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.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2VDX, 2VDY, 4BB2, 4C41, 4C49
Identifiers
Symbols	SERPINA6 ; CBG
External IDs	OMIM: 122500 MGI: 88278 HomoloGene: 20417 ChEMBL: 2421 GeneCards: SERPINA6 Gene
Gene ontology Molecular function • serine-type endopeptidase inhibitor activity • steroid binding Cellular component • extracellular space • extracellular exosome Biological process • transport • glucocorticoid metabolic process • negative regulation of endopeptidase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	866	12401
Ensembl	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: 103.65 – 103.66 Mb
PubMed search	[1]	[2]

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.

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 have evolved by duplication events.

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
• Deoxycorticosterone (DOC)
• 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.
• 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.
• 17-Hydroxyprogesterone

In addition, approximately 4% of serum testosterone is bound to transcortin. 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.

Clinical significance

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

See also

• Serpin
• Circaseptan, 7-day biological cycle

External links

• Transcortin 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)