Factor H
From Wikipedia, the free encyclopedia
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complement factor H
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| Identifiers | |
| Symbol | CFH HF, HF1, HF2 |
| HUGO | 4883 |
| Entrez | 3075 |
| OMIM | 134370 |
| RefSeq | NM_000186 |
| UniProt | P08603 |
| PDB | 2JGW 2JGX 1HFI 1HFH 1HCC 2G7I 2BZM |
| Other data | |
| Locus | Chr. 1 q32 |
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodalton), soluble glycoprotein that circulates in human plasma (at a concentration of 500-800 micrograms per mL). Its main job is to regulate the Alternative Pathway of the complement system, ensuring that the complement system is directed towards pathogens and does not damage host tissue. Factor H regulates complement activation on self cells by possessing both cofactor activity for Factor I mediated C3b cleavage, and decay accelerating activity against the alternative pathway C3 convertase, C3bBb. Factor H protects self cells from complement activation but not bacteria/viruses, in that it binds to glycosaminoglycans (GAGs) that are present on host cells but not pathogen cell surfaces.
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[edit] Structure of Factor H
The molecule is made up of 20 Complement Control Protein (CCP) modules (also refered to as Short Consensus Repeats or sushi domains) arranged head to tail. Each of the CCP modules consists of around 60 amino acids with four cysteine residues disulphide bonded in a 1-3 2-4 arrangement, and a hydrophobic core built around an almost invariant tryptophan residue. To date atomic structures have been determined for CCP 5, CCP 7 (both 402H & 402Y), CCP 15, CCP 16, CCPs 15-16, and CCPs 19-20. Although an atomic resolution structure for intact factor H has not yet been determined lower resolutions techniques indicate that it is bent back in solution.
[edit] Association with age-related macular degeneration
Recently is was discovered that about 35% of individuals carry at an at-risk single nucleotide polymorphism (SNP) in one or both copies of their factor H gene. Homozygous individuals have an approximately seven-fold increased chance of developing age-related macular degeneration, while heterozygotes have a two-to-three-fold increased likelihood of developing the disease. This SNP is located in CCP module 7, a region of factor H which is known to bind to both C-reactive protein and polyanions including heparin and heparan sulphate.
[edit] Sources
- Pangburn, M.K. Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement. Immunopharmacology 49, 149-57 (2000).
- Kirkitadze, M.D. & Barlow, P.N. Structure and flexibility of the multiple domain proteins that regulate complement activation. Immunol Rev 180, 146-61 (2001).
- Hageman, G.S. et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A 102, 7227-32. (2005).
- Kardys, I. et al. A common polymorphism in the complement factor h gene is associated with increased risk of myocardial infarction the rotterdam study. J Am Coll Cardiol. 47, 1568-75. (2006).
