Complement factor I
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Complement Factor I
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| 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.[2]
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[edit] 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 [3] in development of Haemolytic Uremic Syndrome, a renal disease also caused by unregulated complement activation.
[edit] Production
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 disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). Only the mature protein is active.
[edit] 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.[5]
[edit] References
- ^ Nelson R, Jensen J, Gigli I, Tamura N (1966). "Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum". Immunochemistry 3 (2): 111–35. doi:. PMID 5960883.
- ^ Lachmann P, Müller-Eberhard H (1968). "The demonstration in human serum of "conglutinogen-activating factor" and its effect on the third component of complement". J Immunol 100 (4): 691–8. PMID 5645214.
- ^ Saunders R, Abarrategui-Garrido C, Frémeaux-Bacchi V, Goicoechea de Jorge E, Goodship T, López Trascasa M, Noris M, Ponce Castro I, Remuzzi G, Rodríguez de Córdoba S, Sánchez-Corral P, Skerka C, Zipfel P, Perkins S (2007). "The interactive Factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and Factor I mutations with structural models". Hum Mutat 28 (3): 222–34. doi:. PMID 17089378.
- ^ Goldberger G, Bruns G, Rits M, Edge M, Kwiatkowski D (1987). "Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4.". J Biol Chem 262 (21): 10065–71. PMID 2956252.
- ^ Nakamura S, Abe K (1985). "Genetic polymorphism of human factor I (C3b inactivator)". Hum Genet 71 (1): 45–8. doi:. PMID 3897024.
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