P00746 (CFAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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.

Ontologies

Keywords
Biological process	Complement alternate pathway Immunity 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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	complement activation, alternative pathway Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome proteolysis Traceable author statement Ref.5. Source: ProtInc
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: Compara platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	serine-type endopeptidase activity Traceable author statement Ref.5. 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 CFDD. Ref.13

VAR_034866

Natural variant

214

1

C → R in CFDD. Ref.13

VAR_034867

Natural variant

248

1

I → M.
Corresponds to variant rs2230216 [ dbSNP | Ensembl ].

VAR_034868

Experimental info

Sequence conflict

21

1

P → R in AAA35527. Ref.5

Sequence conflict

26

1

I → M in AAA35527. Ref.5

Sequence conflict

35

1

H → F AA sequence Ref.8

Sequence conflict

40

1

M → V AA sequence Ref.8

Sequence conflict

49

1

H → E AA sequence Ref.7

Sequence conflict

49

1

H → E AA sequence Ref.10

Sequence conflict

52

1

G → A in AAA35527. Ref.5

Sequence conflict

59

1

Q → R in AAA35527. Ref.5

Sequence conflict

63

1

S → T AA sequence Ref.7

Sequence conflict

73

1

D → G AA sequence Ref.7

Sequence conflict

83 – 86

4

HSLS → THLP AA sequence Ref.6

Sequence conflict

83 – 84

2

HS → ST AA sequence Ref.7

Sequence conflict

94 – 95

2

Missing AA sequence Ref.7

Sequence conflict

96

1

D → E AA sequence Ref.7

Sequence conflict

136

1

Q → G AA sequence Ref.7

Sequence conflict

178 – 191

14

TCNRR…GAITE → KCRLYDVL AA sequence Ref.7

Sequence conflict

243

1

S → T AA sequence Ref.6

Sequence conflict

250

1

S → H AA sequence Ref.6

Sequence conflict

250

1

Missing AA sequence Ref.7

Secondary structure

1

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253

Helix Strand Turn

Details...

Beta strand

30 – 32

3

Beta strand

40 – 45

6

Beta strand

48 – 57

10

Beta strand

60 – 63

4

Helix

65 – 68

4

Beta strand

72 – 74

3

Beta strand

76 – 81

6

Beta strand

83 – 87

5

Beta strand

93 – 102

10

Helix

108 – 113

6

Beta strand

116 – 122

7

Beta strand

127 – 129

3

Beta strand

147 – 154

8

Beta strand

167 – 174

8

Helix

176 – 179

4

Turn

182 – 187

6

Beta strand

193 – 196

4

Beta strand

199 – 202

4

Turn

205 – 209

5

Beta strand

211 – 214

4

Beta strand

217 – 222

6

Beta strand

226 – 228

3

Beta strand

236 – 240

5

Helix

241 – 244

4

Helix

245 – 252

8

Sequences

	Sequence		Length	Mass (Da)
	P00746 [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]	"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. , 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. , 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.

IPI

IPI00165972.

PIR

DBHU. A40197.

RefSeq

NP_001919.2. NM_001928.2.

UniGene

Hs.155597.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
4D9R	X-ray	2.42	A/B	26-253	[»]

ProteinModelPortal

P00746.

ModBase

Search...

Protein-protein interaction databases

IntAct

P00746. 2 interactions.

STRING

9606.ENSP00000332139.

Protein family/group databases

MEROPS

S01.191.

PTM databases

PhosphoSite

P00746.

Polymorphism databases

DMDM

158515408.

Proteomic databases

PaxDb

P00746.

PRIDE

P00746.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327726; ENSP00000332139; ENSG00000197766.

GeneID

1675.

KEGG

hsa:1675.

UCSC

uc002lqc.3. human.

Organism-specific databases

CTD

1675.

GeneCards

GC19P000859.

HGNC

HGNC:2771. CFD.

HPA

CAB016383.

MIM

134350. gene.
613912. phenotype.

neXtProt

NX_P00746.

Orphanet

169467. Recurrent Neisseria infections due to factor D deficiency.

PharmGKB

PA142.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5640.

HOVERGEN

HBG013304.

InParanoid

P00746.

KO

K01334.

OMA

QPDTIDH.

OrthoDB

EOG4FXR89.

PhylomeDB

P00746.

Enzyme and pathway databases

BRENDA

3.4.21.46. 2681.

Reactome

REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

Bgee

P00746.

CleanEx

HS_CFD.

Genevestigator

P00746.

GermOnline

ENSG00000197766. Homo sapiens.

Family and domain databases

InterPro

IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]

Pfam

PF00089. Trypsin. 1 hit.
[Graphical view]

PRINTS

PR00722. CHYMOTRYPSIN.

SMART

SM00020. Tryp_SPc. 1 hit.
[Graphical view]

SUPFAM

SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

P00746.

GenomeRNAi

1675.

NextBio

6892.

SOURCE

Search...

Entry information

Entry name

CFAD_HUMAN

Accession

Primary (citable) accession number: P00746
Secondary accession number(s): B4DV76 , Q5U5S1, Q86VJ5, Q8N4E0, Q8WZB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	September 11, 2007
Last modified:	May 1, 2013
This is version 148 of the entry and version 5 of the sequence. [Complete history]

Entry status

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.