Thyroglobulin

Thyroglobulin
Identifiers
Symbols	TG; AITD3; TGN
External IDs	OMIM: 188450 MGI: 98733 HomoloGene: 2430 GeneCards: TG Gene
Gene Ontology Molecular function • carboxylesterase activity • hormone activity • protein complex binding • chaperone binding Cellular component • extracellular region • extracellular space • endoplasmic reticulum • Golgi apparatus • perinuclear region of cytoplasm Biological process • signal transduction • response to pH • iodide transport • thyroid gland development • regulation of myelination • response to lipopolysaccharide • thyroid hormone metabolic process • hormone biosynthetic process • transcytosis • regulation of synaptic transmission Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7038	21819
Ensembl	ENSG00000042832	ENSMUSG00000053469
UniProt	P01266	Q2NKY1
RefSeq (mRNA)	NM_003235.4	NM_009375.2
RefSeq (protein)	NP_003226.4	NP_033401.2
Location (UCSC)	Chr 8: 133.88 – 134.15 Mb	Chr 15: 66.5 – 66.68 Mb
PubMed search	[1]	[2]

Thyroglobulin (Tg) is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid.

Thyroglobulin should not be confused with Thyroxine-binding globulin, a carrier protein responsible for carrying the thyroid hormones in the blood.

Function

Thyroid hormone synthesis, following thyroglobulin from production within the rough endoplasmic reticulum until proteolysis to release the thyroid hormones.

Tg is used by the thyroid gland to produce the thyroid hormones thyroxine (T4) and triiodothyronine (T3). The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase (which has been referred to as tetraiodothyronine 5' deiodinase). It is presumed that Tg and thyroid are also an important storage of iodine for all body needs, in particular, for many iodine-concentrating organs such as breast, stomach, salivary glands, thymus, etc. (see iodine in biology).

In fact, the Tg molecule, which contains approximately 120 tyrosyl residues, is able to form only very small amounts of thyroid hormone (5-6 molecules of T4 and T3).

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

• Thyroxine is produced by combining two moieties of DIT.
• Triiodothyronine is produced by combining one molecule of MIT and one molecule of DIT.

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.

Clinical significance

Patients with Hashimoto's thyroiditis or Graves' disease frequently develop antibodies against Tg. Tg-specific antibodies help in the diagnosis of these diseases, but they also may be present in apparently healthy euthyroid individuals.

Thyroglobulin levels in the blood can be used as a tumor marker for certain kinds of thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin levels in the blood can also be elevated in cases of Graves' disease.

Interactions

Thyroglobulin has been shown to interact with Binding immunoglobulin protein.

Further reading

• Mazzaferri EL, Robbins RJ, Spencer CA, et al. (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. doi:10.1210/jc.2002-021702. PMID 12679418. 
• Henry M, Zanelli E, Piechaczyk M, et al. (1992). "A major human thyroglobulin epitope defined with monoclonal antibodies is mainly recognized by human autoantibodies". Eur. J. Immunol. 22 (2): 315–9. doi:10.1002/eji.1830220205. PMID 1371467. 
• 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. doi:10.1016/0303-7207(92)90087-M. PMID 1639210. 
• 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. PMID 1939080. 
• 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. PMID 2760035. 
• 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. doi:10.1016/0014-5793(89)80513-7. PMID 2914619. 
• Christophe D, Cabrer B, Bacolla A, et al. (1985). "An unusually long poly(purine)-poly(pyrimidine) sequence is located upstream from the human thyroglobulin gene". Nucleic Acids Res. 13 (14): 5127–44. doi:10.1093/nar/13.14.5127. PMC 321854. PMID 2991855. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=321854. 
• Baas F, van Ommen GJ, Bikker H, et al. (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. doi:10.1093/nar/14.13.5171. PMC 311533. PMID 3016640. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=311533. 
• Kubak BM, Potempa LA, Anderson B, et al. (1989). "Evidence that serum amyloid P component binds to mannose-terminated sequences of polysaccharides and glycoproteins". Mol. Immunol. 25 (9): 851–8. doi:10.1016/0161-5890(88)90121-6. PMID 3211159. 
• 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. doi:10.1111/j.1432-1033.1987.tb11466.x. PMID 3595599. 
• 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. doi:10.1016/0022-2836(87)90403-7. PMID 3681978. 
• Bergé-Lefranc JL, Cartouzou G, Mattéi MG, et al. (1985). "Localization of the thyroglobulin gene by in situ hybridization to human chromosomes". Hum. Genet. 69 (1): 28–31. doi:10.1007/BF00295525. PMID 3967888. 
• 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. doi:10.1111/j.1432-1033.1985.tb08717.x. PMID 3971976. 
• Avvedimento VE, Di Lauro R, Monticelli A, et al. (1985). "Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization". Hum. Genet. 71 (2): 163–6. doi:10.1007/BF00283375. PMID 4043966. 
• 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. doi:10.1006/abbi.1995.1346. PMID 7793989. 
• Corral J, Martín C, Pérez R, et al. (1993). "Thyroglobulin gene point mutation associated with non-endemic simple goitre". Lancet 341 (8843): 462–4. doi:10.1016/0140-6736(93)90209-Y. PMID 8094490. 
• 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. doi:10.1111/j.1432-1033.1993.tb18414.x. PMID 8269951. 
• Mallet B, Lejeune PJ, Baudry N, et al. (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. doi:10.1074/jbc.270.50.29881. PMID 8530385. 
• 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. doi:10.1006/abbi.1996.0093. PMID 8615697. 
• 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. doi:10.1111/j.1432-1033.1996.0125h.x. PMID 8797845. 

External links

• Histology at KUMC endo-endo11
• Overview at colostate.edu
• Histology at BU 14302loa