CFD

Protein identityUniProt · HPA

UniProt accession

P00746

Gene

CFD

Ensembl

ENSG00000197766

Chromosome

19

Canonical length

253 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of the S1, or chymotrypsin, family of serine peptidases. This protease catalyzes the cleavage of factor B, the rate-limiting step of the alternative pathway of complement activation. This protein also functions as an adipokine, a cell signaling protein secreted by adipocytes, which regulates insulin secretion in mice. Mutations in this gene underlie complement factor D deficiency, which is associated with recurrent bacterial meningitis infections in human patients. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature protease. [provided by RefSeq, Nov 2015]

Canonical amino-acid sequenceUniProt

253 residues, UniProt reviewed canonical sequence.

>P00746|CFD
     1  MHSWERLAVL VLLGAAACAA PPRGRILGGR EAEAHARPYM ASVQLNGAHL CGGVLVAEQW
    61  VLSAAHCLED AADGKVQVLL GAHSLSQPEP SKRLYDVLRA VPHPDSQPDT IDHDLLLLQL
   121  SEKATLGPAV RPLPWQRVDR DVAPGTLCDV AGWGIVNHAG RRPDSLQHVL LPVLDRATCN
   181  RRTHHDGAIT ERLMCAESNR RDSCKGDSGG PLVCGGVLEG VVTSGSRVCG NRKKPGIYTR
   241  VASYAAWIDS VLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CFD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

1,422 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CFD.

Disease | AllUniProt

Conditions CFD is implicated in, by any mechanism.

• Complement factor D deficiency (CFDD) MIM:613912

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 318 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Recurrent Neisseria infections due to factor D deficiency

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.68

gnomAD pLI

0

gnomAD missense Z

-0.63

DepMap mean gene effect

0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• complement activation
• complement activation, alternative pathway
• protein maturation
• proteolysis
• response to bacterium
• zymogen activation

Molecular functions

• serine-type endopeptidase activity
• serine-type peptidase activity

Cellular components

• extracellular exosome
• extracellular region
• extracellular space
• ficolin-1-rich granule lumen
• platelet alpha granule lumen
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Peptidase S1, PA clan
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Trypsin

KeywordsUniProt

• Complement alternate pathway
• Disulfide bond
• Hydrolase
• Immunity
• Innate immunity
• Protease
• Secreted
• Serine protease
• Signal
• Zymogen