Thyroxine-binding globulin (SERPINA7)

The protein contains 415 amino acids for an estimated molecular weight of 46325 Da.

 

Major thyroid hormone transport protein in serum. (updated: Sept. 12, 2018)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 97%
Model score: 36

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VariantDescription
Associated with F-303 in San Diego
Gary
Montreal/TBG-M
TBG-S/Slow
TBG-A/Aborigine
CD5
Associated with T-43 in San Diego
Quebec
Kumamoto

No binding partner found

The reference OMIM entry for this protein is 314200

Thyroxine-binding globulin of serum; tbg
Serpin peptidase inhibitor, clade a, member 7; serpina7
T4-binding globulin
Tbg, serum thyroxine-binding globulin deficiency, included

DESCRIPTION

T4-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Patients are euthyroid (summary by Mori et al., 1995).

CLONING

Hill et al. (1982) isolated a human recombinant DNA sequence corresponding to TBG. They showed polymorphism of restriction fragment length when human DNA was digested with MspI. In a family with X-linked TBG deficiency, close linkage to the polymorphic restriction site was excluded. Flink et al. (1986) used antibodies against TBG to screen a human liver expression library and identified a 1.46-kb clone that encodes nearly the complete amino acid sequence, beginning at amino acid 17, of the mature protein. To complete the protein sequence, this cDNA clone was used to identify a genomic clone coding for TBG in a human X-chromosome library. Unexpectedly, the nucleotide sequence of TBG was found to be closely homologous to those encoding the plasma serine antiproteases alpha-1-antichymotrypsin (107280) and alpha-1-antitrypsin (107400). There was little overall homology, however, between TBG and transthyretin (176300), the other major thyroxine-binding protein of human plasma. Kambe et al. (1988) found 2 TBG mRNA species and suggested that these may be produced by alternative processing and polyadenylation at 2 different sites.

GENE FUNCTION

Jirasakuldech et al. (2000) reported a characteristic serpin cleavage product of TBG in sepsis sera. At 49 to 50 kD, the TBG remnant is 4 to 5 kD smaller than the intact protein and is the same molecular mass as a TBG cleavage product produced by incubation with polymorphonuclear elastase (130130). Incubation with polymorphonuclear leukocytes also produces the 49- to 50-kD remnant, and this proteolysis is stimulated by zymosan activation. Polymorphonuclear cell cleavage of TBG increases the ratio of free/bound T4. In vitro cleavage of TBG by elastase also increases free/bound T4. The authors concluded that their findings are consistent with the hypothesis that serine proteases present at inflammatory sites cleave TBG, releasing its hormonal ligands.

MAPPING

Hill et al. (1982) showed that a human recombinant DNA sequence corresponding to TGB was X-specific by hybridization to DNA from a human-mouse somatic cell hybrid containing X as the only human chromosome. The cloned sequence was located on Xq distal to Xq13 by study of a somatic cell hybrid with a partial human X chromosome. Using DNA blot hybridization, Flink et al. (1986) detected a single-copy TBG gene located on the long arm of the X chromosome. By use of a cDNA clone for analysis of somatic cell hybrids and for in situ hybridization, Trent et al. (1987) assigned the TBG locus to Xq21-q22. Their evidence indicated the presence of a single gene, located on the X chromosome. Thus, the autosomal locus leading to low TBG may be due to mutation in a regulator gene--a suspicion arising from the fact that persons with the autosomal form of TBG deficiency show an increase in TBG level with administration of estrogen. The TBG locus was one of those mapped on Xq by the method of telomere-associated chromosome fragmentation (TACF). The method involves the nontargeted introduction of cloned telomeres into mammalian cells. Farr et al. (1992) used TACF to generate a panel of somatic cell hybrids with nested terminal deletions of the long a ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 314200 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).