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]
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]
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]
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]
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.
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]
^ abcGRCm38: Ensembl release 89: ENSMUSG00000060807 - 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.
^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. PMC298812. PMID 3299377.
^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. PMC1918218. PMID 7912884.
^ ab"Entrez Gene: SERPINA6 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 6".
^ abcE. Edward Bittar; Neville Bittar (1997). Molecular and Cellular Endocrinology. Elsevier. p. 238. ISBN978-1-55938-815-3. Retrieved 23 August 2012.
^Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. 24 April 2001. p. 712. ISBN978-0-7817-1750-2. Retrieved 23 August 2012.
^Negi (2009). Introduction To Endocrinology. PHI Learning Pvt. Ltd. p. 268. ISBN978-81-203-3850-0. Retrieved 23 August 2012.
^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.
^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.
^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.
^Rosen MI, Shnider SM, Levinson G, Hughes (2002). Shnider and Levinson's anesthesia for obstetrics. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 13. ISBN0-683-30665-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
^Ann M. Gronowski (6 May 2004). Handbook of Clinical Laboratory Testing During Pregnancy. Springer Science & Business Media. pp. 408–. ISBN978-1-59259-787-1.
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.
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.
transcortin, also, known, corticosteroid, binding, globulin, serpin, protein, produced, liver, animals, humans, encoded, serpina6, gene, alpha, globulin, serpina6available, structurespdbortholog, search, pdbe, rcsblist, codes2vdx, 2vdy, 4bb2, 4c41, 4c49identif. 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 SERPINA6Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2VDX 2VDY 4BB2 4C41 4C49IdentifiersAliasesSERPINA6 CBG serpin family A member 6External IDsOMIM 122500 MGI 88278 HomoloGene 20417 GeneCards SERPINA6Gene location Human Chr Chromosome 14 human 1 Band14q32 13Start94 304 248 bp 1 End94 323 389 bp 1 Gene location Mouse Chr Chromosome 12 mouse 2 Band12 E 12 52 98 cMStart103 612 889 bp 2 End103 623 471 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inliverright lobe of livergallbladderislet of Langerhansbody of pancreasright uterine tubekidneyrectumcanal of the cervixendometriumTop expressed inleft lobe of liverabdominal wallgallbladderentorhinal cortexureteryolk sacadrenal glandatrioventricular valveendocardial cushionmetanephrosMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionsteroid binding serine type endopeptidase inhibitor activity lipid bindingCellular componentextracellular region extracellular exosome extracellular spaceBiological processglucocorticoid metabolic process negative regulation of endopeptidase activity transportSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez86612401EnsemblENSG00000277405ENSG00000170099ENSMUSG00000060807UniProtP08185Q06770RefSeq mRNA NM 001756NM 007618RefSeq protein NP 001747NP 031644Location UCSC Chr 14 94 3 94 32 MbChr 12 103 61 103 62 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Binding 3 Synthesis 4 Clinical significance 5 See also 6 References 7 Further reading 8 External linksFunction EditThis 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 EditTranscortin 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 17a 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 EditTranscortin is produced by the liver and is increased by estrogens 12 Clinical significance EditMutations 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 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 EditSerpin Circaseptan 7 day biological cycleReferences Edit a b c ENSG00000170099 GRCh38 Ensembl release 89 ENSG00000277405 ENSG00000170099 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000060807 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 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 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 a b Entrez Gene SERPINA6 serpin peptidase inhibitor clade A alpha 1 antiproteinase antitrypsin member 6 a b c E Edward Bittar Neville Bittar 1997 Molecular and Cellular Endocrinology Elsevier p 238 ISBN 978 1 55938 815 3 Retrieved 23 August 2012 Principles and Practice of Endocrinology and Metabolism Lippincott Williams amp Wilkins 24 April 2001 p 712 ISBN 978 0 7817 1750 2 Retrieved 23 August 2012 Negi 2009 Introduction To Endocrinology PHI Learning Pvt Ltd p 268 ISBN 978 81 203 3850 0 Retrieved 23 August 2012 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 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 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 Rosen MI Shnider SM Levinson G Hughes 2002 Shnider and Levinson s anesthesia for obstetrics Hagerstwon MD Lippincott Williams amp Wilkins p 13 ISBN 0 683 30665 0 a href Template Cite book html title Template Cite book cite book a CS1 maint multiple names authors list link Ann M Gronowski 6 May 2004 Handbook of Clinical Laboratory Testing During Pregnancy Springer Science amp Business Media pp 408 ISBN 978 1 59259 787 1 Further reading EditRosner 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 Muller 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 EditTranscortin at the US National Library of Medicine Medical Subject Headings MeSH The MEROPS online database for peptidases and their inhibitors I04 954 SERPINA6 protein human at the US National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Transcortin amp oldid 1136174850, wikipedia, wiki, book, books, library,
