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Transcortin

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Transcortin

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6
Crystal structure of corticosteroid-binding globulin. The reactive loop has been cleaved at the region highlighted in blue.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; CBG
External IDs ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6 is a protein that in humans is encoded by the SERPINA6 gene. It is an alpha-globulin.[2][3][4]

Contents

  • Function 1
  • Binding 2
  • Synthesis 3
  • Clinical significance 4
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

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) which may have evolved by duplication events.[4]

Binding

Transcortin binds several steroid hormones at high rates:

  • Cortisol - Approximately 75% of the cortisol in circulation is bound to transcortin. (The rest is bound to serum albumin.) Cortisol is thought to be biologically active only when it is not bound to transcortin.
  • Cortisone[5]
  • Deoxycorticosterone (DOC)[5]
  • Corticosterone - About 78% of serum corticosterone is bound to transcortin.
  • Aldosterone - Approximately 17% of serum aldosterone is bound to transcortin, while another 47% is bound to serum albumin. The remaining 36% is free.[6]
  • Progesterone - Approximately 18% of serum progesterone is bound to transcortin, while another 80% of it is bound to serum albumin. The remaining 2% is free.[7]
  • 17-Hydroxyprogesterone[5]

In addition, approximately 4% of serum testosterone is bound to transcortin.[8] A similarly small fraction of serum estradiol is bound to transcortin as well.

Synthesis

Transcortin is produced by the liver and is increased by estrogens.[9]

Clinical significance

Mutations in this gene are rare. Only four mutations have been described, often in association with fatigue and chronic pain. [10] 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.

Hepatic synthesis of corticosteroid-binding globulin more than doubles in pregnancy; that is, unbound plasma cortisol in term pregnancy is approximately 2.5 times that of nonpregnant women.[11]

See also

References

  1. ^ ​; Zhou A, Wei Z, Stanley PL, Read RJ, Stein PE, Carrell RW (June 2008). "The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release". J. Mol. Biol. 380 (1): 244–51.  
  2. ^ Hammond GL, Smith CL, Goping IS, Underhill DA, Harley MJ, Reventos J, Musto NA, Gunsalus GL, Bardin CW (Aug 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.  
  3. ^ Byth BC, Billingsley GD, Cox DW (Jul 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.  
  4. ^ a b "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6". 
  5. ^ a b c E. Edward Bittar; Neville Bittar (1997). Molecular and Cellular Endocrinology. Elsevier. p. 238.  
  6. ^ Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. p. 712.  
  7. ^ Negi (2009). Introduction To Endocrinology. PHI Learning Pvt. Ltd. p. 268.  
  8. ^ 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.  
  9. ^ 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.  
  10. ^ 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.  
  11. ^ Rosen MI, Shnider SM, Levinson G, Hughes (2002). Shnider and Levinson's anesthesia for obstetrics. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 13.  

Further reading

  • Rosner W, Beers PC, Awan T, Khan MS (1976). "Identification of corticosteroid-binding globulin in human milk: measurement with a filter disk assay.". J. Clin. Endocrinol. Metab. 42 (6): 1064–73.  
  • Smith CL, Power SG, Hammond GL (1992). "A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol.". J. Steroid Biochem. Mol. Biol. 42 (7): 671–6.  
  • Brotherton J (1990). "Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays.". Andrologia 22 (3): 197–204.  
  • Seralini GE, Bérubé D, Gagné R, Hammond GL (1991). "The human corticosteroid binding globulin gene is located on chromosome 14q31-q32.1 near two other serine protease inhibitor genes.". Hum. Genet. 86 (1): 73–5.  
  • Underhill DA, Hammond GL (1990). "Organization of the human corticosteroid binding globulin gene and analysis of its 5'-flanking region.". Mol. Endocrinol. 3 (9): 1448–54.  
  • Loric S, Egloff M, Domingo M, et al. (1990). "Immunochemical characterization of corticosteroid-binding globulin in human bronchoalveolar fluid.". Clin. Chim. Acta 186 (1): 19–23.  
  • Heubner A, Belovsky O, Müller W, et al. (1987). "Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin.". J. Chromatogr. 397: 419–34.  
  • Kato EA, Hsu BR, Kuhn RW (1988). "Comparative structural analyses of corticosteroid binding globulin.". J. Steroid Biochem. 29 (2): 213–20.  
  • Bardin CW, Gunsalus GL, Musto NA, et al. (1988). "Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors.". J. Steroid Biochem. 30 (1-6): 131–9.  
  • Hammond GL, Langley MS (1986). "Identification and measurement of sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) in human saliva.". Acta Endocrinol. 112 (4): 603–8.  
  • Agrimonti F, Frairia R, Fornaro D, et al. (1983). "Circadian and  
  • Misao R, Hori M, Ichigo S, et al. (1995). "Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis.". Reprod. Nutr. Dev. 35 (2): 155–65.  
  • Misao R, Hori M, Ichigo S, et al. (1995). "Corticosteroid-binding globulin mRNA levels in human uterine endometrium.". Steroids 59 (10): 603–7.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4.  
  • Avvakumov GV, Hammond GL (1994). "Glycosylation of human corticosteroid-binding globulin. Differential processing and significance of carbohydrate chains at individual sites.". Biochemistry 33 (19): 5759–65.  
  • Van Baelen H, Power SG, Hammond GL (1993). "Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93.". Steroids 58 (6): 275–7.  
  • Misao R, Nakanishi Y, Fujimoto J, et al. (1996). "Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers.". Steroids 60 (10): 720–4.  
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56.  

External links

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