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Gene Review

SERPINA6  -  serpin peptidase inhibitor, clade A (alpha...

Homo sapiens

Synonyms: CBG, Corticosteroid-binding globulin, Serpin A6, Transcortin
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Disease relevance of SERPINA6

  • We investigated the hypothesis that corticosteroid-binding globulin (CBG) polymorphism could influence obesity, metabolic, or hypothalamo-pituitary adrenal (HPA) axis activity parameters [1].
  • Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia [2].
  • These results suggest that dedifferentiation of endometrial cancers induces a reduction in intracellular CBG synthesis [3].
  • A steroid binding capacity assay and a radioimmunoassay were both used to measure corticosteroid binding globulin (CBG) in serum samples from 22 patients with sepsis [4].
  • Although relative hypotension and fatigue have recently been associated with CBG deficiency in a family with two CBG mutations (null and Lyon), the two homozygous subjects in this kindred were both normotensive and only the proband presented with fatigue [5].

Psychiatry related information on SERPINA6

  • In addition, CBG was significantly increased in PTSD subjects, and DHEA was significantly decreased in both PTSD and combat-exposed control subjects [6].
  • The binding capacity and apparent binding affinity of corticosteroid-binding globulin (CBG) for cortisol was studied in 20 women hospitalized for anorexia nervosa [7].
  • We were interested in determining if acute food restriction (such as might occur during inclement weather) is a sufficient cue to elicit an increase in locomotor activity, increase CORT secretion, and/or decrease circulating levels of corticosterone binding globulin (CBG) in white-crowned sparrows (Zonotrichia leucophrys gambelii) [8].

High impact information on SERPINA6


Chemical compound and disease context of SERPINA6


Biological context of SERPINA6

  • In 44 obese pre-menopausal women, a microsatellite located within the CBG gene was analyzed, providing three genotypes: 86/86 (n = 29), 86/90 (n = 14), and 90/90 (n = 1) [1].
  • The deduced amino acid sequence of mature CBG contains two cysteine residues and consensus sequences for the attachment of six possible N-linked oligosaccharide chains [17].
  • The liver CBG cDNA contains an open reading frame for a 405-amino acid (Mr 45,149) polypeptide [17].
  • A second, in-frame, 72-base-pair cistron of unknown significance exists between the TAA termination codon for CBG and a possible polyadenylylation signal (AATAAA) located 16 nucleotides before the polyadenylylation site [17].
  • The sequences of the human lung and liver CBG cDNAs differ by only one nucleotide within the proposed leader sequence, and we attribute this to a point mutation [17].

Anatomical context of SERPINA6

  • Our results indicate that CBG mRNA is relatively abundant in the liver but is also present in the lung, testis, and kidney [17].
  • We sought information on the occurrence of CBG in the cytosol, nuclear, and membrane fractions of 6 tissues during decidualization in the hamster [18].
  • Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue [2].
  • Membrane CBG was highest in liver, 5-fold less in deciduoma, 10-fold less in myometrium, and about 20-fold less in other tissues [18].
  • Nuclear CBG concentration was greatest in liver and approximately 10-fold less in other tissues, except for small intestine, where nuclear CBG was undetectable [18].

Associations of SERPINA6 with chemical compounds

  • The antibodies did not crossreact with other rabbit steroid receptors (uterine estradiol receptor and liver glucocorticoid receptor) or with nonreceptor progesterone-binding proteins (transcortin from plasma and uteroglobin from uterine fluid) [19].
  • This includes a predominantly hydrophobic, leader sequence of 22 residues that precedes the known NH2-terminal sequence of human CBG [17].
  • A filter disk assay was developed both for the measurement of plasma corticosteroid-binding globulin (CBG) and for the cortisol-binding protein in milk [20].
  • A detailed comparison of CBG derived from milk and plasma showed that the two proteins co-migrated on Sephadex, sucrose gradient ultracentrifugation, and polyacrylamide gel electrophoresis [20].
  • In addition to low affinity, CBG from squirrel monkeys and other New World primates exhibits differences in electrophoretic mobility and sedimentation behavior in sucrose density ultracentrifugation, suggestive of a molecular weight that is approximately twice that of CBG from other species [21].
  • The steroid binding properties of CBG variants with substitutions at P15 (G335P), P14 (V336R), or P12 (T338P) in the RCL hinge were largely unaffected after elastase cleavage, most likely because the re-orientation and/or insertion of the cleaved RCL was blocked [22].

Physical interactions of SERPINA6


Other interactions of SERPINA6


Analytical, diagnostic and therapeutic context of SERPINA6

  • The high levels of CBG in uterine tissues were not the result of serum contamination because whole-body perfusion with buffered saline failed to remove the majority of cytosol CBG under conditions where over 70% of 51Cr-labeled red blood cells were removed [18].
  • The identity of uterine cytosol CBG with serum CBG was established by ion-exchange chromatography (O-(diethylaminoethyl)-cellulose) and by immunoprecipitation with an antibody generated against serum CBG [18].
  • Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA) [5].
  • In the present work, CBG mRNA was detected in normal human endometrial tissues by Northern blot analysis and reverse transcription-polymerase chain reaction [27].
  • In Western blot analysis, polyclonal anti-CBG antibodies recognized a protein of approximately 55 kD in the protein extracts prepared from 3A (tPA-30-1) cells [28].


  1. Corticosteroid binding globulin gene polymorphism influences cortisol driven fat distribution in obese women. Barat, P., Duclos, M., Gatta, B., Roger, P., Mormede, P., Moisan, M.P. Obes. Res. (2005) [Pubmed]
  2. Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency. Joyner, J.M., Hutley, L.J., Bachmann, A.W., Torpy, D.J., Prins, J.B. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  3. Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers. Misao, R., Nakanishi, Y., Fujimoto, J., Ichigo, S., Hori, M., Tamaya, T. Steroids (1995) [Pubmed]
  4. A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. Smith, C.L., Power, S.G., Hammond, G.L. J. Steroid Biochem. Mol. Biol. (1992) [Pubmed]
  5. Hereditary corticosteroid-binding globulin deficiency due to a missense mutation (Asp367Asn, CBG Lyon) in a Brazilian kindred. Brunner, E., Baima, J., Vieira, T.C., Vieira, J.G., Abucham, J. Clin. Endocrinol. (Oxf) (2003) [Pubmed]
  6. Glucocorticoid feedback sensitivity and adrenocortical responsiveness in posttraumatic stress disorder. Kanter, E.D., Wilkinson, C.W., Radant, A.D., Petrie, E.C., Dobie, D.J., McFall, M.E., Peskind, E.R., Raskind, M.A. Biol. Psychiatry (2001) [Pubmed]
  7. Alterations in serum cortisol and its binding characteristics in anorexia nervosa. Casper, R.C., Chatterton, R.T., Davis, J.M. J. Clin. Endocrinol. Metab. (1979) [Pubmed]
  8. Short-term fasting affects locomotor activity, corticosterone, and corticosterone binding globulin in a migratory songbird. Lynn, S.E., Breuner, C.W., Wingfield, J.C. Hormones and behavior. (2003) [Pubmed]
  9. Identification of breast cancer transcortin and its inhibitory role in cell-mediated immunity. Amaral, L., Werthamer, S. Nature (1976) [Pubmed]
  10. Serum steroid binding proteins and the bioavailability of estradiol in relation to breast diseases. Langley, M.S., Hammond, G.L., Bardsley, A., Sellwood, R.A., Anderson, D.C. J. Natl. Cancer Inst. (1985) [Pubmed]
  11. Placenta, transcortin, and localized immune response. Werthamer, S., Govindaraj, S., Amaral, L. J. Clin. Invest. (1976) [Pubmed]
  12. Expression and function of 3beta hydroxisteroid dehydrogenase (3beta HSD) type II and corticosteroid binding globulin (CBG) in granulosa cells from ovaries of women with and without endometriosis. Garrido, N., Krüssel, J.S., Remohí, J., Simón, C., Pellicer, A. J. Assist. Reprod. Genet. (2002) [Pubmed]
  13. Increased serum cortisol binding in chronic active hepatitis. Orbach, O., Schussler, G.C. Am. J. Med. (1989) [Pubmed]
  14. Altered metabolism and decreased efficacy of prednisolone and prednisone in patients with hyperthyroidism. Frey, F.J., Horber, F.F., Frey, B.M. Clin. Pharmacol. Ther. (1988) [Pubmed]
  15. Effects of ethinylestradiol on the renin-angiotensin-aldosterone-system and on plasma transcortin in women and men. Oelkers, W., Blümel, A., Schöneshöfer, M., Schwartz, U., Hammerstein, J. J. Clin. Endocrinol. Metab. (1976) [Pubmed]
  16. Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder. de Kloet, C.S., Vermetten, E., Heijnen, C.J., Geuze, E., Lentjes, E.G., Westenberg, H.G. Psychoneuroendocrinology (2007) [Pubmed]
  17. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors. Hammond, G.L., Smith, C.L., Goping, I.S., Underhill, D.A., Harley, M.J., Reventos, J., Musto, N.A., Gunsalus, G.L., Bardin, C.W. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  18. Hamster uterine tissues accumulate corticosteroid-binding globulin during decidualization. Selcer, K.W., Leavitt, W.W. Biol. Reprod. (1988) [Pubmed]
  19. Antibodies to rabbit progesterone receptor: crossreaction with human receptor. Logeat, F., Hai, M.T., Milgrom, E. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  20. Identification of corticosteroid-binding globulin in human milk: measurement with a filter disk assay. Rosner, W., Beers, P.C., Awan, T., Khan, M.S. J. Clin. Endocrinol. Metab. (1976) [Pubmed]
  21. Cortisol levels, binding, and properties of corticosteroid-binding globulin in the serum of primates. Klosterman, L.L., Murai, J.T., Siiteri, P.K. Endocrinology (1986) [Pubmed]
  22. Residues in the human corticosteroid-binding globulin reactive center loop that influence steroid binding before and after elastase cleavage. Lin, H.Y., Underhill, C., Gardill, B.R., Muller, Y.A., Hammond, G.L. J. Biol. Chem. (2009) [Pubmed]
  23. Levels of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) messenger ribonucleic acid (mRNAs) in ovarian endometriosis. Misao, R., Hori, M., Ichigo, S., Fujimoto, J., Tamaya, T. Reprod. Nutr. Dev. (1995) [Pubmed]
  24. Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin. Heubner, A., Belovsky, O., Müller, W., Grill, H.J., Manz, B., Juchem, M., Pollow, K. J. Chromatogr. (1987) [Pubmed]
  25. Specific progesterone receptors in human breast cancer. Horwitz, K.B., McGuire, W.L. Steroids (1975) [Pubmed]
  26. Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1. Rollini, P., Fournier, R.E. Mamm. Genome (1997) [Pubmed]
  27. Corticosteroid-binding globulin mRNA levels in human uterine endometrium. Misao, R., Hori, M., Ichigo, S., Fujimoto, J., Tamaya, T. Steroids (1994) [Pubmed]
  28. Evidence for the synthesis of corticosteroid-binding globulin in human placenta. Misao, R., Iwagaki, S., Sun, W.S., Fujimoto, J., Saio, M., Takami, T., Tamaya, T. Horm. Res. (1999) [Pubmed]
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