ID CFAD_HUMAN Reviewed; 253 AA. AC P00746; B4DV76; Q5U5S1; Q86VJ5; Q8N4E0; Q8WZB4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 5. DT 04-NOV-2026, entry version 237. DE RecName: Full=Complement factor D {ECO:0000303|PubMed:1374388}; DE EC=3.4.21.46 {ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:22362762, ECO:0000269|PubMed:6769474, ECO:0000269|PubMed:874324, ECO:0000269|PubMed:9748277}; DE AltName: Full=Adipsin {ECO:0000303|PubMed:1374388}; DE AltName: Full=C3 convertase activator; DE AltName: Full=Properdin factor D; DE Flags: Precursor; GN Name=CFD {ECO:0000312|HGNC:HGNC:2771}; Synonyms=DF, PFD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Relle M.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Small intestine; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta, Skin, Spleen, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-253. RX PubMed=1374388; DOI=10.1016/s0021-9258(19)50409-4; RA White R.T., Damm D., Hancock N., Rosen B.S., Lowell B.B., Usher P., RA Flier J.S., Spiegelman B.M.; RT "Human adipsin is identical to complement factor D and is expressed at high RT levels in adipose tissue."; RL J. Biol. Chem. 267:9210-9213(1992). RN [6] RP PROTEIN SEQUENCE OF 26-34, AND SUBCELLULAR LOCATION. RX PubMed=497171; DOI=10.1021/bi00590a010; RA Davis A.E. III, Zalut C., Rosen F.S., Alper C.A.; RT "Human factor D of the alternative complement pathway. Physicochemical RT characteristics and N-terminal amino acid sequence."; RL Biochemistry 18:5082-5087(1979). RN [7] RP PROTEIN SEQUENCE OF 26-252. RX PubMed=6383466; DOI=10.1021/bi00306a025; RA Niemann M.A., Bhown A.S., Bennett J.C., Volanakis J.E.; RT "Amino acid sequence of human D of the alternative complement pathway."; RL Biochemistry 23:2482-2486(1984). RN [8] RP PROTEIN SEQUENCE OF 26-252. RX PubMed=6363133; DOI=10.1016/0014-5793(84)80110-6; RA Johnson D.M.A., Gagnon J., Reid K.B.M.; RT "Amino acid sequence of human factor D of the complement system. Similarity RT in sequence between factor D and proteases of non-plasma origin."; RL FEBS Lett. 166:347-351(1984). RN [9] RP PROTEIN SEQUENCE OF 26-82. RX PubMed=6987665; DOI=10.1073/pnas.77.2.1116; RA Volanakis J.E., Bhown A.S., Bennett J.C., Mole J.E.; RT "Partial amino acid sequence of human factor D: homology with serine RT proteases."; RL Proc. Natl. Acad. Sci. U.S.A. 77:1116-1119(1980). RN [10] RP PROTEIN SEQUENCE OF 26-78. RX PubMed=6776531; DOI=10.1073/pnas.77.8.4938; RA Davis A.E. III; RT "Active site amino acid sequence of human factor D."; RL Proc. Natl. Acad. Sci. U.S.A. 77:4938-4942(1980). RN [11] RP PROTEIN SEQUENCE OF 26-61 AND 194-220. RX PubMed=6821372; DOI=10.1042/bj1870863; RA Johnson D.M.A., Gagnon J., Reid K.B.M.; RT "Factor D of the alternative pathway of human complement. Purification, RT alignment and N-terminal amino acid sequences of the major cyanogen bromide RT fragments, and localization of the serine residue at the active site."; RL Biochem. J. 187:863-874(1980). RN [12] RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY, AND RP SUBCELLULAR LOCATION. RX PubMed=874324; DOI=10.4049/jimmunol.119.1.337; RA Volanakis J.E., Schrohenloher R.E., Stroud R.M.; RT "Human factor D of the alternative complement pathway: purification and RT characterization."; RL J. Immunol. 119:337-342(1977). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=6769474; DOI=10.1021/bi00549a007; RA Niemann M.A., Volanakis J.E., Mole J.E.; RT "Amino-terminal sequence of human factor B of the alternative complement RT pathway and its cleavage fragments, Ba and Bb."; RL Biochemistry 19:1576-1583(1980). RN [14] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9748277; DOI=10.1074/jbc.273.40.25996; RA Hourcade D.E., Mitchell L.M., Oglesby T.J.; RT "A conserved element in the serine protease domain of complement factor RT B."; RL J. Biol. Chem. 273:25996-26000(1998). RN [15] RP ACTIVE SITE, ACTIVITY REGULATION, AND DOMAIN. RX PubMed=9753554; DOI=10.1006/jmbi.1998.2089; RA Jing H., Babu Y.S., Moore D., Kilpatrick J.M., Liu X.Y., Volanakis J.E., RA Narayana S.V.; RT "Structures of native and complexed complement factor D: implications of RT the atypical His57 conformation and self-inhibitory loop in the regulation RT of specific serine protease activity."; RL J. Mol. Biol. 282:1061-1081(1998). RN [16] RP PROTEOLYTIC CLEAVAGE. RX PubMed=20038603; DOI=10.1084/jem.20090633; RA Takahashi M., Ishida Y., Iwaki D., Kanno K., Suzuki T., Endo Y., Homma Y., RA Fujita T.; RT "Essential role of mannose-binding lectin-associated serine protease-1 in RT activation of the complement factor D."; RL J. Exp. Med. 207:29-37(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P., RA Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [18] RP PROTEOLYTIC CLEAVAGE. RX PubMed=27535802; DOI=10.1038/srep31877; RA Dobo J., Szakacs D., Oroszlan G., Kortvely E., Kiss B., Boros E., Szasz R., RA Zavodszky P., Gal P., Pal G.; RT "MASP-3 is the exclusive pro-factor D activator in resting blood: the RT lectin and the alternative complement pathways are fundamentally linked."; RL Sci. Rep. 6:31877-31877(2016). RN [19] RP X-RAY CRYSTALLOGRAPHY. RX PubMed=8289289; DOI=10.1006/jmbi.1994.1021; RA Narayana S.V.L., Carson M., El-Kabbani O., Kilpatrick J.M., Moore D., RA Chen X., Bugg C.E., Volanakis J.E., Delucas L.J.; RT "Structure of human factor D. A complement system protein at 2.0-A RT resolution."; RL J. Mol. Biol. 235:695-708(1994). RN [20] RP X-RAY CRYSTALLOGRAPHY, ACTIVE SITES, AND DISULFIDE BONDS. RX PubMed=7592653; DOI=10.1074/jbc.270.41.24399; RA Kim S., Narayana S.V., Volanakis J.E.; RT "Crystal structure of a complement factor D mutant expressing enhanced RT catalytic activity."; RL J. Biol. Chem. 270:24399-24405(1995). RN [21] {ECO:0007744|PDB:1FDP} RP X-RAY CRYSTALLOGRAPHY, ACTIVITY REGULATION, DOMAIN, AND DISULFIDE BONDS. RX PubMed=10022823; DOI=10.1093/emboj/18.4.804; RA Jing H., Macon K.J., Moore D., DeLucas L.J., Volanakis J.E., Narayana S.V.; RT "Structural basis of profactor D activation: from a highly flexible zymogen RT to a novel self-inhibited serine protease, complement factor D."; RL EMBO J. 18:804-814(1999). RN [22] {ECO:0007744|PDB:2XW9, ECO:0007744|PDB:2XWA, ECO:0007744|PDB:2XWB} RP X-RAY CRYSTALLOGRAPHY, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, ACTIVITY RP REGULATION, DOMAIN, DISULFIDE BONDS, AND MUTAGENESIS OF HIS-158; ARG-182; RP SER-208; ARG-227 AND VAL-228. RX PubMed=21205667; DOI=10.1126/science.1195821; RA Forneris F., Ricklin D., Wu J., Tzekou A., Wallace R.S., Lambris J.D., RA Gros P.; RT "Structures of C3b in complex with factors B and D give insight into RT complement convertase formation."; RL Science 330:1816-1820(2010). RN [23] {ECO:0007744|PDB:4D9R} RP X-RAY CRYSTALLOGRAPHY, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF RP SER-208. RX PubMed=22362762; DOI=10.1074/jbc.m112.345082; RA Katschke K.J., Wu P., Ganesan R., Kelley R.F., Mathieu M.A., Hass P.E., RA Murray J., Kirchhofer D., Wiesmann C., van Lookeren Campagne M.; RT "Inhibiting alternative pathway complement activation by targeting the RT factor D exosite."; RL J. Biol. Chem. 287:12886-12892(2012). RN [24] RP VARIANTS CFDD DEFICIENCY GLY-213 AND ARG-214. RX PubMed=16527897; DOI=10.1182/blood-2005-07-2820; RA Sprong T., Roos D., Weemaes C., Neeleman C., Geesing C.L., Mollnes T.E., RA van Deuren M.; RT "Deficient alternative complement pathway activation due to factor D RT deficiency by 2 novel mutations in the complement factor D gene in a family RT with meningococcal infections."; RL Blood 107:4865-4870(2006). CC -!- FUNCTION: Serine protease that initiates the alternative pathway of the CC complement system, a cascade of proteins that leads to phagocytosis and CC breakdown of pathogens and signaling that strengthens the adaptive CC immune system (PubMed:21205667, PubMed:22362762, PubMed:6769474, CC PubMed:874324, PubMed:9748277). In contrast to other complement CC pathways (classical, lectin and GZMK) that are directly activated by CC pathogens or antigen-antibody complexes, the alternative complement CC pathway is initiated by the spontaneous hydrolysis of complement C3 CC (PubMed:21205667, PubMed:22362762, PubMed:6769474, PubMed:874324). The CC alternative complement pathway acts as an amplification loop that CC enhances complement activation by mediating the formation of C3 and C5 CC convertases (PubMed:21205667, PubMed:22362762, PubMed:6769474, CC PubMed:874324). Activated CFD cleaves factor B (CFB) when the latter is CC complexed with complement C3b, activating the C3 convertase of the CC alternative pathway (PubMed:21205667, PubMed:6769474, PubMed:874324, CC PubMed:9748277). {ECO:0000269|PubMed:21205667, CC ECO:0000269|PubMed:22362762, ECO:0000269|PubMed:6769474, CC ECO:0000269|PubMed:874324, ECO:0000269|PubMed:9748277}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective cleavage of Arg-|-Lys bond in complement factor B CC when in complex with complement subcomponent C3b or with cobra venom CC factor.; EC=3.4.21.46; Evidence={ECO:0000269|PubMed:21205667, CC ECO:0000269|PubMed:22362762, ECO:0000269|PubMed:6769474, CC ECO:0000269|PubMed:874324, ECO:0000269|PubMed:9748277}; CC -!- ACTIVITY REGULATION: Circulates in plasma in a mature but self- CC inhibited form (PubMed:10022823, PubMed:21205667). Activated by factor CC B (CFB), which displaces the self-inhibition loop (PubMed:21205667). CC Associates with CFB complexed with complement C3b (PubMed:21205667). CC Specifically inhibited by anti-factor D Fab fragment (AFD) antibody CC (PubMed:22362762). {ECO:0000269|PubMed:10022823, CC ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:22362762}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:497171, CC ECO:0000269|PubMed:874324}. CC -!- DOMAIN: The self-inhibition loop inhibits the serine protease activity CC in absence of factor B (CFB) substrate. {ECO:0000269|PubMed:10022823, CC ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:9753554}. CC -!- PTM: CFD is activated by the removal of 5 residues at the N-terminus, CC named activation peptide, by the MASP-3 isoform of MASP1. CC {ECO:0000269|PubMed:20038603, ECO:0000269|PubMed:27535802}. CC -!- DISEASE: Complement factor D deficiency (CFDD) [MIM:613912]: An CC immunologic disorder characterized by increased susceptibility to CC bacterial infections, particularly Neisseria infections, due to a CC defect in the alternative complement pathway. CC {ECO:0000269|PubMed:16527897}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35527.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=CFDbase; Note=CFD mutation db; CC URL="https://databases.lovd.nl/shared/genes/CFD"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ313463; CAC48304.1; -; mRNA. DR EMBL; AK300963; BAG62588.1; -; mRNA. DR EMBL; CH471139; EAW69588.1; -; Genomic_DNA. DR EMBL; BC034529; AAH34529.1; -; mRNA. DR EMBL; BC040146; AAH40146.1; -; mRNA. DR EMBL; BC051001; AAH51001.1; -; mRNA. DR EMBL; BC057807; AAH57807.1; -; mRNA. DR EMBL; M84526; AAA35527.1; ALT_INIT; mRNA. DR CCDS; CCDS12046.1; -. DR PIR; A40197; DBHU. DR RefSeq; NP_001304264.1; NM_001317335.2. DR RefSeq; NP_001919.2; NM_001928.4. DR PDB; 1BIO; X-ray; 1.50 A; A=26-253. DR PDB; 1DFP; X-ray; 2.40 A; A/B=26-253. DR PDB; 1DIC; X-ray; 1.80 A; A=26-253. DR PDB; 1DST; X-ray; 2.00 A; A=26-253. DR PDB; 1DSU; X-ray; 2.00 A; A/B=26-253. DR PDB; 1FDP; X-ray; 2.10 A; A/B/C/D=19-253. DR PDB; 1HFD; X-ray; 2.30 A; A=26-253. DR PDB; 2XW9; X-ray; 1.20 A; A=26-253. DR PDB; 2XWA; X-ray; 2.80 A; A/B=26-253. DR PDB; 2XWB; X-ray; 3.49 A; I/J=26-253. DR PDB; 4CBN; X-ray; 1.80 A; A/B=26-253. DR PDB; 4CBO; X-ray; 1.80 A; A/B=26-253. DR PDB; 4D9R; X-ray; 2.42 A; A/B=26-253. DR PDB; 5FBE; X-ray; 1.43 A; A=26-253. DR PDB; 5FBI; X-ray; 1.47 A; A=26-253. DR PDB; 5FCK; X-ray; 1.86 A; A=26-253. DR PDB; 5MT0; X-ray; 1.29 A; A=26-253. DR PDB; 5MT4; X-ray; 1.65 A; A=26-253. DR PDB; 5NAR; X-ray; 1.55 A; A=26-253. DR PDB; 5NAT; X-ray; 1.17 A; A=26-253. DR PDB; 5NAW; X-ray; 1.25 A; A=26-253. DR PDB; 5NB6; X-ray; 1.75 A; A=26-253. DR PDB; 5NB7; X-ray; 1.33 A; A=26-253. DR PDB; 5NBA; X-ray; 1.87 A; A=26-253. DR PDB; 5TCA; X-ray; 3.15 A; A/B/C/D/E/F/G=26-253. DR PDB; 5TCC; X-ray; 3.37 A; A/B/C/D/E/F/G=26-253. DR PDB; 6FTY; X-ray; 1.67 A; A=26-253. DR PDB; 6FTZ; X-ray; 1.67 A; A=26-253. DR PDB; 6FUG; X-ray; 2.21 A; A/B/C/D/E/F=26-253. DR PDB; 6FUH; X-ray; 1.37 A; A=26-253. DR PDB; 6FUI; X-ray; 1.38 A; A=26-253. DR PDB; 6FUJ; X-ray; 2.25 A; A/B/C/D/E/F=26-253. DR PDB; 6FUT; X-ray; 1.50 A; A=26-253. DR PDB; 6QMR; X-ray; 2.00 A; A/B/C/D/E/F=2-253. DR PDB; 6QMT; X-ray; 1.80 A; A/B=2-253. DR PDB; 6VMJ; X-ray; 2.95 A; W/X/Y/Z=26-253. DR PDB; 6VMK; X-ray; 3.01 A; C/F/I/N/Q/T/W/X/a/d/g/j/m/p/s/v=26-253. DR PDB; 8D95; X-ray; 2.17 A; A=26-253. DR PDB; 8DEA; X-ray; 2.21 A; A/B/C/D=26-253. DR PDB; 8DG6; X-ray; 1.99 A; A=26-253. DR AlphaFoldDB; P00746; -. DR MDposit; P00746; -. DR MDRepo; P00746; -. DR SMR; P00746; -. DR BioGRID; 108039; 5. DR FunCoup; P00746; 252. DR IntAct; P00746; 3. DR NDEx; IQUERY-CP-CFD; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000468253; -. DR BindingDB; P00746; -. DR ChEMBL; CHEMBL2176771; -. DR DrugBank; DB03058; 2-Aminobenzyl alcohol. DR DrugBank; DB04459; 3,4-Dichloroisocoumarin. DR DrugBank; DB15401; Danicopan. DR DrugBank; DB18012; Vemircopan. DR GuidetoPHARMACOLOGY; 2842; -. DR MEROPS; S01.191; -. DR iPTMnet; P00746; -. DR PhosphoSitePlus; P00746; -. DR BioMuta; CFD; -. DR DMDM; 158515408; -. DR jPOST; P00746; -. DR MassIVE; P00746; -. DR PaxDb; 9606-ENSP00000468253; -. DR PeptideAtlas; P00746; -. DR ProteomicsDB; 51276; -. DR ABCD; P00746; 2 sequenced antibodies. DR Antibodypedia; 4290; 702 antibodies from 40 providers. DR DNASU; 1675; -. DR Ensembl; ENST00000327726.11; ENSP00000332139.4; ENSG00000197766.10. DR Ensembl; ENST00000617994.2; ENSP00000478745.1; ENSG00000274619.2. DR Ensembl; ENST00000866187.1; ENSP00000536246.1; ENSG00000197766.10. DR GeneID; 1675; -. DR KEGG; hsa:1675; -. DR MANE-Select; ENST00000327726.11; ENSP00000332139.4; NM_001928.4; NP_001919.2. DR UCSC; uc002lqc.4; human. DR AGR; HGNC:2771; -. DR ClinPGx; PA142; -. DR CTD; 1675; -. DR DisGeNET; 1675; -. DR GeneCards; CFD; -. DR HGNC; HGNC:2771; CFD. DR HPA; ENSG00000197766; Tissue enhanced (adipose). DR MalaCards; CFD; -. DR MIM; 134350; gene. DR MIM; 613912; phenotype. DR OpenTargets; ENSG00000197766; -. DR Orphanet; 169467; Recurrent Neisseria infections due to factor D deficiency. DR VEuPathDB; HostDB:ENSG00000197766; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT00940000162255; -. DR HOGENOM; CLU_006842_1_0_1; -. DR InParanoid; P00746; -. DR OMA; AADRWKN; -. DR OrthoDB; 60866at2759; -. DR PAN-GO; P00746; 3 GO annotations based on evolutionary models. DR PhylomeDB; P00746; -. DR BRENDA; 3.4.21.46; 2681. DR PathwayCommons; P00746; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-173736; Alternative complement activation. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; P00746; -. DR SIGNOR; P00746; -. DR Agora; ENSG00000197766; -. DR BioGRID-ORCS; 1675; 260 hits in 1149 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; CFD; human. DR EvolutionaryTrace; P00746; -. DR GenomeRNAi; 1675; -. DR Pharos; P00746; Tchem. DR PRO; PR:P00746; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P00746; protein. DR Bgee; ENSG00000197766; Expressed in subcutaneous adipose tissue and 96 other cell types or tissues. DR ExpressionAtlas; P00746; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc. DR GO; GO:0006956; P:complement activation; TAS:ProtInc. DR GO; GO:0006957; P:complement activation, alternative pathway; IDA:UniProtKB. DR GO; GO:0051604; P:protein maturation; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000120; Putative serine protease; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF54; COMPLEMENT FACTOR D; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Complement alternate pathway; Direct protein sequencing; KW Disease variant; Disulfide bond; Hydrolase; Immunity; Innate immunity; KW Protease; Proteomics identification; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT PROPEP 21..25 FT /note="Activation peptide" FT /evidence="ECO:0000255" FT /id="PRO_0000027560" FT CHAIN 26..253 FT /note="Complement factor D" FT /evidence="ECO:0000305|PubMed:497171, FT ECO:0000305|PubMed:6363133, ECO:0000305|PubMed:6383466, FT ECO:0000305|PubMed:874324" FT /id="PRO_0000027561" FT DOMAIN 26..253 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT REGION 223..227 FT /note="Self-inhibitor loop" FT /evidence="ECO:0000269|PubMed:10022823, FT ECO:0000269|PubMed:9753554" FT ACT_SITE 66 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:7592653, FT ECO:0000269|PubMed:9753554" FT ACT_SITE 114 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:7592653" FT ACT_SITE 208 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:7592653, FT ECO:0000305|PubMed:21205667, ECO:0000305|PubMed:22362762" FT SITE 25..26 FT /note="Cleavage; by MASP-3 isoform of MASP1" FT /evidence="ECO:0000269|PubMed:20038603" FT DISULFID 51..67 FT /evidence="ECO:0000269|PubMed:10022823, FT ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:7592653, FT ECO:0007744|PDB:1DFP, ECO:0007744|PDB:1FDP, FT ECO:0007744|PDB:2XW9" FT DISULFID 148..214 FT /evidence="ECO:0000269|PubMed:10022823, FT ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:7592653, FT ECO:0007744|PDB:1DFP, ECO:0007744|PDB:1FDP, FT ECO:0007744|PDB:2XW9" FT DISULFID 179..195 FT /evidence="ECO:0000269|PubMed:10022823, FT ECO:0000269|PubMed:21205667, ECO:0000269|PubMed:7592653, FT ECO:0007744|PDB:1DFP, ECO:0007744|PDB:1FDP, FT ECO:0007744|PDB:2XW9" FT DISULFID 204..229 FT /evidence="ECO:0000269|PubMed:21205667, FT ECO:0007744|PDB:2XW9" FT VARIANT 213 FT /note="V -> G (in CFDD; dbSNP:rs267606720)" FT /evidence="ECO:0000269|PubMed:16527897" FT /id="VAR_034866" FT VARIANT 214 FT /note="C -> R (in CFDD; dbSNP:rs267606721)" FT /evidence="ECO:0000269|PubMed:16527897" FT /id="VAR_034867" FT VARIANT 248 FT /note="I -> M (in dbSNP:rs2230216)" FT /id="VAR_034868" FT MUTAGEN 158 FT /note="H->A: Abolished ability to cleave CFB." FT /evidence="ECO:0000269|PubMed:21205667" FT MUTAGEN 182 FT /note="R->A: Abolished ability to cleave CFB." FT /evidence="ECO:0000269|PubMed:21205667" FT MUTAGEN 208 FT /note="S->A: Abolished serine endopeptidase activity." FT /evidence="ECO:0000269|PubMed:21205667, FT ECO:0000269|PubMed:22362762" FT MUTAGEN 227 FT /note="R->A: Increased serine endopeptidase activity in FT absence of CFB, while decreased ability to cleave CFB." FT /evidence="ECO:0000269|PubMed:21205667" FT MUTAGEN 227 FT /note="R->G: Abolished ability to cleave CFB." FT /evidence="ECO:0000269|PubMed:21205667" FT MUTAGEN 228 FT /note="V->A: Abolished ability to cleave CFB." FT /evidence="ECO:0000269|PubMed:21205667" FT CONFLICT 21 FT /note="P -> R (in Ref. 5; AAA35527)" FT /evidence="ECO:0000305" FT CONFLICT 26 FT /note="I -> M (in Ref. 5; AAA35527)" FT /evidence="ECO:0000305" FT CONFLICT 35 FT /note="H -> F (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 40 FT /note="M -> V (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 49 FT /note="H -> E (in Ref. 8; AA sequence and 11; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="G -> A (in Ref. 5; AAA35527)" FT /evidence="ECO:0000305" FT CONFLICT 59 FT /note="Q -> R (in Ref. 5; AAA35527)" FT /evidence="ECO:0000305" FT CONFLICT 63 FT /note="S -> T (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 73 FT /note="D -> G (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 83..86 FT /note="HSLS -> THLP (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 83..84 FT /note="HS -> ST (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 94..95 FT /note="Missing (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 96 FT /note="D -> E (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 136 FT /note="Q -> G (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 178..191 FT /note="TCNRRTHHDGAITE -> KCRLYDVL (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 243 FT /note="S -> T (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 250 FT /note="S -> H (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 250 FT /note="Missing (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:1FDP" FT STRAND 40..45 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 48..57 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 65..68 FT /evidence="ECO:0007829|PDB:5NAT" FT TURN 69..71 FT /evidence="ECO:0007829|PDB:6QMR" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:1BIO" FT STRAND 76..81 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 83..87 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 93..102 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 108..113 FT /evidence="ECO:0007829|PDB:1DSU" FT STRAND 116..122 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 123..126 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:4D9R" FT STRAND 147..154 FT /evidence="ECO:0007829|PDB:5NAT" FT TURN 156..159 FT /evidence="ECO:0007829|PDB:4CBO" FT STRAND 167..174 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 176..179 FT /evidence="ECO:0007829|PDB:5NAT" FT TURN 182..187 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 193..196 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 199..202 FT /evidence="ECO:0007829|PDB:5NB7" FT TURN 205..209 FT /evidence="ECO:0007829|PDB:5NB7" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 217..222 FT /evidence="ECO:0007829|PDB:5NAT" FT STRAND 225..227 FT /evidence="ECO:0007829|PDB:6FUT" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:4CBO" FT STRAND 236..240 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 241..244 FT /evidence="ECO:0007829|PDB:5NAT" FT HELIX 245..252 FT /evidence="ECO:0007829|PDB:5NAT" SQ SEQUENCE 253 AA; 27033 MW; 78B06C209DEEA362 CRC64; MHSWERLAVL VLLGAAACAA PPRGRILGGR EAEAHARPYM ASVQLNGAHL CGGVLVAEQW VLSAAHCLED AADGKVQVLL GAHSLSQPEP SKRLYDVLRA VPHPDSQPDT IDHDLLLLQL SEKATLGPAV RPLPWQRVDR DVAPGTLCDV AGWGIVNHAG RRPDSLQHVL LPVLDRATCN RRTHHDGAIT ERLMCAESNR RDSCKGDSGG PLVCGGVLEG VVTSGSRVCG NRKKPGIYTR VASYAAWIDS VLA //