P08185 (CBG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Corticosteroid-binding globulin
Short name=CBG

Alternative name(s):
Serpin A6
Transcortin

Gene names

Name:	SERPINA6
Synonyms:	CBG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	405 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transport
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Lipid-binding Steroid-binding
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glucocorticoid metabolic process Inferred from electronic annotation. Source: Compara regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	serine-type endopeptidase inhibitor activity Inferred from Biological aspect of Ancestor. Source: RefGenome steroid binding Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.6

Chain

23 – 405

383

Corticosteroid-binding globulin

PRO_0000032429

Sites

Binding site

254

1

Corticosteroid

Binding site

286

1

Corticosteroid

Binding site

390

1

Corticosteroid

Binding site

393

1

Corticosteroid

Site

250

1

Conserved cysteine within steroid binding domain

Amino acid modifications

Glycosylation

31

1

N-linked (GlcNAc...) Ref.8

Glycosylation

96

1

N-linked (GlcNAc...) Ref.7 Ref.8 Ref.9

Glycosylation

176

1

N-linked (GlcNAc...) Potential

Glycosylation

260

1

N-linked (GlcNAc...)

Glycosylation

330

1

N-linked (GlcNAc...) Ref.8 Ref.9

Glycosylation

369

1

N-linked (GlcNAc...) Ref.8

Natural variations

Natural variant

115

1

L → H in CBG deficiency; Leuven; decreased cortisol-binding affinity. Ref.11 Ref.12
Corresponds to variant rs28929488 [ dbSNP | Ensembl ].

VAR_007111

Natural variant

246

1

S → A. Ref.5
Corresponds to variant rs2228541 [ dbSNP | Ensembl ].

VAR_024350

Natural variant

389

1

D → N in CBG deficiency; Lyon; decreased cortisol-binding affinity. Ref.13 Ref.14
Corresponds to variant rs28929488 [ dbSNP | Ensembl ].

VAR_016223

Secondary structure

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405

Helix Strand Turn

Details...

Helix

39 – 57

19

Beta strand

59 – 61

3

Beta strand

63 – 65

3

Helix

67 – 78

12

Helix

83 – 92

10

Turn

97 – 99

3

Helix

102 – 117

16

Beta strand

124 – 134

11

Helix

141 – 151

11

Beta strand

154 – 158

5

Helix

163 – 177

15

Turn

178 – 180

3

Beta strand

194 – 209

16

Helix

213 – 215

3

Beta strand

217 – 224

8

Beta strand

227 – 244

18

Beta strand

246 – 268

23

Helix

273 – 278

6

Helix

282 – 291

10

Beta strand

293 – 302

10

Beta strand

305 – 311

7

Helix

313 – 318

6

Helix

323 – 325

3

Turn

332 – 334

3

Beta strand

335 – 338

4

Beta strand

340 – 353

14

Beta strand

355 – 357

3

Beta strand

375 – 378

4

Beta strand

383 – 389

7

Turn

390 – 392

3

Beta strand

395 – 402

8

Sequences

	Sequence		Length	Mass (Da)
	P08185 [UniParc]. Last modified August 1, 1988. Version 1. Checksum: F0E36EFC3B3C08A1	FASTA	405	45,141
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.

IPI

IPI00027482.

PIR

A28321.

RefSeq

NP_001747.2. NM_001756.3.

UniGene

Hs.532635.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VDX	X-ray	1.84	A/B	33-405	[»]
2VDY	X-ray	2.30	A/B	33-405	[»]
4BB2	X-ray	2.48	A	33-371	[»]
			B	372-405	[»]

ProteinModelPortal

P08185.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000342850.

Protein family/group databases

MEROPS

I04.954.

Polymorphism databases

DMDM

115851.

Proteomic databases

PaxDb

P08185.

PeptideAtlas

P08185.

PRIDE

P08185.

Protocols and materials databases

DNASU

866.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000341584; ENSP00000342850; ENSG00000170099.

GeneID

866.

KEGG

hsa:866.

UCSC

uc001ycv.3. human.

Organism-specific databases

CTD

866.

GeneCards

GC14M094770.

HGNC

HGNC:1540. SERPINA6.

HPA

HPA017864.

MIM

122500. gene.
611489. phenotype.

neXtProt

NX_P08185.

Orphanet

199247. Corticosteroid-binding globulin deficiency.

PharmGKB

PA35033.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOGENOM

HOG000238521.

HOVERGEN

HBG005957.

InParanoid

P08185.

OMA

DLYIPKV.

OrthoDB

EOG4KH2V7.

PhylomeDB

P08185.

Gene expression databases

ArrayExpress

P08185.

Bgee

P08185.

CleanEx

HS_SERPINA6.

Genevestigator

P08185.

GermOnline

ENSG00000170099. Homo sapiens.

Family and domain databases

InterPro

IPR000295. Prot_inh_Lserp2.
IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

PRINTS

PR00780. LEUSERPINII.

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2421.

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.

EvolutionaryTrace

P08185.

GenomeRNAi

866.

NextBio

3614.

SOURCE

Search...

Entry information

Entry name

CBG_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 135 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.