C1 inhibitor （SerpinG1）

Plasma protease C1 inhibitor, also known as C1-inhibiting factor, C1-INH, C1 esterase inhibitor, SERPING1 and C1IN, is a serine proteinase inhibitor (serpin) that regulates activation of both the complement and contact systems. By its C-terminal part (serpin domain), characterized by three beta-sheets and an exposed mobile reactive loop, C1-INH binds, and blocks the activity of its target proteases. The N-terminal end (nonserpin domain) confers to C1-INH the capacity to bind lipopolysaccharides and E-selectin. Owing to this moiety, C1-INH intervenes in regulation of the inflammatory reaction. The heterozygous deficiency of C1-INH results in hereditary angioedema (HAE). Owing to its ability to modulate the contact and complement systems and the convincing safety profile, plasma-derived C1 inhibitor is an attractive therapeutic protein to treat inflammatory diseases other than HAE. Deficiency of C1 inhibitor results in hereditary angioedema, which is characterized by recurrent episodes of localized angioedema of the skin, gastrointestinal mucosa or upper respiratory mucosa. C1 inhibitor may prove useful in a variety of other diseases including septic shock, reperfusion injury, hyperacute transplant rejection, traumatic and hemorrhagic shock, and the increased vascular permeability associated with thermal injury, interleukin-2 therapy and cardiopulmonary bypass.

C1 inhibitor(SerpinG1) Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Serpin Superfamily>>C1 inhibitor/SerpinG1

Immunology>>Innate Immunity>>Complement System>>C1 inhibitor/SerpinG1

C1 inhibitor(SerpinG1) Alternative Names

C1 inhibitor, SERPING1, C1INH, C1NH, C1IN, HAE1, HAE2 [Homo sapiens]

C1 inhibitor, Serping1, C1INH, C1nh, RP23-399J8.3 [Mus musculus]

Summaries for C1 inhibitor(SerpinG1)

Entrez Gene summary for C1 inhibitor(SerpinG1):

This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. Its protein inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. Deficiency of this protein is associated with hereditary angioneurotic oedema (HANE). Alternative splicing results in multiple transcript variants encoding the same isoform

OMIM - description for C1 inhibitor(SerpinG1):

C1 inhibitor is a plasma protein involved in the regulation of the complement cascade. It is a member of a large serine protease inhibitor (serpin) gene family.

Wikipedia summary for C1 inhibitor(SerpinG1):

C1-inhibitor (C1-inh, C1 esterase inhibitor) is a protease inhibitor belonging to the serpin superfamily. Its main function is the inhibition of the complement system to prevent spontaneous activation. C1-inhibitor is an acute-phase protein that circulates in blood at levels of around 0.25 g/L. The levels rise ~2-fold during inflammation. C1-inhibitor irreversibly binds to and inactivates C1r and C1s proteases in the C1 complex of classical pathway of complement. MASP-1 and MASP-2 proteases in MBL complexes of the lectin pathway are also inactivated. This way, C1-inhibitor prevents the proteolytic cleavage of later complement components C4 and C2 by C1 and MBL. Although named after its complement inhibitory activity, C1-inhibitor also inhibits proteases of the fibrinolytic, clotting, and kinin pathways. Note that C1-inhibitor is the most important physiological inhibitor of plasma kallikrein, fXIa, and fXIIa.

Human C1 inhibitor(SerpinG1) Protein General Information

 

• Protein names: Recommended name: Plasma protease C1 inhibitor Short name=C1 Inh Short name=C1Inh
• Sequence length: 500 AA.
• Domain: Repeat Signal
• Sequence similarities: Belongs to the serpin family.
• Post-translational modification: Highly glycosylated (49%) with N- and O-glycosylation. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan heterogeneity at Asn-25: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor).
• Subunit structure: Binds to E.coli stcE which allows localization of SERPING1 to cell membranes thus protecting the bacteria against complement-mediated lysis. Interacts with MASP1.
• Subcellular location: Secreted.
• Involvement in disease: Defects in SERPING1 are the cause of hereditary angioedema (HAE) [MIM:106100]; also called hereditary angioneurotic edema (HANE). HAE is an autosomal dominant disorder characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In HAE type 1, representing 85% of patients, serum levels of C1 esterase inhibitor are less than 35% of normal. In HAE type 2, the levels are normal or elevated, but the protein is non-functional.

General information above from UniProt

Function for C1 inhibitor(SerpinG1) Protein

UniProtKB:

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.

Genatlas:

Homology for human C1 inhibitor(SerpinG1)

• ortholog to chimpanzee LOC461302

Phenotype Information for C1 inhibitor(SerpinG1)

• Gene/Locus: C1NH, HAE1, HAE2, SERPING1
• Phenotype: Angioedema, hereditary, types I and II

Phenotype Information for C1 inhibitor(SerpinG1) from OMIM (Online Mendelian Inheritance in Man)