Complement factor D

UniProt P00746 Organism Homo sapiens Gene CFD, DF, PFD EC 3.4.21.46

Also known as: CFD, DF, PFD

Function

Serine protease that initiates the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. In contrast to other complement pathways (classical, lectin and GZMK) that are directly activated by pathogens or antigen-antibody complexes, the alternative complement pathway is initiated by the spontaneous hydrolysis of complement C3. The alternative complement pathway acts as an amplification loop that enhances complement activation by mediating the formation of C3 and C5 convertases. Activated CFD cleaves factor B (CFB) when the latter is complexed with complement C3b, activating the C3 convertase of the alternative pathway.

Classification

Family (Pfam): PF00089 Trypsin
InterPro: Peptidase_S1_PA, Peptidase_S1_PA_chymotrypsin, Peptidase_S1A, Trypsin_dom, TRYPSIN_HIS, TRYPSIN_SER
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 40

1BIO X-ray 1.50A
1DFP X-ray 2.40A
1DIC X-ray 1.80A
1DST X-ray 2.00A
1DSU X-ray 2.00A
1FDP X-ray 2.10A
1HFD X-ray 2.30A
2XW9 X-ray 1.20A
2XWA X-ray 2.80A
2XWB X-ray 3.49A
4CBN X-ray 1.80A
4CBO X-ray 1.80A
… and 28 more

A predicted model is available from AlphaFold.

Gene Ontology · 13

Disease associations

recurrent Neisseria infections due to factor D deficiency MONDO:0013487

Drugs targeting this protein · 1

DANICOPAN inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Complement factor B 4 shared papers
Mannan-binding lectin serine protease 1 2 shared papers
Properdin 1 shared papers
Complement C3 1 shared papers

Literature · 22 cited papers

MASP-3 is the exclusive pro-factor D activator in resting blood: the lectin and the alternative complement pathways are fundamentally linked. Sci. Rep. · 2016
Resveratrol-induced changes of the human adipocyte secretion profile. J. Proteome Res. · 2012
Inhibiting alternative pathway complement activation by targeting the factor D exosite. J. Biol. Chem. · 2012
Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science · 2010
Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. J. Exp. Med. · 2010
Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood · 2006
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. EMBO J. · 1999
Structures of native and complexed complement factor D: implications of the atypical His57 conformation and self-inhibitory loop in the regulation of specific serine protease activity. J. Mol. Biol. · 1998
A conserved element in the serine protease domain of complement factor B. J. Biol. Chem. · 1998
Structure of human factor D. A complement system protein at 2.0-A resolution. J. Mol. Biol. · 1994
… and 10 more in the literature graph

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