Transcortin

SERPINA6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2VDX, 2VDY, 4BB2, 4C41, 4C49
Identifiers
Aliases	SERPINA6 , CBG, serpin family A member 6
External IDs	OMIM: 122500; MGI: 88278; HomoloGene: 20417; GeneCards: SERPINA6; OMA:SERPINA6 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q32.13 Start 94,304,248 bp [1] End 94,323,389 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12 E|12 52.98 cM Start 103,612,889 bp [2] End 103,623,471 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in liver right lobe of liver gallbladder islet of Langerhans body of pancreas right uterine tube rectum canal of the cervix human kidney mucosa of transverse colon Top expressed in fetal liver hematopoietic progenitor cell human fetus left lobe of liver abdominal wall gallbladder embryo perirhinal cortex entorhinal cortex CA3 field choroid plexus of fourth ventricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function steroid binding serine-type endopeptidase inhibitor activity lipid binding Cellular component extracellular region extracellular exosome extracellular space Biological process glucocorticoid metabolic process negative regulation of endopeptidase activity transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 866 12401 Ensembl ENSG00000277405 ENSG00000170099 ENSMUSG00000060807 UniProt P08185 Q06770 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
View/Edit Human View/Edit Mouse

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]}

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:

• Cortisol - Approximately 90% 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.^{[ citation needed ]}
• Cortisone ^[8]
• Deoxycorticosterone (DOC) ^[8]
• 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. ^[9]
• 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. ^[10]
• 17α-Hydroxyprogesterone ^[8]

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] The 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

• Serpin
• Circaseptan, 7-day biological cycle

References

1. ENSG00000170099 GRCh38: Ensembl release 89: ENSG00000277405, ENSG00000170099 – Ensembl, May 2017
2. 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. "Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".
8. 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. Archived from the original on 14 December 2019. Retrieved 23 August 2012.
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.
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

• 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. doi:10.1210/jcem-42-6-1064. PMID   932172.
• 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. doi:10.1016/0960-0760(92)90107-T. PMID   1504007. S2CID   45601231.
• Brotherton J (1990). "Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays". Andrologia. 22 (3): 197–204. doi: 10.1111/j.1439-0272.1990.tb01966.x . PMID   2240617. S2CID   2577211.
• 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. doi: 10.1210/mend-3-9-1448 . PMID   2608068.
• 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. doi:10.1016/0009-8981(89)90198-8. PMID   2612005.
• 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. doi:10.1016/S0021-9673(01)85027-5. PMID   2821037.
• Kato EA, Hsu BR, Kuhn RW (1988). "Comparative structural analyses of corticosteroid binding globulin". J. Steroid Biochem. 29 (2): 213–20. doi:10.1016/0022-4731(88)90268-3. PMID   3347061.
• 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. doi:10.1016/0022-4731(88)90085-4. PMID   3386241.
• 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. doi:10.1530/acta.0.1120603. PMID   3751467.
• Agrimonti F, Frairia R, Fornaro D, et al. (1983). "Circadian and circaseptan rhythmicities in corticosteroid-binding globulin (CBG) binding activity of human milk". Chronobiologia. 9 (3): 281–90. PMID   7172869.
• 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. doi: 10.1051/rnd:19950204 . PMID   7734053.
• Misao R, Hori M, Ichigo S, et al. (1995). "Corticosteroid-binding globulin mRNA levels in human uterine endometrium". Steroids. 59 (10): 603–7. doi:10.1016/0039-128X(94)90055-8. PMID   7878688. S2CID   24945362.
• 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. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• 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. doi:10.1021/bi00185a012. PMID   8180202.
• 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. doi:10.1016/0039-128X(93)90072-U. PMID   8212073. S2CID   25160586.
• 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. doi:10.1016/0039-128X(95)00106-Z. PMID   8539782. S2CID   37077783.
• 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. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.

External links

• Transcortin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• The MEROPS online database for peptidases and their inhibitors: I04.954
• SERPINA6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)