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Thyroglobulin

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Title: Thyroglobulin  
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Thyroglobulin

Thyroglobulin
PDB rendering based on 1poz.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; AITD3; TGN
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search
Not to be confused with Thyroxine-binding globulin, a carrier protein responsible for carrying the thyroid hormones in the blood.

Thyroglobulin (Tg) is a 660 kDa, dimeric protein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Thyroglobulin protein accounts for approximately half of the protein content of the thyroid gland.[1]

Each thyroglobulin molecule contains approximately 100-120 tyrosyl (Tyrosine) residues. However, because only a small number (>20) of these tyrosine residues are subject to iodination by thyroperoxidase in the follicular colloid, each Tg molecule is only able to form very small amounts of thyroid hormone (5-6 molecules of either T4 and T3).[1]

Contents

  • Function 1
  • Clinical significance 2
    • Tg antibodies 2.1
  • Interactions 3
  • References 4
  • Further reading 5
  • External links 6

Function

Thyroid hormone synthesis, this image traces thyroglobulin from production within the rough endoplasmic reticulum until proteolytic release of the thyroid hormones.

Tg is used by the thyroid gland to produce the

  • Thyroglobulin - Lab Tests Online
  • Histology at KUMC endo-endo11
  • Overview at colostate.edu
  • Histology image: 14302loa – Histology Learning System at Boston University

External links

  • Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, Haugen BR, Sherman SI, Cooper DS, Braunstein GD, Lee S, Davies TF, Arafah BM, Ladenson PW, Pinchera A (2003). "A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma". J. Clin. Endocrinol. Metab. 88 (4): 1433–41.  
  • Henry M, Zanelli E, Piechaczyk M, Pau B, Malthièry Y (1992). "A major human thyroglobulin epitope defined with monoclonal antibodies is mainly recognized by human autoantibodies". Eur. J. Immunol. 22 (2): 315–9.  
  • Targovnik HM, Cochaux P, Corach D, Vassart G (1992). "Identification of a minor Tg mRNA transcript in RNA from normal and goitrous thyroids". Mol. Cell. Endocrinol. 84 (1-2): R23–6.  
  • Dunn AD, Crutchfield HE, Dunn JT (1991). "Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L". J. Biol. Chem. 266 (30): 20198–204.  
  • Lamas L, Anderson PC, Fox JW, Dunn JT (1989). "Consensus sequences for early iodination and hormonogenesis in human thyroglobulin". J. Biol. Chem. 264 (23): 13541–5.  
  • Marriq C, Lejeune PJ, Venot N, Vinet L (1989). "Hormone synthesis in human thyroglobulin: possible cleavage of the polypeptide chain at the tyrosine donor site". FEBS Lett. 242 (2): 414–8.  
  • Christophe D, Cabrer B, Bacolla A, Targovnik H, Pohl V, Vassart G (1985). "An unusually long poly(purine)-poly(pyrimidine) sequence is located upstream from the human thyroglobulin gene". Nucleic Acids Res. 13 (14): 5127–44.  
  • Baas F, van Ommen GJ, Bikker H, Arnberg AC, de Vijlder JJ (1986). "The human thyroglobulin gene is over 300 kb long and contains introns of up to 64 kb". Nucleic Acids Res. 14 (13): 5171–86.  
  • Kubak BM, Potempa LA, Anderson B, Mahklouf S, Venegas M, Gewurz H, Gewurz AT (1989). "Evidence that serum amyloid P component binds to mannose-terminated sequences of polysaccharides and glycoproteins". Mol. Immunol. 25 (9): 851–8.  
  • Malthiéry Y, Lissitzky S (1987). "Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA". Eur. J. Biochem. 165 (3): 491–8.  
  • Parma J, Christophe D, Pohl V, Vassart G (1988). "Structural organization of the 5' region of the thyroglobulin gene. Evidence for intron loss and "exonization" during evolution". J. Mol. Biol. 196 (4): 769–79.  
  • Bergé-Lefranc JL, Cartouzou G, Mattéi MG, Passage E, Malezet-Desmoulins C, Lissitzky S (1985). "Localization of the thyroglobulin gene by in situ hybridization to human chromosomes". Hum. Genet. 69 (1): 28–31.  
  • Malthiéry Y, Lissitzky S (1985). "Sequence of the 5'-end quarter of the human-thyroglobulin messenger ribonucleic acid and of its deduced amino-acid sequence". Eur. J. Biochem. 147 (1): 53–8.  
  • Avvedimento VE, Di Lauro R, Monticelli A, Bernardi F, Patracchini P, Calzolari E, Martini G, Varrone S (1985). "Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization". Hum. Genet. 71 (2): 163–6.  
  • Xiao S, Pollock HG, Taurog A, Rawitch AB (1995). "Characterization of hormonogenic sites in an N-terminal, cyanogen bromide fragment of human thyroglobulin". Arch. Biochem. Biophys. 320 (1): 96–105.  
  • Corral J, Martín C, Pérez R, Sánchez I, Mories MT, San Millan JL, Miralles JM, González-Sarmiento R (1993). "Thyroglobulin gene point mutation associated with non-endemic simple goitre". Lancet 341 (8843): 462–4.  
  • Gentile F, Salvatore G (1994). "Preferential sites of proteolytic cleavage of bovine, human and rat thyroglobulin. The use of limited proteolysis to detect solvent-exposed regions of the primary structure". Eur. J. Biochem. 218 (2): 603–21.  
  • Mallet B, Lejeune PJ, Baudry N, Niccoli P, Carayon P, Franc JL (1996). "N-glycans modulate in vivo and in vitro thyroid hormone synthesis. Study at the N-terminal domain of thyroglobulin". J. Biol. Chem. 270 (50): 29881–8.  
  • Yang SX, Pollock HG, Rawitch AB (1996). "Glycosylation in human thyroglobulin: location of the N-linked oligosaccharide units and comparison with bovine thyroglobulin". Arch. Biochem. Biophys. 327 (1): 61–70.  
  • Molina F, Bouanani M, Pau B, Granier C (1996). "Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families". Eur. J. Biochem. 240 (1): 125–33.  
  • Grani G, Fumarola A (Jun 2014). "Thyroglobulin in Lymph Node Fine-Needle Aspiration Washout: A Systematic Review and Meta-analysis of Diagnostic Accuracy.". The Journal of Clinical Endocrinology and Metabolism 99 (6): 1970–82.  

Further reading

  1. ^ a b Boron WF (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300.  
  2. ^ Venturi S, Donati FM, Venturi A, Venturi M (August 2000). "Environmental iodine deficiency: A challenge to the evolution of terrestrial life?". Thyroid 10 (8): 727–9.  
  3. ^ "ACS :: Tumor Markers". American Cancer Society. Retrieved 2009-03-28. 
  4. ^ Ferracci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M, Papa N, Carnevale A (February 2003). "Antithyroid antibodies in the CSF: their role in the pathogenesis of Hashimoto's encephalopathy". Neurology 60 (4): 712–4.  
  5. ^ Delom F, Mallet B, Carayon P, Lejeune PJ (June 2001). "Role of extracellular molecular chaperones in the folding of oxidized proteins. Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein". J. Biol. Chem. 276 (24): 21337–42.  
  6. ^ Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B (February 1999). "Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen". Biochem. Biophys. Res. Commun. 255 (2): 438–43.  

References

Thyroglobulin has been shown to interact with Binding immunoglobulin protein.[5][6]

Interactions

Anti-thyroglobulin antibodies are often found in patients with Hashimoto's thyroiditis or Graves' disease. These antibodies are of limited use in the diagnosis of these diseases, since they may also be present in healthy euthyroid individuals. Anti-Tg antibodies are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to - but not caused by - Hashimoto's thyroiditis.[4]

In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATA), frequently referred to as TgAb. Anti-thyroglobulin antibodies are present in 1 in 10 normal individuals and a greater percentage of patients with thyroid carcinoma. The presence of these antibodies can result in falsely low (or rarely falsely high) levels on thyroglobulin testing. This problem can be somewhat circumvented by testing for the presence of anti-thryroglobulin antibodies. In patients with anti-thyroglobulin antibodies, a better strategy is to not rely on any single lab result but instead to follow serial quantitative measurements. This can help a clinician/clinical pathologist interpret a test and manage patient care, even with the presence of the confounding factor of anti-thyroglobulin antibodies.

Tg antibodies

Metabolism of thyroglobulin occurs in the liver and via thyroid gland recycling of the protein.

Circulating thyroglobulin has a half-life of 65 hours. Following thyroidectomy, it may take many weeks before thyroglobulin levels become undetectable. After thyroglobulin levels become undetectable following thyroidectomy, levels can be serially monitored. A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma.

Thyroglobulin levels in the blood are mainly used as a tumor marker[3] for certain kinds of thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma.

Clinical significance

Small globules of the follicular colloid (Tg) are endocytosed (hormone (TSH)-mediated) and proteases in lysosomes digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm. The T3 and T4 are then transported across (TSH-mediated) the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism while the lysosome is recycled back to the follicular lumen.

Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).

Tg is produced by the thyroid epithelial cells, called thyrocytes, which form spherical follicles. Tg is secreted and stored in the follicular lumen.

). iodine in biology (see [2]

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