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Protein

Complement factor D

Gene

CFD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei66Charge relay system1
Active sitei114Charge relay system1
Active sitei208Charge relay system1

GO - Molecular functioni

  • serine-type endopeptidase activity Source: Reactome
  • serine-type peptidase activity Source: ProtInc

GO - Biological processi

  • complement activation Source: ProtInc
  • complement activation, alternative pathway Source: Reactome
  • platelet degranulation Source: Reactome
  • proteolysis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Complement alternate pathway, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:HS11198-MONOMER.
BRENDAi3.4.21.46. 2681.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-173736. Alternative complement activation.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiS01.191.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:2771. CFD.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & 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.
See also OMIM:613912
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034866213V → G in CFDD. 1 PublicationCorresponds to variant rs267606720dbSNPEnsembl.1
Natural variantiVAR_034867214C → R in CFDD. 1 PublicationCorresponds to variant rs267606721dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1675.
MalaCardsiCFD.
MIMi613912. phenotype.
OpenTargetsiENSG00000197766.
ENSG00000274619.
Orphaneti169467. Recurrent Neisseria infections due to factor D deficiency.
PharmGKBiPA142.

Chemistry databases

ChEMBLiCHEMBL2176771.
GuidetoPHARMACOLOGYi2842.

Polymorphism and mutation databases

BioMutaiCFD.
DMDMi158515408.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002756021 – 25Activation peptideSequence analysis5
ChainiPRO_000002756126 – 253Complement factor DAdd BLAST228

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi51 ↔ 67
Disulfide bondi148 ↔ 214
Disulfide bondi179 ↔ 195
Disulfide bondi204 ↔ 229

Keywords - PTMi

Disulfide bond, Zymogen

Proteomic databases

PaxDbiP00746.
PeptideAtlasiP00746.
PRIDEiP00746.

PTM databases

iPTMnetiP00746.
PhosphoSitePlusiP00746.

Expressioni

Gene expression databases

BgeeiENSG00000197766.
CleanExiHS_CFD.
ExpressionAtlasiP00746. baseline and differential.
GenevisibleiP00746. HS.

Organism-specific databases

HPAiCAB016383.
HPA052799.

Interactioni

Protein-protein interaction databases

BioGridi108039. 2 interactors.
IntActiP00746. 3 interactors.
STRINGi9606.ENSP00000332139.

Chemistry databases

BindingDBiP00746.

Structurei

Secondary structure

1253
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi30 – 32Combined sources3
Beta strandi40 – 45Combined sources6
Beta strandi48 – 57Combined sources10
Beta strandi60 – 63Combined sources4
Helixi65 – 68Combined sources4
Beta strandi72 – 74Combined sources3
Beta strandi76 – 81Combined sources6
Beta strandi83 – 87Combined sources5
Beta strandi93 – 102Combined sources10
Helixi108 – 113Combined sources6
Beta strandi116 – 122Combined sources7
Beta strandi127 – 129Combined sources3
Beta strandi147 – 154Combined sources8
Turni156 – 159Combined sources4
Beta strandi167 – 174Combined sources8
Helixi176 – 179Combined sources4
Turni182 – 187Combined sources6
Beta strandi193 – 196Combined sources4
Beta strandi200 – 202Combined sources3
Turni205 – 209Combined sources5
Beta strandi211 – 214Combined sources4
Beta strandi217 – 222Combined sources6
Beta strandi226 – 228Combined sources3
Beta strandi231 – 233Combined sources3
Beta strandi236 – 240Combined sources5
Helixi241 – 244Combined sources4
Helixi245 – 252Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BIOX-ray1.50A26-253[»]
1DFPX-ray2.40A/B26-253[»]
1DICX-ray1.80A26-253[»]
1DSTX-ray2.00A26-253[»]
1DSUX-ray2.00A/B26-253[»]
1FDPX-ray2.10A/B/C/D19-253[»]
1HFDX-ray2.30A26-253[»]
2XW9X-ray1.20A26-253[»]
2XWAX-ray2.80A/B26-253[»]
2XWBX-ray3.49I/J26-253[»]
4CBNX-ray1.80A/B26-253[»]
4CBOX-ray1.80A/B26-253[»]
4D9RX-ray2.42A/B26-253[»]
5TCAX-ray3.15A/B/C/D/E/F/G26-253[»]
5TCCX-ray3.37A/B/C/D/E/F/G26-253[»]
ProteinModelPortaliP00746.
SMRiP00746.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00746.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 253Peptidase S1PROSITE-ProRule annotationAdd BLAST228

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118895.
HOVERGENiHBG013304.
InParanoidiP00746.
KOiK01334.
OMAiGAITQRM.
OrthoDBiEOG091G0DF7.
PhylomeDBiP00746.
TreeFamiTF333630.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00746-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:253
Mass (Da):27,033
Last modified:September 11, 2007 - v5
Checksum:i78B06C209DEEA362
GO

Sequence cautioni

The sequence AAA35527 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21P → R in AAA35527 (PubMed:1374388).Curated1
Sequence conflicti26I → M in AAA35527 (PubMed:1374388).Curated1
Sequence conflicti35H → F AA sequence (PubMed:6987665).Curated1
Sequence conflicti40M → V AA sequence (PubMed:6987665).Curated1
Sequence conflicti49H → E AA sequence (PubMed:6363133).Curated1
Sequence conflicti49H → E AA sequence (PubMed:6821372).Curated1
Sequence conflicti52G → A in AAA35527 (PubMed:1374388).Curated1
Sequence conflicti59Q → R in AAA35527 (PubMed:1374388).Curated1
Sequence conflicti63S → T AA sequence (PubMed:6363133).Curated1
Sequence conflicti73D → G AA sequence (PubMed:6363133).Curated1
Sequence conflicti83 – 86HSLS → THLP AA sequence (PubMed:6383466).Curated4
Sequence conflicti83 – 84HS → ST AA sequence (PubMed:6363133).Curated2
Sequence conflicti94 – 95Missing AA sequence (PubMed:6363133).Curated2
Sequence conflicti96D → E AA sequence (PubMed:6363133).Curated1
Sequence conflicti136Q → G AA sequence (PubMed:6363133).Curated1
Sequence conflicti178 – 191TCNRR…GAITE → KCRLYDVL AA sequence (PubMed:6363133).CuratedAdd BLAST14
Sequence conflicti243S → T AA sequence (PubMed:6383466).Curated1
Sequence conflicti250S → H AA sequence (PubMed:6383466).Curated1
Sequence conflicti250Missing AA sequence (PubMed:6363133).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034866213V → G in CFDD. 1 PublicationCorresponds to variant rs267606720dbSNPEnsembl.1
Natural variantiVAR_034867214C → R in CFDD. 1 PublicationCorresponds to variant rs267606721dbSNPEnsembl.1
Natural variantiVAR_034868248I → M.Corresponds to variant rs2230216dbSNPEnsembl.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.
CCDSiCCDS12046.1.
PIRiA40197. DBHU.
RefSeqiNP_001304264.1. NM_001317335.1.
NP_001919.2. NM_001928.3.
UniGeneiHs.155597.

Genome annotation databases

EnsembliENST00000327726; ENSP00000332139; ENSG00000197766.
ENST00000617994; ENSP00000478745; ENSG00000274619.
GeneIDi1675.
KEGGihsa:1675.
UCSCiuc002lqc.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS12046.1.
PIRiA40197. DBHU.
RefSeqiNP_001304264.1. NM_001317335.1.
NP_001919.2. NM_001928.3.
UniGeneiHs.155597.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BIOX-ray1.50A26-253[»]
1DFPX-ray2.40A/B26-253[»]
1DICX-ray1.80A26-253[»]
1DSTX-ray2.00A26-253[»]
1DSUX-ray2.00A/B26-253[»]
1FDPX-ray2.10A/B/C/D19-253[»]
1HFDX-ray2.30A26-253[»]
2XW9X-ray1.20A26-253[»]
2XWAX-ray2.80A/B26-253[»]
2XWBX-ray3.49I/J26-253[»]
4CBNX-ray1.80A/B26-253[»]
4CBOX-ray1.80A/B26-253[»]
4D9RX-ray2.42A/B26-253[»]
5TCAX-ray3.15A/B/C/D/E/F/G26-253[»]
5TCCX-ray3.37A/B/C/D/E/F/G26-253[»]
ProteinModelPortaliP00746.
SMRiP00746.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108039. 2 interactors.
IntActiP00746. 3 interactors.
STRINGi9606.ENSP00000332139.

Chemistry databases

BindingDBiP00746.
ChEMBLiCHEMBL2176771.
GuidetoPHARMACOLOGYi2842.

Protein family/group databases

MEROPSiS01.191.

PTM databases

iPTMnetiP00746.
PhosphoSitePlusiP00746.

Polymorphism and mutation databases

BioMutaiCFD.
DMDMi158515408.

Proteomic databases

PaxDbiP00746.
PeptideAtlasiP00746.
PRIDEiP00746.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327726; ENSP00000332139; ENSG00000197766.
ENST00000617994; ENSP00000478745; ENSG00000274619.
GeneIDi1675.
KEGGihsa:1675.
UCSCiuc002lqc.4. human.

Organism-specific databases

CTDi1675.
DisGeNETi1675.
GeneCardsiCFD.
HGNCiHGNC:2771. CFD.
HPAiCAB016383.
HPA052799.
MalaCardsiCFD.
MIMi134350. gene.
613912. phenotype.
neXtProtiNX_P00746.
OpenTargetsiENSG00000197766.
ENSG00000274619.
Orphaneti169467. Recurrent Neisseria infections due to factor D deficiency.
PharmGKBiPA142.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118895.
HOVERGENiHBG013304.
InParanoidiP00746.
KOiK01334.
OMAiGAITQRM.
OrthoDBiEOG091G0DF7.
PhylomeDBiP00746.
TreeFamiTF333630.

Enzyme and pathway databases

BioCyciZFISH:HS11198-MONOMER.
BRENDAi3.4.21.46. 2681.
ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-173736. Alternative complement activation.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiCFD. human.
EvolutionaryTraceiP00746.
GenomeRNAii1675.
PROiP00746.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197766.
CleanExiHS_CFD.
ExpressionAtlasiP00746. baseline and differential.
GenevisibleiP00746. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR018114. TRYPSIN_HIS.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
PROSITEiPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCFAD_HUMAN
AccessioniPrimary (citable) accession number: P00746
Secondary accession number(s): B4DV76
, Q5U5S1, Q86VJ5, Q8N4E0, Q8WZB4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: September 11, 2007
Last modified: November 30, 2016
This is version 182 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.