PROFILPELAJAR.COM

TG
Identifiers
Aliases	TG, AITD3, TGN, thyroglobulin
External IDs	OMIM: 188450; MGI: 98733; HomoloGene: 2430; GeneCards: TG; OMA:TG - orthologs
Gene location (Human)
Chr.	Chromosome 8 (human)
End	133,134,903 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	66,722,570 bp
RNA expression pattern
	Top expressed in
	left lobe of thyroid gland; ; right lobe of thyroid gland; ; apex of heart; ; skin of leg; ; skin of abdomen; ; right adrenal cortex; ; Amygdala; ; testicle; ; right lobe of liver; ; left ventricle;
	Top expressed in
	trachea; ; thyroid gland; ; lobe of thyroid gland; ; tail of embryo; ; embryo; ; blood; ; spermatocyte; ; granulocyte; ; endocardial cushion; ; atrium;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	hormone activity;
Cellular component	extracellular region; extracellular space;
Biological process	thyroid hormone metabolic process; thyroid gland development; regulation of myelination; iodide transport; signal transduction; hormone biosynthetic process; regulation of signaling receptor activity;
	Sources:Amigo / QuickGO
Orthologs
	7038
	21819
	ENSG00000042832
	ENSMUSG00000053469
	P01266
	O08710
	NM_003235
	NM_009375
	NP_003226
	NP_033401
	Wikidata
View/Edit Human	View/Edit Mouse

Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment of the thyroid follicles, accounting for approximately half of the protein content of the thyroid gland.^[5] Human TG (hTG) is a homodimer of subunits each containing 2768 amino acids as synthesized (a short signal peptide of 19 amino acids may be removed from the N-terminus in the mature protein).^[6]

Thyroglobulin is in all vertebrates the main precursor to thyroid hormones, which are produced when thyroglobulin's tyrosine residues are combined with iodine and the protein is subsequently cleaved. Each thyroglobulin molecule contains approximately 16 tyrosine residues, but only a small number 10 of these are subject to iodination by thyroperoxidase in the follicular colloid. It takes two iodinated tyrosines to make a thyroid hormone molecule; therefore, each Tg molecule forms approximately 5 thyroid hormone molecules.^[5]

Function

Thyroglobulin (Tg) acts as a substrate for the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), as well as the storage of the inactive forms of thyroid hormone and iodine within the follicular lumen of a thyroid follicle.^[7]

Newly synthesized thyroid hormones (T3 and T4) are attached to thyroglobulin and comprise the colloid within the follicle. When stimulated by thyroid stimulating hormone (TSH), the colloid is endocytosed from the follicular lumen into the surrounding thyroid follicular epithelial cells. The colloid is subsequently cleaved by proteases to release thyroglobulin from its T3 and T4 attachments.^[8]

The active forms of thyroid hormone: T3 and T4, are then released into circulation where they are either unbound or attached to plasma proteins, and thyroglobulin is recycled back into the follicular lumen where it can continue to serve as a substrate for thyroid hormone synthesis.^[8]

Clinical significance

Half-life and clinical elevation

Metabolism of thyroglobulin occurs in the liver 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. Thyroglobulin levels may be tested regularly for a few weeks or months following the removal of the thyroid.^[9] After thyroglobulin levels become undetectable (following thyroidectomy), levels can be serially monitored in follow-up of patients with papillary or follicular thyroid carcinoma.^{[clarification needed]}

A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma. In other words, a rise in thyroglobulin levels in the blood may be a sign that thyroid cancer cells are growing and/or the cancer is spreading.^[9] Hence, thyroglobulin levels in the blood are mainly used as a tumor marker^[10]^[9] for certain kinds of thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma.

Thyroglobulin levels are tested via a simple blood test. Tests are often ordered after thyroid cancer treatment.^[9]

Thyroglobulin antibodies

In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATAs, alternatively 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 of reported thyroglobulin, a problem that can be somewhat circumvented by concomitant testing for the presence of ATAs. The ideal strategy for a clinician's interpretation and management of patient care in the event of confounding detection of ATAs is testing to follow serial quantitative measurements (rather than a single laboratory measurement).

ATAs are often found in patients with Hashimoto's thyroiditis or Graves' disease. Their presence is of limited use in the diagnosis of these diseases, since they may also be present in healthy euthyroid individuals. ATAs are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to—but not caused by—Hashimoto's thyroiditis.^[11]

Interactions

Thyroglobulin has been shown to interact with Binding immunoglobulin protein.^[12]^[13]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000042832 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000053469 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Boron WF (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. p. 1044. ISBN 1-4160-2328-3.
^ "Protein" thyroglobulin precursor [Homo sapiens]". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "TG thyroglobulin [Homo sapiens (human)] – Gene – NCBI". National Center for Biotechnology Information (NCBI). Retrieved 2019-09-16.
^ ^a ^b Rousset BL, Dupuy C, Miot F, Dumont J (2000). "Chapter 2 Thyroid Hormone Synthesis and Secretion". In Feingold KR, Anawalt B, Boyce A, Chrousos G (eds.). Endotext. MDText.com, Inc. PMID 25905405. Retrieved 2019-09-17.
^ ^a ^b ^c ^d "Thyroglobulin: MedlinePlus Lab Test Information". medlineplus.gov. Retrieved 2019-05-06.
^ "ACS :: Tumor Markers". American Cancer Society. Archived from the original on 2010-05-13. Retrieved 2009-03-28.
^ Ferracci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M, et al. (February 2003). "Antithyroid antibodies in the CSF: their role in the pathogenesis of Hashimoto's encephalopathy". Neurology. 60 (4): 712–714. doi:10.1212/01.wnl.0000048660.71390.c6. PMID 12601119. S2CID 21610036.
^ 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". The Journal of Biological Chemistry. 276 (24): 21337–21342. doi:10.1074/jbc.M101086200. PMID 11294872.
^ 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". Biochemical and Biophysical Research Communications. 255 (2): 438–443. doi:10.1006/bbrc.1999.0229. PMID 10049727.