BioPAX pathway converted from "Ficolin-3 binds to molecular patterns on the target cell surface " in the Reactome database.LEFT-TO-RIGHTFicolin-3 binds to molecular patterns on the target cell surface Ficolin-3 (H-ficolin, FCN3, Hakata antigen) consists of a collagen-like strand and three C-terminal recognition domains, which bind to carbohydrates on the target surface. Circulating FCN3 is associated with mannan-binding lectin-associated serine proteases (MASP). Upon ligand binding the FCN3:MASP complex triggers activation of the lectin pathway (Matsushita et al. 2002, Teillet et al. 2008, Zacho et al. 2012). FCN3 can specifically recognize Aerococcus viridans (Tsujimura et al. 2002, Zacho et al. 2012) and binds patterns of bacterial polysaccharides such as d-fucose and galactose (Garlatti et al. 2007). In adition to pathogenic ligands, FCN3 was reported to bind apoptotic Jurkat cells (Kuraya et al. 2005). Authored: Shamovsky, V, 2012-10-17Reviewed: Bradley, DTEdited: Shamovsky, V, 2013-05-28Converted from EntitySet in ReactomeFCN3 ligandsFicolin-3 ligandsReactome DB_ID: 2855098N-acetyl-D-glucosamineN-acetyl-beta-D-glucosamineReactome DB_ID: 2855066plasma membraneGENE ONTOLOGYGO:0005886N-acetyl-beta-D-glucosamine [ChEBI:28009]N-acetyl-beta-D-glucosamineN-Acetyl-D-glucosamineAcetylglucosaminebetaGlcNAcN-acetylglucosamine2-Acetylamino-2-deoxy-D-glucose2-Acetamido-2-deoxy-D-glucoseGlcNAc-betaChEBICHEBI:28009Reactome Database ID Release 752855066Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855066ReactomeR-ALL-28550663Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-2855066.3Reactomehttp://www.reactome.orgD-fucoseReactome DB_ID: 2855088D-fucose [ChEBI:28847]D-fucoseD-FucChEBICHEBI:28847Reactome Database ID Release 752855088Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855088ReactomeR-ALL-28550882Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-2855088.2Reactome Database ID Release 752855098Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855098ReactomeR-ALL-28550982Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-2855098.2Ca2+Calciumcalcium(2+)Reactome DB_ID: 74112extracellular regionGENE ONTOLOGYGO:0005576calcium(2+) [ChEBI:29108]calcium(2+)ChEBICHEBI:29108Reactome Database ID Release 7574112Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=74112ReactomeR-ALL-741124Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-74112.4COMPOUNDC00076additional informationMIMI:03614FCN3 oligomer:MASP1 dimer:MASP2-1 dimerReactome DB_ID: 2855122MASP1 dimerReactome DB_ID: 166693MASP1MASP1(20-699)MASP-1Reactome DB_ID: 166687UniProt:P48740 MASP1MASP1CRARFCRARF1PRSS5FUNCTION Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5. Also plays a role in development (PubMed:21258343).ACTIVITY REGULATION Inhibited by SERPING1 and A2M.SUBUNIT Homodimer. Interacts with the oligomeric lectins MBL2, FCN2 and FCN3; triggers the lectin pathway of complement through activation of C3. Interacts with SERPING1. Interacts with COLEC11; probably triggers the lectin pathway of complement (PubMed:20956340).TISSUE SPECIFICITY Protein of the plasma which is primarily expressed by liver.PTM The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.PTM N-glycosylated. Some N-linked glycan are of the complex-type (By similarity).PTM Autoproteolytic processing of the proenzyme produces the active enzyme composed on the heavy and the light chain held together by a disulfide bond. Isoform 1 but not isoform 2 is activated through autoproteolytic processing.SIMILARITY Belongs to the peptidase S1 family.Homo sapiensNCBI Taxonomy9606UniProtP4874020EQUAL699EQUALReactome Database ID Release 75166687Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=166687ReactomeR-HSA-1666871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-166687.12Reactome Database ID Release 75166693Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=166693ReactomeR-HSA-1666931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-166693.11MASP2-1 dimerReactome DB_ID: 166694MASP-2MASP2-1MASP2 isoform 1Reactome DB_ID: 166689UniProt:O00187-1 MASP2MASP2FUNCTION Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.SUBUNIT Homodimer; disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1. Dimerization and MBL2 binding requires calcium ions.TISSUE SPECIFICITY Plasma.PTM The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.PTM Activated by cleavage after Arg-444. The uncleaved zymogen is inactive towards synthetic substrates, but has sufficient activity to effect autocatalytic cleavage.SIMILARITY Belongs to the peptidase S1 family.UniProt IsoformO00187-116EQUAL686EQUALReactome Database ID Release 75166689Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=166689ReactomeR-HSA-1666891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-166689.12Reactome Database ID Release 75166694Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=166694ReactomeR-HSA-1666942Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-166694.21FCN3 oligomerReactome DB_ID: 2530450FCN3 trimerReactome DB_ID: 2530444FCN3ficolin 3H-ficolinReactome DB_ID: 2530443UniProt:O75636 FCN3FCN3FCNHHAKA1FUNCTION May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide and lipopolysaccharides from S.typhimurium and S.minnesota.SUBUNIT Homotrimer (PubMed:17215869). May form an octadecamer consisting of an elementary trimer unit. Does not interact with fibronectin, elastin or zymosan. Interacts with MASP1 and MASP2.TISSUE SPECIFICITY Liver and lung. In liver it is produced by bile duct epithelial cells and hepatocytes. In lung it is produced by both ciliated bronchial epithelial cells and type II alveolar epithelial cells.PTM The N-terminus is blocked.SIMILARITY Belongs to the ficolin lectin family.UniProtO7563624EQUAL299EQUALReactome Database ID Release 752530443Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2530443ReactomeR-HSA-25304431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2530443.13Reactome Database ID Release 752530444Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2530444ReactomeR-HSA-25304442Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2530444.26Reactome Database ID Release 752530450Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2530450ReactomeR-HSA-25304503Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2530450.31Reactome Database ID Release 752855122Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855122ReactomeR-HSA-28551223Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2855122.3FCN3 ligands:FCN3 multimer:MASP1 dimer:MASP2 dimer:4xCa2+Reactome DB_ID: 2855093141Reactome Database ID Release 752855093Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855093ReactomeR-HSA-28550932Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2855093.2Reactome Database ID Release 752855077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2855077ReactomeR-HSA-28550771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2855077.111907111Pubmed2002Activation of the lectin complement pathway by H-ficolin (Hakata antigen)Matsushita, MKuraya, MikioHamasaki, NaotakaTsujimura, MitsushiShiraki, HiroshiFujita, TJ. Immunol. 168:3502-620375619Pubmed2010Structural insights into the recognition properties of human ficolinsGarlatti, VMartin, LLacroix, MGout, EArlaud, Gérard JThielens, Nicole MGaboriaud, CJ Innate Immun 2:17-2322238349Pubmed2012Studies of the pattern recognition molecule H-ficolin: specificity and purificationZacho, Rikke MJensen, LisbethTerp, RandiJensenius, Jens CThiel, SJ. Biol. Chem. 287:8071-8115804047Pubmed2005Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activationKuraya, MikioMing, ZhenpingLiu, XianzhouMatsushita, MFujita, TImmunobiology 209:689-9712367778Pubmed2002Serum concentration of Hakata antigen, a member of the ficolins, is linked with inhibition of Aerococcus viridans growthTsujimura, MitsushiMiyazaki, TakashiKojima, EijiroSagara, YasukoShiraki, HiroshiOkochi, KazuoMaeda, YoshiakiClin. Chim. Acta 325:139-4617215869Pubmed2007Structural insights into the innate immune recognition specificities of L- and H-ficolinsGarlatti, VBelloy, NicolasMartin, LLacroix, MMatsushita, MEndo, YFujita, TFontecilla-Camps, Juan CarlosArlaud, Gérard JThielens, Nicole MGaboriaud, CEMBO J. 26:623-3318596036Pubmed2008Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 and identification of its interaction sites with mannan-binding lectin and ficolinsTeillet, FGaboriaud, CLacroix, MMartin, LArlaud, GJThielens, NMJ Biol Chem 283:25715-24