Transcortin

Last updated
SERPINA6
2VDX.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SERPINA6 , CBG, serpin family A member 6
External IDs OMIM: 122500 MGI: 88278 HomoloGene: 20417 GeneCards: SERPINA6
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001756

NM_007618

RefSeq (protein)

NP_001747

NP_031644

Location (UCSC) Chr 14: 94.3 – 94.32 Mb Chr 12: 103.61 – 103.62 Mb
PubMed search [3] [4]
Wikidata
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Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin. [5] [6] [7]

Contents

Function

This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucocorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors (serpins). [7]

Binding

Transcortin binds several steroid hormones at high rates:

In addition, approximately 4% of serum testosterone is bound to transcortin. [11] A similarly small fraction of serum estradiol is bound to transcortin as well.[ citation needed ]

Synthesis

Transcortin is produced by the liver and is increased by estrogens. [12]

Clinical significance

Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain. [13] This mechanism for these symptoms is not known. This condition must be distinguished from secondary hypocortisolism. Exogenous hydrocortisone does not appear to improve the fatigue.[ citation needed ]

Hepatic synthesis of corticosteroid-binding globulin more than doubles in pregnancy; that is, bound plasma cortisol in term pregnancy is approximately 2 to 3 times that of nonpregnant women. [14] [15]

See also

Related Research Articles

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<span class="mw-page-title-main">Steroid hormone</span> Substance with biological function

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids and sex steroids. Within those two classes are five types according to the receptors to which they bind: glucocorticoids and mineralocorticoids and androgens, estrogens, and progestogens. Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones and a stress hormone. When used as a medication, it is known as hydrocortisone.

<span class="mw-page-title-main">Thyroxine-binding globulin</span> Mammalian protein found in Homo sapiens

Thyroxine-binding globulin (TBG) is a globulin protein that in humans is encoded by the SERPINA7 gene. TBG binds thyroid hormones in circulation. It is one of three transport proteins (along with transthyretin and serum albumin) responsible for carrying the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3 but is present in the lowest concentration relative to transthyretin and albumin, which also bind T3 and T4 in circulation. Despite its low concentration, TBG carries the majority of T4 in the blood plasma. Due to the very low concentration of T4 and T3 in the blood, TBG is rarely more than 25% saturated with its ligand. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver as a 54-kDa protein. In terms of genomics, TBG is a serpin; however, it has no inhibitory function like many other members of this class of proteins.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

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<span class="mw-page-title-main">TSHB</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">7α-Thiospironolactone</span> Chemical compound

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<span class="mw-page-title-main">7α-Thioprogesterone</span> Chemical compound

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<span class="mw-page-title-main">5α-Dihydroethisterone</span> Chemical compound

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<span class="mw-page-title-main">Pharmacodynamics of spironolactone</span> Mechanisms of action

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References

  1. 1 2 3 ENSG00000170099 GRCh38: Ensembl release 89: ENSG00000277405, ENSG00000170099 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000060807 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW (August 1987). "Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors". Proc Natl Acad Sci U S A. 84 (15): 5153–7. Bibcode:1987PNAS...84.5153H. doi: 10.1073/pnas.84.15.5153 . PMC   298812 . PMID   3299377.
  6. Byth BC, Billingsley GD, Cox DW (July 1994). "Physical and genetic mapping of the serpin gene cluster at 14q32.1: allelic association and a unique haplotype associated with alpha 1-antitrypsin deficiency". Am J Hum Genet. 55 (1): 126–33. PMC   1918218 . PMID   7912884.
  7. 1 2 "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".
  8. 1 2 3 E. Edward Bittar; Neville Bittar (1997). Molecular and Cellular Endocrinology. Elsevier. p. 238. ISBN   978-1-55938-815-3 . Retrieved 23 August 2012.
  9. Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. p. 712. ISBN   978-0-7817-1750-2 . Retrieved 23 August 2012.
  10. Negi (2009). Introduction To Endocrinology. PHI Learning Pvt. Ltd. p. 268. ISBN   978-81-203-3850-0 . Retrieved 23 August 2012.
  11. Dunn JF, Nisula BC, Rodbard D (July 1981). "Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma". The Journal of Clinical Endocrinology and Metabolism. 53 (1): 58–68. doi:10.1210/jcem-53-1-58. PMID   7195404.
  12. Musa BU, Seal US, Doe RP (September 1965). "Elevation of certain plasma proteins in man following estrogen administration: a dose-response relationship". J. Clin. Endocrinol. Metab. 25 (9): 1163–6. doi:10.1210/jcem-25-9-1163. PMID   4284083.
  13. Torpy DJ, Lundgren BA, Ho JT, Lewis JG, Scott HS, Mericq V (January 2012). "CBG Santiago: a novel CBG mutation". J. Clin. Endocrinol. Metab. 97 (1): E151–5. doi: 10.1210/jc.2011-2022 . PMID   22013108.
  14. Rosen MI, Shnider SM, Levinson G, Hughes (2002). Shnider and Levinson's anesthesia for obstetrics. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 13. ISBN   0-683-30665-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
  15. Ann M. Gronowski (6 May 2004). Handbook of Clinical Laboratory Testing During Pregnancy. Springer Science & Business Media. pp. 408–. ISBN   978-1-59259-787-1.

Further reading