Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P08185 (CBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticosteroid-binding globulin

Short name=CBG
Alternative name(s):
Serpin A6
Transcortin
Gene names
Name:SERPINA6
Synonyms:CBG
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length405 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. Ref.10

Subcellular location

Secreted.

Tissue specificity

Plasma; synthesized in liver. Has also been identified in a number of glycocorticoid responsive cells.

Domain

Proteolytic cleavage leads to an important conformation change. This reduces the affinity for steroids. Ref.10

Post-translational modification

N-glycosylated; binds 5 oligosaccharide chains.

Glycosylation in position Asn-260 is needed for steroid binding.

Involvement in disease

Corticosteroid-binding globulin deficiency (CBG deficiency) [MIM:611489]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the serpin family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.6
Chain23 – 405383Corticosteroid-binding globulin
PRO_0000032429

Sites

Binding site2541Corticosteroid
Binding site2861Corticosteroid
Binding site3901Corticosteroid
Binding site3931Corticosteroid
Site2501Conserved cysteine within steroid binding domain

Amino acid modifications

Glycosylation311N-linked (GlcNAc...) Ref.8
Glycosylation961N-linked (GlcNAc...) Ref.7 Ref.8 Ref.9
Glycosylation1761N-linked (GlcNAc...) Potential
Glycosylation2601N-linked (GlcNAc...)
Glycosylation3301N-linked (GlcNAc...) Ref.8 Ref.9
Glycosylation3691N-linked (GlcNAc...) Ref.8

Natural variations

Natural variant1151L → H in CBG deficiency; Leuven; decreased cortisol-binding affinity. Ref.11 Ref.12
Corresponds to variant rs28929488 [ dbSNP | Ensembl ].
VAR_007111
Natural variant2461S → A. Ref.5
Corresponds to variant rs2228541 [ dbSNP | Ensembl ].
VAR_024350
Natural variant3891D → N in CBG deficiency; Lyon; decreased cortisol-binding affinity. Ref.13 Ref.14
Corresponds to variant rs28929488 [ dbSNP | Ensembl ].
VAR_016223

Secondary structure

.............................................................. 405
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08185 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: F0E36EFC3B3C08A1

FASTA40545,141
        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 

« Hide

References

« Hide 'large scale' references
[1]"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. 84:5153-5157(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver and Lung.
[2]"Corticosteroid binding globulin, testosterone-estradiol binding globulin, and androgen binding protein belong to protein families distinct from steroid receptors."
Bardin C.W., Gunsalus G.L., Musto N.A., Cheng C.Y., Reventos J., Smith C., Underhill D.A., Hammond G.
J. Steroid Biochem. 30:131-139(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-246.
[6]"Comparative structural analyses of corticosteroid binding globulin."
Kato E.A., Hsu B.R.-S., Kuhn R.W.
J. Steroid Biochem. 29:213-220(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-30.
[7]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96.
Tissue: Plasma.
[8]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-31; ASN-96; ASN-330 AND ASN-369.
Tissue: Plasma.
[9]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96 AND ASN-330.
Tissue: Liver.
[10]"The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release."
Zhou A., Wei Z., Stanley P.L., Read R.J., Stein P.E., Carrell R.W.
J. Mol. Biol. 380:244-251(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 33-405 IN COMPLEX WITH CORTISOL, FUNCTION, DOMAIN.
[11]"A Leu-->His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol."
Smith C.L., Power S.G.A., Hammond G.L.
J. Steroid Biochem. Mol. Biol. 42:671-676(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CBG DEFICIENCY HIS-115.
[12]"Decreased cortisol-binding affinity of transcortin Leuven is associated with an amino acid substitution at residue-93."
van Baelen H., Power S.G.A., Hammond G.L.
Steroids 58:275-277(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CBG DEFICIENCY HIS-115.
[13]"Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity."
Emptoz-Bonneton A., Cousin P., Seguchi K., Avvakumov G.V., Bully C., Hammond G.L., Pugeat M.
J. Clin. Endocrinol. Metab. 85:361-367(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CBG DEFICIENCY ASN-389.
[14]"Haploinsufficiency of the SERPINA6 gene is associated with severe muscle fatigue: A de novo mutation in corticosteroid-binding globulin deficiency."
Buss C., Schuelter U., Hesse J., Moser D., Phillips D.I., Hellhammer D., Meyer J.
J. Neural Transm. 114:563-569(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CBG DEFICIENCY ASN-389.
+Additional computationally mapped references.

Web resources

Wikipedia

Transcortin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02943 mRNA. Translation: AAB59523.1.
AK290821 mRNA. Translation: BAF83510.1.
CH471061 Genomic DNA. Translation: EAW81568.1.
BC056259 mRNA. Translation: AAH56259.1.
BC058021 mRNA. Translation: AAH58021.1.
PIRA28321.
RefSeqNP_001747.2. NM_001756.3.
UniGeneHs.532635.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VDXX-ray1.84A/B33-405[»]
2VDYX-ray2.30A/B33-405[»]
4BB2X-ray2.48A33-371[»]
B372-405[»]
ProteinModelPortalP08185.
SMRP08185. Positions 35-371, 373-405.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107314. 1 interaction.
STRING9606.ENSP00000342850.

Chemistry

ChEMBLCHEMBL2421.
DrugBankDB00240. 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.

Protein family/group databases

MEROPSI04.954.

Polymorphism databases

DMDM115851.

Proteomic databases

PaxDbP08185.
PeptideAtlasP08185.
PRIDEP08185.

Protocols and materials databases

DNASU866.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341584; ENSP00000342850; ENSG00000170099.
GeneID866.
KEGGhsa:866.
UCSCuc001ycv.3. human.

Organism-specific databases

CTD866.
GeneCardsGC14M094770.
HGNCHGNC:1540. SERPINA6.
HPAHPA017864.
MIM122500. gene.
611489. phenotype.
neXtProtNX_P08185.
Orphanet199247. Corticosteroid-binding globulin deficiency.
PharmGKBPA35033.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4826.
HOGENOMHOG000238521.
HOVERGENHBG005957.
InParanoidP08185.
OMASTREENF.
PhylomeDBP08185.
TreeFamTF343201.

Gene expression databases

ArrayExpressP08185.
BgeeP08185.
CleanExHS_SERPINA6.
GenevestigatorP08185.

Family and domain databases

InterProIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERPTHR11461. PTHR11461. 1 hit.
PfamPF00079. Serpin. 1 hit.
[Graphical view]
SMARTSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMSSF56574. SSF56574. 1 hit.
PROSITEPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08185.
GeneWikiTranscortin.
GenomeRNAi866.
NextBio3614.
PROP08185.
SOURCESearch...

Entry information

Entry nameCBG_HUMAN
AccessionPrimary (citable) accession number: P08185
Secondary accession number(s): A8K456, Q7Z2Q9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM