ID CFAD_RAT Reviewed; 263 AA. AC P32038; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 02-SEP-2026, entry version 146. DE RecName: Full=Complement factor D; DE EC=3.4.21.46; DE AltName: Full=Adipsin; DE AltName: Full=C3 convertase activator; DE AltName: Full=Endogenous vascular elastase; DE AltName: Full=Properdin factor D; DE Flags: Precursor; GN Name=Cfd; Synonyms=Adn, Df; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8083356; DOI=10.1172/jci117432; RA Zhu L., Wigle D., Hinek A., Kobayashi J., Ye C., Zuker M., Dodo H., RA Keeley F.W., Rabinovitch M.; RT "The endogenous vascular elastase that governs development and progression RT of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme RT related to the serine proteinase adipsin."; RL J. Clin. Invest. 94:1163-1171(1994). RN [2] RP PROTEIN SEQUENCE OF 26-55, AND SUBCELLULAR LOCATION. RX PubMed=1953671; DOI=10.1042/bj2790775; RA Baker B.C., Campbell C.J., Grinham C.J., Turcatti G.; RT "Purification and partial characterization of rat factor D."; RL Biochem. J. 279:775-779(1991). 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. In contrast to other complement pathways (classical, CC lectin and GZMK) that are directly activated by pathogens or antigen- CC antibody complexes, the alternative complement pathway is initiated by CC the spontaneous hydrolysis of complement C3. The alternative complement CC pathway acts as an amplification loop that enhances complement CC activation by mediating the formation of C3 and C5 convertases. CC Activated CFD cleaves factor B (CFB) when the latter is complexed with CC complement C3b, activating the C3 convertase of the alternative CC pathway. {ECO:0000250|UniProtKB:P00746}. 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:0000250|UniProtKB:P00746}; CC -!- ACTIVITY REGULATION: Circulates in plasma in a mature but self- CC inhibited form. Activated by factor B (CFB), which displaces the self- CC inhibition loop. Associates with CFB complexed with complement C3b. CC {ECO:0000250|UniProtKB:P00746}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1953671}. CC -!- DOMAIN: The self-inhibition loop inhibits the serine protease activity CC in absence of factor B (CFB) substrate. {ECO:0000250|UniProtKB:P00746}. 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:0000250|UniProtKB:P00746}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. 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; S73894; AAB31922.1; -; mRNA. DR PIR; I55608; I55608. DR RefSeq; NP_001071110.1; NM_001077642.1. DR AlphaFoldDB; P32038; -. DR SMR; P32038; -. DR FunCoup; P32038; 89. DR STRING; 10116.ENSRNOP00000015029; -. DR BindingDB; P32038; -. DR ChEMBL; CHEMBL4295743; -. DR MEROPS; S01.191; -. DR GlyCosmos; P32038; 1 site, No reported glycans. DR GlyGen; P32038; 1 site. DR PhosphoSitePlus; P32038; -. DR PaxDb; 10116-ENSRNOP00000015029; -. DR Ensembl; ENSRNOT00055056642; ENSRNOP00055046748; ENSRNOG00055032763. DR Ensembl; ENSRNOT00060040866; ENSRNOP00060033804; ENSRNOG00060023586. DR Ensembl; ENSRNOT00065034025; ENSRNOP00065027243; ENSRNOG00065020165. DR GeneID; 54249; -. DR KEGG; rno:54249; -. DR UCSC; RGD:2498; rat. DR AGR; RGD:2498; -. DR CTD; 1675; -. DR RGD; 2498; Cfd. DR eggNOG; KOG3627; Eukaryota. DR InParanoid; P32038; -. DR OrthoDB; 60866at2759; -. DR PhylomeDB; P32038; -. DR BRENDA; 3.4.21.46; 5301. DR Reactome; R-RNO-114608; Platelet degranulation. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR PRO; PR:P32038; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:RGD. DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0006957; P:complement activation, alternative pathway; IDA:UniProtKB. DR GO; GO:0007219; P:Notch signaling pathway; IMP:RGD. DR GO; GO:0051604; P:protein maturation; IBA:GO_Central. DR GO; GO:0009617; P:response to bacterium; ISO:RGD. DR GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD. DR GO; GO:0035886; P:vascular associated smooth muscle cell differentiation; ISO:RGD. DR GO; GO:0031638; P:zymogen activation; ISS: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 Complement alternate pathway; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hydrolase; Immunity; Innate immunity; Protease; KW Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT PROPEP 21..25 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:1953671" FT /id="PRO_0000027566" FT CHAIN 26..263 FT /note="Complement factor D" FT /id="PRO_0000027567" FT DOMAIN 26..254 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT REGION 224..228 FT /note="Self-inhibitor loop" FT /evidence="ECO:0000250|UniProtKB:P00746" FT ACT_SITE 66 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00746" FT ACT_SITE 115 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00746" FT ACT_SITE 209 FT /note="Charge relay system" FT /evidence="ECO:0000250|UniProtKB:P00746" FT SITE 25..26 FT /note="Cleavage; by MASP-3 isoform of MASP1" FT /evidence="ECO:0000250|UniProtKB:P00746" FT CARBOHYD 46 FT /note="N-linked (GlcNAc...) asparagine" FT DISULFID 51..67 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 149..215 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 180..196 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 205..230 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" SQ SEQUENCE 263 AA; 28442 MW; D573133568A31CE0 CRC64; MHSSVYLVAL VVLEAAVCVA QPRGRILGGQ EAMAHARPYM ASVQVNGTHV CGGTLVDEQW VLSAAHCMDG VTKDEVVQVL LGAHSLSSPE PYKHLYDVQS VVLHPGSRPD SVEDDLMLFK LSHNASLGPH VRPLPLQRED REVKPGTLCD VAGWGVVTHA GRRPDVLQQL TVSIMDRNTC NLRTYHDGAI TKNMMCAESN RRDTCRGDSG GPLVCGDAVE AVVTWGSRVC GNRRKPGVFT RVATYVPWIE NVLSGNVSVN VTA //