Complement factor I

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Complement Factor I
Identifiers
Symbol	CFI C3b-INA, FI, IF, KAF, factor I
HUGO	5394
Entrez	3426
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.^[2]

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 ^[3] in development of Haemolytic Uremic Syndrome, a renal disease also caused by unregulated complement activation.

The gene for Factor I in humans is located on chromosome 4 ^[4] 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. 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 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.^[5]

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