ID CBG_HUMAN Reviewed; 405 AA. AC P08185; Q7Z2Q9; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 23-SEP-2008, entry version 94. DE RecName: Full=Corticosteroid-binding globulin; DE Short=CBG; DE AltName: Full=Transcortin; DE AltName: Full=Serpin A6; DE Flags: Precursor; GN Name=SERPINA6; Synonyms=CBG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver, and Lung; RX MEDLINE=87260947; PubMed=3299377; RA Hammond G.L., Smith C.L., Goping I.S., Underhill D.A., Harley M.J., RA Reventos J., Musto N.A., Gunsalus G.L., Bardin C.W.; RT "Primary structure of human corticosteroid binding globulin, deduced RT from hepatic and pulmonary cDNAs, exhibits homology with serine RT protease inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 84:5153-5157(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=88260097; PubMed=3386241; DOI=10.1016/0022-4731(88)90085-4; RA Bardin C.W., Gunsalus G.L., Musto N.A., Cheng C.Y., Reventos J., RA Smith C., Underhill D.A., Hammond G.; RT "Corticosteroid binding globulin, testosterone-estradiol binding RT globulin, and androgen binding protein belong to protein families RT distinct from steroid receptors."; RL J. Steroid Biochem. 30:131-139(1988). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-246. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 23-30. RX MEDLINE=88156232; PubMed=3347061; DOI=10.1016/0022-4731(88)90268-3; RA Kato E.A., Hsu B.R.-S., Kuhn R.W.; RT "Comparative structural analyses of corticosteroid binding globulin."; RL J. Steroid Biochem. 29:213-220(1988). RN [5] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96, AND MASS SPECTROMETRY. RC TISSUE=Plasma; RX PubMed=14760718; DOI=10.1002/pmic.200300556; RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.; RT "Screening for N-glycosylated proteins by liquid chromatography mass RT spectrometry."; RL Proteomics 4:454-465(2004). RN [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-31; ASN-96; ASN-330 AND RP ASN-369, AND MASS SPECTROMETRY. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [7] RP VARIANT CBG DEFICIENCY HIS-115. RX MEDLINE=92368995; PubMed=1504007; DOI=10.1016/0960-0760(92)90107-T; RA Smith C.L., Power S.G.A., Hammond G.L.; RT "A Leu-->His substitution at residue 93 in human corticosteroid RT binding globulin results in reduced affinity for cortisol."; RL J. Steroid Biochem. Mol. Biol. 42:671-676(1992). RN [8] RP VARIANT CBG DEFICIENCY HIS-115. RX MEDLINE=94024974; PubMed=8212073; DOI=10.1016/0039-128X(93)90072-U; RA van Baelen H., Power S.G.A., Hammond G.L.; RT "Decreased cortisol-binding affinity of transcortin Leuven is RT associated with an amino acid substitution at residue-93."; RL Steroids 58:275-277(1993). RN [9] RP VARIANT CBG DEFICIENCY ASN-389. RX MEDLINE=20097877; PubMed=10634411; DOI=10.1210/jc.85.1.361; RA Emptoz-Bonneton A., Cousin P., Seguchi K., Avvakumov G.V., Bully C., RA Hammond G.L., Pugeat M.; RT "Novel human corticosteroid-binding globulin variant with low RT cortisol-binding affinity."; RL J. Clin. Endocrinol. Metab. 85:361-367(2000). RN [10] RP VARIANT CBG DEFICIENCY ASN-389. RX PubMed=17245537; DOI=10.1007/s00702-006-0620-5; RA Buss C., Schuelter U., Hesse J., Moser D., Phillips D.I., RA Hellhammer D., Meyer J.; RT "Haploinsufficiency of the SERPINA6 gene is associated with severe RT muscle fatigue: A de novo mutation in corticosteroid-binding globulin RT deficiency."; RL J. Neural Transm. 114:563-569(2007). CC -!- FUNCTION: Major transport protein for glucocorticoids and CC progestins in the blood of almost all vertebrate species. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Plasma; synthesized in liver. Has also been CC identified in a number of glycocorticoid responsive cells. CC -!- PTM: N-glycosylated; binds 5 oligosaccharide chains. CC -!- PTM: Glycosylation in position Asn-260 is needed for steroid CC binding. CC -!- DISEASE: Defects in SERPINA6 are a cause of corticosteroid-binding CC globulin deficiency (CBG deficiency) [MIM:611489]. CBG deficiency CC is an extremely rare hereditary disorder characterized by reduced CC corticosteroid-binding capacity with normal or low plasma CC corticosteroid-binding globulin concentration, and normal or low CC basal cortisol levels associated with hypo/hypertension and muscle CC fatigue. CC -!- SIMILARITY: Belongs to the serpin family. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Transcortin entry; CC URL="http://en.wikipedia.org/wiki/Transcortin"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; J02943; AAB59523.1; -; mRNA. DR EMBL; BC056259; AAH56259.1; -; mRNA. DR EMBL; BC058021; AAH58021.1; -; mRNA. DR PIR; A28321; A28321. DR RefSeq; NP_001747.2; -. DR UniGene; Hs.532635; -. DR PDB; 2VDX; X-ray; 1.84 A; A/B=33-405. DR PDB; 2VDY; X-ray; 2.30 A; A/B=33-405. DR PDBsum; 2VDX; -. DR PDBsum; 2VDY; -. DR MEROPS; I04.954; -. DR PeptideAtlas; P08185; -. DR Ensembl; ENSG00000170099; Homo sapiens. DR GeneID; 866; -. DR KEGG; hsa:866; -. DR HGNC; HGNC:1540; SERPINA6. DR MIM; 122500; gene. DR MIM; 611489; phenotype. DR PharmGKB; PA35033; -. DR HOGENOM; P08185; -. DR HOVERGEN; P08185; -. DR DrugBank; DB00240; Alclometasone. DR DrugBank; DB00394; Beclomethasone. DR DrugBank; DB01410; Ciclesonide. DR DrugBank; DB00663; Flumethasone Pivalate. DR DrugBank; DB00180; Flunisolide. DR DrugBank; DB00591; Fluocinolone Acetonide. DR DrugBank; DB01047; Fluocinonide. DR DrugBank; DB00324; Fluorometholone. DR DrugBank; DB00846; Flurandrenolide. DR DrugBank; DB00588; Fluticasone Propionate. DR DrugBank; DB00596; Halobetasol Propionate. DR DrugBank; DB00253; Medrysone. DR DrugBank; DB00648; Mitotane. DR DrugBank; DB01384; Paramethasone. DR DrugBank; DB00860; Prednisolone. DR DrugBank; DB00896; Rimexolone. DR DrugBank; DB00620; Triamcinolone. DR LinkHub; P08185; -. DR ArrayExpress; P08185; -. DR CleanEx; HS_SERPINA6; -. DR GermOnline; ENSG00000170099; Homo sapiens. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; TAS:ProtInc. DR InterPro; IPR000295; Prot_inh_Lserp2. DR InterPro; IPR000215; Protease_inhib_I4_serpin. DR PANTHER; PTHR11461; Prot_inh_serpin; 1. DR Pfam; PF00079; Serpin; 1. DR PRINTS; PR00780; LEUSERPINII. DR SMART; SM00093; SERPIN; 1. DR PROSITE; PS00284; SERPIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disease mutation; KW Glycoprotein; Lipid-binding; Polymorphism; Secreted; Signal; KW Steroid-binding; Transport. FT SIGNAL 1 22 FT CHAIN 23 405 Corticosteroid-binding globulin. FT /FTId=PRO_0000032429. FT BINDING 254 254 Corticosteroid (By similarity). FT BINDING 286 286 Corticosteroid (By similarity). FT BINDING 393 393 Corticosteroid (By similarity). FT SITE 250 250 Conserved cysteine within steroid binding FT domain. FT CARBOHYD 31 31 N-linked (GlcNAc...). FT CARBOHYD 96 96 N-linked (GlcNAc...). FT CARBOHYD 176 176 N-linked (GlcNAc...) (Potential). FT CARBOHYD 260 260 N-linked (GlcNAc...). FT CARBOHYD 330 330 N-linked (GlcNAc...). FT CARBOHYD 369 369 N-linked (GlcNAc...). FT VARIANT 115 115 L -> H (in CBG deficiency; Leuven; FT decreased cortisol-binding affinity; FT dbSNP:rs28929488). FT /FTId=VAR_007111. FT VARIANT 246 246 S -> A (in dbSNP:rs2228541). FT /FTId=VAR_024350. FT VARIANT 389 389 D -> N (in CBG deficiency; Lyon; FT decreased cortisol-binding affinity). FT /FTId=VAR_016223. SQ SEQUENCE 405 AA; 45141 MW; F0E36EFC3B3C08A1 CRC64; MPLLLYTCLL WLPTSGLWTV QAMDPNAAYV NMSNHHRGLA SANVDFAFSL YKHLVALSPK KNIFISPVSI SMALAMLSLG TCGHTRAQLL QGLGFNLTER SETEIHQGFQ HLHQLFAKSD TSLEMTMGNA LFLDGSLELL ESFSADIKHY YESEVLAMNF QDWATASRQI NSYVKNKTQG KIVDLFSGLD SPAILVLVNY IFFKGTWTQP FDLASTREEN FYVDETTVVK VPMMLQSSTI SYLHDSELPC QLVQMNYVGN GTVFFILPDK GKMNTVIAAL SRDTINRWSA GLTSSQVDLY IPKVTISGVY DLGDVLEEMG IADLFTNQAN FSRITQDAQL KSSKVVHKAV LQLNEEGVDT AGSTGVTLNL TSKPIILRFN QPFIIMIFDH FTWSSLFLAR VMNPV //