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P00746 (CFAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement factor D

EC=3.4.21.46
Alternative name(s):
Adipsin
C3 convertase activator
Properdin factor D
Gene names
Name:CFD
Synonyms:DF, PFD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length253 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

Selective cleavage of Arg-|-Lys bond in complement factor B when in complex with complement subcomponent C3b or with cobra venom factor.

Subcellular location

Secreted.

Involvement in disease

Complement factor D deficiency (CFDD) [MIM:613912]: An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the peptidase S1 family.

Contains 1 peptidase S1 domain.

Sequence caution

The sequence AAA35527.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Propeptide21 – 255Activation peptide Potential
PRO_0000027560
Chain26 – 253228Complement factor D
PRO_0000027561

Regions

Domain26 – 253228Peptidase S1

Sites

Active site661Charge relay system
Active site1141Charge relay system
Active site2081Charge relay system

Amino acid modifications

Disulfide bond51 ↔ 67
Disulfide bond148 ↔ 214
Disulfide bond179 ↔ 195
Disulfide bond204 ↔ 229

Natural variations

Natural variant2131V → G in CFDD. Ref.13
VAR_034866
Natural variant2141C → R in CFDD. Ref.13
VAR_034867
Natural variant2481I → M.
Corresponds to variant rs2230216 [ dbSNP | Ensembl ].
VAR_034868

Experimental info

Sequence conflict211P → R in AAA35527. Ref.5
Sequence conflict261I → M in AAA35527. Ref.5
Sequence conflict351H → F AA sequence Ref.8
Sequence conflict401M → V AA sequence Ref.8
Sequence conflict491H → E AA sequence Ref.7
Sequence conflict491H → E AA sequence Ref.10
Sequence conflict521G → A in AAA35527. Ref.5
Sequence conflict591Q → R in AAA35527. Ref.5
Sequence conflict631S → T AA sequence Ref.7
Sequence conflict731D → G AA sequence Ref.7
Sequence conflict83 – 864HSLS → THLP AA sequence Ref.6
Sequence conflict83 – 842HS → ST AA sequence Ref.7
Sequence conflict94 – 952Missing AA sequence Ref.7
Sequence conflict961D → E AA sequence Ref.7
Sequence conflict1361Q → G AA sequence Ref.7
Sequence conflict178 – 19114TCNRR…GAITE → KCRLYDVL AA sequence Ref.7
Sequence conflict2431S → T AA sequence Ref.6
Sequence conflict2501S → H AA sequence Ref.6
Sequence conflict2501Missing AA sequence Ref.7

Secondary structure

..................................................... 253
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00746 [UniParc].

Last modified September 11, 2007. Version 5.
Checksum: 78B06C209DEEA362

FASTA25327,033
        10         20         30         40         50         60 
MHSWERLAVL VLLGAAACAA PPRGRILGGR EAEAHARPYM ASVQLNGAHL CGGVLVAEQW 

        70         80         90        100        110        120 
VLSAAHCLED AADGKVQVLL GAHSLSQPEP SKRLYDVLRA VPHPDSQPDT IDHDLLLLQL 

       130        140        150        160        170        180 
SEKATLGPAV RPLPWQRVDR DVAPGTLCDV AGWGIVNHAG RRPDSLQHVL LPVLDRATCN 

       190        200        210        220        230        240 
RRTHHDGAIT ERLMCAESNR RDSCKGDSGG PLVCGGVLEG VVTSGSRVCG NRKKPGIYTR 

       250 
VASYAAWIDS VLA 

« Hide

References

« Hide 'large scale' references
[1]Relle M.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Small intestine.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta, Skin, Spleen and Testis.
[5]"Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue."
White R.T., Damm D., Hancock N., Rosen B.S., Lowell B.B., Usher P., Flier J.S., Spiegelman B.M.
J. Biol. Chem. 267:9210-9213(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-253.
[6]"Amino acid sequence of human D of the alternative complement pathway."
Niemann M.A., Bhown A.S., Bennett J.C., Volanakis J.E.
Biochemistry 23:2482-2486(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-252.
[7]"Amino acid sequence of human factor D of the complement system. Similarity in sequence between factor D and proteases of non-plasma origin."
Johnson D.M.A., Gagnon J., Reid K.B.M.
FEBS Lett. 166:347-351(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-252.
[8]"Partial amino acid sequence of human factor D: homology with serine proteases."
Volanakis J.E., Bhown A.S., Bennett J.C., Mole J.E.
Proc. Natl. Acad. Sci. U.S.A. 77:1116-1119(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-82.
[9]"Active site amino acid sequence of human factor D."
Davis A.E. III
Proc. Natl. Acad. Sci. U.S.A. 77:4938-4942(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-78.
[10]"Factor D of the alternative pathway of human complement. Purification, alignment and N-terminal amino acid sequences of the major cyanogen bromide fragments, and localization of the serine residue at the active site."
Johnson D.M.A., Gagnon J., Reid K.B.M.
Biochem. J. 187:863-874(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-61 AND 194-220.
[11]"Structure of human factor D. A complement system protein at 2.0-A resolution."
Narayana S.V.L., Carson M., El-Kabbani O., Kilpatrick J.M., Moore D., Chen X., Bugg C.E., Volanakis J.E., Delucas L.J.
J. Mol. Biol. 235:695-708(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[12]"Crystal structure of a complement factor D mutant expressing enhanced catalytic activity."
Kim S., Narayana S.V., Volanakis J.E.
J. Biol. Chem. 270:24399-24405(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[13]"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."
Sprong T., Roos D., Weemaes C., Neeleman C., Geesing C.L., Mollnes T.E., van Deuren M.
Blood 107:4865-4870(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CFDD DEFICIENCY GLY-213 AND ARG-214.
+Additional computationally mapped references.

Web resources

CFDbase

CFD mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRDBHU. A40197.
RefSeqNP_001919.2. NM_001928.2.
UniGeneHs.155597.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP00746.
SMRP00746. Positions 26-253.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108039. 3 interactions.
IntActP00746. 2 interactions.
STRING9606.ENSP00000332139.

Chemistry

ChEMBLCHEMBL2176771.

Protein family/group databases

MEROPSS01.191.

PTM databases

PhosphoSiteP00746.

Polymorphism databases

DMDM158515408.

Proteomic databases

PaxDbP00746.
PRIDEP00746.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000327726; ENSP00000332139; ENSG00000197766.
GeneID1675.
KEGGhsa:1675.
UCSCuc002lqc.3. human.

Organism-specific databases

CTD1675.
GeneCardsGC19P000859.
HGNCHGNC:2771. CFD.
HPACAB016383.
MIM134350. gene.
613912. phenotype.
neXtProtNX_P00746.
Orphanet169467. Recurrent Neisseria infections due to factor D deficiency.
PharmGKBPA142.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG013304.
InParanoidP00746.
KOK01334.
OrthoDBEOG7MKW6Q.
PhylomeDBP00746.
TreeFamTF333630.

Enzyme and pathway databases

BRENDA3.4.21.46. 2681.
ReactomeREACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP00746.
BgeeP00746.
CleanExHS_CFD.
GenevestigatorP00746.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00746.
GenomeRNAi1675.
NextBio6892.
PROP00746.
SOURCESearch...

Entry information

Entry nameCFAD_HUMAN
AccessionPrimary (citable) accession number: P00746
Secondary accession number(s): B4DV76 expand/collapse secondary AC list , Q5U5S1, Q86VJ5, Q8N4E0, Q8WZB4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: September 11, 2007
Last modified: April 16, 2014
This is version 157 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM