Complement factor D (CFD)
The protein contains 253 amino acids for an estimated molecular weight of 27033 Da.
Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway. (updated: Sept. 11, 2007)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| CFDD | |
| CFDD | |
| dbSNP:rs2230216 |
No binding partner found
Biological Process
Complement activation
Complement activation, alternative pathway
Neutrophil degranulation
Notch signaling pathway
Platelet degranulation
Proteolysis
The reference OMIM entry for this protein is 134350
Complement factor d; cfd
Factor d; df
Adipsin; adn
DESCRIPTION
The CFD gene encodes complement factor D, a serine protease that acts in the alternative complement pathway to complete the formation of the C3 convertase enzyme by cleaving factor B (CFB; 138470) bound to C3b (120700), yielding C3bBb. Factor D is the initial obligatory and rate-limiting catalytic component in the alternative complement pathway (summary by White et al., 1992 and Biesma et al., 2001).CLONING
White et al. (1992) isolated clones corresponding to the human CFD gene from a human glioma cDNA library. The deduced mature protein contains 228 amino acids and was determined to be the same as the adipsin protein identified in mice (Rosen et al., 1989). Northern blot analysis detected a 1.1-kb mRNA transcript in adipocytes, monocytes, and macrophages. The recombinant protein showed enzymatic activity of complement factor D, cleaving factor B only when B was complexed with activated component C3b. The findings suggested that adipose tissue may have a role in immune system biology.MAPPING
Gross (2014) mapped the CFD gene to chromosome 19p13.3 based on an alignment of the CFD sequence (GenBank GENBANK BC057807) with the genomic sequence (GRCh37).GENE FUNCTION
White et al. (1992) found that adipose cells are the main source of factor D. There is a gradient in the concentration of factor D in the fat cells of the body; more is present in the upper than in the lower half of the body (Mathieson and Peters, 1997). In a review of the complement system, Walport (2001) noted that the C3 nephritic autoantibody can be associated with acquired partial lipodystrophy (613913). The C3 nephritic autoantibody stabilizes the C3bBb C3 convertase that forms in the immediate vicinity of adipocytes. The abnormally stabilized enzyme may then cleave enough C3 to allow assembly of the membrane-attack complex, which lyses adipocytes. The pattern of fat loss, which involves the upper half of the body, may reflect the content of factor D.BIOCHEMICAL FEATURES
- Crystal Structure Forneris et al. (2010) presented crystal structures of the proconvertase C3bB at 4-angstrom resolution and its complex with factor D at 3.5-angstrom resolution. Their data showed how factor B (138470) binding to C3b forms an open 'activation' state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which if cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.MOLECULAR GENETICS
Factor D is unusual among serum proteins in having a single-banded pattern in isoelectric focusing. Hobart and Lachmann (1976) found a variant in 3 persons of West African parentage (2 Nigerians and a West Indian) among 120 tested. No variants were found among 115 British and 26 Asian Indians. The presence of the variant band was associated with weakening of the normal band. Both bands were of equal strength (Martin et al., 1976). - Complement Factor D Deficiency In a Dutch family with factor D deficiency (CFDD; 613912), Biesma et al. (2001) identified a homozygous mutation in the CFD gene (134350.0001). The proband was a 23-year-old woman who presented with septic shock due to Neisseria meningitidis in blood and cerebrospinal fluid. A deceased family member had a history of recurrent bacterial ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 134350 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).