSKYISSLKTSADGAKGGQSAESEEEELTAGSGLREDL
LSLQEPGSKTYSK
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

HGRLLGRSQAIQVGTSWKQVDQFLGVPYAAPPLAERRFQAPEPLNWTGSW
DASKPRASCWQPGTRTSTSPGVSEDCLYLNVFIPQNVAPNASVLVFFHNT
MDREESEGWPAIDGSFLAAVGNLIVVTASYRVGVFGFLSSGSGEVSGNWG
LLDQVAALTWVQTHIRGFGGDPRRVSLAADRGGADVASIHLLTARATNSQ
LFRRAVLMGGSALSPAAVISHERAQQQAIALAKEVSCPMSSSQEVVSCLR
QKPANVLNDAQTKLLAVSGPFHYWGPVIDGHFLREPPARALKRSLWVEVD
LLIGSSQDDGLINRAKAVKQFEESRGRTSSKTAFYQALQNSLGGEDSDAR
VEAAATWYYSLEHSTDDYASFSRALENATRDYFIICPIIDMASAWAKRAR
GNVFMYHAPENYGHGSLELLADVQFALGLPFYPAYEGQFSLEEKSLSLKI
MQYFSHFIRSGNPNYPYEFSRKVPTFATPWPDFVPRAGGENYKEFSELLP
NRQGLKKADCSFWSKYISSLKTSADGAKGGQSAESEEEELTAGSGLREDL
LSLQEPGSKTYSK


References
71 more
    Title: Cryo-EM structure of native human thyroglobulin
    Adaixo R, Steiner EM, Righetto RD, Schmidt A, Stahlberg H, Taylor NMI
    Ref: Biorxiv, :, 2021 : PubMed

            

    Title: The cholinesterase-like domain of thyroglobulin functions as an intramolecular chaperone
    Lee J, Di Jeso B, Arvan P
    Ref: J Clinical Investigation, 118:2950, 2008 : PubMed

            


Other Papers
Adaixo 2022 Nat.Commun 13 61
Bernal Barquero 2022 Int.J.Mol.Sci 23 9251
Matsuyama 2022 Pediatr.Endocrinol 31 185


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.
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