Complement C1s

Complement is an integral component of the adaptive and innate immune systems and represents one of the major effector systems for the immune responses. The classical complement pathway is triggered by C1, a complex composed of the binding protein C1q and two proenzymes, C1r and C1s. Upon binding of IgG to the head of C1q, C1r undergoes autoactivation and in turn cleaves and activates C1s. C1r and C1s, the proteases responsible for activation and proteolytic activity of the C1 complex of complement, share similar overall structural organizations featuring five nonenzymic protein modules (two CUB modules surrounding a single EGF module, and a pair of CCP modules) followed by a serine protease domain. Besides highly specific proteolytic activities, both proteases exhibit interaction properties associated with their N-terminal regions. In contrast, C1r and C1s widely differ from each other by their glycosylation patterns: both proteins contain Asn-linked carbohydrates, but four glycosylation sites are present on C1r, and only two on C1s. As a highly specific serine protease, C1s executes the catalytic function of the C1 complex: the cleavage of C4 and C2, and thus instigates a sequence of activation steps of other components of the complement system, culminating in the formation of the membrane attack complex which induces cell lysis. Like other complement serine proteases C1s has restricted substrate specificity and it is engaged into specific interactions with other subcomponents of the complement system. The only other protein known to interact with C1s physiologically is SerpinC1, an inhibitor of serine protease, which inhibits C1s activity and thus plays a regulatory role in controlling the function of C1s enzyme.

Complement C1s Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Complement System>>Complement C1s

Immunology>>Innate Immunity>>Complement System>>Complement C1s

Complement C1s Alternative Names

C1S, FLJ44757

Summaries for Complement C1s

Entrez Gene summary for Complement C1s :

This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency

OMIM - description for Complement C1s :

MacKinnon et al. (1987) derived the complete amino acid sequence of C1s from molecular cloning of cDNA. Tosi et al. (1987) presented the complete cDNA sequence of C1s. Kusumoto et al. (1988) found that the amino acid sequence of C1s was 40.5% identical to that of C1r (216950), with excellent matches of tentative disulfide bond locations conserving the overall domain structure of C1r.

Wikipedia summary for Complement C1s :

Complement component 1S is a protein involved in the complement system. C1s cleaves C4, which eventually leads to the production of the C4b-C2a form of C3-convertase.

Human Complement C1s Protein General Information

 

• Protein names: Recommended name: Complement C1s subcomponent
• Sequence length: 688 AA.
• Domain: EGF-like domain Repeat Signal Sushi
• Sequence similarities: Belongs to the peptidase S1 family. Contains 2 CUB domains. Contains 1 EGF-like domain. Contains 1 peptidase S1 domain. Contains 2 Sushi (CCP/SCR) domains.
• Post-translational modification: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
• Subunit structure: C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.
• Catalytic activity: Cleavage of Arg-|-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase.
• Involvement in disease: Defects in C1S are the cause of complement component C1s deficiency (C1SD) [MIM:613783]. A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.

General information above from UniProt

Function for Complement C1s Protein

UniProtKB:

C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.

Genatlas:

• Complement C1s complement component, s subcomponent, activating C2 and C4 after cleavage
• Complement C1s is theclassical pathway of C3 activation

Homology for human Complement C1s

• ortholog to murine C1s

Phenotype Information for Complement C1s

• Gene/Locus: C1S
• Phenotype: C1s deficiency

Phenotype Information for Complement C1s from OMIM (Online Mendelian Inheritance in Man)

Drugs for Complement C1s

Target	Drug Name	Disease	Drug Status
Complement C1s	Cinryze	Hereditary Angioedema	Approved
Complement C1s	C1-INH	Hereditary Angioedema	Phase III completed
Complement C1s	Romiplostim	Chemotherapy-induced thrombocytopenia and Myelodysplastic syndromes	Phase II
Complement C1s	Recombinant human C1 inhibitor	Painful diabetic neuropathy	MAA filing
Complement C1s	Rhucin	Graft rejection in heart transplantation	Preclinical
Complement C1s	Tanaproget	Heart transplantation	Preclinical

Drugs for Complement C1s from TTD (Therapeutic Targets Database)