Complement factor B

The CFB gene encodes a stimulating factor to the alternative complement pathway. Gain-of-function mutations have been described in atypical HUS and age-related macula degeneration.

Protein Structure

The N-terminal fragment, Ba, is released during activation. It is composed of three complement control protein (CCP) domains. The active fragment Bb attains a dumbbell shape, and consists of two domains, one on each side. The N-terminal is a von Willebrand factor type A (vWFA) domain, and the C-terminal domain is a serine protease (SP). The vWFA domain (202 residues) shows structural similarities to the I domain of integrins. This domain contains a motif called Mg ion-dependent adhesion site (MIDAS), which is supposed to take part in C3b binding and SP activation. The Asn residue at codon position 260 is glycosylated. The SP domain consists of 283 residues. The proteolytic site is opposite the MIDAS motif.[Error: Macro 'ref' doesn't exist]

Expression

Before activation, factor B circulates in the blood as a single polypeptide chain.

Gene Regulation

Nativ Factor B is cleaved and activated by Factor D when bound to C3b. Ba is released, and the remaining complex C3bBb is a proficient C3-convertase that accelerates C3 activation by a positive feedback loop. The complex C3bBb is inherently unstable and easily dissociates. This inactivation is promoted by MCP, CFH, and CFI.

Genetests:

Related Diseases:

Hemolytic-Uremic Syndrome
	ADAMTS13
	C3
	C4BPA
	C4BPB
	CD46
	CFB
	CFH
	CFHR1
	CFHR2
	CFHR3
	CFHR4
	CFHR5
	CFI
	CLU
	DGKE
	Methylmalonic aciduria
		Methylmalonic aciduria and homocystinuria cblC
			MMACHC
		Methylmalonic aciduria and homocystinuria cblD
			MMADHC
		Methylmalonic aciduria type mut
			MUT
	PIGA
	PLG
	THBD

Meningococcal infection susceptibility
	C3
	C5
	C7
	C8A
	C8B
	C8G
	C9
	CD46
	CFB
	CFD
	CFH
	CFP

References:

1.	Nürnberger J et al. (2009) Eculizumab for atypical hemolytic-uremic syndrome.

2.	Zheng XL et al. (2008) Pathogenesis of thrombotic microangiopathies.

3.	Maller J et al. (2006) Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration.

4.	Ponnuraj K et al. (2004) Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.

5.	Kavanagh D et al. (2006) Does complement factor B have a role in the pathogenesis of atypical HUS?

6.	Gold B et al. (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.

7.	Goicoechea de Jorge E et al. (2007) Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.

8.	Wyatt RJ et al. (1981) Properdin deficiency with IgA nephropathy.

9.	Orphanet article Orphanet ID 158379

10.	NCBI article NCBI 629

11.	OMIM.ORG article Omim 138470

12.	Wikipedia article Wikipedia EN (Complement_factor_B)