Recombinant Human Complement factor I (CFI)

Function

Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins (PubMed:17320177, PubMed:7360115). Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces (PubMed:12055245, PubMed:2141838, PubMed:9605165). The presence of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement activation, while in apoptotic cells or microbes, the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization (PubMed:28671664)

Subcellular Location

Secreted, extracellular space; Secreted

Disease Association

Hemolytic uremic syndrome, atypical, 3 (AHUS3) : An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. [Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype] | Complement factor I deficiency (CFI deficiency) : Autosomal recessive condition associated with a propensity to pyogenic infections. [The disease is caused by variants affecting the gene represented in this entry] | Macular degeneration, age-related, 13 (ARMD13) : A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. [Disease susceptibility is associated with variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in the liver by hepatocytes (PubMed:6327681). Also present in other cells such as monocytes, fibroblasts or keratinocytes (PubMed:17320177, PubMed:6444659)

Subunit

(Microbial infection) Interacts with Staphylococcus aureus clumping factor A/ClfA; this interaction enhances cleavage of C3b into iC3b by CFI

• Catterall C.F. et al. Characterization of primary amino acid sequence of human complement control protein factor I from an analysis of cDNA clones. — Biochem. J. (1987)
• Goldberger G. et al. Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4. — J. Biol. Chem. (1987)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• Minta J.O. et al. Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene. — Gene (1998)
• Whaley K. et al. Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes. — J. Exp. Med. (1980)
• Harrison R.A. et al. The physiological breakdown of the third component of human complement. — Mol. Immunol. (1980)
• Goldberger G. et al. Biosynthesis and postsynthetic processing of human C3b/C4b inactivator (factor I) in three hepatoma cell lines. — J. Biol. Chem. (1984)
• Seya T. et al. Regulation of proteolytic activity of complement factor I by pH: C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) have different pH optima for factor I-mediated cleavage of C3b. — J. Biochem. (1990)