Complement cascade (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none cytosolMBL-IIMASP-2 dimerMASP-1 dimer complexMBL-II tetramerMBL subunitMASP2 dimerMASP1 dimerMBL bound to mannose-based carbohydrates on bacterial surfacesMBL-IIMASP-2 dimerMASP-1 dimer complexMBL-II tetramerMBL subunitMASP2 dimerMASP1 dimerMBLactivated MASPsmannose-based carbohydratesMBL-IIActivated MASP-1 dimerActivated MASP-2 dimer complexMBL-II tetramerMBL subunitActivated MASP-2 dimerActivated MASP-1 dimerAntigen antibody C1 complexAntigen-antibody complexIgGIg Antibody Light ChainImmunoglobulin Kappa Light ChainIg Kappa Light Chain V RegionImmunoglobulin Lambda Light ChainIg Lamda Light Chain V RegionIg Lambda C regionIgG Heavy ChainIg Heavy Chain V RegionIgG C regionC1 complement factorC1QC1Q subunitC1SC1R tetramerAntigen antibody C1Antigen-antibody complexIgGIg Antibody Light ChainImmunoglobulin Kappa Light ChainIg Kappa Light Chain V RegionImmunoglobulin Lambda Light ChainIg Lamda Light Chain V RegionIg Lambda C regionIgG Heavy ChainIg Heavy Chain V RegionIgG C regionC1 complement factorC1QC1Q subunitC1Sactivated C1R tetramerActivated C1RAntigen antibody C1Antigen-antibody complexIgGIg Antibody Light ChainImmunoglobulin Kappa Light ChainIg Kappa Light Chain V RegionImmunoglobulin Lambda Light ChainIg Lamda Light Chain V RegionIg Lambda C regionIgG Heavy ChainIg Heavy Chain V RegionIgG C regionC1 complement factorC1QC1Q subunitActivated C1Sactivated C1R tetramerActivated C1RActivated C1SCell surfaceC4bC2aCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bComplement factor 3C3C3C3Cell surfaceC3bFactor B complexCell surfaceC3bC3bCell surfaceC3bFactor BbC3bC3C3Cell surfaceC3bFactor BbProperdinC3bC3bFactor BbC3bProperdin complexC3bCell surfaceC3bFactor BbProperdinC3bC4bC2aC3bCell surfaceC4bC2aCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bCell surfaceC3bC3bComplement factor 5C5bC5bC6 complexC5bC5bC6C7 complexC5bC5bC6C7 complexC5bC8C5bC6C7C8 complexC5bC8Membrane Attack ComplexC5bC8Cell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bCell surfaceC3bC3bFactor HC3bC3bCell surfaceFH,FHR3C3bCell surfaceC3bC3bCell surfaceFH,FHR3C3bBbCell surfaceC3bFactor BbC3bComplement factor IComplement factor IFactor HC3bFactor HC3bC3bComplement factor IC3biC3bComplement factor ICell surfaceFH,FHR3C3bComplement factor ICell surfaceFH,FHR3C3bCell surfaceC3bC3biC3bFactor IMCP, CR1C4b, C3b complexesComplement factor IMCP, CR1C4bC3b complexesMCPC3bC3bMCPC4bCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bCR1C3bCR1C4bDAFC3bC3bDAFC4bCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bC4b-binding proteinC4-binding proteinC4bC4b-binding proteinthioester-C1010-Q1013-C4bthioester-C1010-Q1013- C4A-derived C4bthioester-C1010-Q1013-C4B-derived C4bC4b-binding proteinFactor IC4-binding proteinC4bC4b-binding proteinthioester-C1010-Q1013-C4bthioester-C1010-Q1013- C4A-derived C4bthioester-C1010-Q1013-C4B-derived C4bComplement factor IC4 binding proteinC4bC2aC4b-binding proteinCell surfaceC4bC2aCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bFactor HHost cell surfaceHost cell surfaceCR1C3bC3bCR1C4bCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bHost cell surfaceMCPC3bC3bMCPC4bCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bC4 binding proteinprotein SC4b-binding proteinthioester-C1010-Q1013-C4bthioester-C1010-Q1013- C4A-derived C4bthioester-C1010-Q1013-C4B-derived C4bCell surfaceC3bC3bC-reactive protein pentamerphosphocholineC1QC-reactive protein pentamerphosphocholineC-reactive protein homopentamerC1QC1Q subunitFCN1MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-1 tetramerFCN1 subunitFCN1MASPsCa2+FCN1 ligandFCN1 ligandFCN1MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-1 tetramerFCN1 subunitFCN2MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-2 tetramerFCN2 subunitFCN2MASPsCa2+FCN2 ligandFCN2MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-2 tetramerFCN2 subunitFCN2 ligandFCN3MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-3 hexamerFCN3 subunitFCN3MASPsCa2+FCN3 ligandFCN3 ligandFCN3MASP2 dimerMASP1 dimerMASP2 dimerMASP1 dimerFicolin-3 hexamerFCN3 subunitCell surfaceC3bFactor BbC3bCR1iC3biC3bC3cCD59C5b-C9C5bC6C7C8 complexC5bC8VTNC5bC6C7C5bC6C7 complexC5bVTNC5bC6C7C8C9VTNC5bC6C7C5bC6C7 complexC5bC8C3bC3bC3Cell surfaceC4bC2aCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bCell surfaceC4bC4bdeamidated-Q1013-C4B-derived C4bdeamidated-Q1013-C4A-derived C4bCa2+Bacterial mannose-based carbohydrate surface patternMBL-IIMASP-2 dimerMASP-1 dimer complexMBL bound to mannose-based carbohydrates on bacterial surfacesMBLactivated MASPsmannose-based carbohydratesAntigen antibody C1 complexAntigen antibody C1Antigen antibody C1C4 activatorC2C2bC2aCell surfaceC4bC2aComplement factor 3H2OC3CFBC3Cell surfaceC3bFactor B complexCFBCell surfaceC3bFactor BbC3CFDProperdin oligomerCell surfaceC3bFactor BbProperdinC3aC3bFactor BbC3bProperdin complexC3bC3 convertasesC4bC2aC3bComplement factor 5C5aC5bC5 convertasesC6C5bC6 complexC7C5bC6C7 complexC5bC6C7 complexC8C5bC6C7C8 complexC9Membrane Attack ComplexComplement Factor 4thioester-C1010-Q1013-C4bC4aCell surfaceC4bCell surfaceC3bCFBFactor HC3bCell surfaceFH,FHR3C3bCFHCell surfaceFH,FHR3C3bBbCFICFIComplement factor IComplement factor IFactor HC3bC3biC3bC3fComplement factor ICell surfaceFH,FHR3C3biC3bMCP, CR1C4bC2a, C3bBbCR1C3bBb, C4bC2a complexesMCP, CR1C4bC3b complexesFactor IMCP, CR1C4b, C3b complexesC4d, iC3bC4c, C3fDAFC3 convertase complexesDAFC3bDAFC4bC4b-binding proteinC4-binding proteinC4bC4b-binding proteinFactor IC4dC4cC4 binding proteinC4bC2aCD55Cell surfaceFactor HHost cell surfaceCR1CR1C3bCR1C4bHost cell surfaceC4b, C3bCD46MCPC3bMCPC4b11xCbxE-PROS1C4 binding proteinprotein Sthioester-C1010-Q1013-C4bCell surfaceC3bCell surfaceC3aC2aC2aC2aC-reactive protein pentamerphosphocholineC1QFH, FHR-3Complement factor DMBL/FicolinMASPs bound to carbohydrate patternsMBL/FCNactivated MASPcarbohydrate patternsFCN1MASP2 dimerMASP1 dimerFCN1 ligandFCN1MASPsCa2+FCN1 ligandFCN2 ligandFCN2MASP2 dimerMASP1 dimerFCN2MASPsCa2+FCN2 ligandFCN3 ligandFCN3MASP2 dimerMASP1 dimerFCN3MASPsCa2+FCN3 ligandCell surfaceC3bFactor BbCR1iC3bC3dgC3cCD59CD59C5b-C9VTNC5bC6C7VTNC5bC6C7C8C9VTNC9H2OC4b with hydrolysed thioesterC3 convertasesC3bC3bC2aC3Cell surfaceC4bC2aCell surfaceC4bMBL2MASP2-1MASP1MBL2MASP2-1MASP1Ca2+Ca2+MBL2MASP2-1MASP2-1MASP1MASP1IGKCIGKV4-1IGKV1-5IGLVIGKVA18Ig kappa chain V region EV15Ig kappa chain V-I region AGIg kappa chain V-I region AUIg kappa chain V-I region BANIg kappa chain V-I region BiIg kappa chain V-I region CARIg kappa chain V-I region DEEIg kappa chain V-I region DaudiIg kappa chain V-I region EUIg kappa chain V-I region GalIg kappa chain V-I region HK101Ig kappa chain V-I region HauIg kappa chain V-I region KaIg kappa chain V-I region KueIg kappa chain V-I region LayIg kappa chain V-I region MevIg kappa chain V-I region NiIg kappa chain V-I region OUIg kappa chain V-I region ReiIg kappa chain V-I region RoyIg kappa chain V-I region ScwIg kappa chain V-I region WATIg kappa chain V-I region WEAIg kappa chain V-I region WalkerIg kappa chain V-I region WesIg kappa chain V-II region CumIg kappa chain V-II region FRIg kappa chain V-II region GM607Ig kappa chain V-II region MILIg kappa chain V-II region RPMI 6410Ig kappa chain V-II region TEWIg kappa chain V-III region B6Ig kappa chain V-III region CLLIg kappa chain V-III region GOLIg kappa chain V-III region HAHIg kappa chain V-III region HICIg kappa chain V-III region IARC/BL41Ig kappa chain V-III region NG9Ig kappa chain V-III region POMIg kappa chain V-III region SIEIg kappa chain V-III region TiIg kappa chain V-III region VGIg kappa chain V-III region VHIg kappa chain V-III region WOLIg kappa chain V-IV region B17Ig kappa chain V-IV region JIIg kappa chain V-IV region LenIg kappa chain V-IV region STHIGLV8-61IGLV4-3IGLV1-36IGLV2-18IGLV2-33IGLV3-16IGLV5-37IGLV1-40IGLV1-44IGLV3-22IGLV7-43IGLV5-45IGLV4-60IGLV10-54IGLV2-11IGLV2-23IGLV3-25IGLV3-27IGLV3-12IGLV7-46IGLV11-55IGLV4-69Ig lambda chain V region 4AIg lambda chain V-I region BL2Ig lambda chain V-I region EPSIg lambda chain V-I region HAIg lambda chain V-I region MEMIg lambda chain V-I region NEWIg lambda chain V-I region NEWMIg lambda chain V-I region NIG-64Ig lambda chain V-I region VORIg lambda chain V-I region WAHIg lambda chain V-II region BOIg lambda chain V-II region BOHIg lambda chain V-II region BURIg lambda chain V-II region MGCIg lambda chain V-II region NEIIg lambda chain V-II region NIG-58Ig lambda chain V-II region NIG-84Ig lambda chain V-II region TOGIg lambda chain V-II region TROIg lambda chain V-II region VILIg lambda chain V-II region WINIg lambda chain V-III region LOIIg lambda chain V-III region SHIg lambda chain V-IV region BauIg lambda chain V-IV region HilIg lambda chain V-IV region KernIg lambda chain V-IV region MOLIg lambda chain V-IV region XIg lambda chain V-V region DELIg lambda chain V-VI region ARIg lambda chain V-VI region EB4Ig lambda chain V-VI region NIG-48Ig lambda chain V-VI region SUTIg lambda chain V-VI region WLTIg lambda chain V-VII region MOTIGLC1IGLC2IGLC3IGLC6IGLC7IgH heavy chain V-III region VH26 precursorIGHV7-81IGHVIg heavy chain V-I region EUIg heavy chain V-I region HG3Ig heavy chain V-I region NDIg heavy chain V-I region SIEIg heavy chain V-I region WOLIg heavy chain V-II region CORIg heavy chain V-II region DAWIg heavy chain V-II region HEIg heavy chain V-II region MCEIg heavy chain V-II region NEWMIg heavy chain V-II region OUIg heavy chain V-II region WAHIg heavy chain V-III region BROIg heavy chain V-III region BURIg heavy chain V-III region BUTIg heavy chain V-III region CAMIg heavy chain V-III region DOBIg heavy chain V-III region GAIg heavy chain V-III region GALIg heavy chain V-III region HILIg heavy chain V-III region JONIg heavy chain V-III region KOLIg heavy chain V-III region LAYIg heavy chain V-III region NIEIg heavy chain V-III region POMIg heavy chain V-III region TEIIg heavy chain V-III region TILIg heavy chain V-III region TROIg heavy chain V-III region TURIg heavy chain V-III region WASIg heavy chain V-III region WEAIg heavy chain V-III region ZAPIg heavy chain V-I region MotIg heavy chain V-II region ARH-77Ig heavy chain V-II region SESSIGHG1IGHG2IGHG3IGHG4C1QAC1QBC1QCC1RC1SIGKCIGKV4-1IGKV1-5IGLVIGKVA18Ig kappa chain V region EV15Ig kappa chain V-I region AGIg kappa chain V-I region AUIg kappa chain V-I region BANIg kappa chain V-I region BiIg kappa chain V-I region CARIg kappa chain V-I region DEEIg kappa chain V-I region DaudiIg kappa chain V-I region EUIg kappa chain V-I region GalIg kappa chain V-I region HK101Ig kappa chain V-I region HauIg kappa chain V-I region KaIg kappa chain V-I region KueIg kappa chain V-I region LayIg kappa chain V-I region MevIg kappa chain V-I region NiIg kappa chain V-I region OUIg kappa chain V-I region ReiIg kappa chain V-I region RoyIg kappa chain V-I region ScwIg kappa chain V-I region WATIg kappa chain V-I region WEAIg kappa chain V-I region WalkerIg kappa chain V-I region WesIg kappa chain V-II region CumIg kappa chain V-II region FRIg kappa chain V-II region GM607Ig kappa chain V-II region MILIg kappa chain V-II region RPMI 6410Ig kappa chain V-II region TEWIg kappa chain V-III region B6Ig kappa chain V-III region CLLIg kappa chain V-III region GOLIg kappa chain V-III region HAHIg kappa chain V-III region HICIg kappa chain V-III region IARC/BL41Ig kappa chain V-III region NG9Ig kappa chain V-III region POMIg kappa chain V-III region SIEIg kappa chain V-III region TiIg kappa chain V-III region VGIg kappa chain V-III region VHIg kappa chain V-III region WOLIg kappa chain V-IV region B17Ig kappa chain V-IV region JIIg kappa chain V-IV region LenIg kappa chain V-IV region STHIGLV8-61IGLV4-3IGLV1-36IGLV2-18IGLV2-33IGLV3-16IGLV5-37IGLV1-40IGLV1-44IGLV3-22IGLV7-43IGLV5-45IGLV4-60IGLV10-54IGLV2-11IGLV2-23IGLV3-25IGLV3-27IGLV3-12IGLV7-46IGLV11-55IGLV4-69Ig lambda chain V region 4AIg lambda chain V-I region BL2Ig lambda chain V-I region EPSIg lambda chain V-I region HAIg lambda chain V-I region MEMIg lambda chain V-I region NEWIg lambda chain V-I region NEWMIg lambda chain V-I region NIG-64Ig lambda chain V-I region VORIg lambda chain V-I region WAHIg lambda chain V-II region BOIg lambda chain V-II region BOHIg lambda chain V-II region BURIg lambda chain V-II region MGCIg lambda chain V-II region NEIIg lambda chain V-II region NIG-58Ig lambda chain V-II region NIG-84Ig lambda chain V-II region TOGIg lambda chain V-II region TROIg lambda chain V-II region VILIg lambda chain V-II region WINIg lambda chain V-III region LOIIg lambda chain V-III region SHIg lambda chain V-IV region BauIg lambda chain V-IV region HilIg lambda chain V-IV region KernIg lambda chain V-IV region MOLIg lambda chain V-IV region XIg lambda chain V-V region DELIg lambda chain V-VI region ARIg lambda chain V-VI region EB4Ig lambda chain V-VI region NIG-48Ig lambda chain V-VI region SUTIg lambda chain V-VI region WLTIg lambda chain V-VII region MOTIGLC1IGLC2IGLC3IGLC6IGLC7IgH heavy chain V-III region VH26 precursorIGHV7-81IGHVIg heavy chain V-I region EUIg heavy chain V-I region HG3Ig heavy chain V-I region NDIg heavy chain V-I region SIEIg heavy chain V-I region WOLIg heavy chain V-II region CORIg heavy chain V-II region DAWIg heavy chain V-II region HEIg heavy chain V-II region MCEIg heavy chain V-II region NEWMIg heavy chain V-II region OUIg heavy chain V-II region WAHIg heavy chain V-III region BROIg heavy chain V-III region BURIg heavy chain V-III region BUTIg heavy chain V-III region CAMIg heavy chain V-III region DOBIg heavy chain V-III region GAIg heavy chain V-III region GALIg heavy chain V-III region HILIg heavy chain V-III region JONIg heavy chain V-III region KOLIg heavy chain V-III region LAYIg heavy chain V-III region NIEIg heavy chain V-III region POMIg heavy chain V-III region TEIIg heavy chain V-III region TILIg heavy chain V-III region TROIg heavy chain V-III region TURIg heavy chain V-III region WASIg heavy chain V-III region WEAIg heavy chain V-III region ZAPIg heavy chain V-I region MotIg heavy chain V-II region ARH-77Ig heavy chain V-II region SESSIGHG1IGHG2IGHG3IGHG4C1QAC1QBC1QCC1SC1R C-terminal fragmentC1R N-terminal fragmentIGKCIGKV4-1IGKV1-5IGLVIGKVA18Ig kappa chain V region EV15Ig kappa chain V-I region AGIg kappa chain V-I region AUIg kappa chain V-I region BANIg kappa chain V-I region BiIg kappa chain V-I region CARIg kappa chain V-I region DEEIg kappa chain V-I region DaudiIg kappa chain V-I region EUIg kappa chain V-I region GalIg kappa chain V-I region HK101Ig kappa chain V-I region HauIg kappa chain V-I region KaIg kappa chain V-I region KueIg kappa chain V-I region LayIg kappa chain V-I region MevIg kappa chain V-I region NiIg kappa chain V-I region OUIg kappa chain V-I region ReiIg kappa chain V-I region RoyIg kappa chain V-I region ScwIg kappa chain V-I region WATIg kappa chain V-I region WEAIg kappa chain V-I region WalkerIg kappa chain V-I region WesIg kappa chain V-II region CumIg kappa chain V-II region FRIg kappa chain V-II region GM607Ig kappa chain V-II region MILIg kappa chain V-II region RPMI 6410Ig kappa chain V-II region TEWIg kappa chain V-III region B6Ig kappa chain V-III region CLLIg kappa chain V-III region GOLIg kappa chain V-III region HAHIg kappa chain V-III region HICIg kappa chain V-III region IARC/BL41Ig kappa chain V-III region NG9Ig kappa chain V-III region POMIg kappa chain V-III region SIEIg kappa chain V-III region TiIg kappa chain V-III region VGIg kappa chain V-III region VHIg kappa chain V-III region WOLIg kappa chain V-IV region B17Ig kappa chain V-IV region JIIg kappa chain V-IV region LenIg kappa chain V-IV region STHIGLV8-61IGLV4-3IGLV1-36IGLV2-18IGLV2-33IGLV3-16IGLV5-37IGLV1-40IGLV1-44IGLV3-22IGLV7-43IGLV5-45IGLV4-60IGLV10-54IGLV2-11IGLV2-23IGLV3-25IGLV3-27IGLV3-12IGLV7-46IGLV11-55IGLV4-69Ig lambda chain V region 4AIg lambda chain V-I region BL2Ig lambda chain V-I region EPSIg lambda chain V-I region HAIg lambda chain V-I region MEMIg lambda chain V-I region NEWIg lambda chain V-I region NEWMIg lambda chain V-I region NIG-64Ig lambda chain V-I region VORIg lambda chain V-I region WAHIg lambda chain V-II region BOIg lambda chain V-II region BOHIg lambda chain V-II region BURIg lambda chain V-II region MGCIg lambda chain V-II region NEIIg lambda chain V-II region NIG-58Ig lambda chain V-II region NIG-84Ig lambda chain V-II region TOGIg lambda chain V-II region TROIg lambda chain V-II region VILIg lambda chain V-II region WINIg lambda chain V-III region LOIIg lambda chain V-III region SHIg lambda chain V-IV region BauIg lambda chain V-IV region HilIg lambda chain V-IV region KernIg lambda chain V-IV region MOLIg lambda chain V-IV region XIg lambda chain V-V region DELIg lambda chain V-VI region ARIg lambda chain V-VI region EB4Ig lambda chain V-VI region NIG-48Ig lambda chain V-VI region SUTIg lambda chain V-VI region WLTIg lambda chain V-VII region MOTIGLC1IGLC2IGLC3IGLC6IGLC7IgH heavy chain V-III region VH26 precursorIGHV7-81IGHVIg heavy chain V-I region EUIg heavy chain V-I region HG3Ig heavy chain V-I region NDIg heavy chain V-I region SIEIg heavy chain V-I region WOLIg heavy chain V-II region CORIg heavy chain V-II region DAWIg heavy chain V-II region HEIg heavy chain V-II region MCEIg heavy chain V-II region NEWMIg heavy chain V-II region OUIg heavy chain V-II region WAHIg heavy chain V-III region BROIg heavy chain V-III region BURIg heavy chain V-III region BUTIg heavy chain V-III region CAMIg heavy chain V-III region DOBIg heavy chain V-III region GAIg heavy chain V-III region GALIg heavy chain V-III region HILIg heavy chain V-III region JONIg heavy chain V-III region KOLIg heavy chain V-III region LAYIg heavy chain V-III region NIEIg heavy chain V-III region POMIg heavy chain V-III region TEIIg heavy chain V-III region TILIg heavy chain V-III region TROIg heavy chain V-III region TURIg heavy chain V-III region WASIg heavy chain V-III region WEAIg heavy chain V-III region ZAPIg heavy chain V-I region MotIg heavy chain V-II region ARH-77Ig heavy chain V-II region SESSIGHG1IGHG2IGHG3IGHG4C1QAC1QBC1QCC1R C-terminal fragmentC1R N-terminal fragmentC1S C-terminal fragmentC1S N-terminal fragmentC2aC4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AC3 alpha chainC3 beta chaindNQ-C3C3 beta chainCFBdNQ-C3C3 beta chainCFBC3 beta chainC3b alpha'CFBC3 beta chainC3b alpha'dNQ-C3C3 beta chainCFBCFBC3 beta chainC3b alpha'C3 beta chainC3b alpha'CFBC3 beta chainC3b alpha'C2aC4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AC3 beta chainC3b alpha'C5 alphaC5 betaC5 betaC5b alpha'C5 betaC5b alpha'C6C5 betaC5b alpha'C6C7C5 betaC5b alpha'C6C7C8AC8BC8GC5 betaC5b alpha'C6C7C8AC8BC8GC5 betaC5b alpha'C6C7C8AC8BC8GC9C4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AC3 beta chainC3b alpha'CFHC3 beta chainC3b alpha'C3 beta chainC3b alpha'CFBC3 beta chainC3b alpha'CFICFICFHC3 beta chainC3b alpha'CFICFIC3 beta chainC3b alpha'C3 beta chainC3c alpha' chain fragment 1 precursorC3c alpha' chain fragment 2CFICFIC3 beta chainC3b alpha'C3 beta chainC3c alpha' chain fragment 1 precursorC3c alpha' chain fragment 2CFICFICD46C3 beta chainC3b alpha'C4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4ACR1CD55C3 beta chainC3b alpha'C4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4ACD55C4BPAC4BPBC4BPAC4BPBC4A alpha bC4A betaC4A gammaC4B alpha chain fragment bC4B betaC4B gammaC4BPAC4BPBC4A alpha bC4A betaC4A gammaC4B alpha chain fragment bC4B betaC4B gammaCFICFIC4BPAC4BPBC2aC4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4ACFHHeparinsSialic acidCR1C3 beta chainC3b alpha'CR1C4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AHeparinsSialic acidCD46C3 beta chainC3b alpha'CD46C4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AC4BPAC4BPB11xCbxE-PROS1C4A alpha bC4A betaC4A gammaC4B alpha chain fragment bC4B betaC4B gammaC3 beta chainC3b alpha'CRPCa2+PChoC1QAC1QBC1QCMASP2-1MASP1FCN1Ca2+N-acetyl-D-glucosamineN-acetylgalactosamineSialic acidMASP2-1MASP1FCN1MASP2-1MASP1FCN2Ca2+MASP2-1MASP1FCN2N-acetyl-D-glucosamine1,3-beta-D-glucanLipoteichoic acidN-acetylgalactosamineMASP2-1MASP1FCN3Ca2+N-acetyl-D-glucosamineD-fucoseMASP2-1MASP1FCN3CFBC3 beta chainC3b alpha'CR1C3 beta chainC3c alpha' chain fragment 1 precursorC3c alpha' chain fragment 2C3 beta chainC3c alpha' chain fragment 2C3c alpha' chain fragment 1C5 betaC5b alpha'C6C7C8AC8BC8GC9CD59VTNC5 betaC5b alpha'C6C7VTNC5 betaC5b alpha'C6C7C8AC8BC8GC9C3 beta chainC3b alpha'C3 beta chainC3b alpha'dNQ-C3C3 beta chainC2aC4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AC4B betaC4B gammadNQ-C4BC4A betaC4A gammadNQ-C4AName: Complement cascadeOrganism: Homo sapiens


Description

The complement system is a biochemical cascade, so named because it 'complements' the ability of antibodies to clear pathogens. It is part of the innate immune system. Complement system proteins circulate in the blood as inactive precursors (pro-proteins). When triggered by the presence of microbes, complement proteases cleave complement proteins, initiating a cascade of further cleavages. The end-result of this activation is the activation of the Membrane Attack Complex and cell lysis. The C3 and C5 components also lead to phagocytosis by leukocytes.

There are three branches that lead to activation of the complement system: the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. Complement proteins are always present in the blood and a small percentage spontaneously activate. Innapropriate activation leads to host cell damage, so the activation process is tightly controlled by several regulatory mechanisms.

N.B. Originally the larger fragment of Complement Factor 2 (C2) was designated C2a. However, complement scientists decided that the smaller of all C fragments should be designated with an 'a', the larger with a 'b', changing the nomenclature for C2. Recent literature may use the updated nomenclature and refer to the larger C2 fragment as C2b, and refer to the classical C3 convertase as C4bC2b. Throughout this pathway Reactome adheres to the original convention to agree with the current (Feb 2012) Uniprot names for C2 fragments.

Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=166658

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Ontology Terms

Pathway Ontology : hormone signaling pathway
 

Bibliography

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  1. Chen CB, Wallis R.; ''Stoichiometry of complexes between mannose-binding protein and its associated serine proteases. Defining functional units for complement activation.''; PubMed Europe PMC Scholia
  2. Liu Y, Endo Y, Iwaki D, Nakata M, Matsushita M, Wada I, Inoue K, Munakata M, Fujita T.; ''Human M-ficolin is a secretory protein that activates the lectin complement pathway.''; PubMed Europe PMC Scholia
  3. Law SK, Levine RP.; ''Interaction between the third complement protein and cell surface macromolecules.''; PubMed Europe PMC Scholia
  4. Fujita T, Gigli I, Nussenzweig V.; ''Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator.''; PubMed Europe PMC Scholia
  5. Kuraya M, Ming Z, Liu X, Matsushita M, Fujita T.; ''Specific binding of L-ficolin and H-ficolin to apoptotic cells leads to complement activation.''; PubMed Europe PMC Scholia
  6. Tsujimura M, Miyazaki T, Kojima E, Sagara Y, Shiraki H, Okochi K, Maeda Y.; ''Serum concentration of Hakata antigen, a member of the ficolins, is linked with inhibition of Aerococcus viridans growth.''; PubMed Europe PMC Scholia
  7. Hourcade DE, Mitchell L, Kuttner-Kondo LA, Atkinson JP, Medof ME.; ''Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb.''; PubMed Europe PMC Scholia
  8. Aleshin AE, DiScipio RG, Stec B, Liddington RC.; ''Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex.''; PubMed Europe PMC Scholia
  9. Campbell WD, Lazoura E, Okada N, Okada H.; ''Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N.''; PubMed Europe PMC Scholia
  10. Daha MR, Fearon DT, Austen KF.; ''C3 requirements for formation of alternative pathway C5 convertase.''; PubMed Europe PMC Scholia
  11. Rawal N, Pangburn MK.; ''Formation of high affinity C5 convertase of the classical pathway of complement.''; PubMed Europe PMC Scholia
  12. Alcorlo M, Tortajada A, Rodríguez de Córdoba S, Llorca O.; ''Structural basis for the stabilization of the complement alternative pathway C3 convertase by properdin.''; PubMed Europe PMC Scholia
  13. Teillet F, Gaboriaud C, Lacroix M, Martin L, Arlaud GJ, Thielens NM.; ''Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 and identification of its interaction sites with mannan-binding lectin and ficolins.''; PubMed Europe PMC Scholia
  14. Scharfstein J, Ferreira A, Gigli I, Nussenzweig V.; ''Human C4-binding protein. I. Isolation and characterization.''; PubMed Europe PMC Scholia
  15. Krisinger MJ, Goebeler V, Lu Z, Meixner SC, Myles T, Pryzdial EL, Conway EM.; ''Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway.''; PubMed Europe PMC Scholia
  16. DiScipio RG, Davie EW.; ''Characterization of protein S, a gamma-carboxyglutamic acid containing protein from bovine and human plasma.''; PubMed Europe PMC Scholia
  17. Zacho RM, Jensen L, Terp R, Jensenius JC, Thiel S.; ''Studies of the pattern recognition molecule H-ficolin: specificity and purification.''; PubMed Europe PMC Scholia
  18. Ziccardi RJ, Dahlback B, Müller-Eberhard HJ.; ''Characterization of the interaction of human C4b-binding protein with physiological ligands.''; PubMed Europe PMC Scholia
  19. Aoyagi Y, Adderson EE, Rubens CE, Bohnsack JF, Min JG, Matsushita M, Fujita T, Okuwaki Y, Takahashi S.; ''L-Ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway.''; PubMed Europe PMC Scholia
  20. Weiler JM, Daha MR, Austen KF, Fearon DT.; ''Control of the amplification convertase of complement by the plasma protein beta1H.''; PubMed Europe PMC Scholia
  21. Kjaer TR, Hansen AG, Sørensen UB, Nielsen O, Thiel S, Jensenius JC.; ''Investigations on the pattern recognition molecule M-ficolin: quantitative aspects of bacterial binding and leukocyte association.''; PubMed Europe PMC Scholia
  22. Lynch NJ, Roscher S, Hartung T, Morath S, Matsushita M, Maennel DN, Kuraya M, Fujita T, Schwaeble WJ.; ''L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement.''; PubMed Europe PMC Scholia
  23. Law SK, Lichtenberg NA, Holcombe FH, Levine RP.; ''Interaction between the labile binding sites of the fourth (C4) and fifth (C5) human complement proteins and erythrocyte cell membranes.''; PubMed Europe PMC Scholia
  24. Gigli I, Fujita T, Nussenzweig V.; ''Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator.''; PubMed Europe PMC Scholia
  25. Keshi H, Sakamoto T, Kawai T, Ohtani K, Katoh T, Jang SJ, Motomura W, Yoshizaki T, Fukuda M, Koyama S, Fukuzawa J, Fukuoh A, Yoshida I, Suzuki Y, Wakamiya N.; ''Identification and characterization of a novel human collectin CL-K1.''; PubMed Europe PMC Scholia
  26. Masaki T, Matsumoto M, Nakanishi I, Yasuda R, Seya T.; ''Factor I-dependent inactivation of human complement C4b of the classical pathway by C3b/C4b receptor (CR1, CD35) and membrane cofactor protein (MCP, CD46).''; PubMed Europe PMC Scholia
  27. Vorup-Jensen T, Petersen SV, Hansen AG, Poulsen K, Schwaeble W, Sim RB, Reid KB, Davis SJ, Thiel S, Jensenius JC.; ''Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation revealed by reconstitution of MBL with recombinant MBL-associated serine protease-2.''; PubMed Europe PMC Scholia
  28. Scibek JJ, Plumb ME, Sodetz JM.; ''Binding of human complement C8 to C9: role of the N-terminal modules in the C8 alpha subunit.''; PubMed Europe PMC Scholia
  29. Alcorlo M, Martínez-Barricarte R, Fernández FJ, Rodríguez-Gallego C, Round A, Vega MC, Harris CL, de Cordoba SR, Llorca O.; ''Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy.''; PubMed Europe PMC Scholia
  30. Dahlbäck B, Smith CA, Müller-Eberhard HJ.; ''Visualization of human C4b-binding protein and its complexes with vitamin K-dependent protein S and complement protein C4b.''; PubMed Europe PMC Scholia
  31. Goldberger G, Bruns GA, Rits M, Edge MD, Kwiatkowski DJ.; ''Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4.''; PubMed Europe PMC Scholia
  32. Honoré C, Rørvig S, Hummelshøj T, Skjoedt MO, Borregaard N, Garred P.; ''Tethering of Ficolin-1 to cell surfaces through recognition of sialic acid by the fibrinogen-like domain.''; PubMed Europe PMC Scholia
  33. Lehto T, Morgan BP, Meri S.; ''Binding of human and rat CD59 to the terminal complement complexes.''; PubMed Europe PMC Scholia
  34. Sim RB, Reboul A, Arlaud GJ, Villiers CL, Colomb MG.; ''Interaction of 125I-labelled complement subcomponents C-1r and C-1s with protease inhibitors in plasma.''; PubMed Europe PMC Scholia
  35. Kalant D, Cain SA, Maslowska M, Sniderman AD, Cianflone K, Monk PN.; ''The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein.''; PubMed Europe PMC Scholia
  36. Davis AE, Harrison RA, Lachmann PJ.; ''Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d,g (alpha 2D), and C3g.''; PubMed Europe PMC Scholia
  37. Kishore U, Ghai R, Greenhough TJ, Shrive AK, Bonifati DM, Gadjeva MG, Waters P, Kojouharova MS, Chakraborty T, Agrawal A.; ''Structural and functional anatomy of the globular domain of complement protein C1q.''; PubMed Europe PMC Scholia
  38. Ziccardi RJ, Cooper NR.; ''Activation of C1r by proteolytic cleavage.''; PubMed Europe PMC Scholia
  39. Teh C, Le Y, Lee SH, Lu J.; ''M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli.''; PubMed Europe PMC Scholia
  40. Jokiranta TS, Cheng ZZ, Seeberger H, Jòzsi M, Heinen S, Noris M, Remuzzi G, Ormsby R, Gordon DL, Meri S, Hellwage J, Zipfel PF.; ''Binding of complement factor H to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site.''; PubMed Europe PMC Scholia
  41. Butkowski RJ, Elion J, Downing MR, Mann KG.; ''Primary structure of human prethrombin 2 and alpha-thrombin.''; PubMed Europe PMC Scholia
  42. Fearon DT.; ''Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane.''; PubMed Europe PMC Scholia
  43. Bokisch VA, Müller-Eberhard HJ.; ''Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase.''; PubMed Europe PMC Scholia
  44. Bhakdi S, Käflein R, Halstensen TS, Hugo F, Preissner KT, Mollnes TE.; ''Complement S-protein (vitronectin) is associated with cytolytic membrane-bound C5b-9 complexes.''; PubMed Europe PMC Scholia
  45. Teillet F, Dublet B, Andrieu JP, Gaboriaud C, Arlaud GJ, Thielens NM.; ''The two major oligomeric forms of human mannan-binding lectin: chemical characterization, carbohydrate-binding properties, and interaction with MBL-associated serine proteases.''; PubMed Europe PMC Scholia
  46. Dahlbäck B, Stenflo J.; ''High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein.''; PubMed Europe PMC Scholia
  47. Müller-Eberhard HJ.; ''Molecular organization and function of the complement system.''; PubMed Europe PMC Scholia
  48. Gasque P.; ''Complement: a unique innate immune sensor for danger signals.''; PubMed Europe PMC Scholia
  49. Sheehan M, Morris CA, Pussell BA, Charlesworth JA.; ''Complement inhibition by human vitronectin involves non-heparin binding domains.''; PubMed Europe PMC Scholia
  50. Nagasawa S, Ichihara C, Stroud RM.; ''Cleavage of C4b by C3b inactivator: production of a nicked form of C4b, C4b', as an intermediate cleavage product of C4b by C3b inactivator.''; PubMed Europe PMC Scholia
  51. Kishore U, Reid KB.; ''C1q: structure, function, and receptors.''; PubMed Europe PMC Scholia
  52. Nonaka M, Yoshizaki F.; ''Evolution of the complement system.''; PubMed Europe PMC Scholia
  53. Matsumoto AK, Martin DR, Carter RH, Klickstein LB, Ahearn JM, Fearon DT.; ''Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.''; PubMed Europe PMC Scholia
  54. Garlatti V, Martin L, Lacroix M, Gout E, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural insights into the recognition properties of human ficolins.''; PubMed Europe PMC Scholia
  55. Farries TC, Lachmann PJ, Harrison RA.; ''Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products.''; PubMed Europe PMC Scholia
  56. Tschopp J, Chonn A, Hertig S, French LE.; ''Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9.''; PubMed Europe PMC Scholia
  57. Wu J, Wu YQ, Ricklin D, Janssen BJ, Lambris JD, Gros P.; ''Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.''; PubMed Europe PMC Scholia
  58. Fearon DT, Austen KF.; ''Initiation of C3 cleavage in the alternative complement pathway.''; PubMed Europe PMC Scholia
  59. Wittenborn T, Thiel S, Jensen L, Nielsen HJ, Jensenius JC.; ''Characteristics and biological variations of M-ficolin, a pattern recognition molecule, in plasma.''; PubMed Europe PMC Scholia
  60. Budayova-Spano M, Lacroix M, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C.; ''The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex.''; PubMed Europe PMC Scholia
  61. Ma YG, Cho MY, Zhao M, Park JW, Matsushita M, Fujita T, Lee BL.; ''Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement.''; PubMed Europe PMC Scholia
  62. Matsushita M, Kuraya M, Hamasaki N, Tsujimura M, Shiraki H, Fujita T.; ''Activation of the lectin complement pathway by H-ficolin (Hakata antigen).''; PubMed Europe PMC Scholia
  63. Petersen SV, Thiel S, Jensenius JC.; ''The mannan-binding lectin pathway of complement activation: biology and disease association.''; PubMed Europe PMC Scholia
  64. Preissner KP, Podack ER, Müller-Eberhard HJ.; ''SC5b-7, SC5b-8 and SC5b-9 complexes of complement: ultrastructure and localization of the S-protein (vitronectin) within the macromolecules.''; PubMed Europe PMC Scholia
  65. Ross GD, Lambris JD, Cain JA, Newman SL.; ''Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity.''; PubMed Europe PMC Scholia
  66. Huang Y, Fedarovich A, Tomlinson S, Davies C.; ''Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex.''; PubMed Europe PMC Scholia
  67. Pangburn MK, Schreiber RD, Müller-Eberhard HJ.; ''Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution.''; PubMed Europe PMC Scholia
  68. Lehto T, Meri S.; ''Interactions of soluble CD59 with the terminal complement complexes. CD59 and C9 compete for a nascent epitope on C8.''; PubMed Europe PMC Scholia
  69. Hadders MA, Bubeck D, Roversi P, Hakobyan S, Forneris F, Morgan BP, Pangburn MK, Llorca O, Lea SM, Gros P.; ''Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9.''; PubMed Europe PMC Scholia
  70. Krych-Goldberg M, Hauhart RE, Subramanian VB, Yurcisin BM, Crimmins DL, Hourcade DE, Atkinson JP.; ''Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases.''; PubMed Europe PMC Scholia
  71. Schmidt BZ, Colten HR.; ''Complement: a critical test of its biological importance.''; PubMed Europe PMC Scholia
  72. Schreiber RD, Pangburn MK, Lesavre PH, Müller-Eberhard HJ.; ''Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.''; PubMed Europe PMC Scholia
  73. Kerr MA.; ''The human complement system: assembly of the classical pathway C3 convertase.''; PubMed Europe PMC Scholia
  74. Lesavre PH, Müller-Eberhard HJ.; ''Mechanism of action of factor D of the alternative complement pathway.''; PubMed Europe PMC Scholia
  75. Huang Y, Smith CA, Song H, Morgan BP, Abagyan R, Tomlinson S.; ''Insights into the human CD59 complement binding interface toward engineering new therapeutics.''; PubMed Europe PMC Scholia
  76. Fujita T, Matsushita M, Endo Y.; ''The lectin-complement pathway--its role in innate immunity and evolution.''; PubMed Europe PMC Scholia
  77. Ponnuraj K, Xu Y, Macon K, Moore D, Volanakis JE, Narayana SV.; ''Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.''; PubMed Europe PMC Scholia
  78. Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW.; ''Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition.''; PubMed Europe PMC Scholia
  79. Mold C, Medof ME.; ''C3 nephritic factor protects bound C3bBb from cleavage by factor I and human erythrocytes.''; PubMed Europe PMC Scholia
  80. Podack ER, Tschoop J, Müller-Eberhard HJ.; ''Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b-8 assembly.''; PubMed Europe PMC Scholia
  81. Morgan HP, Schmidt CQ, Guariento M, Blaum BS, Gillespie D, Herbert AP, Kavanagh D, Mertens HD, Svergun DI, Johansson CM, Uhrín D, Barlow PN, Hannan JP.; ''Structural basis for engagement by complement factor H of C3b on a self surface.''; PubMed Europe PMC Scholia
  82. Seya T, Atkinson JP.; ''Functional properties of membrane cofactor protein of complement.''; PubMed Europe PMC Scholia
  83. Harris CL, Pettigrew DM, Lea SM, Morgan BP.; ''Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay.''; PubMed Europe PMC Scholia
  84. Brodbeck WG, Liu D, Sperry J, Mold C, Medof ME.; ''Localization of classical and alternative pathway regulatory activity within the decay-accelerating factor.''; PubMed Europe PMC Scholia
  85. MUELLER-EBERHARD HJ, LEPOW IH.; ''C'1 ESTERASE EFFECT ON ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF THE FOURTH COMPONENT OF COMPLEMENT.''; PubMed Europe PMC Scholia
  86. Nagasawa S, Stroud RM.; ''Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b.''; PubMed Europe PMC Scholia
  87. Troegeler A, Lugo-Villarino G, Hansen S, Rasolofo V, Henriksen ML, Mori K, Ohtani K, Duval C, Mercier I, Bénard A, Nigou J, Hudrisier D, Wakamiya N, Neyrolles O.; ''Collectin CL-LK Is a Novel Soluble Pattern Recognition Receptor for Mycobacterium tuberculosis.''; PubMed Europe PMC Scholia
  88. Müller-Eberhard HJ, Polley MJ, Calcott MA.; ''Formation and functional significance of a molecular complex derived from the second and the fourth component of human complement.''; PubMed Europe PMC Scholia
  89. Pangburn MK, Schreiber RD, Müller-Eberhard HJ.; ''Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3.''; PubMed Europe PMC Scholia
  90. Gerard NP, Gerard C.; ''The chemotactic receptor for human C5a anaphylatoxin.''; PubMed Europe PMC Scholia
  91. Garlatti V, Martin L, Gout E, Reiser JB, Fujita T, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch.''; PubMed Europe PMC Scholia
  92. Weis JJ, Tedder TF, Fearon DT.; ''Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes.''; PubMed Europe PMC Scholia
  93. Medicus RG, Götze O, Müller-Eberhard HJ.; ''Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway.''; PubMed Europe PMC Scholia
  94. Barilla-LaBarca ML, Liszewski MK, Lambris JD, Hourcade D, Atkinson JP.; ''Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells.''; PubMed Europe PMC Scholia
  95. Becherer JD, Lambris JD.; ''Identification of the C3b receptor-binding domain in third component of complement.''; PubMed Europe PMC Scholia
  96. Matsushita M, Endo Y, Fujita T.; ''Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease.''; PubMed Europe PMC Scholia
  97. Hajela K, Kojima M, Ambrus G, Wong KH, Moffatt BE, Ferluga J, Hajela S, Gál P, Sim RB.; ''The biological functions of MBL-associated serine proteases (MASPs).''; PubMed Europe PMC Scholia
  98. Sepp A, Dodds AW, Anderson MJ, Campbell RD, Willis AC, Law SK.; ''Covalent binding properties of the human complement protein C4 and hydrolysis rate of the internal thioester upon activation.''; PubMed Europe PMC Scholia
  99. Cain SA, Monk PN.; ''The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74).''; PubMed Europe PMC Scholia
  100. Kinoshita T, Medof ME, Nussenzweig V.; ''Endogenous association of decay-accelerating factor (DAF) with C4b and C3b on cell membranes.''; PubMed Europe PMC Scholia
  101. Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, Fujita T, Fontecilla-Camps JC, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural insights into the innate immune recognition specificities of L- and H-ficolins.''; PubMed Europe PMC Scholia
  102. Ziccardi RJ, Cooper NR.; ''Physicochemical and functional characterization of the C1r subunit of the first complement component.''; PubMed Europe PMC Scholia
  103. Pangburn MK, Müller-Eberhard HJ.; ''Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins factors H and I.''; PubMed Europe PMC Scholia
  104. Medof ME, Kinoshita T, Nussenzweig V.; ''Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.''; PubMed Europe PMC Scholia
  105. Goicoechea de Jorge E, Caesar JJ, Malik TH, Patel M, Colledge M, Johnson S, Hakobyan S, Morgan BP, Harris CL, Pickering MC, Lea SM.; ''Dimerization of complement factor H-related proteins modulates complement activation in vivo.''; PubMed Europe PMC Scholia
  106. Degen SJ, Davie EW.; ''Nucleotide sequence of the gene for human prothrombin.''; PubMed Europe PMC Scholia
  107. Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P.; ''Structures of C3b in complex with factors B and D give insight into complement convertase formation.''; PubMed Europe PMC Scholia
  108. Smith CA, Pangburn MK, Vogel CW, Müller-Eberhard HJ.; ''Molecular architecture of human properdin, a positive regulator of the alternative pathway of complement.''; PubMed Europe PMC Scholia
  109. Gout E, Garlatti V, Smith DF, Lacroix M, Dumestre-Pérard C, Lunardi T, Martin L, Cesbron JY, Arlaud GJ, Gaboriaud C, Thielens NM.; ''Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of M-ficolin.''; PubMed Europe PMC Scholia
  110. Honoré C, Rørvig S, Munthe-Fog L, Hummelshøj T, Madsen HO, Borregaard N, Garred P.; ''The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma.''; PubMed Europe PMC Scholia
  111. Christmas SE, Christmas SE, de la Mata Espinosa CT, Halliday D, Buxton CA, Cummerson JA, Johnson PM.; ''Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on resting and activated human peripheral blood leucocytes.''; PubMed Europe PMC Scholia
  112. Sim RB, Laich A.; ''Serine proteases of the complement system.''; PubMed Europe PMC Scholia
  113. Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C.; ''Molecular cloning and characterization of the human anaphylatoxin C3a receptor.''; PubMed Europe PMC Scholia
  114. Dodds AW, Ren XD, Willis AC, Law SK.; ''The reaction mechanism of the internal thioester in the human complement component C4.''; PubMed Europe PMC Scholia
  115. Arlaud GJ, Reboul A, Sim RB, Colomb MG.; ''Interaction of C1-inhibitor with the C1r and C1s subcomponents in human C1.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
115062
Reactome
view17:00, 25 January 2021ReactomeTeamReactome version 75
113506view11:58, 2 November 2020ReactomeTeamReactome version 74
112706view16:10, 9 October 2020ReactomeTeamReactome version 73
101621view11:49, 1 November 2018ReactomeTeamreactome version 66
101157view21:35, 31 October 2018ReactomeTeamreactome version 65
100683view20:08, 31 October 2018ReactomeTeamreactome version 64
100233view16:53, 31 October 2018ReactomeTeamreactome version 63
99785view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99338view12:47, 31 October 2018ReactomeTeamreactome version 62
93740view13:33, 16 August 2017ReactomeTeamreactome version 61
93254view11:18, 9 August 2017ReactomeTeamreactome version 61
86332view09:15, 11 July 2016ReactomeTeamreactome version 56
83391view11:06, 18 November 2015ReactomeTeamVersion54
81582view13:07, 21 August 2015ReactomeTeamVersion53
77042view08:34, 17 July 2014ReactomeTeamFixed remaining interactions
76747view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76072view10:13, 11 June 2014ReactomeTeamRe-fixing comment source
75782view11:30, 10 June 2014ReactomeTeamReactome 48 Update
75419view10:07, 29 May 2014LifishModified description
75132view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74779view08:52, 30 April 2014ReactomeTeamReactome46
44996view14:41, 6 October 2011MartijnVanIerselOntology Term : 'signaling pathway in the innate immune response' added !
42021view21:50, 4 March 2011MaintBotAutomatic update
39824view05:51, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
1,3-beta-D-glucan MetaboliteCHEBI:37671 (ChEBI)
11xCbxE-PROS1 ProteinP07225 (Uniprot-TrEMBL)
11xCbxE-PROS1ProteinP07225 (Uniprot-TrEMBL)
Antigen 
antibody
C1 		ComplexREACT_8066 (Reactome)
Antigen 
antibody
C1 		ComplexREACT_8973 (Reactome)
Antigen 
antibody
C1 complex		ComplexREACT_8034 (Reactome)
Bacterial mannose-based carbohydrate surface patternREACT_8923 (Reactome)
C-reactive protein pentamer

phosphocholine

C1Q		ComplexREACT_25403 (Reactome)
C1QA ProteinP02745 (Uniprot-TrEMBL)
C1QBProteinP02746 (Uniprot-TrEMBL)
C1QC ProteinP02747 (Uniprot-TrEMBL)
C1R C-terminal fragment ProteinP00736 (Uniprot-TrEMBL)
C1R N-terminal fragment ProteinP00736 (Uniprot-TrEMBL)
C1RProteinP00736 (Uniprot-TrEMBL)
C1S C-terminal fragment ProteinP09871 (Uniprot-TrEMBL)
C1S N-terminal fragment ProteinP09871 (Uniprot-TrEMBL)
C1SProteinP09871 (Uniprot-TrEMBL)
C2ProteinP06681 (Uniprot-TrEMBL)
C2a ProteinP06681 (Uniprot-TrEMBL)
C2aProteinP06681 (Uniprot-TrEMBL)
C2bProteinP06681 (Uniprot-TrEMBL)
C3 alpha chain ProteinP01024 (Uniprot-TrEMBL)
C3 beta chain ProteinP01024 (Uniprot-TrEMBL)
C3 convertasesREACT_8751 (Reactome)
C3ComplexREACT_8268 (Reactome)
C3ComplexREACT_8649 (Reactome)
C3ComplexREACT_8857 (Reactome)
C3aProteinP01024 (Uniprot-TrEMBL)
C3b

Factor Bb C3b

Properdin complex		ComplexREACT_8784 (Reactome)
C3b alpha' ProteinP01024 (Uniprot-TrEMBL)
C3bComplexREACT_8621 (Reactome) Linked by disulphide bond between positions 559 and 816.
C3c alpha' chain fragment 1 ProteinP01024 (Uniprot-TrEMBL)
C3c alpha' chain fragment 1 precursor ProteinP01024 (Uniprot-TrEMBL)
C3c alpha' chain fragment 2 ProteinP01024 (Uniprot-TrEMBL)
C3cComplexREACT_164188 (Reactome)
C3dgProteinP01024 (Uniprot-TrEMBL)
C3fProteinP01024 (Uniprot-TrEMBL)
C4 activatorREACT_8154 (Reactome)
C4 binding protein C4bC2aComplexREACT_120190 (Reactome)
C4 binding protein protein SComplexREACT_119894 (Reactome)
C4-binding protein C4bComplexREACT_118966 (Reactome)
C4A alpha b ProteinP0C0L4 (Uniprot-TrEMBL) C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
C4A beta ProteinP0C0L4 (Uniprot-TrEMBL)
C4A gamma ProteinP0C0L4 (Uniprot-TrEMBL)
C4B alpha chain fragment b ProteinP0C0L5 (Uniprot-TrEMBL)
C4B beta ProteinP0C0L5 (Uniprot-TrEMBL)
C4B gamma ProteinP0C0L5 (Uniprot-TrEMBL)
C4BPA ProteinP04003 (Uniprot-TrEMBL)
C4BPB ProteinP20851 (Uniprot-TrEMBL)
C4aProteinREACT_25991 (Reactome)
C4b

C2a

C3b		ComplexREACT_8556 (Reactome)
C4b with hydrolysed thioesterComplexREACT_164040 (Reactome)
C4b, C3bComplexREACT_119260 (Reactome)
C4b-binding protein Factor IComplexREACT_119445 (Reactome)
C4b-binding proteinComplexREACT_120080 (Reactome)
C4bC2a, C3bBbComplexREACT_119171 (Reactome)
C4c, C3fComplexREACT_119917 (Reactome)
C4cComplexREACT_119729 (Reactome)
C4d, iC3bProteinREACT_119732 (Reactome)
C4dProteinREACT_119059 (Reactome)
C5 alpha ProteinP01031 (Uniprot-TrEMBL)
C5 beta ProteinP01031 (Uniprot-TrEMBL)
C5 convertasesREACT_8864 (Reactome)
C5aProteinP01031 (Uniprot-TrEMBL)
C5b

C6 C7

C8 complex		ComplexREACT_8352 (Reactome)
C5b

C6

C7 complex		ComplexREACT_8333 (Reactome)
C5b

C6

C7 complex		ComplexREACT_8454 (Reactome)
C5b C6 complexComplexREACT_8500 (Reactome)
C5b alpha' ProteinP01031 (Uniprot-TrEMBL)
C5bComplexREACT_8814 (Reactome) Linked by disulphide bond between positions 559 and 816.
C6 ProteinP13671 (Uniprot-TrEMBL)
C6ProteinP13671 (Uniprot-TrEMBL)
C7ProteinP10643 (Uniprot-TrEMBL)
C8A ProteinP07357 (Uniprot-TrEMBL)
C8B ProteinP07358 (Uniprot-TrEMBL)
C8G ProteinP07360 (Uniprot-TrEMBL)
C8ComplexREACT_8563 (Reactome)
C9ProteinP02748 (Uniprot-TrEMBL)
CD46 ProteinP15529 (Uniprot-TrEMBL)
CD46ProteinP15529 (Uniprot-TrEMBL)
CD55 ProteinP08174 (Uniprot-TrEMBL)
CD55ProteinP08174 (Uniprot-TrEMBL)
CD59 C5b-C9ComplexREACT_164087 (Reactome)
CD59 ProteinP13987 (Uniprot-TrEMBL)
CD59ProteinP13987 (Uniprot-TrEMBL)
CFBProteinP00751 (Uniprot-TrEMBL)
CFDProteinP00746 (Uniprot-TrEMBL)
CFH ProteinP08603 (Uniprot-TrEMBL)
CFHProteinP08603 (Uniprot-TrEMBL)
CFIProteinP05156 (Uniprot-TrEMBL)
CR1 C3bBb, C4bC2a complexesComplexREACT_120030 (Reactome)
CR1 C3bComplexREACT_119014 (Reactome)
CR1 C4bComplexREACT_119535 (Reactome)
CR1 iC3bComplexREACT_164751 (Reactome)
CR1 ProteinP17927 (Uniprot-TrEMBL)
CR1ProteinP17927 (Uniprot-TrEMBL)
CRPProteinP02741 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Cell surface

C3b

Factor B complex		ComplexREACT_8205 (Reactome)
Cell surface

C3b Factor Bb

Properdin		ComplexREACT_8531 (Reactome)
Cell surface

C3b

Factor Bb		ComplexREACT_8668 (Reactome)
Cell surface C3bComplexREACT_26114 (Reactome)
Cell surface

C4b

C2a		ComplexREACT_8917 (Reactome)
Cell surface C4bComplexREACT_25739 (Reactome)
Cell surface

FH,FHR3

C3bBb		ComplexREACT_118983 (Reactome)
Cell surface

FH,FHR3

C3b		ComplexREACT_119386 (Reactome)
Cell surfaceREACT_26575 (Reactome) This entity is intended to represent any molecule that might be at the outer cell surface of any cell, host or microbial.
Complement Factor 4ComplexREACT_26761 (Reactome)
Complement factor 3ComplexREACT_8213 (Reactome) Linked by disulphide bond between positions 559 and 816.
Complement factor 5ComplexREACT_8215 (Reactome)
Complement factor DProteinREACT_161511 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
Complement factor I

Cell surface FH,FHR3

C3b		ComplexREACT_119579 (Reactome)
Complement factor I

Factor H

C3b		ComplexREACT_119450 (Reactome)
Complement factor IComplexREACT_119465 (Reactome)
D-fucose MetaboliteCHEBI:28847 (ChEBI)
DAF C3 convertase complexesComplexREACT_119393 (Reactome)
DAF C3bComplexREACT_119929 (Reactome)
DAF C4bComplexREACT_119228 (Reactome)
FCN1

MASP2 dimer

MASP1 dimer		ComplexREACT_164741 (Reactome)
FCN1

MASPs Ca2+

FCN1 ligand		ComplexREACT_165421 (Reactome)
FCN1 ProteinO00602 (Uniprot-TrEMBL)
FCN1 ligandMetaboliteREACT_165133 (Reactome)
FCN2

MASP2 dimer

MASP1 dimer		ComplexREACT_165253 (Reactome)
FCN2

MASPs Ca2+

FCN2 ligand		ComplexREACT_164948 (Reactome)
FCN2 ProteinQ15485 (Uniprot-TrEMBL)
FCN2 ligandMetaboliteREACT_164334 (Reactome)
FCN3

MASP2 dimer

MASP1 dimer		ComplexREACT_165152 (Reactome)
FCN3

MASPs Ca2+

FCN3 ligand		ComplexREACT_164302 (Reactome)
FCN3 ProteinO75636 (Uniprot-TrEMBL)
FCN3 ligandMetaboliteREACT_165296 (Reactome)
FH, FHR-3ProteinREACT_119141 (Reactome)
Factor H C3bComplexREACT_120113 (Reactome)
Factor H Host cell surfaceComplexREACT_119254 (Reactome)
Factor I

MCP, CR1

C4b, C3b complexes		ComplexREACT_120091 (Reactome)
H2OMetaboliteCHEBI:15377 (ChEBI)
Heparins MetaboliteCHEBI:24505 (ChEBI)
Host cell surfaceComplexREACT_119096 (Reactome)
IGHG1ProteinP01857 (Uniprot-TrEMBL)
IGHG2ProteinP01859 (Uniprot-TrEMBL)
IGHG3 ProteinP01860 (Uniprot-TrEMBL)
IGHG4ProteinP01861 (Uniprot-TrEMBL)
IGHV7-81ProteinQ6PIL0 (Uniprot-TrEMBL)
IGHVProteinA2KUC3 (Uniprot-TrEMBL)
IGKCProteinP01834 (Uniprot-TrEMBL)
IGKV1-5ProteinP01602 (Uniprot-TrEMBL)
IGKV4-1ProteinP06312 (Uniprot-TrEMBL)
IGKVA18ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2ProteinP0CG05 (Uniprot-TrEMBL)
IGLC3ProteinP0CG06 (Uniprot-TrEMBL)
IGLC6ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV1-36ProteinQ5NV67 (Uniprot-TrEMBL)
IGLV1-40ProteinQ5NV69 (Uniprot-TrEMBL)
IGLV1-44ProteinQ5NV81 (Uniprot-TrEMBL)
IGLV10-54ProteinQ5NV86 (Uniprot-TrEMBL)
IGLV11-55ProteinQ5NV87 (Uniprot-TrEMBL)
IGLV2-11ProteinQ5NV84 (Uniprot-TrEMBL)
IGLV2-18ProteinQ5NV65 (Uniprot-TrEMBL)
IGLV2-23ProteinQ5NV89 (Uniprot-TrEMBL)
IGLV2-33ProteinQ5NV66 (Uniprot-TrEMBL)
IGLV3-12ProteinQ5NV85 (Uniprot-TrEMBL)
IGLV3-16ProteinQ5NV64 (Uniprot-TrEMBL)
IGLV3-22ProteinQ5NV75 (Uniprot-TrEMBL)
IGLV3-25ProteinQ5NV90 (Uniprot-TrEMBL)
IGLV3-27ProteinQ5NV91 (Uniprot-TrEMBL)
IGLV4-3ProteinQ5NV61 (Uniprot-TrEMBL)
IGLV4-60ProteinQ5NV79 (Uniprot-TrEMBL)
IGLV4-69ProteinQ5NV92 (Uniprot-TrEMBL)
IGLV5-37ProteinQ5NV68 (Uniprot-TrEMBL)
IGLV5-45ProteinQ5NV82 (Uniprot-TrEMBL)
IGLV7-43ProteinQ5NV80 (Uniprot-TrEMBL)
IGLV7-46ProteinQ5NV83 (Uniprot-TrEMBL)
IGLV8-61ProteinQ5NV62 (Uniprot-TrEMBL)
IGLVProteinA2NXD2 (Uniprot-TrEMBL)
Ig heavy chain V-I region EU ProteinP01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 ProteinP01743 (Uniprot-TrEMBL)
Ig heavy chain V-I region Mot ProteinP06326 (Uniprot-TrEMBL)
Ig heavy chain V-I region ND ProteinP01744 (Uniprot-TrEMBL)
Ig heavy chain V-I region SIE ProteinP01761 (Uniprot-TrEMBL)
Ig heavy chain V-I region WOL ProteinP01760 (Uniprot-TrEMBL)
Ig heavy chain V-II region ARH-77 ProteinP06331 (Uniprot-TrEMBL)
Ig heavy chain V-II region COR ProteinP01815 (Uniprot-TrEMBL)
Ig heavy chain V-II region DAW ProteinP01816 (Uniprot-TrEMBL)
Ig heavy chain V-II region HE ProteinP01818 (Uniprot-TrEMBL)
Ig heavy chain V-II region MCE ProteinP01817 (Uniprot-TrEMBL)
Ig heavy chain V-II region NEWM ProteinP01825 (Uniprot-TrEMBL)
Ig heavy chain V-II region OU ProteinP01814 (Uniprot-TrEMBL)
Ig heavy chain V-II region SESS ProteinP04438 (Uniprot-TrEMBL)
Ig heavy chain V-II region WAH ProteinP01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO ProteinP01766 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUR ProteinP01773 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUT ProteinP01767 (Uniprot-TrEMBL)
Ig heavy chain V-III region CAM ProteinP01768 (Uniprot-TrEMBL)
Ig heavy chain V-III region DOB ProteinP01782 (Uniprot-TrEMBL)
Ig heavy chain V-III region GA ProteinP01769 (Uniprot-TrEMBL)
Ig heavy chain V-III region GAL ProteinP01781 (Uniprot-TrEMBL)
Ig heavy chain V-III region HIL ProteinP01771 (Uniprot-TrEMBL)
Ig heavy chain V-III region JON ProteinP01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL ProteinP01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region LAY ProteinP01775 (Uniprot-TrEMBL)
Ig heavy chain V-III region NIE ProteinP01770 (Uniprot-TrEMBL)
Ig heavy chain V-III region POM ProteinP01774 (Uniprot-TrEMBL)
Ig heavy chain V-III region TEI ProteinP01777 (Uniprot-TrEMBL)
Ig heavy chain V-III region TIL ProteinP01765 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO ProteinP01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region TUR ProteinP01779 (Uniprot-TrEMBL)
Ig heavy chain V-III region WAS ProteinP01776 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA ProteinP01763 (Uniprot-TrEMBL)
Ig heavy chain V-III region ZAP ProteinP01778 (Uniprot-TrEMBL)
Ig kappa chain V region EV15 ProteinP06315 (Uniprot-TrEMBL)
Ig kappa chain V-I region AG ProteinP01593 (Uniprot-TrEMBL)
Ig kappa chain V-I region AU ProteinP01594 (Uniprot-TrEMBL)
Ig kappa chain V-I region BAN ProteinP04430 (Uniprot-TrEMBL)
Ig kappa chain V-I region Bi ProteinP01595 (Uniprot-TrEMBL)
Ig kappa chain V-I region CAR ProteinP01596 (Uniprot-TrEMBL)
Ig kappa chain V-I region DEE ProteinP01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi ProteinP04432 (Uniprot-TrEMBL)
Ig kappa chain V-I region EU ProteinP01598 (Uniprot-TrEMBL)
Ig kappa chain V-I region Gal ProteinP01599 (Uniprot-TrEMBL)
Ig kappa chain V-I region HK101 ProteinP01601 (Uniprot-TrEMBL)
Ig kappa chain V-I region Hau ProteinP01600 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ka ProteinP01603 (Uniprot-TrEMBL)
Ig kappa chain V-I region Kue ProteinP01604 (Uniprot-TrEMBL)
Ig kappa chain V-I region Lay ProteinP01605 (Uniprot-TrEMBL)
Ig kappa chain V-I region Mev ProteinP01612 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ni ProteinP01613 (Uniprot-TrEMBL)
Ig kappa chain V-I region OU ProteinP01606 (Uniprot-TrEMBL)
Ig kappa chain V-I region Rei ProteinP01607 (Uniprot-TrEMBL)
Ig kappa chain V-I region Roy ProteinP01608 (Uniprot-TrEMBL)
Ig kappa chain V-I region Scw ProteinP01609 (Uniprot-TrEMBL)
Ig kappa chain V-I region WAT ProteinP80362 (Uniprot-TrEMBL)
Ig kappa chain V-I region WEA ProteinP01610 (Uniprot-TrEMBL)
Ig kappa chain V-I region Walker ProteinP04431 (Uniprot-TrEMBL)
Ig kappa chain V-I region Wes ProteinP01611 (Uniprot-TrEMBL)
Ig kappa chain V-II region Cum ProteinP01614 (Uniprot-TrEMBL)
Ig kappa chain V-II region FR ProteinP01615 (Uniprot-TrEMBL)
Ig kappa chain V-II region GM607 ProteinP06309 (Uniprot-TrEMBL)
Ig kappa chain V-II region MIL ProteinP01616 (Uniprot-TrEMBL)
Ig kappa chain V-II region RPMI 6410 ProteinP06310 (Uniprot-TrEMBL)
Ig kappa chain V-II region TEW ProteinP01617 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 ProteinP01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region CLL ProteinP04207 (Uniprot-TrEMBL)
Ig kappa chain V-III region GOL ProteinP04206 (Uniprot-TrEMBL)
Ig kappa chain V-III region HAH ProteinP18135 (Uniprot-TrEMBL)
Ig kappa chain V-III region HIC ProteinP18136 (Uniprot-TrEMBL)
Ig kappa chain V-III region IARC/BL41 ProteinP06311 (Uniprot-TrEMBL)
Ig kappa chain V-III region NG9 ProteinP01621 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM ProteinP01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region SIE ProteinP01620 (Uniprot-TrEMBL)
Ig kappa chain V-III region Ti ProteinP01622 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG ProteinP04433 (Uniprot-TrEMBL)
Ig kappa chain V-III region VH ProteinP04434 (Uniprot-TrEMBL)
Ig kappa chain V-III region WOL ProteinP01623 (Uniprot-TrEMBL)
Ig kappa chain V-IV region B17 ProteinP06314 (Uniprot-TrEMBL)
Ig kappa chain V-IV region JI ProteinP06313 (Uniprot-TrEMBL)
Ig kappa chain V-IV region Len ProteinP01625 (Uniprot-TrEMBL)
Ig kappa chain V-IV region STH ProteinP83593 (Uniprot-TrEMBL)
Ig lambda chain V region 4A ProteinP04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region BL2 ProteinP06316 (Uniprot-TrEMBL)
Ig lambda chain V-I region EPS ProteinP06888 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA ProteinP01700 (Uniprot-TrEMBL)
Ig lambda chain V-I region MEM ProteinP06887 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEW ProteinP01701 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEWM ProteinP01703 (Uniprot-TrEMBL)
Ig lambda chain V-I region NIG-64 ProteinP01702 (Uniprot-TrEMBL)
Ig lambda chain V-I region VOR ProteinP01699 (Uniprot-TrEMBL)
Ig lambda chain V-I region WAH ProteinP04208 (Uniprot-TrEMBL)
Ig lambda chain V-II region BO ProteinP01710 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH ProteinP01706 (Uniprot-TrEMBL)
Ig lambda chain V-II region BUR ProteinP01708 (Uniprot-TrEMBL)
Ig lambda chain V-II region MGC ProteinP01709 (Uniprot-TrEMBL)
Ig lambda chain V-II region NEI ProteinP01705 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-58 ProteinP01713 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-84 ProteinP04209 (Uniprot-TrEMBL)
Ig lambda chain V-II region TOG ProteinP01704 (Uniprot-TrEMBL)
Ig lambda chain V-II region TRO ProteinP01707 (Uniprot-TrEMBL)
Ig lambda chain V-II region VIL ProteinP01711 (Uniprot-TrEMBL)
Ig lambda chain V-II region WIN ProteinP01712 (Uniprot-TrEMBL)
Ig lambda chain V-III region LOI ProteinP80748 (Uniprot-TrEMBL)
Ig lambda chain V-III region SH ProteinP01714 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Bau ProteinP01715 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Hil ProteinP01717 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Kern ProteinP01718 (Uniprot-TrEMBL)
Ig lambda chain V-IV region MOL ProteinP06889 (Uniprot-TrEMBL)
Ig lambda chain V-IV region X ProteinP01716 (Uniprot-TrEMBL)
Ig lambda chain V-V region DEL ProteinP01719 (Uniprot-TrEMBL)
Ig lambda chain V-VI region AR ProteinP01721 (Uniprot-TrEMBL)
Ig lambda chain V-VI region EB4 ProteinP06319 (Uniprot-TrEMBL)
Ig lambda chain V-VI region NIG-48 ProteinP01722 (Uniprot-TrEMBL)
Ig lambda chain V-VI region SUT ProteinP06317 (Uniprot-TrEMBL)
Ig lambda chain V-VI region WLT ProteinP06318 (Uniprot-TrEMBL)
Ig lambda chain V-VII region MOT ProteinP01720 (Uniprot-TrEMBL)
IgH heavy chain V-III region VH26 precursor ProteinP01764 (Uniprot-TrEMBL)
Lipoteichoic acid MetaboliteCHEBI:28640 (ChEBI)
MASP1ProteinP48740 (Uniprot-TrEMBL)
MASP2-1 ProteinO00187-1 (Uniprot-TrEMBL)
MASP2-1ProteinO00187-1 (Uniprot-TrEMBL)
MBL

activated MASPs

mannose-based carbohydrates		ComplexREACT_8515 (Reactome)
MBL bound to mannose-based carbohydrates on bacterial surfacesComplexREACT_8711 (Reactome)
MBL-II

MASP-2 dimer

MASP-1 dimer complex		ComplexREACT_8380 (Reactome)
MBL/FCN

activated MASP

carbohydrate patterns		ComplexREACT_165602 (Reactome)
MBL/Ficolin MASPs bound to carbohydrate patternsComplexREACT_165125 (Reactome)
MBL2 ProteinP11226 (Uniprot-TrEMBL)
MCP C3bComplexREACT_119903 (Reactome)
MCP C4bComplexREACT_119237 (Reactome)
MCP, CR1

C4b

C3b complexes		ComplexREACT_120251 (Reactome)
MCP, CR1ProteinREACT_119720 (Reactome) CR1 and MCP are widely distributed cell surface molecules that bind C4b and C3b, and act as cofactors for Complement factor I, thereby regulating the classical and alternative C3 convertases.
Membrane Attack ComplexComplexREACT_8325 (Reactome)
N-acetyl-D-glucosamine MetaboliteCHEBI:28009 (ChEBI)
N-acetylgalactosamine MetaboliteCHEBI:40356 (ChEBI)
PCho MetaboliteCHEBI:36700 (ChEBI)
Properdin oligomerREACT_8730 (Reactome)
Sialic acid MetaboliteCHEBI:28879 (ChEBI)
VTN

C5b C6 C7 C8

C9		ComplexREACT_164606 (Reactome)
VTN

C5b C6

C7		ComplexREACT_165289 (Reactome)
VTNProteinP04004 (Uniprot-TrEMBL)
dNQ-C3ProteinP01024 (Uniprot-TrEMBL)
dNQ-C4AProteinP0C0L4 (Uniprot-TrEMBL)
dNQ-C4BProteinP0C0L5 (Uniprot-TrEMBL)
iC3bComplexREACT_119218 (Reactome)
iC3bComplexREACT_120169 (Reactome)
thioester-C1010-Q1013-C4bComplexREACT_26471 (Reactome)

Annotated Interactions

View all...
Source  ↓Target  ↓Type  ↓Database reference  ↓Comment  ↓
11xCbxE-PROS1REACT_118836 (Reactome)
Antigen 
antibody
C1 		REACT_7977 (Reactome)
Antigen 
antibody
C1 complex		REACT_7978 (Reactome)
Bacterial mannose-based carbohydrate surface patternREACT_7983 (Reactome)
C-reactive protein pentamer

phosphocholine

C1Q		ArrowREACT_7978 (Reactome)
C2aArrowREACT_118584 (Reactome)
C2aArrowREACT_118641 (Reactome)
C2aArrowREACT_118692 (Reactome)
C2aArrowREACT_118738 (Reactome)
C2aArrowREACT_7959 (Reactome)
C2aREACT_8014 (Reactome)
C2bArrowREACT_7959 (Reactome)
C3 convertasesREACT_7990 (Reactome)
C3ArrowREACT_118641 (Reactome)
C3ArrowREACT_7981 (Reactome)
C3REACT_7948 (Reactome)
C3REACT_8013 (Reactome)
C3aArrowREACT_7948 (Reactome)
C3aArrowREACT_7986 (Reactome)
C3aArrowREACT_7990 (Reactome)
C3b

Factor Bb C3b

Properdin complex		ArrowREACT_7986 (Reactome)
C3bArrowREACT_118641 (Reactome)
C3bArrowREACT_7948 (Reactome)
C3bArrowREACT_7990 (Reactome)
C3bREACT_118712 (Reactome)
C3bREACT_25075 (Reactome)
C3cArrowREACT_163860 (Reactome)
C3dgArrowREACT_163860 (Reactome)
C3fArrowREACT_118650 (Reactome)
C3fArrowREACT_118841 (Reactome)
C4 activatorREACT_7959 (Reactome)
C4 activatorREACT_8002 (Reactome)
C4-binding protein C4bArrowREACT_118738 (Reactome)
C4-binding protein C4bREACT_118647 (Reactome)
C4aArrowREACT_8002 (Reactome)
C4b, C3bREACT_118575 (Reactome)
C4b-binding proteinArrowREACT_118719 (Reactome)
C4b-binding proteinREACT_118752 (Reactome)
C4b-binding proteinREACT_118763 (Reactome)
C4b-binding proteinREACT_118836 (Reactome)
C4bC2a, C3bBbREACT_118580 (Reactome)
C4bC2a, C3bBbREACT_118782 (Reactome)
C4c, C3fArrowREACT_118673 (Reactome)
C4cArrowREACT_118719 (Reactome)
C4d, iC3bArrowREACT_118673 (Reactome)
C4dArrowREACT_118719 (Reactome)
C5 convertasesREACT_7989 (Reactome)
C5aArrowREACT_7989 (Reactome)
C5b

C6 C7

C8 complex		REACT_163829 (Reactome)
C5b

C6 C7

C8 complex		REACT_7988 (Reactome)
C5b

C6

C7 complex		REACT_163759 (Reactome)
C5b

C6

C7 complex		REACT_7946 (Reactome)
C5b C6 complexREACT_7950 (Reactome)
C5bArrowREACT_7989 (Reactome)
C5bREACT_7976 (Reactome)
C6REACT_7976 (Reactome)
C7REACT_7950 (Reactome)
C8REACT_163870 (Reactome)
C8REACT_7946 (Reactome)
C9REACT_163829 (Reactome)
C9REACT_163870 (Reactome)
C9REACT_7988 (Reactome)
CD46REACT_118575 (Reactome)
CD55REACT_118782 (Reactome)
CD59REACT_163829 (Reactome)
CFBArrowREACT_118584 (Reactome)
CFBArrowREACT_118641 (Reactome)
CFBArrowREACT_118692 (Reactome)
CFBArrowREACT_118727 (Reactome)
CFBArrowREACT_7981 (Reactome)
CFBArrowREACT_8026 (Reactome)
CFBREACT_7966 (Reactome)
CFBREACT_8013 (Reactome)
CFHArrowREACT_118650 (Reactome)
CFHREACT_118604 (Reactome)
CFHREACT_118712 (Reactome)
CFIREACT_118674 (Reactome)
CR1 C3bArrowREACT_118692 (Reactome)
CR1 C4bArrowREACT_118692 (Reactome)
CR1ArrowREACT_163860 (Reactome)
CR1REACT_118580 (Reactome)
Ca2+REACT_163715 (Reactome)
Ca2+REACT_163747 (Reactome)
Ca2+REACT_163758 (Reactome)
Ca2+REACT_7983 (Reactome)
Cell surface

C3b Factor Bb

Properdin		REACT_7986 (Reactome)
Cell surface

C3b

Factor Bb		ArrowREACT_8026 (Reactome)
Cell surface

C3b

Factor Bb		REACT_118710 (Reactome)
Cell surface

C3b

Factor Bb		REACT_8018 (Reactome)
Cell surface C3bREACT_118815 (Reactome)
Cell surface C3bREACT_7966 (Reactome)
Cell surface C3bREACT_8022 (Reactome)
Cell surface

C4b

C2a		ArrowREACT_118641 (Reactome)
Cell surface

C4b

C2a		REACT_118752 (Reactome)
Cell surface

C4b

C2a		REACT_8022 (Reactome)
Cell surface C4bArrowREACT_118641 (Reactome)
Cell surface C4bREACT_8014 (Reactome)
Cell surface

FH,FHR3

C3b		ArrowREACT_118727 (Reactome)
Cell surface

FH,FHR3

C3b		REACT_118844 (Reactome)
Cell surfaceREACT_25075 (Reactome)
Cell surfaceREACT_25166 (Reactome)
Complement factor 3REACT_7986 (Reactome)
Complement factor 3REACT_8007 (Reactome)
Complement factor DREACT_7981 (Reactome)
Complement factor DREACT_8026 (Reactome)
Complement factor I

Cell surface FH,FHR3

C3b		REACT_118841 (Reactome)
Complement factor I

Factor H

C3b		REACT_118650 (Reactome)
Complement factor IArrowREACT_118650 (Reactome)
Complement factor IArrowREACT_118673 (Reactome)
Complement factor IArrowREACT_118719 (Reactome)
Complement factor IArrowREACT_118841 (Reactome)
Complement factor IREACT_118583 (Reactome)
Complement factor IREACT_118631 (Reactome)
Complement factor IREACT_118647 (Reactome)
Complement factor IREACT_118844 (Reactome)
DAF C3bArrowREACT_118584 (Reactome)
DAF C4bArrowREACT_118584 (Reactome)
FCN1

MASP2 dimer

MASP1 dimer		REACT_163715 (Reactome)
FCN1 ligandREACT_163715 (Reactome)
FCN2

MASP2 dimer

MASP1 dimer		REACT_163747 (Reactome)
FCN2 ligandREACT_163747 (Reactome)
FCN3

MASP2 dimer

MASP1 dimer		REACT_163758 (Reactome)
FCN3 ligandREACT_163758 (Reactome)
FH, FHR-3ArrowREACT_118841 (Reactome)
FH, FHR-3REACT_118710 (Reactome)
FH, FHR-3REACT_118815 (Reactome)
Factor H C3bREACT_118583 (Reactome)
Factor H Host cell surfaceArrowREACT_118710 (Reactome)
Factor H Host cell surfaceArrowREACT_118815 (Reactome)
Factor I

MCP, CR1

C4b, C3b complexes		REACT_118673 (Reactome)
H2OREACT_163768 (Reactome)
H2OREACT_8007 (Reactome)
Host cell surfaceREACT_118604 (Reactome)
MBL-II

MASP-2 dimer

MASP-1 dimer complex		REACT_7983 (Reactome)
MCP C3bArrowREACT_118575 (Reactome)
MCP C4bArrowREACT_118575 (Reactome)
MCP, CR1

C4b

C3b complexes		REACT_118631 (Reactome)
MCP, CR1ArrowREACT_118673 (Reactome)
Properdin oligomerArrowREACT_118641 (Reactome)
Properdin oligomerREACT_8018 (Reactome)
REACT_118575 (Reactome) Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding cell surface glycoprotein which is a cofactor for Complement factor I.
REACT_118580 (Reactome) Complement Receptor 1 (CR1) is a widely distributed cell surface protein that is a decay accelerating factor for the conventional (C4bC2a) and alternative (C3bBb) C3 convertases (Coico & Sunshine 2009).
REACT_118583 (Reactome) Complement factor I binds the factor H:C3b complex.
REACT_118584 (Reactome) Decay accelerating factor (DAF, CD55) is a widely distributed membrane protein. It accelerates the dissociation of C3bBb and C4C2a, thereby inhibiting the amplification of complement. DAF can bind C3b and Bb but must bind both for efficient decay acceleration. The regulatory function of DAF is believed to be inhibition of activated C3 convertase enzymes rather than binding of inactive proenzymes (Harris et al. 2007).
REACT_118604 (Reactome) Factor H preferentially binds to host cells and surfaces that have negatively charged cell surface polyanions such as heparin and sialic acid commonly found on host cells (Kazatchkine et al. 1979, Meri & Pangburn 1990). This mediates protection of plasma-exposed host structures.
REACT_118631 (Reactome) Membrane cofactor protein (MCP) and Complement Receptor 1 (CR1) act as cofactors for the protease activity of complement factor I which binds MCP or CR1 complexes with C3b or C4b, inactivating C3b/C4b.
REACT_118641 (Reactome) C3b:Bb is naturally labile with a half-life of ~90 s. unless bound to properdin on the cell surface (Medicus et al. 1976). C4bC2a is also unstable, lasting at best a few minutes (Kerr et al. 1980). Decay is associated with the release of the Bb or C2a fragments respectively into the fluid phase. The liberated C3b/C4b is able to re-bind Bb/C2a if Factor B/C2 are present.
REACT_118647 (Reactome) C4b-binding protein is a cofactor for Complement Factor I, allowing it to bind and thereby mediating C4b proteolysis.
REACT_118650 (Reactome) Complement factor I cleaves the alpha chain of C3b at two positions, generating inactivated C3b (iC3b) and a small fragment C3f which is released. The majority of the alpha chain is retained as two fragments which are tethered by disulphide bonds. iC3b is proteolytically inactive.
REACT_118673 (Reactome) Factor I cleaves the truncated alpha (a') chain of C4b between Arg-1336 and Asn-1337 and then again between Arg-956 and Thr-957, producing a 16 kDa fragment known as alpha4, derived from the C terminus of the a' chain, followed by a 27 kDa alpha3 fragment. The remaining alpha 2 (C4d) fragment stays covalently bound to the cell membrane while the complex of disulfide-linked alpha3, alpha4, beta chain and gamma chain are released (C4c) into the fluid phase (Fujita et al. 1978).
REACT_118674 (Reactome) Complement factor I (CFI) is a complex of one heavy and one light chain, both cleaved from the same precursor peptide. It inactivates complement subcomponents C3b, iC3b and C4b by proteolytic cleavage of the alpha chains of C4b and C3b in the presence of cofactors such as Factor H, C4b binding protein, Complement receptor 1 (CR1) or MCP (CD46).
REACT_118692 (Reactome) Complement Receptor 1 (CR1) displaces the activated enzyme components Bb and C2a from the conventional and alternative C3 convertases C4bC2a and C3bBb, respectivley.
REACT_118710 (Reactome) Factor H (FH) binds to C3bBb, leading to displacement of Bb. Complement factor H-related protein 3 (FHR-3) has also been reported to bind C3Bb leading to inhibition of C3Bb C3 convertase activity (Fritsche et al. 2010). FH also acts as a cofactor for the factor I-mediated proteolytic inactivation of C3b to iC3b.
REACT_118712 (Reactome) Factor H (FH) regulates the alternative pathway C3 convertase C3bBb and its C3b component both in plasma and at host cell surfaces. FH binds to plasma C3b, making it unavailable, and acts as a cofactor for the factor I-mediated proteolytic inactivation of C3b to iC3b.
REACT_118719 (Reactome) C4b-binding protein is a cofactor in Factor I mediated C4b proteolysis. C4b is cleaved, releasing C4c, leaving C4d bound to the cell surface.
REACT_118727 (Reactome) Factor H greatly accelerates the displacement (decay) of Complement factor Bb from C3b.
REACT_118738 (Reactome) C4 binding protein accelerates the decay of C4bC2a in a dose-dependent fashion. The mechanism of this is poorly understood, but is distinct from Factor I mediated degradation of C4b and believed to represent the displacement of C2a from specific binding sites on C4b (Gigli et al. 1979).
REACT_118752 (Reactome) C4 binding protein accelerates the decay of C4bC2a in a dose-dependent fashion, without causing degradation of C4b, and is presumed to bind to the convertase to mediate this effect.
REACT_118763 (Reactome) The most abundant form of C4b-binding protein (C4BP) consists of seven alpha-chains (70kDa) and one beta-chain (45kDa) all linked by disulphide bonds to form a native protein with a molecular weight of 570kDa (Hilarp et al. 1989). Each alpha chain can bind C4b; it is not known whether full occupancy is necessary for subsequent events. The beta chain binds and inactivates Protein S, a component of the coagulation system. C4BP down-regulates complement activity in several ways: It binds to C4b thus inhibiting the formation of the classical pathway C3 convertase C4bC2a; it acts as a decay accelerating factor for existing convertases, probably by promoting dissociation of C2a; it is a cofactor in Factor I mediated C4b proteolysis.
REACT_118782 (Reactome) Decay-accelerating-factor (DAF, CD55) is a membrane- bound complement regulatory protein that inhibits autologous complement cascade activation. It is expressed on all cells that are in close contact with serum complement proteins, but also on cells outside the vascular space and on tumour cells. DAF binds to C3bBb and C4bC2a on cell surfaces, accelerating their dissociation and thereby inhibiting the amplification of complement. DAF can bind C3b and Bb, and must bind both for efficient decay acceleration. Although it can bind the inactive proenzymes C3b and C4b, the regulatory function of DAF is believed to be inhibition of activated C3 convertase enzymes (Harris et al. 2007).
REACT_118815 (Reactome) Factor H (FH) regulates the alternative pathway C3 convertase C3bBb and its C3b component both in plasma and at host cell surfaces. FH binds to membrane-associated C3b, competing with Factor B and thereby preventing formation of the active C3 convertase C3bBb. In addition, it acts as a cofactor for the Factor I-mediated proteolytic inactivation of C3b to iC3b.
REACT_118836 (Reactome) The beta subunit of C4b binding protein binds and inactivates Protein S, a vitamin K dependent anticoagulation factor. This may represent part of a mechanism for fine-tuning the process of phagocytosis (Kask et al. 2004).
REACT_118841 (Reactome) Following the displacement of Bb from C3bBb, Factor I cleaves Factor H-bound C3b producing iC3b, which remains bound to the membrane. The majority of the C3b alpha chain is retained as two fragments which are tethered to the beta chain by disulphide bonds. iC3b is proteolytically inactive and cannot contribute to the complement cascade process, though it still contributes to opsonization.
REACT_118844 (Reactome) Complement factor I binds to the Factor H:C3b complex.
REACT_163715 (Reactome) Ficolin-1 (M-ficolin or FCN1) was shown to localize at the cell surface of circulating monocytes and granulocytes, despite lacking an obvious transmembrane domain, (Teh C et al. 2000; Honore C et al. 2010). Ficolin-1 has also been found in human plasma (Honore C et al. 2008; Wittenborn T et al. 2010; Kjaer TR et al. 2011). Monocytes and macrophages, but not immature dendritic cells were reported to secrete Ficolin-1 into the serum (Honore C et al. 2010). Moreover, early studies revealed its presence in secretory granules of peripheral blood monocytes and granulocytes (Liu Y et al. 2005). Soluble Ficolin-1 was found to form a complex with MASP2, while cell surface-bound Ficolin-1 did not associate with MASP (Honore C et al. 2010; Kjaer TR et al. 2011).

Ficolin-1 specifically recognizes sialic acid and can bind to acetylated compounds such as N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) (Garlatti V et al. 2007; Gout E et al. 2010; Kjaer TR et al. 2011).

REACT_163747 (Reactome) Human ficolin-2 (L-ficolin, P35 or FCN2) is synthesised in the liver and secreted into the bloodstream where it recognizes various capsulated bacteria and exhibits binding specificity for diverse ligands, such as lipoteichoic acid, 1,3-beta-d-glucan, and acetylated compounds [Lynch NJ et al. 2004; Aoyagi Y et al. 2008; Ma YG et al. 2004; Garlatti V et al. 2007; Gout E et al 2010]. Ficolin-2 also binds to apoptotic HL60, U937, and Jurkat cells [Kuraya M, et al. 2005].
REACT_163758 (Reactome) Ficolin-3 (H-ficolin, FCN3 or Hakata antigen) activates the lectin pathway of complement similar to mannose-binding lectin. Ficolin-3 is composed by a collagen-like strand and three C-terminal recognition domains which bind to carbohydrates on the target surface. Ficolin-3 circulates in plasma associated with mannan-binding lectin-associated serine proteases (MASPs). Upon ligand binding ficolin-3:MASPs complex triggers activation of the lectin pathway [Matsushita M et al. 2002; Teillet F et al. 2008; Zacho RM et al. 2012]. Ficolin-3 (FCN3 or H-ficolin) can specifically recognize Aerococcus viridans [Tsujimura M et al. 2002; Zacho RM et al. 2012]. Ficolin-3 has been shown to bind to patterns of bacterial polysaccharides such as d-fucose and galactose [Garlatti V et al. 2007]. In adition to pathogenic ligands ficolin-3 was reported to bind to apoptotic Jurkat cells [Kuraya M et al. 2005].
REACT_163759 (Reactome) Vitronectin interacts with C5b:C6:C7 complex preventing it from the binding with the cell membrane
REACT_163768 (Reactome) Cleavage of C4 exposes a highly reactive thioester bond on the C4b molecule. The thioester bond is rapidly inactivated by hydrolysis if C4b does not bind to the target cell surface [Sepp A et al 1993].
REACT_163829 (Reactome) CD59, the major inhibitor of the complement membrane attack complex, is an 18–20 kDa glycoprotein, linked to the membrane via a glycosylphosphatidylinositol (GPI)-anchor. It interacts with complement components C8 and C9 during assembly of the membrane attack complex (MAC) and inhibits C9 polymerization, thus preventing the formation of MAC [Lehto T and Meri S. 1993;Rollins SA et al 1991]
REACT_163860 (Reactome) Factor I (FI) inactivates C3 convertase activity by cleavage C3b producing iC3b, which remains bound to the membrane. A final proteolytic cleavage converts iC3b into two molecules, C3c, which is released into solution, and C3dg, which remains attached to the membrane. This cleavage requires CR1, which serves as a cofactor for cleavage of iC3b by factor I (Medof ME et al. 1982).

iC3b and C3dg are active molecules, that can bind CR2 (CD21) to enhance B-cell immunity (Tuveson DA et al.1991; Sarrias MR et al. 2001).

REACT_163870 (Reactome) Complement proteins C8 and C9 can bind to VTN:C5b:C6:C7 to form soluble C5b-C9 complex in plasma. The vitronectin binding to C5b-C9 complex prevents C9 polymerization by rendering it water-soluble and lytic inactive.
REACT_25075 (Reactome) Metastable C3b can bind a wide variety of proteins and carbohydrates expressed on biological surfaces (Coico & Sunshine, 2009; Kimball 2010). This is an essentially random event (Dodds & Law, 1998); binding may be to host or microorganism. However, certain surface sugars have greater C3b binding rates, perhaps explaining variations in microorganism suceptibility (Pangburn, M. in The Complement System, Ed. Rother et al. 1998).
REACT_25166 (Reactome) The cleavage of C4 into C4a and C4b releases an acyl group from the intrachain thioester bond, allowing C4b to bond covalently to any adjacent biological substrates (Dodds & Law 1998). C4 is encoded at two loci, C4A and C4B. The C4b proteins derived from these genes are not identical and have different binding preferences (Law et al 1984, Sepp et al. 1993); C4A-derived C4b binds more efficiently than C4B-derived C4b to amino groups, while C4B-derived C4b is more effective than C4A in binding to hydroxyl groups. The site of C4b deposition is not clearly established (Møller-Kristensen et al. 2003) but generally accepted to be the activating cell membrane surface, though it may be the activating complex itself.
REACT_7946 (Reactome)
REACT_7948 (Reactome) C3(H2O):Factor Bb is a C3 convertase, sometimes referred to as the initial C3 convertase (iC3). The Factor Bb component catalyzes the hydrolysis of C3 to produce C3b and C3a. This reaction is not known to be directly coupled to the association of C3b complexes with a cell surface. It is believed that a small proportion of C3b spontaneously associates with the cell surface, otherwise it is rapidly inactivated (Muller-Eberhard 1988).
REACT_7950 (Reactome)
REACT_7959 (Reactome) C2 is cleaved into the large C2a and the small C2b fragment. This irreversible, extracellular reaction can be catalyzed by activated MBL, generated through the lectin pathway of complement activation (Vorup-Jensen et al. 2000), and by activated C1, generated through the classical pathway (Nasagawa and Stroud 1977). N.B. Early literature refers to the larger fragment of C2 as C2a. However, complement scientists decided that the smaller of all C fragments should be designated with an 'a', the larger with a 'b', changing the nomenclature for C2. For this reason recent literature may refer to the larger C2 fragment as C2b, and the classical C3 convertase as C4bC2b. Throughout this pathway, Reactome uses the current (Feb 2012) Uniprot names which adhere to the original naming practice.
REACT_7965 (Reactome) MBL or ficolins binding to carbohydrates on the target surface results in conformational changes in the lectin:MASPs complex. It in turn promotes a cleavage of proenzyme form of MASP between the CCP2 and the serine protease domains, which results in the generation of the active form. The active form of MASP-2 is able to cleave C4 and C2 to generate the C3 convertase (Vorup-Jensen T et al. 2000; Chen CB and Wallis R 2004). The active form of MASP-1 was shown to facilitate the complement activation by either direct cleavage of complex-bound MASP-2 or cleavage of C2 bound to C4 (Matsushita M et al. 2000; Heja D et al. 2012).
REACT_7966 (Reactome) C3b on a surface binds Factor B from solution to form a complex (Schreiber et al. 1978; Muller-Eberhard 1988).
REACT_7976 (Reactome)
REACT_7977 (Reactome) In this irreversible reaction, the activated C1r subunit of the C1:antibody:antigen complex cleaves the C1s subunit of the complex, activating it in turn (Ziccardi and Cooper 1976). The resulting complex is a C4 activator.
REACT_7978 (Reactome) C1 activation requires interaction with two separate Fc domains, so pentavalent IgM antibody is far more efficient at complement activation than IgG antibody (Muller-Eberhard and Kunkel 1961). Antibody binding results in a conformational change in the C1r component of the C1 complex and a proteolytic cleavage of C1r, activating it (Ziccardi and Cooper 1976). This reaction is irreversible under physiological conditions.
REACT_7981 (Reactome) Factor D, a constitutively active serine protease found in trace amounts in the blood, cleaves a specific Arg-Lys bond in the Factor B component of the soluble C3(H2O):Factor B complex, yielding C3(H2O):Factor Bb and an inactive polypeptide, Factor Ba (Fearon and Austin 1975; Lesavre and Muller-Eberhard 1978; Lesavre et al. 1979; Schreiber et al. 1978).
REACT_7982 (Reactome)
REACT_7983 (Reactome) The MBL polypeptide chain consists of a short N-terminal cysteine-rich region, a collagen-like region comprising 19 Gly-X-Y triplets, a 34-residue hydrophobic stretch, and a C-terminal C-type lectin domain. MBL monomers associate via their cysteine-rich and collagen-like regions to form homotrimers, and these in turn associate into oligomers. The predominant oligomers found in human serum contain three (MBL-I) or four (MBL-II) homotrimers (Fujita et al. 2004; Teillet et al. 2005). Extracellular MBL oligomers circulate in plasma in complexes with MASP1/2. The carbohydrate recognition domain (CRD) of MBL binds carbohydrates with 3- and 4- OH groups in the pyranose ring, such as mannose and N-acetyl-D-glucosamine, in the presence of Ca2+. Such motifs occur on the surfaces of viruses, bacteria, fungi and protozoa. The affinity of any one MBL binding site for a carbohydrate ligand is low, but interaction between multiple binding sites on an MBL oligomer and a repetitive carbohydrate motif on a target surface allow high-avidity binding. The specificity of the MBL binding site (it does not bind glucose or sialic acid) and the requirement for a repeated target motif may account for the failure of MBL to bind human glycoproteins under normal conditions (Petersen et al. 2001). This reaction in particular represents the interaction of MBL with bacterial mannose repeats.
REACT_7986 (Reactome) The complex of C3b:Factor Bb, stabilized on the cell surface by properdin, catalyzes the cleavage of C3 to yield C3b and C3a. The C3b is recruited to the C3b:Factor B complex through its interaction with properdin (Daha et al. 1976; Medicus et al. 1976; Hourcade 2006), yielding the alternate C5 convertase.
REACT_7988 (Reactome) The membrane attack complex is composed of one C5:C6:C7:C8 complex and between 12-15 C9 molecules (Podack et al. 1982 - 12 represented in this reaction).
REACT_7989 (Reactome) The same complexes as for C3 activation are employed for the cleavage of C5. C3 convertases with an additional C3b molecule covalently deposited in the immediate vicinity form the C5 convertases C3bBbC3b and C4b2aC3b, respectively. The second C3b acts like an anvil for C5: it interacts with C5 and presents C5 in the correct conformation for cleavage by the C2a or Bb enzyme.
REACT_7990 (Reactome) C4b and C2a bind to form the classical pathway C3-convertase (C4b2a complex), C3b and the Bb fragment of Factor B form the alternative pathway C3 convertase. The C3(H2O):Bb C3 convertase is sometimes called the initiating convertase, and the C5 convertases also have C3 convertase activity (Rawal & Pangburn 2001).
REACT_8002 (Reactome) The alpha chain of C4 is cleaved, releasing an N-terminal portion of this chain as C4a. The beta and gamma chains are not cleaved and remain linked to the alpha chain by disulfide bonds (Nagasawa et al. 1976, 1980). The resulting C4b heterotrimer undergoes a gross conformational change; the internal thioester in C4b becomes exposed and able to form covalent bonds with surrounding molecules (Law and Dodds 1997). A large proportion of the bonds formed are with water, but some will attach C4b to biological surfaces (Rother et al. 1998). This irreversible reaction can be catalyzed by activated MBL, generated through the lectin pathway of complement activation (Fujita et al. 2004; Hajela et al. 2002), and by activated C1, generated through the classical pathway (Muller-Eberhard and Lepow 1965).

N.B. Humans have two highly polymorphic loci for Complement factor 4, C4A and C4B. C4A alleles carry the Rodgers (Rg) blood group antigens while the C4B alleles carry the Chido (Ch) blood group antigens. The two loci encode non identical C4 peptides; C4 derived from C4A reacts more rapidly with the amino groups of peptide antigens while C4B allotypes react more rapidly with the hydroxyl group of carbohydrate antigens. The names of the two loci are always represented in uppercase. C4a and C4b refer to the peptide products of Complement Factor 4 cleavage.
REACT_8007 (Reactome) The thioester linkage between cysteine residue 1010 and glutamine residue 1013 in the alpha chain of Complement factor 3 (C3) can spontaneously hydrolyze, yielding so-called C3(H2O) (Tack et al. 1980; Pangburn & Muller-Eberhard 1980; Pangburn et al. 1981). Thioester bond hydrolysis causes conformational rearrangements that give C3(H2O) the ability to bind Factor B. The spontaneous hydrolysis rate of C3 under physiological conditions and temperature is about l% per hour, thus the C3b-like properties of C3(H2O) provide a continuous low level initiation of the alternative pathway of complement activation (Pangburn & Muller-Eberhard 1983). If not bound by Factor B, C3(H2O) binds Factor H and is inactivated by Factor I
REACT_8013 (Reactome) Thioester bond hydrolysis causes conformational rearrangements that give C3(H2O) the ability to bind Factor B (Schreiber et al. 1978). The spontaneous hydrolysis rate of C3 under physiological conditions and temperature is about l% per hour, thus the C3b-like properties of C3(H2O) provide a continuous low level initiation of the alternative pathway of complement activation (Pangburn & Muller-Eberhard 1983).
REACT_8014 (Reactome) C4b and C2a form a complex termed the classical pathway C3 convertase (Muller-Eberhard et al. 1967). C2a that fails to bind C4b is rapidly inactivated.
REACT_8018 (Reactome) C3b:Bb is naturally labile with a half-life of ~90 s; association of the complex with properdin extends the half-life to ~30 min. (Medicus et al. 1976). Properdin is found in the blood as a mixture of multivalent oligomers: 30% dimers, 45% trimers, 10% tetramers, and 15% higher oligomers. Monomers associate with one another in a head-to-tail arrangement, producing closed circular structures (Smith et al. 1984). These features suggest that the properdin oligomer associated with a C3b:Bb complex on a surface such as a cell membrane can facilitate recruitment of additional C3b:Bb complexes to the site (Farries et al. 1988; Hourcade 2006).
REACT_8022 (Reactome) C5 convertases are serine proteases that cleave C5 with high efficiency; the C3 convertases can cleave C5 but have a poor affinity for C5, with a Km of 6-9 microM. The high affinity C5 convertases are generated when the low affinity C3/C5 convertases such as C4b:C2a deposit C3b by cleaving native C3. These C3b-containing C3/C5 convertases have Km values of 0.005 microM, well below the normal concentration of C5 in blood (0.37 microM). They have very low Vmax rates, just one C5 cleaved per 1–4 min per enzyme (Rawal & Pangburn 1998).
REACT_8026 (Reactome) Factor D, a constitutively active serine protease found in trace amounts in the blood, cleaves a specific Arg-Lys bond in the Factor B component of the cell surface-associated C3b:Factor B complex, yielding the alternate C3 convertase C3bBb on the surface and releasing an inactive polypeptide, Factor Ba (Lesavre and Muller-Eberhard 1978; Lesavre et al. 1979; Schreiber et al. 1978).
VTN

C5b C6

C7		REACT_163870 (Reactome)
VTNREACT_163759 (Reactome)
iC3bArrowREACT_118650 (Reactome)
iC3bArrowREACT_118841 (Reactome)
thioester-C1010-Q1013-C4bArrowREACT_8002 (Reactome)
thioester-C1010-Q1013-C4bREACT_118763 (Reactome)
thioester-C1010-Q1013-C4bREACT_163768 (Reactome)
thioester-C1010-Q1013-C4bREACT_25166 (Reactome)
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