Complement factor I
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| Complement Factor I
| |
| Identifiers | |
| Symbol | CFI |
| Alt. Symbols | C3b-INA, FI, IF, KAF, factor I |
| Entrez | 3426 |
| HUGO | 5394 |
| OMIM | 217030 |
| RefSeq | NM_000204 |
| UniProt | P05156 |
| Other data | |
| EC number | 3.4.21.45 |
| Locus | Chr. 4 q25 |
Complement Factor I (fI) is a protein of the Complement system, first isolated in 1966 in guinea pig serum[1] that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b.[1]
Contents |
Pathology
Factor I deficiency in turn leads to low levels of complement component 3 (C3) in plasma, due to unregulated activation of the complement alternative pathway, and it has been associated with recurrent bacterial infections in children; more recently, mutations in the Factor I gene have been shown to be implicated [1] in development of Haemolytic Uremic Syndrome, a renal disease also caused by unregulated complement activation.
Production
The gene for Factor I in humans is located on chromosome 4 [1] Factor I is synthesised mostly in the liver, and is initially secreted as a single 88 kDalton gene product; this precursor protein is then cleaved by furin to yield the mature fI protein, which is a disulphide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). Only the mature protein is active.
Structure
Both heavy and light chains bear Asn-linked glycans, on three distinct glycosylation sites each.
The fI heavy chain has four domains: a FIMAC domain, a Scavenger Receptor Cysteine Rich (SRCR) domain and two LDL-receptor Class A domains; the precise biological function of the heavy chain is not known, but it is likely to play a key role in recognising the fI cleavage substrates (C3b and C4b) and the cofactor proteins needed for cleavage of C3b (Factor H, CR1, MCP) and C4b (C4BP). The LDL-receptor domains are likely to contain one Calcium-binding site each.
The fI light chain is the serine protease domain containing the catalytic triad responsible for specific cleavage of C3b and C4b.
Genetic polymorphism in Factor I has been observed.[1]
References
Proteins: complement system (C, L, A) | |
|---|---|
| Activators | CLA: C3-convertase - MAC (C6, C7, C8, C9) - L: Mannan-binding lectin - A: Factor P/Properdin |
| Enzymes | C: C1Q/C1R/C1S - C4 - C2 - CLA: C3 - C5 (C5a) - L: MASP1 - MASP2 - A: Factor B - Factor D |
| Inhibitors | CLA: C1-inhibitor - Decay accelerating factor - Factor I - CL: C4BP - A: Factor H |
| Complement receptors | CR1 - CR2 - CR3 - CR4 - CD11b/CD11c/CD18 - Anaphylatoxin (C3a, C5a) |
