Reviewed, UniProtKB/Swiss-Prot P00746 (CFAD_HUMAN)

Names and origin

Protein names

Recommended name:
    Complement factor D
    EC=3.4.21.46
Alternative name(s):
    C3 convertase activator
    Properdin factor D
    Adipsin

Gene names

Name:	CFD
Synonyms:	DF, PFD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	253 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in CFD are the cause of complement factor D deficiency [MIM:134350]. This deficiency predisposes to invasive meningococcal disease. Ref.11
Sequence similarities	Belongs to the peptidase S1 family. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Complement alternate pathway Immune response Innate immunity
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase Protease Serine protease
PTM	Disulfide bond Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	complement activation, alternative pathway Inferred from Experiment. Source: Reactome proteolysis Ref.3 Traceable author statement. Source: ProtInc
Cellular component	platelet alpha granule lumen Inferred from Experiment. Source: Reactome
Molecular function	serine-type endopeptidase activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 25

5

Activation peptide Potential

PRO_0000027560

Chain

26 – 253

228

Complement factor D

PRO_0000027561

Regions

Domain

26 – 253

228

Peptidase S1

Sites

Active site

66

1

Charge relay system

Active site

114

1

Charge relay system

Active site

208

1

Charge relay system

Amino acid modifications

Disulfide bond

51 ↔ 67

Disulfide bond

148 ↔ 214

Disulfide bond

179 ↔ 195

Disulfide bond

204 ↔ 229

Natural variations

Natural variant

213

1

V → G in complement factor D deficiency. Ref.11

VAR_034866

Natural variant

214

1

C → R in complement factor D deficiency. Ref.11

VAR_034867

Natural variant

248

1

I → M: dbSNP rs2230216.

VAR_034868

Experimental info

Sequence conflict

21

1

P → R in AAA35527. Ref.3

Sequence conflict

26

1

I → M in AAA35527. Ref.3

Sequence conflict

35

1

H → F AA sequence Ref.6

Sequence conflict

40

1

M → V AA sequence Ref.6

Sequence conflict

49

1

H → E AA sequence Ref.5

Sequence conflict

49

1

H → E AA sequence Ref.8

Sequence conflict

52

1

G → A in AAA35527. Ref.3

Sequence conflict

59

1

Q → R in AAA35527. Ref.3

Sequence conflict

63

1

S → T AA sequence Ref.5

Sequence conflict

73

1

D → G AA sequence Ref.5

Sequence conflict

83 – 86

4

HSLS → THLP AA sequence Ref.4

Sequence conflict

83 – 84

2

HS → ST AA sequence Ref.5

Sequence conflict

94 – 95

2

Missing AA sequence Ref.5

Sequence conflict

96

1

D → E AA sequence Ref.5

Sequence conflict

136

1

Q → G AA sequence Ref.5

Sequence conflict

178 – 191

14

TCNRR…GAITE → KCRLYDVL AA sequence Ref.5

Sequence conflict

243

1

S → T AA sequence Ref.4

Sequence conflict

250

1

S → H AA sequence Ref.4

Sequence conflict

250

1

Missing AA sequence Ref.5

Secondary structure

1

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253

Helix Strand Turn

Details...

Beta strand

40 – 45

6

Beta strand

48 – 57

10

Beta strand

60 – 63

4

Helix

65 – 70

6

Beta strand

72 – 74

3

Beta strand

76 – 81

6

Beta strand

83 – 87

5

Beta strand

93 – 102

10

Beta strand

116 – 122

7

Beta strand

147 – 154

8

Beta strand

167 – 174

8

Helix

176 – 180

5

Turn

182 – 187

6

Beta strand

193 – 196

4

Turn

205 – 209

5

Beta strand

211 – 214

4

Beta strand

217 – 222

6

Beta strand

236 – 240

5

Helix

241 – 244

4

Helix

245 – 252

8

Sequences

	Sequence		Length	Mass (Da)
	P00746-1 [UniParc]. Last modified September 11, 2007. Version 5. Checksum: 78B06C209DEEA362	FASTA	253	27,033
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Relle M. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta, Skin, Spleen and Testis.
[3]	"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: 1374388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-253.
[4]	"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: 6383466] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-252.
[5]	"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: 6363133] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 26-252.
[6]	"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: 6987665] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 26-82.
[7]	"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: 6776531] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 26-78.
[8]	"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: 6821372] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 26-61 AND 194-220.
[9]	"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: 8289289] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[10]	"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: 7592653] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[11]	"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: 16527897] [Abstract] Cited for: VARIANTS COMPLEMENT FACTOR D DEFICIENCY GLY-213 AND ARG-214.
+	Additional computationally mapped references.

Web resources

CFDbase

CFD mutation db

Cross-references

Sequence databases

EMBLGenBankDDBJ

AJ313463 mRNA. Translation: CAC48304.1.
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.

IPI

IPI00165972.

PIR

DBHU. A40197.

RefSeq

NP_001919.2.

UniGene

Hs.155597

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S01.191.

Proteomic databases

PRIDE

P00746.

Genome annotation databases

Ensembl

ENSG00000197766. Homo sapiens. [Contig view]

GeneID

1675.

KEGG

hsa:1675.

Organism-specific databases

GeneCards

GC19P000811.

HGNC

HGNC:2771. CFD.

HPA

CAB016383.

MIM

134350. gene+phenotype.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P00746.

HOVERGEN

P00746.

OMA

P00746. AESNRRD.

Enzyme and pathway databases

BRENDA

3.4.21.46. 247.

Reactome

REACT_604. Hemostasis.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P00746.

Bgee

P00746.

CleanEx

HS_CFD.

GermOnline

ENSG00000197766. Homo sapiens.

Family and domain databases

InterPro

IPR018114. Peptidase_S1/S6_AS.
IPR001254. Peptidase_S1_S6.
IPR001314. Peptidase_S1A.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

PROSITE

PS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6892.

SOURCE

Search...

Entry information

Entry name

CFAD_HUMAN

Accession

Primary (citable) accession number: P00746
Secondary accession number(s): Q5U5S1 , Q86VJ5, Q8N4E0, Q8WZB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	September 11, 2007
Last modified:	June 16, 2009
This is version 110 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)