Plasma protease C1 inhibitor

Details

Name
Plasma protease C1 inhibitor
Synonyms
  • C1 esterase inhibitor
  • C1 Inh
  • C1-inhibiting factor
  • C1IN
  • C1NH
  • Serpin G1
Gene Name
SERPING1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004827|Plasma protease C1 inhibitor
MASRLTLLTLLLLLLAGDRASSNPNATSSSSQDPESLQDRGEGKVATTVISKMLFVEPIL
EVSSLPTTNSTTNSATKITANTTDEPTTQPTTEPTTQPTIQPTQPTTQLPTDSPTQPTTG
SFCPGPVTLCSDLESHSTEAVLGDALVDFSLKLYHAFSAMKKVETNMAFSPFSIASLLTQ
VLLGAGENTKTNLESILSYPKDFTCVHQALKGFTTKGVTSVSQIFHSPDLAIRDTFVNAS
RTLYSSSPRVLSNNSDANLELINTWVAKNTNNKISRLLDSLPSDTRLVLLNAIYLSAKWK
TTFDPKKTRMEPFHFKNSVIKVPMMNSKKYPVAHFIDQTLKAKVGQLQLSHNLSLVILVP
QNLKHRLEDMEQALSPSVFKAIMEKLEMSKFQPTLLTLPRIKVTTSQDMLSIMEKLEFFD
FSYDLNLCGLTEDPDLQVSAMQHQTVLELTETGVEAAAASAISVARTLLVFEVQQPFLFV
LWDQQHKFPVFMGRVYDPRA
Number of residues
500
Molecular Weight
55153.645
Theoretical pI
6.52
GO Classification
Functions
serine-type endopeptidase inhibitor activity
Processes
aging / blood circulation / blood coagulation / blood coagulation, intrinsic pathway / complement activation, classical pathway / fibrinolysis / innate immune response / negative regulation of complement activation, lectin pathway / negative regulation of endopeptidase activity / platelet activation / platelet degranulation
Components
blood microparticle / extracellular exosome / extracellular region / extracellular space / platelet alpha granule lumen
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0016798|Plasma protease C1 inhibitor (SERPING1)
ATGGCCTCCAGGCTGACCCTGCTGACCCTCCTGCTGCTGCTGCTGGCTGGGGATAGAGCC
TCCTCAAATCCAAATGCTACCAGCTCCAGCTCCCAGGATCCAGAGAGTTTGCAAGACAGA
GGCGAAGGGAAGGTCGCAACAACAGTTATCTCCAAGATGCTATTCGTTGAACCCATCCTG
GAGGTTTCCAGCTTGCCGACAACCAACTCAACAACCAATTCAGCCACCAAAATAACAGCT
AATACCACTGATGAACCCACCACACAACCCACCACAGAGCCCACCACCCAACCCACCATC
CAACCCACCCAACCAACTACCCAGCTCCCAACAGATTCTCCTACCCAGCCCACTACTGGG
TCCTTCTGCCCAGGACCTGTTACTCTCTGCTCTGACTTGGAGAGTCATTCAACAGAGGCC
GTGTTGGGGGATGCTTTGGTAGATTTCTCCCTGAAGCTCTACCACGCCTTCTCAGCAATG
AAGAAGGTGGAGACCAACATGGCCTTTTCCCCATTCAGCATCGCCAGCCTCCTTACCCAG
GTCCTGCTCGGGGCTGGGGAGAACACCAAAACAAACCTGGAGAGCATCCTCTCTTACCCC
AAGGACTTCACCTGTGTCCACCAGGCCCTGAAGGGCTTCACGACCAAAGGTGTCACCTCA
GTCTCTCAGATCTTCCACAGCCCAGACCTGGCCATAAGGGACACCTTTGTGAATGCCTCT
CGGACCCTGTACAGCAGCAGCCCCAGAGTCCTAAGCAACAACAGTGACGCCAACTTGGAG
CTCATCAACACCTGGGTGGCCAAGAACACCAACAACAAGATCAGCCGGCTGCTAGACAGT
CTGCCCTCCGATACCCGCCTTGTCCTCCTCAATGCTATCTACCTGAGTGCCAAGTGGAAG
ACAACATTTGATCCCAAGAAAACCAGAATGGAACCCTTTCACTTCAAAAACTCAGTTATA
AAAGTGCCCATGATGAATAGCAAGAAGTACCCTGTGGCCCATTTCATTGACCAAACTTTG
AAAGCCAAGGTGGGGCAGCTGCAGCTCTCCCACAATCTGAGTTTGGTGATCCTGGTACCC
CAGAACCTGAAACATCGTCTTGAAGACATGGAACAGGCTCTCAGCCCTTCTGTTTTCAAG
GCCATCATGGAGAAACTGGAGATGTCCAAGTTCCAGCCCACTCTCCTAACACTACCCCGC
ATCAAAGTGACGACCAGCCAGGATATGCTCTCAATCATGGAGAAATTGGAATTCTTCGAT
TTTTCTTATGACCTTAACCTGTGTGGGCTGACAGAGGACCCAGATCTTCAGGTTTCTGCG
ATGCAGCACCAGACAGTGCTGGAACTGACAGAGACTGGGGTGGAGGCGGCTGCAGCCTCC
GCCATCTCTGTGGCCCGCACCCTGCTGGTCTTTGAAGTGCAGCAGCCCTTCCTCTTCGTG
CTCTGGGACCAGCAGCACAAGTTCCCTGTCTTCATGGGGCGAGTATATGACCCCAGGGCC
TGA
Chromosome Location
11
Locus
11q12-q13.1
External Identifiers
ResourceLink
UniProtKB IDP05155
UniProtKB Entry NameIC1_HUMAN
GenBank Gene IDX54486
GenAtlas IDSERPING1
HGNC IDHGNC:1228
General References
  1. Que BG, Petra PH: Isolation and analysis of a cDNA coding for human C1 inhibitor. Biochem Biophys Res Commun. 1986 Jun 13;137(2):620-5. [Article]
  2. Bock SC, Skriver K, Nielsen E, Thogersen HC, Wiman B, Donaldson VH, Eddy RL, Marrinan J, Radziejewska E, Huber R, et al.: Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization. Biochemistry. 1986 Jul 29;25(15):4292-301. [Article]
  3. Carter PE, Dunbar B, Fothergill JE: Genomic and cDNA cloning of the human C1 inhibitor. Intron-exon junctions and comparison with other serpins. Eur J Biochem. 1988 Apr 5;173(1):163-9. [Article]
  4. Carter PE, Duponchel C, Tosi M, Fothergill JE: Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements. Eur J Biochem. 1991 Apr 23;197(2):301-8. [Article]
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  8. Rauth G, Schumacher G, Buckel P, Muller-Esterl W: Molecular cloning of the cDNA coding for human C1 inhibitor. Protein Seq Data Anal. 1988;1(4):251-7. [Article]
  9. Bos IG, Lubbers YT, Roem D, Abrahams JP, Hack CE, Eldering E: The functional integrity of the serpin domain of C1-inhibitor depends on the unique N-terminal domain, as revealed by a pathological mutant. J Biol Chem. 2003 Aug 8;278(32):29463-70. Epub 2003 May 27. [Article]
  10. Harrison RA: Human C1 inhibitor: improved isolation and preliminary structural characterization. Biochemistry. 1983 Oct 11;22(21):5001-7. [Article]
  11. Stoppa-Lyonnet D, Carter PE, Meo T, Tosi M: Clusters of intragenic Alu repeats predispose the human C1 inhibitor locus to deleterious rearrangements. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1551-5. [Article]
  12. Tosi M, Duponchel C, Bourgarel P, Colomb M, Meo T: Molecular cloning of human C1 inhibitor: sequence homologies with alpha 1-antitrypsin and other members of the serpins superfamily. Gene. 1986;42(3):265-72. [Article]
  13. Pillai S, Wright D, Gupta A, Zhou G, Hull G, Jiang H, Zhang H: Molecular weights and isoelectric points of sperm antigens relevant to autoimmune infertility in men. J Urol. 1996 Jun;155(6):1928-33. [Article]
  14. Davis AE 3rd, Whitehead AS, Harrison RA, Dauphinais A, Bruns GA, Cicardi M, Rosen FS: Human inhibitor of the first component of complement, C1: characterization of cDNA clones and localization of the gene to chromosome 11. Proc Natl Acad Sci U S A. 1986 May;83(10):3161-5. [Article]
  15. Verpy E, Couture-Tosi E, Eldering E, Lopez-Trascasa M, Spath P, Meo T, Tosi M: Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function. J Clin Invest. 1995 Jan;95(1):350-9. [Article]
  16. Aulak KS, Davis AE 3rd, Donaldson VH, Harrison RA: Chymotrypsin inhibitory activity of normal C1-inhibitor and a P1 Arg to His mutant: evidence for the presence of overlapping reactive centers. Protein Sci. 1993 May;2(5):727-32. [Article]
  17. Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T: Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol. 2000 Sep 1;165(5):2637-42. [Article]
  18. Lathem WW, Grys TE, Witowski SE, Torres AG, Kaper JB, Tarr PI, Welch RA: StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Mol Microbiol. 2002 Jul;45(2):277-88. [Article]
  19. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [Article]
  20. Lathem WW, Bergsbaken T, Welch RA: Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7. J Exp Med. 2004 Apr 19;199(8):1077-87. [Article]
  21. Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. Proteomics. 2004 Feb;4(2):454-65. [Article]
  22. Liu D, Cramer CC, Scafidi J, Davis AE 3rd: N-linked glycosylation at Asn3 and the positively charged residues within the amino-terminal domain of the c1 inhibitor are required for interaction of the C1 Inhibitor with Salmonella enterica serovar typhimurium lipopolysaccharide and lipid A. Infect Immun. 2005 Aug;73(8):4478-87. [Article]
  23. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80. [Article]
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  28. Halim A, Ruetschi U, Larson G, Nilsson J: LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins. J Proteome Res. 2013 Feb 1;12(2):573-84. doi: 10.1021/pr300963h. Epub 2013 Jan 11. [Article]
  29. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
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  31. Stein PE, Carrell RW: What do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol. 1995 Feb;2(2):96-113. [Article]
  32. Aulak KS, Pemberton PA, Rosen FS, Carrell RW, Lachmann PJ, Harrison RA: Dysfunctional C1-inhibitor(At), isolated from a type II hereditary-angio-oedema plasma, contains a P1 'reactive centre' (Arg444----His) mutation. Biochem J. 1988 Jul 15;253(2):615-8. [Article]
  33. Aulak KS, Cicardi M, Harrison RA: Identification of a new P1 residue mutation (444Arg----Ser) in a dysfunctional C1 inhibitor protein contained in a type II hereditary angioedema plasma. FEBS Lett. 1990 Jun 18;266(1-2):13-6. [Article]
  34. Levy NJ, Ramesh N, Cicardi M, Harrison RA, Davis AE 3rd: Type II hereditary angioneurotic edema that may result from a single nucleotide change in the codon for alanine-436 in the C1 inhibitor gene. Proc Natl Acad Sci U S A. 1990 Jan;87(1):265-8. [Article]
  35. Parad RB, Kramer J, Strunk RC, Rosen FS, Davis AE 3rd: Dysfunctional C1 inhibitor Ta: deletion of Lys-251 results in acquisition of an N-glycosylation site. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6786-90. [Article]
  36. Frangi D, Aulak KS, Cicardi M, Harrison RA, Davis AE 3rd: A dysfunctional C1 inhibitor protein with a new reactive center mutation (Arg-444-->Leu). FEBS Lett. 1992 Apr 13;301(1):34-6. [Article]
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  38. Davis AE 3rd, Bissler JJ, Cicardi M: Mutations in the C1 inhibitor gene that result in hereditary angioneurotic edema. Behring Inst Mitt. 1993 Dec;(93):313-20. [Article]
  39. Zahedi R, Bissler JJ, Davis AE 3rd, Andreadis C, Wisnieski JJ: Unique C1 inhibitor dysfunction in a kindred without angioedema. II. Identification of an Ala443-->Val substitution and functional analysis of the recombinant mutant protein. J Clin Invest. 1995 Mar;95(3):1299-305. [Article]
  40. Ocejo-Vinyals JG, Leyva-Cobian F, Fernandez-Luna JL: A mutation unique in serine protease inhibitors (serpins) identified in a family with type II hereditary angioneurotic edema. Mol Med. 1995 Sep;1(6):700-5. [Article]
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  43. Kang HR, Yim EY, Oh SY, Chang YS, Kim YK, Cho SH, Min KU, Kim YY: Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations. Allergy. 2006 Feb;61(2):260-4. [Article]
  44. Xu YY, Zhi YX, Yin J, Wang LL, Wen LP, Gu JQ, Guan K, Craig T, Zhang HY: Mutational spectrum and geno-phenotype correlation in Chinese families with hereditary angioedema. Allergy. 2012 Nov;67(11):1430-6. doi: 10.1111/all.12024. Epub 2012 Sep 21. [Article]
  45. Bafunno V, Bova M, Loffredo S, Divella C, Petraroli A, Marone G, Montinaro V, Margaglione M, Triggiani M: Mutational spectrum of the c1 inhibitor gene in a cohort of Italian patients with hereditary angioedema: description of nine novel mutations. Ann Hum Genet. 2014 Mar;78(2):73-82. doi: 10.1111/ahg.12052. Epub 2014 Jan 24. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05961PPL-100investigationalunknownDetails
DB09130Copperapproved, investigationalunknownDetails