ID FURIN_MOUSE Reviewed; 793 AA. AC P23188; Q6GTN6; DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 217. DE RecName: Full=Furin; DE EC=3.4.21.75 {ECO:0000269|PubMed:18713856}; DE AltName: Full=Dibasic-processing enzyme; DE AltName: Full=Paired basic amino acid residue-cleaving enzyme; DE Short=PACE; DE AltName: Full=Prohormone convertase 3; DE Flags: Precursor; GN Name=Furin; Synonyms=Fur, Pcsk3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=2266110; DOI=10.1016/s0021-9258(18)45669-4; RA Hatsuzawa K., Hosaka M., Nakagawa T., Nagase M., Shoda A., Murakami K., RA Nakayama K.; RT "Structure and expression of mouse furin, a yeast Kex2-related protease. RT Lack of processing of coexpressed prorenin in GH4C1 cells."; RL J. Biol. Chem. 265:22075-22078(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RA Creemers J.W.M., Roebroek A.J.M., van den Ouweland A.M.W., RA van Duijnhoven H.L.P., van de Ven W.J.M.; RT "Cloning and functional expression of a 4.3 kbp mouse fur cDNA: evidence RT for differential expression."; RL Life Sci. Adv. (Mol. Biol.) 11:127-138(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; 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 INTERACTION WITH FLNA. RX PubMed=9412467; DOI=10.1083/jcb.139.7.1719; RA Liu G., Thomas L., Warren R.A., Enns C.A., Cunningham C.C., Hartwig J.H., RA Thomas G.; RT "Cytoskeletal protein ABP-280 directs the intracellular trafficking of RT furin and modulates proprotein processing in the endocytic pathway."; RL J. Cell Biol. 139:1719-1733(1997). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=18713856; DOI=10.1073/pnas.0800340105; RA Louagie E., Taylor N.A., Flamez D., Roebroek A.J., Bright N.A., RA Meulemans S., Quintens R., Herrera P.L., Schuit F., Van de Ven W.J., RA Creemers J.W.; RT "Role of furin in granular acidification in the endocrine pancreas: RT identification of the V-ATPase subunit Ac45 as a candidate substrate."; RL Proc. Natl. Acad. Sci. U.S.A. 105:12319-12324(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 108-578 IN COMPLEX WITH CALCIUM RP AND INHIBITOR, GLYCOSYLATION AT ASN-387 AND ASN-440, AND DISULFIDE BONDS. RX PubMed=12794637; DOI=10.1038/nsb941; RA Henrich S., Cameron A., Bourenkov G.P., Kiefersauer R., Huber R., RA Lindberg I., Bode W., Than M.E.; RT "The crystal structure of the proprotein processing proteinase furin RT explains its stringent specificity."; RL Nat. Struct. Biol. 10:520-526(2003). CC -!- FUNCTION: Ubiquitous endoprotease within constitutive secretory CC pathways capable of cleavage at the RX(K/R)R consensus motif CC (PubMed:18713856). Mediates processing of TGFB1, an essential step in CC TGF-beta-1 activation (By similarity). Converts through proteolytic CC cleavage the non-functional Brain natriuretic factor prohormone into CC its active hormone BNP(1-45) (By similarity). By mediating processing CC of accessory subunit ATP6AP1/Ac45 of the V-ATPase, regulates the CC acidification of dense-core secretory granules in islets of Langerhans CC cells (PubMed:18713856). {ECO:0000250|UniProtKB:P09958, CC ECO:0000269|PubMed:18713856}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of mature proteins from their proproteins by cleavage CC of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and CC Yaa is Arg or Lys. Releases albumin, complement component C3 and von CC Willebrand factor from their respective precursors.; EC=3.4.21.75; CC Evidence={ECO:0000269|PubMed:18713856}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:12794637}; CC Note=Binds 3 calcium ions per subunit. {ECO:0000250|UniProtKB:P09958}; CC -!- ACTIVITY REGULATION: Inhibited by the not secondly cleaved propeptide. CC Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)- CC benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl- CC phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148). Inhibited by CC Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK). CC Inhibited by heparin/heparan sulfate-binding. CC {ECO:0000250|UniProtKB:P09958}. CC -!- SUBUNIT: Interacts with FLNA (PubMed:9412467). Binds to PACS1 which CC mediates TGN localization and connection to clathrin adapters (By CC similarity). {ECO:0000250|UniProtKB:P09958, CC ECO:0000269|PubMed:9412467}. CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane CC {ECO:0000250|UniProtKB:P09958}; Single-pass type I membrane protein CC {ECO:0000305}. Cell membrane {ECO:0000250|UniProtKB:P09958}; Single- CC pass type I membrane protein {ECO:0000305}. Secreted CC {ECO:0000250|UniProtKB:Q28193}. Endosome membrane CC {ECO:0000250|UniProtKB:P09958}; Single-pass type I membrane protein CC {ECO:0000305}. Note=Shuttles between the trans-Golgi network and the CC cell surface. Propeptide cleavage is a prerequisite for exit of furin CC molecules out of the endoplasmic reticulum (ER). A second cleavage CC within the propeptide occurs in the trans Golgi network (TGN), followed CC by the release of the propeptide and the activation of furin. CC {ECO:0000250|UniProtKB:P09958}. CC -!- TISSUE SPECIFICITY: Seems to be expressed ubiquitously CC (PubMed:2266110). Expressed in islets of Langerhans (PubMed:18713856). CC {ECO:0000269|PubMed:18713856, ECO:0000269|PubMed:2266110}. CC -!- DOMAIN: Contains a cytoplasmic domain responsible for its TGN CC localization and recycling from the cell surface. CC {ECO:0000250|UniProtKB:P09958}. CC -!- PTM: The inhibition peptide, which plays the role of an intramolecular CC chaperone, is autocatalytically removed in the endoplasmic reticulum CC (ER) and remains non-covalently bound to furin as a potent CC autoinhibitor. Following transport to the trans Golgi, a second CC cleavage within the inhibition propeptide results in propeptide CC dissociation and furin activation. {ECO:0000250|UniProtKB:P09958}. CC -!- PTM: Phosphorylation is required for TGN localization of the CC endoprotease. In vivo, exists as di-, mono- and non-phosphorylated CC forms. {ECO:0000250|UniProtKB:P09958}. CC -!- DISRUPTION PHENOTYPE: Conditional knockout in pancreas causes mild CC glucose intolerance (PubMed:18713856). Insulin secretion by islets of CC Langerhans cells is reduced (PubMed:18713856). In islets of Langerhans CC cells, processing of pro-proteins including Pcsk2, Ins2/proinsulin II CC and Gcg/proglucagon and acidification of dense-core secretory granules CC are reduced (PubMed:18713856). Islets of Langerhans are normal CC (PubMed:18713856). {ECO:0000269|PubMed:18713856}. CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily. CC {ECO:0000305}. 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; X54056; CAA37988.1; -; mRNA. DR EMBL; L26489; AAA37643.1; -; mRNA. DR EMBL; CH466543; EDL06988.1; -; Genomic_DNA. DR EMBL; BC048234; AAH48234.1; -; mRNA. DR CCDS; CCDS21397.1; -. DR PIR; A23679; KXMSF. DR RefSeq; NP_001074923.1; NM_001081454.2. DR RefSeq; NP_035176.1; NM_011046.3. DR PDB; 1P8J; X-ray; 2.60 A; A/B/C/D/E/F/G/H=108-578. DR PDBsum; 1P8J; -. DR AlphaFoldDB; P23188; -. DR SMR; P23188; -. DR BioGRID; 202059; 4. DR ELM; P23188; -. DR STRING; 10090.ENSMUSP00000113793; -. DR MEROPS; S08.071; -. DR GlyCosmos; P23188; 2 sites, No reported glycans. DR GlyGen; P23188; 2 sites. DR iPTMnet; P23188; -. DR PhosphoSitePlus; P23188; -. DR SwissPalm; P23188; -. DR EPD; P23188; -. DR MaxQB; P23188; -. DR PaxDb; 10090-ENSMUSP00000113370; -. DR PeptideAtlas; P23188; -. DR ProteomicsDB; 271646; -. DR Pumba; P23188; -. DR Antibodypedia; 4013; 496 antibodies from 39 providers. DR DNASU; 18550; -. DR Ensembl; ENSMUST00000107362.10; ENSMUSP00000102985.4; ENSMUSG00000030530.16. DR Ensembl; ENSMUST00000120753.3; ENSMUSP00000113793.2; ENSMUSG00000030530.16. DR Ensembl; ENSMUST00000122232.8; ENSMUSP00000113370.2; ENSMUSG00000030530.16. DR GeneID; 18550; -. DR KEGG; mmu:18550; -. DR UCSC; uc009iau.1; mouse. DR AGR; MGI:97513; -. DR CTD; 5045; -. DR MGI; MGI:97513; Furin. DR VEuPathDB; HostDB:ENSMUSG00000030530; -. DR eggNOG; KOG3525; Eukaryota. DR GeneTree; ENSGT00940000157220; -. DR HOGENOM; CLU_002976_4_0_1; -. DR InParanoid; P23188; -. DR OMA; FREWAFM; -. DR OrthoDB; 5474719at2759; -. DR PhylomeDB; P23188; -. DR TreeFam; TF314277; -. DR BRENDA; 3.4.21.75; 3474. DR Reactome; R-MMU-1442490; Collagen degradation. DR Reactome; R-MMU-1566948; Elastic fibre formation. DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-MMU-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins. DR Reactome; R-MMU-167060; NGF processing. DR Reactome; R-MMU-186797; Signaling by PDGF. DR Reactome; R-MMU-1912420; Pre-NOTCH Processing in Golgi. DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-MMU-8963889; Assembly of active LPL and LIPC lipase complexes. DR BioGRID-ORCS; 18550; 10 hits in 83 CRISPR screens. DR ChiTaRS; Furin; mouse. DR EvolutionaryTrace; P23188; -. DR PRO; PR:P23188; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P23188; Protein. DR Bgee; ENSMUSG00000030530; Expressed in epithelium of stomach and 230 other cell types or tissues. DR ExpressionAtlas; P23188; baseline and differential. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0005769; C:early endosome; TAS:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031985; C:Golgi cisterna; ISO:MGI. DR GO; GO:0000139; C:Golgi membrane; ISO:MGI. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0045121; C:membrane raft; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005802; C:trans-Golgi network; ISO:MGI. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; ISO:MGI. DR GO; GO:0012510; C:trans-Golgi network transport vesicle membrane; TAS:MGI. DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI. DR GO; GO:1904399; F:heparan sulfate binding; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0048406; F:nerve growth factor binding; ISO:MGI. DR GO; GO:0008233; F:peptidase activity; ISO:MGI. DR GO; GO:0042277; F:peptide binding; ISO:MGI. DR GO; GO:0002020; F:protease binding; ISO:MGI. DR GO; GO:0004252; F:serine-type endopeptidase activity; EXP:Reactome. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISO:MGI. DR GO; GO:0008236; F:serine-type peptidase activity; ISO:MGI. DR GO; GO:0001825; P:blastocyst formation; IGI:CACAO. DR GO; GO:0140447; P:cytokine precursor processing; ISS:UniProtKB. DR GO; GO:0090472; P:dibasic protein processing; ISO:MGI. DR GO; GO:0032804; P:negative regulation of low-density lipoprotein particle receptor catabolic process; ISO:MGI. DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; ISO:MGI. DR GO; GO:0032902; P:nerve growth factor production; ISO:MGI. DR GO; GO:0043043; P:peptide biosynthetic process; ISO:MGI. DR GO; GO:0016486; P:peptide hormone processing; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:MGI. DR GO; GO:0051604; P:protein maturation; ISO:MGI. DR GO; GO:0016485; P:protein processing; IDA:MGI. DR GO; GO:0032374; P:regulation of cholesterol transport; IMP:MGI. DR GO; GO:0042176; P:regulation of protein catabolic process; ISO:MGI. DR GO; GO:0009966; P:regulation of signal transduction; IDA:MGI. DR GO; GO:0032940; P:secretion by cell; ISO:MGI. DR GO; GO:0006465; P:signal peptide processing; ISO:MGI. DR GO; GO:0019058; P:viral life cycle; IEA:Ensembl. DR GO; GO:0031638; P:zymogen activation; ISO:MGI. DR GO; GO:0097341; P:zymogen inhibition; ISO:MGI. DR CDD; cd00064; FU; 2. DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1. DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR034182; Kexin/furin. DR InterPro; IPR002884; P_dom. DR InterPro; IPR000209; Peptidase_S8/S53_dom. DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf. DR InterPro; IPR023827; Peptidase_S8_Asp-AS. DR InterPro; IPR022398; Peptidase_S8_His-AS. DR InterPro; IPR023828; Peptidase_S8_Ser-AS. DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel. DR InterPro; IPR032815; S8_pro-domain. DR InterPro; IPR038466; S8_pro-domain_sf. DR PANTHER; PTHR42884:SF1; FURIN; 1. DR PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1. DR Pfam; PF01483; P_proprotein; 1. DR Pfam; PF00082; Peptidase_S8; 1. DR Pfam; PF16470; S8_pro-domain; 1. DR PRINTS; PR00723; SUBTILISIN. DR SMART; SM00261; FU; 2. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1. DR SUPFAM; SSF52743; Subtilisin-like; 1. DR PROSITE; PS51829; P_HOMO_B; 1. DR PROSITE; PS51892; SUBTILASE; 1. DR PROSITE; PS00136; SUBTILASE_ASP; 1. DR PROSITE; PS00137; SUBTILASE_HIS; 1. DR PROSITE; PS00138; SUBTILASE_SER; 1. DR Genevisible; P23188; MM. PE 1: Evidence at protein level; KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane; KW Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein; KW Golgi apparatus; Heparin-binding; Hydrolase; Membrane; Metal-binding; KW Phosphoprotein; Protease; Reference proteome; Repeat; Secreted; KW Serine protease; Signal; Transmembrane; Transmembrane helix; Zymogen. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT PROPEP 25..107 FT /note="Inhibition peptide" FT /evidence="ECO:0000250|UniProtKB:P09958" FT /id="PRO_0000027030" FT CHAIN 108..793 FT /note="Furin" FT /id="PRO_0000027031" FT TOPO_DOM 108..714 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 715..735 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 736..793 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT DOMAIN 121..435 FT /note="Peptidase S8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT DOMAIN 444..576 FT /note="P/Homo B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173" FT REPEAT 577..620 FT /note="FU 1" FT /evidence="ECO:0000255" FT REPEAT 638..681 FT /note="FU 2" FT /evidence="ECO:0000255" FT REGION 160..182 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 673..697 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 758..761 FT /note="Cell surface signal" FT /evidence="ECO:0000250|UniProtKB:P09958" FT REGION 766..793 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 498..500 FT /note="Cell attachment site" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00293" FT MOTIF 772..778 FT /note="Trans Golgi network signal" FT /evidence="ECO:0000250|UniProtKB:P09958" FT COMPBIAS 673..689 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 153 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT ACT_SITE 194 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT ACT_SITE 368 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT BINDING 115 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 154 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 162 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 174 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P09958" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P09958" FT BINDING 181 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P09958" FT BINDING 191..192 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 212 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 236 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 253..258 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 258 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 264 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 292..295 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 301 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 306 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 308 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 331 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT BINDING 368 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT SITE 75..76 FT /note="Cleavage, second; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P09958" FT SITE 107..108 FT /note="Cleavage, first; by autolysis" FT /evidence="ECO:0000250|UniProtKB:P09958" FT MOD_RES 772 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09958" FT MOD_RES 774 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09958" FT CARBOHYD 387 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT CARBOHYD 440 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12794637, FT ECO:0007744|PDB:1P8J" FT DISULFID 211..360 FT /evidence="ECO:0000269|PubMed:12794637" FT DISULFID 303..333 FT /evidence="ECO:0000269|PubMed:12794637" FT DISULFID 450..474 FT /evidence="ECO:0000269|PubMed:12794637" FT CONFLICT 746 FT /note="V -> M (in Ref. 1; CAA37988)" FT /evidence="ECO:0000305" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 122..124 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 135..139 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 148..154 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 161..163 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 169..171 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 175..178 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 194..203 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 206..211 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 215..218 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 233..240 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 249..252 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 268..280 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 288..292 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 297..299 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 307..310 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 314..320 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 338..341 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 356..358 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 359..364 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 367..384 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 390..400 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 431..438 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 448..455 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 464..471 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 482..496 FT /evidence="ECO:0007829|PDB:1P8J" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 501..506 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 512..516 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 528..535 FT /evidence="ECO:0007829|PDB:1P8J" FT TURN 537..540 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 545..553 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 555..557 FT /evidence="ECO:0007829|PDB:1P8J" FT STRAND 561..573 FT /evidence="ECO:0007829|PDB:1P8J" SQ SEQUENCE 793 AA; 86772 MW; 0F120C2DE2E1A431 CRC64; MELRSWLLWV VAAAGAVVLL AADAQGQKIF TNTWAVHIPG GPAVADRVAQ KHGFHNLGQI FGDYYHFWHR AVTKRSLSPH RPRHSRLQRE PQVKWLEQQV AKRRAKRDVY QEPTDPKFPQ QWYLSGVTQR DLNVKEAWAQ GFTGHGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNADD WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IVEILVEPKD IGKRLEVRKA VTACLGEPNH ITRLEHVQAR LTLSYNRRGD LAIHLISPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPAGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLST PPESSGCKTL TSSQACVVCE EGYSLHQKSC VQHCPPGFIP QVLDTHYSTE NDVEIIRASV CTPCHASCAT CQGPAPTDCL SCPSHASLDP VEQTCSRQSQ SSRESRPQQQ PPALRPEVEM EPRLQAGLAS HLPEVLAGLS CLIIVLIFGI VFLFLHRCSG FSFRGVKVYT MDRGLISYKG LPPEAWQEEC PSDSEEDEGR GERTAFIKDQ SAL //