C1 Esterase Inhibitor | SERPING1, inhibitor

C1 Esterase Inhibitor (C1-INH)

Cat. Num. AAA655480

• Gene Names: SERPING1; C1IN; C1NH; HAE1; HAE2; C1INH
• Purity: Highly Purified; 95% by SDS-PAGE
• Synonyms: C1 Esterase Inhibitor; C1 Esterase Inhibitor (C1-INH); SERPING1; inhibitor

• Host: Human plasma
• Purity/Purification: Highly Purified; 95% by SDS-PAGE
• Form/Format: Supplied as a liquid in 20mM potassium phosphate, pH 7.0, 250mM potassium chloride.

• Preparation and Storage: May be stored at 4 degree C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -70 degree C. Aliquots are stable for 6 months at -70 degree C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

Related Product Information for SERPING1, inhibitor

C1-INH is a member of the serpin family of proteases, as are alpha-antitrypsin, antithrombin III, and angiotensinogen. These proteins stoichiometrically inactivate their target proteases by forming stable, one-to-one complexes with the protein to be inhibited. Although synthesized primarily by hepatocytes, C1-INH is also synthesized by monocytes. The regulation of the protein production is not completely understood, but, since patients respond clinically to androgen therapy serum levels of C1-INH increase, it is believed that androgens may stimulate C1-INH synthesis. All C1-INH deficient patients are heterozygous; half the normal level of C1-INH is not believed sufficient to prevent attacks.

Although named for its action on the first component of complement (C1 esterase), C1-INH also inhibits components of the fibrinolytic, clotting, and kinin pathways. Specifically, C1-INH inactivates plasmin-activated Hageman factor (factor XII), activated factor XI, PTA, and kallikrein. Within the complement system, C1-INH blocks the activation of C1 and the rest of the classic complement pathway by binding to C1r and C1s. Without C1-INH, unchecked activation of C1, C2, and C4 occur before other inhibitors (C4-binding protein and factor I) can halt the cascade.
The actual factor or factors responsible for the edema formation remain somewhat controversial. Researchers have demonstrated activation of the kinin system and increased bradykinin concentration associated with clinical flares. Bradykinin is an important inflammatory mediator that causes neutrophil chemotaxis, capillary dilation, and smooth muscle relaxation, and it has been linked to other forms of angioedema. In an animal model of C1-INH deficiency, bradykinin antagonists prevent capillary leakage. Others implicate C2 kinin, a metabolite of C2b, as the active agent in the presence of plasmin.

Product Categories/Family for SERPING1, inhibitor

Molecular Biology; MB-Disease Markers

NCBI and Uniprot Product Information

• NCBI GI #: 20385946
• NCBI GeneID: 710
• UniProt Accession #: P05155; Q16304; Q547W3; Q59EI5; Q7Z455; Q96FE0; Q9UC49; Q9UCF9; A6NMU0; A8KAI9; B2R6L5
• Molecular Weight: 55,154 Da
• NCBI Official Full Name: C1 esterase inhibitor
• NCBI Official Synonym Full Names: serpin peptidase inhibitor, clade G (C1 inhibitor), member 1
• NCBI Official Symbol: SERPING1
• NCBI Official Synonym Symbols: C1IN; C1NH; HAE1; HAE2; C1INH
• NCBI Protein Information: plasma protease C1 inhibitor; serpin G1; C1-inhibiting factor; C1 esterase inhibitor; complement component 1 inhibitor; serine/cysteine proteinase inhibitor clade G member 1
• UniProt Protein Name: Plasma protease C1 inhibitor
• Protein Family: Plasma protease C1 inhibitor
• UniProt Gene Name: SERPING1
• UniProt Synonym Gene Names: C1IN; C1NH; C1 Inh; C1Inh
• UniProt Entry Name: IC1_HUMAN

NCBI Description

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. [provided by RefSeq, Jul 2008]

Uniprot Description

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. Ref.21

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. Ref.22 Ref.23 Ref.25

Subcellular location: Secreted.

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). Ref.2 Ref.24 Ref.27 Ref.31 Ref.32 Ref.33Can be proteolytically cleaved by E.coli stcE. Ref.23 Ref.25

Polymorphism: Chymotrypsin uses Ala-465 as its reactive site in normal plasma protease C1 inhibitor, and His-466 as its reactive site in the variant His-466.

Involvement in disease: Hereditary angioedema (HAE) [MIM:106100]: An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.20 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48

Sequence similarities: Belongs to the serpin family.

Sequence caution: The sequence AAA53096.1 differs from that shown. Reason: Erroneous gene model prediction.