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UniProtKB/Swiss-Prot entry P08185


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CBG_HUMAN
Primary accession number P08185
Secondary accession number Q7Z2Q9
Integrated into Swiss-Prot on August 1, 1988
Sequence was last modified on August 1, 1988 (Sequence version 1)
Annotations were last modified on    April 29, 2008 (Entry version 91)
Name and origin of the protein
Protein name Corticosteroid-binding globulin [Precursor]
Synonyms CBG
Transcortin
Serpin A6
Gene name
Name: SERPINA6
Synonyms: CBG
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver, and Lung;
PubMed=3299377 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"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. 84:5153-5157(1987).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1016/0022-4731(88)90085-4; PubMed=3386241 [NCBI, ExPASy, EBI, Israel, Japan]
Bardin C.W., Gunsalus G.L., Musto N.A., Cheng C.Y., Reventos J., Smith C., Underhill D.A., Hammond G.;
"Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors.";
J. Steroid Biochem. 30:131-139(1988).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-246.
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
PROTEIN SEQUENCE OF 23-30.
DOI=10.1016/0022-4731(88)90268-3; PubMed=3347061 [NCBI, ExPASy, EBI, Israel, Japan]
Kato E.A., Hsu B.R.-S., Kuhn R.W.;
"Comparative structural analyses of corticosteroid binding globulin.";
J. Steroid Biochem. 29:213-220(1988).
[5]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1002/pmic.200300556; PubMed=14760718 [NCBI, ExPASy, EBI, Israel, Japan]
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.";
Proteomics 4:454-465(2004).
[6]
GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-31; ASN-96; ASN-330 AND ASN-369, AND MASS SPECTROMETRY.
TISSUE=Plasma;
DOI=10.1021/pr0502065; PubMed=16335952 [NCBI, ExPASy, EBI, Israel, Japan]
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.;
"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.";
J. Proteome Res. 4:2070-2080(2005).
[7]
VARIANT CBG DEFICIENCY HIS-115.
DOI=10.1016/0960-0760(92)90107-T; PubMed=1504007 [NCBI, ExPASy, EBI, Israel, Japan]
Smith C.L., Power S.G.A., Hammond G.L.;
"A Leu-->His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol.";
J. Steroid Biochem. Mol. Biol. 42:671-676(1992).
[8]
VARIANT CBG DEFICIENCY HIS-115.
DOI=10.1016/0039-128X(93)90072-U; PubMed=8212073 [NCBI, ExPASy, EBI, Israel, Japan]
van Baelen H., Power S.G.A., Hammond G.L.;
"Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93.";
Steroids 58:275-277(1993).
[9]
VARIANT CBG DEFICIENCY ASN-389.
DOI=10.1210/jc.85.1.361; PubMed=10634411 [NCBI, ExPASy, EBI, Israel, Japan]
Emptoz-Bonneton A., Cousin P., Seguchi K., Avvakumov G.V., Bully C., Hammond G.L., Pugeat M.;
"Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity.";
J. Clin. Endocrinol. Metab. 85:361-367(2000).
[10]
VARIANT CBG DEFICIENCY ASN-389.
DOI=10.1007/s00702-006-0620-5; PubMed=17245537 [NCBI, ExPASy, EBI, Israel, Japan]
Buss C., Schuelter U., Hesse J., Moser D., Phillips D.I., Hellhammer D., Meyer J.;
"Haploinsufficiency of the SERPINA6 gene is associated with severe muscle fatigue: A de novo mutation in corticosteroid-binding globulin deficiency.";
J. Neural Transm. 114:563-569(2007).
Comments
  • FUNCTION: Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
  • SUBCELLULAR LOCATION: Secreted.
  • TISSUE SPECIFICITY: Plasma; synthesized in liver. Has also been identified in a number of glycocorticoid responsive cells.
  • PTM: N-glycosylated; binds 5 oligosaccharides chains.
  • PTM: Glycosylation in position Asn-260 is needed for steroid binding.
  • DISEASE: Defects in SERPINA6 are a cause of corticosteroid-binding globulin deficiency (CBG deficiency) [MIM:611489]. CBG deficiency is an extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo/hypertension and muscle fatigue.
  • SIMILARITY: Belongs to the serpin family.
  • WEB RESOURCE: Name=Wikipedia; Note=Transcortin entry; URL="http://en.wikipedia.org/wiki/Transcortin";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
J02943; AAB59523.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC056259; AAH56259.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC058021; AAH58021.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A28321; A28321.
RefSeq NP_001747.2; -.
UniGene Hs.532635
3D structure databases
HSSP P01011; 1QMN. [HSSP ENTRY / PDB]
ModBase P08185.
Protein family/group databases
MEROPS I04.954; -.
Organism-specific databases
HGNC HGNC:1540; SERPINA6.
GeneLynx SERPINA6; Homo sapiens.
GenAtlas SERPINA6.
MIM 122500; gene. [NCBI / EBI]
611489; phenotype. [NCBI / EBI]
PharmGKB PA35033; -.
GeneCards P08185.
Gene expression databases
ArrayExpress P08185; -.
CleanEx HS_SERPINA6; -.
GermOnline ENSG00000170099; Homo sapiens.
Ontologies
GO
GO:0004867; Molecular function: serine-type endopeptidase inhibitor activity (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR000295; Prot_inh_Lserp2.
IPR000215; Protease_inhib_I4_serpin.
Graphical view of domain structure.
PANTHER PTHR11461; Prot_inh_serpin; 1.
Pfam PF00079; Serpin; 1.
Pfam graphical view of domain structure.
PRINTS PR00780; LEUSERPINII.
SMART SM00093; SERPIN; 1.
SMART graphical view of domain structure.
PROSITE PS00284; SERPIN; 1.
BLOCKS P08185.
Proteomic databases
PeptideAtlas P08185; -.
Genome annotation databases
Ensembl ENSG00000170099; Homo sapiens. [Contig view]
GeneID 866; -.
KEGG hsa:866; -.
Other
DrugBank DB00240; Alclometasone.
DB00394; Beclomethasone.
DB01410; Ciclesonide.
DB00663; Flumethasone Pivalate.
DB00180; Flunisolide.
DB00591; Fluocinolone Acetonide.
DB01047; Fluocinonide.
DB00324; Fluorometholone.
DB00846; Flurandrenolide.
DB00588; Fluticasone Propionate.
DB00596; Halobetasol Propionate.
DB00253; Medrysone.
DB00648; Mitotane.
DB01384; Paramethasone.
DB00860; Prednisolone.
DB00896; Rimexolone.
DB00620; Triamcinolone.
LinkHub P08185; -.
SOURCE SERPINA6; Homo sapiens.
ProtoNet P08185.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Direct protein sequencing; Disease mutation; Glycoprotein; Lipid-binding; Polymorphism; Secreted; Signal; Steroid-binding; Transport.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
SIGNAL   1    22  22      
CHAIN   23   405  383     Corticosteroid-binding globulin. PRO_0000032429
SITE   250   250  1     Conserved cysteine within steroid binding domain. 
CARBOHYD   31    31        N-linked (GlcNAc...). 
CARBOHYD   96    96        N-linked (GlcNAc...). 
CARBOHYD   176   176        N-linked (GlcNAc...) (Potential). 
CARBOHYD   260   260        N-linked (GlcNAc...). 
CARBOHYD   330   330        N-linked (GlcNAc...). 
CARBOHYD   369   369        N-linked (GlcNAc...). 
VARIANT   115   115  1     L -> H (in CBG deficiency; Leuven; decreased cortisol-binding affinity; dbSNP:rs28929488 [NCBI]). VAR_007111 
VARIANT   246   246  1     S -> A (in dbSNP:rs2228541 [NCBI]). VAR_024350 
VARIANT   389   389  1     D -> N (in CBG deficiency; Lyon; decreased cortisol-binding affinity). VAR_016223 
Sequence information
Length: 405 AA [This is the length of the unprocessed precursor] Molecular weight: 45141 Da [This is the MW of the unprocessed precursor] CRC64: F0E36EFC3B3C08A1 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MPLLLYTCLL WLPTSGLWTV QAMDPNAAYV NMSNHHRGLA SANVDFAFSL YKHLVALSPK 

        70         80         90        100        110        120 
KNIFISPVSI SMALAMLSLG TCGHTRAQLL QGLGFNLTER SETEIHQGFQ HLHQLFAKSD 

       130        140        150        160        170        180 
TSLEMTMGNA LFLDGSLELL ESFSADIKHY YESEVLAMNF QDWATASRQI NSYVKNKTQG 

       190        200        210        220        230        240 
KIVDLFSGLD SPAILVLVNY IFFKGTWTQP FDLASTREEN FYVDETTVVK VPMMLQSSTI 

       250        260        270        280        290        300 
SYLHDSELPC QLVQMNYVGN GTVFFILPDK GKMNTVIAAL SRDTINRWSA GLTSSQVDLY 

       310        320        330        340        350        360 
IPKVTISGVY DLGDVLEEMG IADLFTNQAN FSRITQDAQL KSSKVVHKAV LQLNEEGVDT 

       370        380        390        400 
AGSTGVTLNL TSKPIILRFN QPFIIMIFDH FTWSSLFLAR VMNPV 

P08185 in FASTA format

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