Factor H-related proteins

Factor H-related proteins comprise a group of five plasma proteins: CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5. Each member of this group binds to the central complement component C3b. CFHR proteins form both homo- and heterodimers .

All FHRP proteins are composed exclusively of SCR domains of different numbers: FHRP1 has 5, FHRP2 has 4, and FHRP 3 and 4 are composed of 5 SCR domains each. The strong conservation of certain SCR domains indicates a possible functional importance. Some FHRPs are glycosylated. Differently glycosylated forms of FHRP1 and -2 occur in serum. Genetic abnormalities within the CFHR gene locus may result in hybrid proteins with impaired dimerization or recognition domains that cause defective functions.

Mutations, genetic deletions, duplications, or rearrangements in the single CFHR genes are associated with a number of diseases (Skerka C et al. 2013), including:

• Atypical hemolytic uremic syndrome (aHUS).
• C3 glomerulopathies (C3 glomerulonephritis (C3GN).
• Dense Deposit Disease (DDD)
• CFHR5 nephropathy
• IgA nephropathy
• Age-related macular degeneration (AMD)
• Systemic lupus erythematosus (SLE).

Although most members of the CFHR protein family have been attributed with complement-regulating functions, the exact role of each CFHR protein in complement activation and the precise contribution to disease pathology is still unclear.

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4. Skerka C et al (2013) Complement factor H related proteins (CFHRs). Mol Immunol 56:170-180.
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