UniProtKB - P00746 (CFAD_HUMAN)
Protein
Complement factor D
Gene
CFD
Organism
Homo sapiens (Human)
Status
Functioni
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.
Catalytic activityi
- Selective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor. EC:3.4.21.46
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 66 | Charge relay system | 1 | |
Active sitei | 114 | Charge relay system | 1 | |
Active sitei | 208 | Charge relay system | 1 |
GO - Molecular functioni
- serine-type endopeptidase activity Source: ProtInc
- serine-type peptidase activity Source: ProtInc
GO - Biological processi
- complement activation Source: ProtInc
- complement activation, alternative pathway Source: Reactome
- neutrophil degranulation Source: Reactome
- Notch signaling pathway Source: InterPro
- platelet degranulation Source: Reactome
- proteolysis Source: ProtInc
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Biological process | Complement alternate pathway, Immunity, Innate immunity |
Enzyme and pathway databases
BRENDAi | 3.4.21.46, 2681 |
PathwayCommonsi | P00746 |
Reactomei | R-HSA-114608, Platelet degranulation R-HSA-173736, Alternative complement activation R-HSA-6798695, Neutrophil degranulation |
Protein family/group databases
MEROPSi | S01.191 |
Names & Taxonomyi
Protein namesi | Recommended name: Complement factor D (EC:3.4.21.46)Alternative name(s): Adipsin C3 convertase activator Properdin factor D |
Gene namesi | Name:CFD Synonyms:DF, PFD |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000197766.7 |
HGNCi | HGNC:2771, CFD |
MIMi | 134350, gene |
neXtProti | NX_P00746 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
Other locations
- ficolin-1-rich granule lumen Source: Reactome
- platelet alpha granule lumen Source: Reactome
- secretory granule lumen Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Complement factor D deficiency (CFDD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034866 | 213 | V → G in CFDD. 1 PublicationCorresponds to variant dbSNP:rs267606720EnsemblClinVar. | 1 | |
Natural variantiVAR_034867 | 214 | C → R in CFDD. 1 PublicationCorresponds to variant dbSNP:rs267606721EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 1675 |
MalaCardsi | CFD |
MIMi | 613912, phenotype |
OpenTargetsi | ENSG00000197766 |
Orphaneti | 169467, Recurrent Neisseria infections due to factor D deficiency |
PharmGKBi | PA142 |
Miscellaneous databases
Pharosi | P00746, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2176771 |
DrugBanki | DB03058, 2-Aminobenzyl alcohol DB04459, 3,4-Dichloroisocoumarin |
GuidetoPHARMACOLOGYi | 2842 |
Polymorphism and mutation databases
BioMutai | CFD |
DMDMi | 158515408 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
PropeptideiPRO_0000027560 | 21 – 25 | Activation peptideSequence analysis | 5 | |
ChainiPRO_0000027561 | 26 – 253 | Complement factor DAdd BLAST | 228 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 51 ↔ 67 | |||
Disulfide bondi | 148 ↔ 214 | |||
Disulfide bondi | 179 ↔ 195 | |||
Disulfide bondi | 204 ↔ 229 |
Keywords - PTMi
Disulfide bond, ZymogenProteomic databases
jPOSTi | P00746 |
MassIVEi | P00746 |
PaxDbi | P00746 |
PeptideAtlasi | P00746 |
PRIDEi | P00746 |
ProteomicsDBi | 51276 |
PTM databases
iPTMneti | P00746 |
PhosphoSitePlusi | P00746 |
Expressioni
Gene expression databases
Bgeei | ENSG00000197766, Expressed in adipose tissue of abdominal region and 211 other tissues |
ExpressionAtlasi | P00746, baseline and differential |
Genevisiblei | P00746, HS |
Organism-specific databases
HPAi | ENSG00000197766, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 108039, 2 interactors |
IntActi | P00746, 3 interactors |
STRINGi | 9606.ENSP00000332139 |
Chemistry databases
BindingDBi | P00746 |
Miscellaneous databases
RNActi | P00746, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P00746 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P00746 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 253 | Peptidase S1PROSITE-ProRule annotationAdd BLAST | 228 |
Sequence similaritiesi
Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000162255 |
HOGENOMi | CLU_006842_1_0_1 |
InParanoidi | P00746 |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P00746 |
TreeFami | TF333630 |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR037561, Complement_factor_D IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24271:SF54, PTHR24271:SF54, 1 hit |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P00746-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MHSWERLAVL VLLGAAACAA PPRGRILGGR EAEAHARPYM ASVQLNGAHL
60 70 80 90 100
CGGVLVAEQW VLSAAHCLED AADGKVQVLL GAHSLSQPEP SKRLYDVLRA
110 120 130 140 150
VPHPDSQPDT IDHDLLLLQL SEKATLGPAV RPLPWQRVDR DVAPGTLCDV
160 170 180 190 200
AGWGIVNHAG RRPDSLQHVL LPVLDRATCN RRTHHDGAIT ERLMCAESNR
210 220 230 240 250
RDSCKGDSGG PLVCGGVLEG VVTSGSRVCG NRKKPGIYTR VASYAAWIDS
VLA
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketK7ERG9 | K7ERG9_HUMAN | Adipsin | CFD | 260 | Annotation score: |
Sequence cautioni
The sequence AAA35527 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 21 | P → R in AAA35527 (PubMed:1374388).Curated | 1 | |
Sequence conflicti | 26 | I → M in AAA35527 (PubMed:1374388).Curated | 1 | |
Sequence conflicti | 35 | H → F AA sequence (PubMed:6987665).Curated | 1 | |
Sequence conflicti | 40 | M → V AA sequence (PubMed:6987665).Curated | 1 | |
Sequence conflicti | 49 | H → E AA sequence (PubMed:6363133).Curated | 1 | |
Sequence conflicti | 49 | H → E AA sequence (PubMed:6821372).Curated | 1 | |
Sequence conflicti | 52 | G → A in AAA35527 (PubMed:1374388).Curated | 1 | |
Sequence conflicti | 59 | Q → R in AAA35527 (PubMed:1374388).Curated | 1 | |
Sequence conflicti | 63 | S → T AA sequence (PubMed:6363133).Curated | 1 | |
Sequence conflicti | 73 | D → G AA sequence (PubMed:6363133).Curated | 1 | |
Sequence conflicti | 83 – 86 | HSLS → THLP AA sequence (PubMed:6383466).Curated | 4 | |
Sequence conflicti | 83 – 84 | HS → ST AA sequence (PubMed:6363133).Curated | 2 | |
Sequence conflicti | 94 – 95 | Missing AA sequence (PubMed:6363133).Curated | 2 | |
Sequence conflicti | 96 | D → E AA sequence (PubMed:6363133).Curated | 1 | |
Sequence conflicti | 136 | Q → G AA sequence (PubMed:6363133).Curated | 1 | |
Sequence conflicti | 178 – 191 | TCNRR…GAITE → KCRLYDVL AA sequence (PubMed:6363133).CuratedAdd BLAST | 14 | |
Sequence conflicti | 243 | S → T AA sequence (PubMed:6383466).Curated | 1 | |
Sequence conflicti | 250 | S → H AA sequence (PubMed:6383466).Curated | 1 | |
Sequence conflicti | 250 | Missing AA sequence (PubMed:6363133).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034866 | 213 | V → G in CFDD. 1 PublicationCorresponds to variant dbSNP:rs267606720EnsemblClinVar. | 1 | |
Natural variantiVAR_034867 | 214 | C → R in CFDD. 1 PublicationCorresponds to variant dbSNP:rs267606721EnsemblClinVar. | 1 | |
Natural variantiVAR_034868 | 248 | I → M. Corresponds to variant dbSNP:rs2230216Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ313463 mRNA Translation: CAC48304.1 AK300963 mRNA Translation: BAG62588.1 CH471139 Genomic DNA Translation: EAW69588.1 BC034529 mRNA Translation: AAH34529.1 BC040146 mRNA Translation: AAH40146.1 BC051001 mRNA Translation: AAH51001.1 BC057807 mRNA Translation: AAH57807.1 M84526 mRNA Translation: AAA35527.1 Different initiation. |
CCDSi | CCDS12046.1 |
PIRi | A40197, DBHU |
RefSeqi | NP_001304264.1, NM_001317335.1 NP_001919.2, NM_001928.3 |
Genome annotation databases
Ensembli | ENST00000327726; ENSP00000332139; ENSG00000197766 ENST00000617994; ENSP00000478745; ENSG00000274619 |
GeneIDi | 1675 |
KEGGi | hsa:1675 |
UCSCi | uc002lqc.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
CFDbase CFD mutation db |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ313463 mRNA Translation: CAC48304.1 AK300963 mRNA Translation: BAG62588.1 CH471139 Genomic DNA Translation: EAW69588.1 BC034529 mRNA Translation: AAH34529.1 BC040146 mRNA Translation: AAH40146.1 BC051001 mRNA Translation: AAH51001.1 BC057807 mRNA Translation: AAH57807.1 M84526 mRNA Translation: AAA35527.1 Different initiation. |
CCDSi | CCDS12046.1 |
PIRi | A40197, DBHU |
RefSeqi | NP_001304264.1, NM_001317335.1 NP_001919.2, NM_001928.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BIO | X-ray | 1.50 | A | 26-253 | [»] | |
1DFP | X-ray | 2.40 | A/B | 26-253 | [»] | |
1DIC | X-ray | 1.80 | A | 26-253 | [»] | |
1DST | X-ray | 2.00 | A | 26-253 | [»] | |
1DSU | X-ray | 2.00 | A/B | 26-253 | [»] | |
1FDP | X-ray | 2.10 | A/B/C/D | 19-253 | [»] | |
1HFD | X-ray | 2.30 | A | 26-253 | [»] | |
2XW9 | X-ray | 1.20 | A | 26-253 | [»] | |
2XWA | X-ray | 2.80 | A/B | 26-253 | [»] | |
2XWB | X-ray | 3.49 | I/J | 26-253 | [»] | |
4CBN | X-ray | 1.80 | A/B | 26-253 | [»] | |
4CBO | X-ray | 1.80 | A/B | 26-253 | [»] | |
4D9R | X-ray | 2.42 | A/B | 26-253 | [»] | |
5FBE | X-ray | 1.43 | A | 26-253 | [»] | |
5FBI | X-ray | 1.47 | A | 26-253 | [»] | |
5FCK | X-ray | 1.86 | A | 26-253 | [»] | |
5MT0 | X-ray | 1.29 | A | 26-253 | [»] | |
5MT4 | X-ray | 1.65 | A | 26-253 | [»] | |
5NAR | X-ray | 1.55 | A | 26-253 | [»] | |
5NAT | X-ray | 1.17 | A | 26-253 | [»] | |
5NAW | X-ray | 1.25 | A | 26-253 | [»] | |
5NB6 | X-ray | 1.75 | A | 26-253 | [»] | |
5NB7 | X-ray | 1.33 | A | 26-253 | [»] | |
5NBA | X-ray | 1.87 | A | 26-253 | [»] | |
5TCA | X-ray | 3.15 | A/B/C/D/E/F/G | 26-253 | [»] | |
5TCC | X-ray | 3.37 | A/B/C/D/E/F/G | 26-253 | [»] | |
6FTY | X-ray | 1.67 | A | 26-253 | [»] | |
6FTZ | X-ray | 1.67 | A | 26-253 | [»] | |
6FUG | X-ray | 2.21 | A/B/C/D/E/F | 26-253 | [»] | |
6FUH | X-ray | 1.37 | A | 26-253 | [»] | |
6FUI | X-ray | 1.38 | A | 26-253 | [»] | |
6FUJ | X-ray | 2.25 | A/B/C/D/E/F | 26-253 | [»] | |
6FUT | X-ray | 1.50 | A | 26-253 | [»] | |
6QMR | X-ray | 2.00 | A/B/C/D/E/F | 2-253 | [»] | |
6QMT | X-ray | 1.80 | A/B | 2-253 | [»] | |
SMRi | P00746 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108039, 2 interactors |
IntActi | P00746, 3 interactors |
STRINGi | 9606.ENSP00000332139 |
Chemistry databases
BindingDBi | P00746 |
ChEMBLi | CHEMBL2176771 |
DrugBanki | DB03058, 2-Aminobenzyl alcohol DB04459, 3,4-Dichloroisocoumarin |
GuidetoPHARMACOLOGYi | 2842 |
Protein family/group databases
MEROPSi | S01.191 |
PTM databases
iPTMneti | P00746 |
PhosphoSitePlusi | P00746 |
Polymorphism and mutation databases
BioMutai | CFD |
DMDMi | 158515408 |
Proteomic databases
jPOSTi | P00746 |
MassIVEi | P00746 |
PaxDbi | P00746 |
PeptideAtlasi | P00746 |
PRIDEi | P00746 |
ProteomicsDBi | 51276 |
Protocols and materials databases
ABCDi | P00746, 1 sequenced antibody |
Antibodypediai | 4290, 464 antibodies |
Genome annotation databases
Ensembli | ENST00000327726; ENSP00000332139; ENSG00000197766 ENST00000617994; ENSP00000478745; ENSG00000274619 |
GeneIDi | 1675 |
KEGGi | hsa:1675 |
UCSCi | uc002lqc.4, human |
Organism-specific databases
CTDi | 1675 |
DisGeNETi | 1675 |
EuPathDBi | HostDB:ENSG00000197766.7 |
GeneCardsi | CFD |
HGNCi | HGNC:2771, CFD |
HPAi | ENSG00000197766, Low tissue specificity |
MalaCardsi | CFD |
MIMi | 134350, gene 613912, phenotype |
neXtProti | NX_P00746 |
OpenTargetsi | ENSG00000197766 |
Orphaneti | 169467, Recurrent Neisseria infections due to factor D deficiency |
PharmGKBi | PA142 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3627, Eukaryota |
GeneTreei | ENSGT00940000162255 |
HOGENOMi | CLU_006842_1_0_1 |
InParanoidi | P00746 |
OrthoDBi | 1314811at2759 |
PhylomeDBi | P00746 |
TreeFami | TF333630 |
Enzyme and pathway databases
BRENDAi | 3.4.21.46, 2681 |
PathwayCommonsi | P00746 |
Reactomei | R-HSA-114608, Platelet degranulation R-HSA-173736, Alternative complement activation R-HSA-6798695, Neutrophil degranulation |
Miscellaneous databases
BioGRID-ORCSi | 1675, 255 hits in 840 CRISPR screens |
ChiTaRSi | CFD, human |
EvolutionaryTracei | P00746 |
GenomeRNAii | 1675 |
Pharosi | P00746, Tchem |
PROi | PR:P00746 |
RNActi | P00746, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000197766, Expressed in adipose tissue of abdominal region and 211 other tissues |
ExpressionAtlasi | P00746, baseline and differential |
Genevisiblei | P00746, HS |
Family and domain databases
CDDi | cd00190, Tryp_SPc, 1 hit |
Gene3Di | 2.40.10.10, 2 hits |
InterProi | View protein in InterPro IPR037561, Complement_factor_D IPR009003, Peptidase_S1_PA IPR043504, Peptidase_S1_PA_chymotrypsin IPR001314, Peptidase_S1A IPR001254, Trypsin_dom IPR018114, TRYPSIN_HIS IPR033116, TRYPSIN_SER |
PANTHERi | PTHR24271:SF54, PTHR24271:SF54, 1 hit |
Pfami | View protein in Pfam PF00089, Trypsin, 1 hit |
PRINTSi | PR00722, CHYMOTRYPSIN |
SMARTi | View protein in SMART SM00020, Tryp_SPc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit |
PROSITEi | View protein in PROSITE PS50240, TRYPSIN_DOM, 1 hit PS00134, TRYPSIN_HIS, 1 hit PS00135, TRYPSIN_SER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CFAD_HUMAN | |
Accessioni | P00746Primary (citable) accession number: P00746 Secondary accession number(s): B4DV76 Q8WZB4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | September 11, 2007 | |
Last modified: | December 2, 2020 | |
This is version 211 of the entry and version 5 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries