Thyroglobulin

Thyroglobulin
PDB rendering based on 1poz.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1POZ, 1UUH, 2I83
Identifiers
Symbols	TG ; AITD3; TGN
External IDs	OMIM: 188450 MGI: 88338 HomoloGene: 2430 GeneCards: TG Gene
Gene ontology Molecular function • hormone activity • protein complex binding • protein homodimerization activity • anion binding • chaperone binding • carboxylic ester hydrolase activity Cellular component • extracellular region • extracellular space • endoplasmic reticulum • Golgi apparatus • protein complex • 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 Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7038	21819
Ensembl	ENSG00000042832	ENSMUSG00000053469
UniProt	P01266	O08710
RefSeq (mRNA)	NM_003235	NM_009375
RefSeq (protein)	NP_003226	NP_033401
Location (UCSC)	Chr 8: 132.87 – 133.13 Mb	Chr 15: 66.67 – 66.85 Mb
PubMed search	[1]	[2]

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.

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).

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 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, choroid plexus and cerebrospinal fluid, etc. (see iodine in biology).

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

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

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.

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

Tg antibodies

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.

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.

Interactions

Thyroglobulin has been shown to interact with Binding immunoglobulin protein.

External links

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