Complement cascade (Homo sapiens)

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9, 16, 50, 61, 6419, 42, 6683, 9015, 947239, 87505034, 4454, 56, 7025036, 90111, 10, 32392, 68, 76, 9343, 50843, 5011, 26, 38485054, 56, 7045609134, 692011, 264118, 27, 46, 62, 73...8257, 5950724412, 21, 33, 51, 58...34, 444781, 881, 8, 402278, 80, 90523, 4, 6331, 37, 52, 859328, 43, 776, 13, 18, 33, 46...443960, 725, 17, 25, 49, 8624, 52, 684323cytosolTarget CellInnocent bystander cellcytosolIg heavy chain V-Iregion WOL C1QB C4A beta C5b alpha' C4B alpha4 fragment C3b alpha' C4B alpha3 Cell surface:C4b:C2aC3aC4A beta FCN1 IgH heavy chainV-III region VH26precursor MASP1(20-699) C7 Ig heavy chain V-IIIregion GA Ig lambda chain V-IIregion BOH Ig lambda chainV-III region LOI Ig kappa chain V-IIregion FR dNQ-C4A(757-1446) C4BPA CD59:C5b-C9Ig kappa chain V-Iregion WAT IGHG1 IGHG3 Ig heavy chain V-IIregion ARH-77 CR1 C6 C5b alpha' Ig kappa chain V-Iregion Roy C4B beta Ig kappa chain V-Iregion Kue C6 CR1C3fdNQ-C4B(757-1446) Ig kappa chain V-Iregion Lay C8A IGLC6 C4B beta C4b-bindingprotein:Factor IdNQ-C4A(757-1446) C4A beta CD55 Cell surface:C4bIGKC C2Ig lambda chain V-IVregion X Ig kappa chain V-Iregion Ni Properdin oligomerIGLV7-43(1-?) MASP1(20-699) dNQ-C4B(757-1446) Ig kappa chain V-Iregion Kue C3b alpha' Ig heavy chain V-IIIregion DOB Ig kappa chain V-IIIregion VG C4A gamma C3 beta chain IGLV4-60(1-?) Ig heavy chain V-IIregion COR C5b:C6 complexIg kappa chain V-Iregion Rei IGLV4-69(1-?) Ig heavy chain V-IIIregion TEI Cell surface:C3bIg kappa chain V-IIregion FR Ig lambda chain V-IIregion NIG-84 IGLV7-43(1-?) Ig heavy chain V-IIIregion TUR FCN2 ligandC4B gamma Ig kappa chain V-IIIregion IARC/BL41 dNQ-C3(672-1663) C2a Ig heavy chain V-IIregion WAH C2a Ig kappa chain V-Iregion Scw Ig heavy chain V-IIIregion WEA C7 Ig kappa chain V-Iregion BAN Ig kappa chain V-Iregion EU C5 beta FCN2:MASPs:Ca2+:FCN2ligandIg kappa chain V-Iregion Ni IGLC2 Ig heavy chain V-Iregion ND Ig kappa chain V-IIIregion B6 C4B beta 1,3-beta-D-glucan CFI(19-335) Ig kappa chain V-Iregion Roy C4A gamma Ig kappa chain V-Iregion Ka C4A beta Ig kappa chain V-Iregion Walker dNQ-C4A(757-1446) IGKVA18(21-?) Ig kappa chain V-IIIregion HIC Ig kappa chain V-Iregion Scw FCN1 Ig kappa chain V-IIregion MIL Ig lambda chain V-IIregion NEI FCN2 Ig lambda chain V-IIregion BO Ig heavy chain V-IIIregion JON FCN3 CFI(340-583) IGLV3-16(1-?) Ig kappa chain V-Iregion Walker Ig kappa chain V-Iregion AG C4B alpha chainfragment b Ig lambda chain V-IVregion Hil Ig lambda chain V-IIregion BO CFH, FHR-3Ig lambda chain V-Iregion NIG-64 CD46:C3bC5 beta C8G C2a H2OC3c alpha' chainfragment 2 C5 beta IGLV7-46(1-?) C4B beta dNQ-C4B(757-1446) Ig kappa chain V-Iregion Gal Ig kappa chain V-IIIregion Ti IgH heavy chainV-III region VH26precursor Ig lambda chain V-Iregion WAH C2a Ig heavy chain V-IIregion SESS CD46 Ig kappa chain V-IIregion RPMI 6410 C4BPB C5 beta C3c alpha' chainfragment 1precursor Ig heavy chain V-IIIregion POM Ig heavy chain V-IIIregion BUR Cell surface:C3bIGKVA18(21-?) Ig lambda chain V-Vregion DEL IGLV8-61(1-?) C4B gamma Ig lambda chain V-IVregion Bau C4B beta C3 beta chain CFHIGKC CFI:CFH,FHR3:C3bC3b alpha' C3 beta chain C4A beta Ig lambda chain V-VIregion EB4 Ig heavy chain V-IIIregion WEA Ig kappa chain V-IIIregion HAH C4B gamma IGLV11-55(1-?) C4A beta Ig kappa chain V-IIregion TEW Sialic acid Ig lambda chain V-IVregion Bau Ig lambda chain V-IVregion MOL Ig kappa chain V-Iregion Daudi FCN1 C3b alpha' C3b alpha' IGLV3-12(1-?) Ig lambda chain V-Iregion MEM C3 beta chain C4B gamma IGLV3-12(1-?) Ig heavy chain V-IIIregion CAM Ig lambda chain V-VIregion EB4 11xCbxE-PROS1IGLC3 Ig lambda chain V-VIregion NIG-48 VTN Ig kappa chain V-Iregion WEA IGHG4 Ig lambda chain V-IVregion Kern C2aC3b alpha' C4bC2a, C3bBbIg lambda chain V-Iregion EPS Ig kappa chain V-IIregion Cum FCN2 CFI(19-335) Ig heavy chain V-Iregion SIE Ig lambda chain V-IIregion BO Ig lambda chain V-IIregion NEI C8Ig kappa chain V-IIIregion IARC/BL41 VTN Ig heavy chain V-IIIregion ZAP IGLV5-37(1-?) Ig heavy chain V-IIregion NEWM Ca2+C3aC4A alpha4 fragment Ig kappa chain V-Iregion CAR Ig heavy chain V-IIregion COR Ig kappa chain V-IIIregion POM dNQ-C4B(757-1446) IGHV7-81(1-?) C8G Antigen: antibody:C1 (activated C1Rand C1S) complexMASP1(20-699) C3c alpha' chainfragment 1precursor Ig kappa chain V-IIIregion Ti dNQ-C4B(757-1446) Ig heavy chain V-IIregion SESS C3 beta chain C4B gamma N-acetylgalactosamine Ig lambda chain V-Iregion NEWM FCN1 C4B alpha chainfragment b C3b alpha' dNQ-C4A(757-1446) Ig lambda chain V-IIregion VIL IGLV4-60(1-?) Ig kappa chain V-IIIregion SIE C4B gamma C3bIGLV2-33(1-?) dNQ-C4A(757-1446) C5b:C6:C7 complexCa2+ IGHV(1-?) IGKV1-5(23-?) C3 beta chain C6 C3cdNQ-C3(672-1663) Ig lambda chain V-VIregion EB4 thioester-C1010-Q1013-C4bIg heavy chain V-IIIregion ZAP MASP1(20-699) CD55 C4B gamma Ig heavy chain V-IIregion NEWM Ig heavy chain V-IIIregion GA C4A gamma VTN:C5b:C6:C7:C8:C9dNQ-C4B(757-1446) C3 beta chain Ig kappa chain V-Iregion Gal C3c alpha' chainfragment 1 Ig heavy chain V-IIIregion WAS CFB(260-764) Ig kappa chain V-IIIregion HIC IGLV7-43(1-?) Ig lambda chain V-IIregion TOG Ig kappa chain V-Iregion Ka C3b alpha' C7 Ig kappa chain V-IIIregion NG9 Sialic acid IGHV(1-?) IGLV3-22(1-?) C5b alpha' IGLV(23-?) Ig lambda chain V-IIregion VIL C9(22-559)C4A gamma FCN1:MASP2dimer:MASP1 dimerIg kappa chain V-IIIregion VG C4A beta C5b alpha' C4B beta Ig heavy chain V-IIregion DAW Ig kappa chain V-IIIregion HIC C5b alpha' Ig lambda chain V-IIregion TOG C3b alpha' C3bC4A beta C5 beta C3 beta chain C4A gamma C8G PCho C4A beta Sialic acid N-acetylgalactosamine Cell surface:C3b:BbC3b alpha' Ig heavy chain V-Iregion ND C5 convertasesdNQ-C4B(757-1446) Ig lambda chain V-Iregion EPS dNQ-C4A(757-1446) FCN3:MASPs:Ca2+:FCN3ligandIg heavy chain V-Iregion EU Ig lambda chain V-IIregion MGC C5b alpha' C3c alpha' chainfragment 2 Ig kappa chain V-IIIregion Ti IGLV2-18(1-?) Ig kappa chain V-IIregion GM607 Ig kappa chain V-Iregion Rei Ig kappa chain V-IVregion Len Ig heavy chain V-IIIregion POM Ig kappa chain V-IIregion GM607 IGLC3 Ig lambda chain V-IIregion TRO C3 beta chain Ig lambda chain V-VIregion SUT C9(22-559) C4A gamma C1S(16-688) Ig heavy chain V-IIIregion BUT MASP2-1(445-686) C6 Ig lambda chain V-IIregion WIN IGLV3-27(1-?) Ig heavy chain V-IIIregion TIL MASP1(20-699) Ig lambda chain V-VIregion WLT C5b alpha' C8G Ig heavy chain V-IIIregion CAM C5 beta N-acetylgalactosamine C7 Ig heavy chain V-IIIregion BUT C3 convertasesIg lambda chain V-Iregion HA CFB(260-764) Ig lambda chain V-Iregion HA Lipoteichoic acid Ig heavy chain V-IIregion MCE IGLV4-3(1-?) Ig kappa chain V-IVregion Len dNQ-C4A(757-1446) C5 beta Complement factor DCR1:C4bC1R C-terminalfragment FCN3:MASP2dimer:MASP1 dimerIGHG1 N-acetyl-D-glucosamine Ig lambda chain V-Iregion NEW Ig kappa chain V-IIregion Cum C3 beta chain C3 beta chain 1,3-beta-D-glucan C4A beta IGHG3 IGLV2-23(1-?) Ca2+ C4A gamma Lipoteichoic acid C4A alpha b C2a IGLV3-25(1-?) C4B gamma C4BPA C3 beta chain Ig kappa chain V-IVregion B17 1,3-beta-D-glucan Ig lambda chain V-IVregion X Lipoteichoic acid Ig lambda chain V-IVregion Kern dNQ-C4A(757-1446) Ig kappa chain V-IVregion B17 CR1:C3bBb, C4bC2acomplexesIg kappa chain V-IIIregion HAH Ig lambda chain V-Iregion NEW Ig kappa chain V-IIIregion SIE Ig lambda chain V-VIregion NIG-48 Ig kappa chain V-Iregion EU IGLV11-55(1-?) Ig kappa chain V-Iregion Kue MASP2-1 C3b:Bb:C3b:ProperdinIGLV2-33(1-?) Ig kappa chain V-Iregion WEA Ig kappa chain V-Iregion EU Ig heavy chain V-IIIregion HIL CR1 C4 activatorIg kappa chain V-Iregion AU CFB(26-259)CD46, CR1C3b alpha' C4B gamma Ig heavy chain V-IIIregion BUR C1QA Properdin oligomerCFI(19-335) C8A Ig heavy chain V-IIIregion DOB Ig lambda chain V-Iregion VOR C4B beta C3b alpha' Ig lambda chain V-Iregion MEM Ig lambda chain V-VIregion SUT C3b alpha' IGLV3-22(1-?) Cell surfaceIg kappa chain Vregion EV15 C4B beta MASP1(20-448) Ig kappa chain V-Iregion Lay Ig heavy chain V-IIIregion BRO Ca2+ Ig heavy chain V-IIregion HE Ig kappa chain V-Iregion Hau DAF:C3bC3b alpha' Ig kappa chain V-IVregion Len IGLV10-54(1-?) MBL/FCN:activatedMASP:carbohydratepatternsCFH:Host cellsurfaceIg heavy chain V-IIIregion NIE C3 beta chain C4B beta IGHV(1-?) CD55:C3 convertasecomplexesIg kappa chain V-IIIregion HAH Ig kappa chain V-Iregion Rei C6 C4A gamma IGLV1-40(1-?) Ig heavy chain V-IIIregion GA Ig heavy chain V-IIIregion POM Ig kappa chain V-IIIregion NG9 Ig heavy chain V-IIIregion TUR Ig kappa chain V-Iregion Scw MASP2-1(16-444) C4dC4A beta C2aIGHG2 Ig lambda chain V-Iregion VOR C7C3b alpha' C4A gamma Ig heavy chain V-IIIregion GAL Ig kappa chain V-IIIregion VH C4B gamma CD46 C5b alpha' Ig kappa chain V-IIIregion WOL Ig kappa chain V-Iregion OU IGLC1 IGLV5-45(1-?) FCN1:MASPs:Ca2+:FCN1ligandN-acetyl-D-glucosamine Ig kappa chain V-Iregion Mev IGLV2-11(1-?) Ig lambda chain V-IVregion Bau C8A dNQ-C4A(757-1446) C3f C4A gamma Ig lambda chain V-IVregion MOL MBL2 CFB(260-764) C4B gamma CFI(19-335) Cell surface:C3b:CFBIg lambda chain V-Iregion BL2 C2aMBL2 Ig heavy chain V-IIregion SESS CFB(26-764) C5 alpha Ig lambda chain V-IVregion Hil Cell surface:C3b:BbIg heavy chain V-IIIregion JON Ig lambda chainV-III region SH Ig heavy chain V-IIIregion TEI Ig heavy chain V-IIIregion HIL C6 C3 beta chain Ig heavy chain V-IIIregion TIL Ig heavy chain V-IIIregion BRO MBL2 IGLV2-18(1-?) C4B alpha chainfragment b C4A alpha b C4A gamma IGLV4-3(1-?) C4B alpha chainfragment b N-acetyl-D-glucosamine Ig heavy chain V-IIregion WAH C4c, C3fCa2+ D-fucose C4A gamma FCN3 Ig kappa chain V-Iregion Roy MBL2 Ig kappa chain V-Iregion AG IGHG4 Ig heavy chain V-IIIregion HIL Ig kappa chain V-Iregion OU Host cell surfaceCFB(260-764) Ig kappa chain V-Iregion Ni IGLV3-27(1-?) Ig kappa chain V-IIIregion GOL Ig lambda chain Vregion 4A Ig lambda chain V-VIregion AR CFDCFB(26-764)C1QA Ig heavy chain V-IIIregion TRO IGLV4-60(1-?) Ig kappa chain V-IIIregion B6 CD46, CR1:C4b:C3bcomplexesIGLV5-45(1-?) C3 beta chain CFB(260-764) IGKV4-1(21-?) C1QB C4BPB Ig heavy chain V-IIIregion BRO C4A beta IGKVA18(21-?) C4A beta C4BPB C4B beta C4B gamma C9(22-559)Ig lambda chain V-Iregion BL2 MASP1(449-699) CD46 C3 beta chain IGLV2-18(1-?) C4B gamma C4A alpha b C3(H2O):BbC4B gamma IGLV2-33(1-?) C4b with hydrolysedthioesterC4BPA C4B gamma C4-bindingprotein:C4bIg kappa chain V-Iregion Wes Ig kappa chain V-IVregion JI Ig kappa chain V-Iregion Lay C4A gamma IGLV(23-?) Ig heavy chain V-IIIregion BUR C4B beta C4A gamma C1QA Ig kappa chain V-IIIregion IARC/BL41 IGLC1 CFI(340-583) IGLV5-37(1-?) Ig lambda chain V-Iregion NEWM Ig heavy chain V-Iregion SIE C7 IGLV8-61(1-?) C2aCFB(260-764)dNQ-C4A(757-1446) Ig heavy chain V-IIIregion CAM Ig heavy chain V-Iregion HG3 IGLV2-11(1-?) CD55CFB(260-764) C3 beta chain C1S N-terminalfragment dNQ-C4A(757-1446) Ig heavy chain V-IIregion DAW MASP2-1 IGLV8-61(1-?) C5bFCN3 C7 C4B beta Ig heavy chain V-IIIregion LAY Ig heavy chain V-IIIregion TRO C2a Ig kappa chain V-Iregion Walker MASP1(20-699) IGLV11-55(1-?) C4A beta IGLV3-27(1-?) C3 beta chain C4A beta C4B gamma MBL/Ficolin:MASPsbound tocarbohydratepatternsIg lambda chain V-Iregion WAH C5b alpha' D-fucose Ig kappa chain V-IIIregion WOL C4B beta MASP2-1(16-444) Ig lambda chainV-VII region MOT C4A alpha4 fragment IGLV2-23(1-?) Bacterialmannose-basedcarbohydratesurface patternIg kappa chain V-IVregion STH Ig kappa chain V-Iregion DEE C9(22-559) Ig lambda chain V-Iregion EPS Ig kappa chain V-IIIregion POM Ig kappa chain V-Iregion Hau IGLV5-37(1-?) Ig kappa chain V-IIIregion CLL Ig heavy chain V-IIIregion ZAP C4B gamma IGLV4-69(1-?) Ig kappa chain V-Iregion HK101 Heparins Ig kappa chain Vregion EV15 Ig lambda chain V-IIregion TRO VTN:C5b:C6:C7C3b alpha' Ig heavy chain V-IIIregion LAY C5 beta C4B gamma Cell surface:C4b:C2aCa2+ Sialic acid CFI(340-583) IGLV1-44(1-?) C4B beta Ig kappa chain V-IIIregion VH dNQ-C4A(757-1446) C4A gamma CFIIGHG2 Ig heavy chain V-IIIregion TRO Ig kappa chain V-Iregion Ka Ig lambda chain V-Iregion NEWM Ig heavy chain V-IIregion HE IGLV1-36(1-?) C4BPA C8B ?FI:CD46, CR1:C4b,C3b complexesCa2+ C8B FCN3 ligandIg lambda chain V-VIregion AR Ig heavy chain V-IIregion ARH-77 CR1 Ig heavy chain V-IIregion OU C4d, iC3bC4B beta C3 beta chain dNQ-C4B(757-1446) CD46:C4bC4B beta C4A beta Ig kappa chain V-IVregion JI C4B beta dNQ-C4B(757-1446) C3(H2O)C3 beta chain Ig lambda chain V-VIregion SUT Ig kappa chain V-IIregion FR Ig lambda chain V-VIregion AR MASP2-1 dNQ-C3(672-1663) FCN2 Ig lambda chain V-IIregion VIL Ig kappa chain V-Iregion Daudi thioester-C1010-Q1013-C4bC4A alpha3 Ig kappa chain V-IIregion TEW Ig heavy chain V-Iregion Mot IGLV2-11(1-?) IGLV3-16(1-?) C8B C8G IGHV7-81(1-?) C5b:C6:C7 complexIg lambda chainV-III region SH Ig lambda chain V-IIregion TRO Ig lambda chainV-VII region MOT Ig lambda chain V-IIregion TOG C4B beta Ig kappa chain V-IVregion JI Ig kappa chain V-IIIregion CLL Ig lambda chain V-VIregion NIG-48 dNQ-C4A(757-1446) C3 beta chain Membrane AttackComplexCell surface:C3bIg kappa chain V-IIIregion GOL CRP(19-224) N-acetyl-D-glucosamine C4aMASP2-1 Ig heavy chain V-IIIregion TUR DAF:C4bC3(H2O):CFBN-acetylgalactosamine Ig kappa chain V-IIregion GM607 Ig lambda chain V-VIregion WLT C7 MASP2-1 Ig kappa chain V-Iregion CAR Ig lambda chain Vregion 4A dNQ-C4B(757-1446) IGLV7-46(1-?) CFI(19-335)MBL bound tomannose-basedcarbohydrates onbacterial surfacesC3 beta chain CD59 C4B beta Complement Factor 4Cellsurface:FH,FHR3:C3bCR1:iC3bCD46Ig kappa chain V-Iregion AG IGLV10-54(1-?) C3 beta chain Ig heavy chain V-IIIregion KOL IGHV7-81(1-?) C4BPB FCN2 Sialic acid C3(H2O)C4B beta C3 beta chain C4A beta Ig heavy chain V-Iregion Mot Cell surfaceIg kappa chain V-Iregion Mev IGLV3-25(1-?) Ig kappa chain V-IIIregion VG C9(22-559) Ig kappa chain V-Iregion Wes CFH Ig lambda chain V-Iregion VOR Ig kappa chain V-Iregion Bi C3 alpha chain 11xCbxE-PROS1 MASP1(20-699) MASP2-1 MASP1(20-699) C3b alpha' C4A gamma Ig heavy chain V-IIIregion NIE dNQ-C4B(757-1446) FCN3 Ig lambda chain V-IIregion BUR FCN1 ligandC1R(18-705) Ig heavy chain V-IIIregion JON C4B gamma IGLV1-40(1-?) C4BPB dNQ-C4B(757-1446) IGLV7-46(1-?) Ig kappa chain V-IIregion RPMI 6410 FCN2:MASP2dimer:MASP1 dimerIg kappa chain V-IIIregion VH Ig heavy chain V-IIregion NEWM C3dgIg heavy chain V-Iregion HG3 IGLC3 Ig kappa chain V-Iregion Bi Ig lambda chain V-Iregion BL2 C4b, C3bIg lambda chain V-IIregion NIG-58 CFI(340-583)C4B alpha C3b alpha' CFH dNQ-C4A(757-1446) C8B CFB(26-764) C4A alpha3 C1S(16-688) C8B Ig lambda chain V-IIregion BUR Ig lambda chain Vregion 4A iC3bCa2+ Ig heavy chain V-IIIregion GAL C3b alpha' IGLV1-40(1-?) CFI(340-583) IGLV1-36(1-?) C4 alpha C5 beta IGLV1-44(1-?) Ig heavy chain V-Iregion WOL dNQ-C4A(757-1446) IGLC6 IGHG4 C4cIg kappa chain V-Iregion DEE C1QB C3 beta chain Ig lambda chain V-IIregion WIN C4 bindingprotein:protein SIg kappa chain V-IIIregion GOL C4A gamma C4A gamma C1QC C3 beta chain Ig heavy chain V-IIIregion KOL C4b:C2a:C3bMASP2-1 Ig lambda chain V-Iregion NEW IGLV2-23(1-?) C1R C-terminalfragment Ig kappa chain Vregion EV15 Ig heavy chain V-IIIregion GAL C4B beta MASP2-1(445-686) C2a Ig heavy chain V-Iregion WOL C4B gamma Ig kappa chain V-Iregion Mev Ig heavy chain V-IIregion COR Cellsurface:C3b:Bb:ProperdinIGKV4-1(21-?) Ig heavy chain V-IIregion OU CD55 Ig kappa chain V-Iregion CAR C3 beta chain Ig lambda chainV-VII region MOT MASP1(20-448) C3b alpha' Ig lambda chain V-IIregion MGC IGLV3-12(1-?) C4A beta C8A CFB(260-764) Ig heavy chain V-IIIregion WAS C3b alpha' Ig heavy chain V-IIregion DAW C4A beta C3b alpha' C3b alpha' Ig kappa chain V-IIIregion B6 Ig heavy chain V-IIIregion BUT IGLV3-25(1-?) C3 beta chain CFI(340-583) Ig lambda chainV-III region LOI Ig lambda chain V-IIregion BUR MBL2 Ig heavy chain V-IIregion MCE Ig heavy chain V-IIregion MCE CFI:CFH:C3bC1QB C1QA C4BPA C4A gamma C3 beta chain C4A gamma CR1 C4B gamma C4B alpha4 fragment C5aIGLC7 C7 C2bC3b alpha' CR1:C3bC4 bindingprotein:C4bC2aC4B beta Ig kappa chain V-Iregion Hau Ig lambda chain V-IIregion MGC H2OC1QC C6 Ig kappa chain V-IVregion STH C3 beta chain C3 beta chain Ig lambda chain V-Vregion DEL Heparins IGKV4-1(21-?) Ig heavy chain V-IIIregion LAY C-reactiveproteinpentamer:phosphocholine:C1QMBL-II:MASP-2dimer:MASP-1 dimercomplexCR1 Ig lambda chain V-VIregion WLT MBL:activatedMASPs:mannose-basedcarbohydratesIg kappa chain V-Iregion Bi dNQ-C4B(757-1446) Ig lambda chain V-IIregion NIG-58 Antigen: antibody:C1 complexC4A alpha b Ig heavy chain V-Iregion SIE IGLV(23-?) Ig lambda chain V-Iregion WAH Ig lambda chain V-IIregion NEI C4A gamma Cell surface:C4bIg lambda chain V-IIregion WIN Ig heavy chain V-IIIregion DOB Ig kappa chain V-Iregion WEA Ig heavy chain V-IIIregion NIE C4A gamma C6 C1R N-terminalfragment IGLV4-69(1-?) CD46 IGLV3-22(1-?) C3 beta chain C6IGKV1-5(23-?) Ig lambda chain V-Iregion MEM Ig lambda chain V-IVregion MOL Ig heavy chain V-Iregion EU Ig heavy chain V-Iregion EU C5b:C6:C7:C8 complexC5 beta CFH iC3bIg kappa chain V-IIregion MIL Ig kappa chain V-Iregion HK101 Ig kappa chain V-IIregion RPMI 6410 CD59Ig kappa chain V-IIregion MIL C5 beta Ig kappa chain V-Iregion AU IGLV10-54(1-?) Ig kappa chain V-Iregion WAT C4A gamma C4B gamma IGLV3-16(1-?) IGLC2 C5b alpha' C3c alpha' chainfragment 2 N-acetyl-D-glucosamine dNQ-C4B(757-1446) IGKC C8A IGHG1 Ig heavy chain V-IIIregion KOL MASP1(20-699) C8A Ig lambda chainV-III region LOI C4A beta Ig kappa chain V-IIregion Cum Ig lambda chain V-IIregion NIG-84 Ig kappa chain V-Iregion AU C2aCFH:C3bIg lambda chain V-Vregion DEL VTNIg kappa chain V-Iregion BAN dNQ-C4B(757-1446) IGLV1-44(1-?) C3b alpha' Cell surface:C4b:C2aIg lambda chainV-III region SH Ig kappa chain V-IIIregion WOL Ig lambda chain V-IIregion BOH Antigen: antibody:C1 (activated C1R)complexIg heavy chain V-IIIregion TIL IGLC2 C4A gamma CFI(19-335) C3 beta chain Ig lambda chain V-Iregion HA Ig heavy chain V-Iregion ND Ig heavy chain V-IIregion ARH-77 MASP2-1 dNQ-C4B(757-1446) C3c alpha' chainfragment 2 MASP1(449-699) Complement factor 5C4A beta Ig kappa chain V-IIIregion CLL IGLV1-36(1-?) C8B C4B alpha3 Ig lambda chain V-Iregion NIG-64 Ig kappa chain V-Iregion Gal C8G Cellsurface:CFH,FHR3:C3bBbIg heavy chain V-IIregion WAH dNQ-C4A(757-1446) Ig heavy chain V-IIIregion WAS Ig kappa chain V-IVregion B17 CFB(260-764) Ig lambda chain V-IIregion NIG-84 Ig heavy chain V-Iregion Mot Ig lambda chain V-IVregion X C4B beta dNQ-C4B(757-1446) IGKV1-5(23-?) C4B gamma Ig heavy chain V-IIIregion TEI IGLC1 C1QC C3 convertasesIg kappa chain V-Iregion OU MASP2-1 Ca2+ Ig lambda chain V-Iregion NIG-64 C2a C3 beta chain C4B gamma C3b alpha' Ig kappa chain V-Iregion Daudi IgH heavy chainV-III region VH26precursor dNQ-C3(672-1663) C5b:C6:C7:C8 complexC6 Ig kappa chain V-IIIregion NG9 IGLC7 C4b-binding proteinIGLV4-3(1-?) Ig heavy chain V-IIregion OU Ig kappa chain V-IIregion TEW Ig kappa chain V-Iregion BAN IGLV5-45(1-?) C1S C-terminalfragment C4A beta IGHG2 D-fucose Ig lambda chain V-IIregion BOH Ig heavy chain V-Iregion HG3 IGHG3 C3bIg kappa chain V-IIIregion SIE C3 beta chain C1R N-terminalfragment Ig kappa chain V-Iregion Wes C4B beta Ig lambda chain V-IVregion Kern Complement factor 3C1QC Ig lambda chain V-IIregion NIG-58 IGLC7 Ig lambda chain V-IVregion Hil dNQ-C4A(757-1446) CR1 Ig kappa chain V-IIIregion POM Ig kappa chain V-IVregion STH C4A beta Ig kappa chain V-Iregion HK101 Ig heavy chain V-IIregion HE Ig kappa chain V-Iregion DEE IGLC6 C4A beta C3c alpha' chainfragment 1precursor Ig kappa chain V-Iregion WAT CFB(260-764) Ig heavy chain V-IIIregion WEA 14, 307329633, 4773, 955354355571, 897675818, 756775515252


Description

In the complement cascade, a panel of soluble molecules rapidly and effectively senses a danger or damage and triggers reactions to provide a response that discriminates among foreign intruders, cellular debris, healthy and altered host cells (Ricklin D et al. 2010). Complement proteins circulate in the blood stream in functionally inactive states. When triggered the complement cascade generates enzymatically active molecules (such as C3/C5 convertases) and biological effectors: opsonins (C3b, C3d and C4b), anaphylatoxins (C3a and C5a), and C5b, which initiates assembly of the lytic membrane attack complex (MAC). Three branches lead to complement activation: the classical, lectin and alternative pathways (Kang YH et al. 2009; Ricklin D et al. 2010). The classical pathway is initiated by C1 complex binding to immune complexes, pentraxins or other targets such as apoptotic cells leading to cleavage of C4 and C2 components and formation of the classical C3 convertase, C4bC2a. The lectin pathway is activated by binding of mannan-binding lectin (MBL) to repetitive carbohydrate residues, or by binding of ficolins to carbohydrate or acetylated groups on target surfaces. MBL and ficolins interact with MBL-associated serine proteases (MASP) leading to cleavage of C4 and C2 and formation of the classical C3 convertase, C4bC2a. The alternative pathway is spontaneously activated by the hydrolysis of the internal thioester group of C3 to give C3(H2O). Alternative pathway activation involves interaction of C3(H2O) and/or previously generated C3b with factor B, which is cleaved by factor D to generate the alternative C3 convertases C3(H2O)Bb and/or C3bBb. All three pathways merge at the proteolytic cleavage of component C3 by C3 convertases to form opsonin C3b and anaphylatoxin C3a. C3b covalently binds to glycoproteins scattered across the target cell surface. This is followed by an amplification reaction that generates additional C3 convertases and deposits more C3b at the local site. C3b can also bind to C3 convertases switching them to C5 convertases, which mediate C5 cleavage leading to MAC formation. Thus, the activation of the complement system leads to several important outcomes:
  • opsonization of target cells to enhance phagocytosis,
  • lysis of target cells via membrane attack complex (MAC) assembly on the cell surface,
  • production of anaphylatoxins C3a/C5a involved in the host inflammatory response,
  • C5a-mediated leukocyte chemotaxis,
  • and clearance of antibody-antigen complexes.

The complement system is able to distinguish between pathological and physiological challenges, i.e. the outcomes of complement activation are predetermined by the trigger and are tightly tuned by a combination of initiation events with several regulatory mechanisms. These regulatory mechanisms use soluble (e.g., C4BP, CFI and CFH) and membrane-bound regulators (e.g., CR1, CD46(MCP), CD55(DAF) and CD59) and are coordinated by complement receptors such as CR1, CR2, etc.

In response to microbial infection complement activation results in flagging microorganisms with opsonins for facilitated phagocytosis, formation of MAC on cells such as Gram-negative bacteria leading to cell lysis, and release of C3a and C5a to stimulate downstream immune responses and to attract leukocytes. Most pathogens can be eliminated by these complement-mediated host responses, though some pathogenic microorganisms have developed ways of avoiding complement recognition or blocking host complement attack resulting in greater virulence (Lambris JD et al. 2008; Serruto D et al. 2010).<p>All three complement pathways (classical, lectin and alternative) have been implicated in clearance of dying cells (Mevorach D et al. 1998; Ogden CA et al. 2001; Gullstrand B et al.2009; Kemper C et al. 2008). Altered surfaces of apoptotic cells are recognized by complement proteins leading to opsonization and subsequent phagocytosis. In contrast to pathogens, apoptotic cells are believed to induce only a limited complement activation by allowing opsonization of altered surfaces but restricting the terminal pathway of MAC formation (Gershov D et al. 2000; Braunschweig A and Jozsi M 2011). Thus, opsonization facilitates clearance of dying cells and cell debris without triggering danger signals and further inflammatory responses (Fraser DA et al. 2007, 2009; Benoit ME et al. 2012). C1q-mediated complement activation by apoptotic cells has been shown in a variety of human cells: keratinocytes, human umbilical vein endothelial cells (HUVEC), Jurkat T lymphoblastoid cells, lung adenocarcinoma cells (Korb LC and Ahearn JM 1997; Mold C and Morris CA 2001; Navratil JS et al. 2001; Nauta AJ et al. 2004). In addition to C1q the opsonization of apoptotic Jurkat T cells with MBL also facilitated clearance of these cells by both dendritic cells (DC) and macrophages (Nauta AJ et al. 2004). Also C3b, iC3b and C4b deposition on apoptotic cells as a consequence of activation of the complement cascade may promote complement-mediated phagocytosis. C1q, MBL and cleavage fragments of C3/C4 can bind to several receptors expressed on macrophages (e.g. cC1qR (calreticulin), CR1, CR3, CR4) suggesting a potential clearance mechanism through this interaction (Mevorach D et al. 1998; Ogden CA et al. 2001). Apoptosis is also associated with an altered expression of complement regulators on the surface of apoptotic cells. CD46 (MCP) bound to the plasma membrane of a healthy cell protects it from complement-mediated attack by preventing deposition of C3b and C4b, and reduced expression of CD46 on dying cells may lead to enhanced opsonization (Elward K et al. 2005). Upregulation of CD55 (DAF) and CD59 on apoptotic cell surfaces may protect damaged cells against complement mediated lysis (Pedersen ED et al. 2007; Iborra A et al. 2003; Hensel F et al. 2001). In addition, fluid-phase complement regulators such as C4BP, CFH may also inhibit lysis of apoptotic cells by limiting complement activation (Trouw LA et al 2007; Braunschweig A and Jozsi M. 2011).<p>Complement facilitates the clearance of immune complexes (IC) from the circulation (Chevalier J and Kazatchkine MD 1989; Nielsen CH et al. 1997). Erythrocytes bear clusters of complement receptor 1 (CR1 or CD35), which serves as an immune adherence receptor for C3 and/or C4 fragments deposited on IC that are shuttled to liver and spleen, where IC are transferred and processed by tissue macrophages through an Fc receptor-mediated process.<p>Complement proteins are always present in the blood and a small percentage spontaneously activate. Inappropriate activation leads to host cell damage, so on healthy human cells any complement activation or amplification is strictly regulated by surface-bound regulators that accelerate decay of the convertases (CR1, CD55), act as a cofactor for the factor I (CFI)-mediated degradation of C3b and C4b (CR1, CD46), or prevent the formation of MAC (CD59). Soluble regulators such as C4BP, CFH and FHL1 recognize self surface pattern-like glycosaminoglycans and further impair activation.<p>Complement components interact with other biological systems. Upon microbial infection complement acts in cooperation with Toll-like receptors (TLRs) to amplify innate host defense. Anaphylatoxin C5a binds C5a receptor (C5aR) resulting in a synergistic enhancement of the TLR and C5aR-mediated proinflammatory cytokine response to infection. This interplay is negatively modulated by co-ligation of TLR and the second C5a receptor, C5L2, suggesting the existence of complex immunomodulatory interactions (Kohl J 2006; Hajishengallis G and Lambris JD 2010). In addition to C5aR and C5L2, complement receptor 3 (CR3) facilitates TLR2 or TLR4 signaling pathways by promoting a recruitment of their sorting adaptor TIRAP (MAL) to the receptor complex (van Bruggen R et al. 2007; Kagan JC and Medzhitov R 2006). Complement may activate platelets or facilitate biochemical and morphological changes in the endothelium potentiating coagulation and contributing to homeostasis in response to injury (Oikonomopoulou K et al. 2012). The interplay of complement and coagulation also involves cleavage of C3 and C5 convertases by coagulation proteases, generating biologically active anaphylatoxins (Amara U et al. 2010). Complement is believed to link the innate response to both humoral and cell-mediated immunity (Toapanta FR and Ross TM 2006; Mongini PK et al. 1997). The majority of published data is based on experiments using mouse as a model organism. Further characterization of the influence of complement on B or T cell activation is required for the human system, since differences between murine models and the human system are not yet fully determined. Complement is also involved in regulation of mobilization and homing of hematopoietic stem/progenitor cells (HSPCs) from bone marrow to the circulation and peripheral tissue in order to accommodate blood cell replenishment (Reca R et al. 2006).<p>Thus, the complement system orchestrates the host defense by sensing a danger signal and transmitting it into specific cellular responses while extensively communicating with associated biological pathways ranging from immunity and inflammation to homeostasis and development.

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 (Sep 2013) Uniprot names for C2 fragments. Source:Reactome.</div>

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  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

View all...
CompareRevisionActionTimeUserComment
115062view17:00, 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...
NameTypeDatabase referenceComment
1,3-beta-D-glucan MetaboliteCHEBI:37671 (ChEBI)
11xCbxE-PROS1 ProteinP07225 (Uniprot-TrEMBL)
11xCbxE-PROS1ProteinP07225 (Uniprot-TrEMBL)
?FI:CD46, CR1:C4b, C3b complexesComplexR-HSA-977599 (Reactome)
Antigen: antibody:

C1 (activated C1R

and C1S) complex
ComplexR-HSA-173618 (Reactome)
Antigen: antibody:

C1 (activated C1R)

complex
ComplexR-HSA-173619 (Reactome)
Antigen: antibody: C1 complexComplexR-HSA-173582 (Reactome)
Bacterial

mannose-based carbohydrate

surface pattern
R-NUL-166718 (Reactome)
C-reactive

protein

pentamer:phosphocholine:C1Q
ComplexR-HSA-976769 (Reactome)
C1QA ProteinP02745 (Uniprot-TrEMBL)
C1QB ProteinP02746 (Uniprot-TrEMBL)
C1QC ProteinP02747 (Uniprot-TrEMBL)
C1R C-terminal fragment ProteinP00736 (Uniprot-TrEMBL)
C1R N-terminal fragment ProteinP00736 (Uniprot-TrEMBL)
C1R(18-705) ProteinP00736 (Uniprot-TrEMBL)
C1S C-terminal fragment ProteinP09871 (Uniprot-TrEMBL)
C1S N-terminal fragment ProteinP09871 (Uniprot-TrEMBL)
C1S(16-688) ProteinP09871 (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 convertasesR-HSA-173750 (Reactome)
C3(H2O):BbComplexR-HSA-182451 (Reactome)
C3(H2O):CFBComplexR-HSA-182529 (Reactome)
C3(H2O)ComplexR-HSA-182450 (Reactome)
C3aProteinP01024 (Uniprot-TrEMBL)
C3b alpha' ProteinP01024 (Uniprot-TrEMBL)
C3b:Bb:C3b:ProperdinComplexR-HSA-174554 (Reactome)
C3bComplexR-HSA-166832 (Reactome) Linked by disulphide bond between positions 559 and 816.
C3c alpha' chain

fragment 1

precursor
ProteinP01024 (Uniprot-TrEMBL)
C3c alpha' chain fragment 1 ProteinP01024 (Uniprot-TrEMBL)
C3c alpha' chain fragment 2 ProteinP01024 (Uniprot-TrEMBL)
C3cComplexR-HSA-3266497 (Reactome)
C3dgProteinP01024 (Uniprot-TrEMBL)
C3f ProteinP01024 (Uniprot-TrEMBL)
C3fProteinP01024 (Uniprot-TrEMBL)
C4 activatorR-HSA-166763 (Reactome)
C4 alpha ProteinP0C0L4 (Uniprot-TrEMBL) C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
C4 binding protein:C4bC2aComplexR-HSA-981663 (Reactome)
C4 binding protein:protein SComplexR-HSA-981655 (Reactome)
C4-binding protein:C4bComplexR-HSA-981642 (Reactome)
C4A alpha b ProteinP0C0L4 (Uniprot-TrEMBL) C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
C4A alpha3 ProteinP0C0L4 (Uniprot-TrEMBL)
C4A alpha4 fragment ProteinP0C0L4 (Uniprot-TrEMBL)
C4A beta ProteinP0C0L4 (Uniprot-TrEMBL)
C4A gamma ProteinP0C0L4 (Uniprot-TrEMBL)
C4B alpha ProteinP0C0L5 (Uniprot-TrEMBL)
C4B alpha chain fragment b ProteinP0C0L5 (Uniprot-TrEMBL)
C4B alpha3 ProteinP0C0L5 (Uniprot-TrEMBL)
C4B alpha4 fragment ProteinP0C0L5 (Uniprot-TrEMBL)
C4B beta ProteinP0C0L5 (Uniprot-TrEMBL)
C4B gamma ProteinP0C0L5 (Uniprot-TrEMBL)
C4BPA ProteinP04003 (Uniprot-TrEMBL)
C4BPB ProteinP20851 (Uniprot-TrEMBL)
C4aProteinR-HSA-981725 (Reactome)
C4b with hydrolysed thioesterComplexR-HSA-2855046 (Reactome)
C4b, C3bComplexR-HSA-977600 (Reactome)
C4b-binding protein:Factor IComplexR-HSA-981633 (Reactome)
C4b-binding proteinComplexR-HSA-981649 (Reactome)
C4b:C2a:C3bComplexR-HSA-173635 (Reactome)
C4bC2a, C3bBbComplexR-HSA-977357 (Reactome)
C4c, C3fComplexR-HSA-977621 (Reactome)
C4cComplexR-HSA-981715 (Reactome)
C4d, iC3bProteinR-HSA-977624 (Reactome)
C4dProteinR-HSA-981702 (Reactome)
C5 alpha ProteinP01031 (Uniprot-TrEMBL)
C5 beta ProteinP01031 (Uniprot-TrEMBL)
C5 convertasesR-HSA-173759 (Reactome)
C5aProteinP01031 (Uniprot-TrEMBL)
C5b alpha' ProteinP01031 (Uniprot-TrEMBL)
C5b:C6 complexComplexR-HSA-173711 (Reactome)
C5b:C6:C7 complexComplexR-HSA-173708 (Reactome)
C5b:C6:C7 complexComplexR-HSA-173719 (Reactome)
C5b:C6:C7:C8 complexComplexR-HSA-173722 (Reactome)
C5bComplexR-HSA-173671 (Reactome) Linked by disulphide bond between positions 559 and 816.
C6 ProteinP13671 (Uniprot-TrEMBL)
C6ProteinP13671 (Uniprot-TrEMBL)
C7 ProteinP10643 (Uniprot-TrEMBL)
C7ProteinP10643 (Uniprot-TrEMBL)
C8A ProteinP07357 (Uniprot-TrEMBL)
C8B ProteinP07358 (Uniprot-TrEMBL)
C8G ProteinP07360 (Uniprot-TrEMBL)
C8ComplexR-HSA-173713 (Reactome)
C9(22-559) ProteinP02748 (Uniprot-TrEMBL)
C9(22-559)ProteinP02748 (Uniprot-TrEMBL)
CD46 ProteinP15529 (Uniprot-TrEMBL)
CD46, CR1:C4b:C3b complexesComplexR-HSA-981661 (Reactome)
CD46, CR1ProteinR-HSA-977360 (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.
CD46:C3bComplexR-HSA-981623 (Reactome)
CD46:C4bComplexR-HSA-981669 (Reactome)
CD46ProteinP15529 (Uniprot-TrEMBL)
CD55 ProteinP08174 (Uniprot-TrEMBL)
CD55:C3 convertase complexesComplexR-HSA-981657 (Reactome)
CD55ProteinP08174 (Uniprot-TrEMBL)
CD59 ProteinP13987 (Uniprot-TrEMBL)
CD59:C5b-C9ComplexR-HSA-2530426 (Reactome)
CD59ProteinP13987 (Uniprot-TrEMBL)
CFB(26-259)ProteinP00751 (Uniprot-TrEMBL)
CFB(26-764) ProteinP00751 (Uniprot-TrEMBL)
CFB(26-764)ProteinP00751 (Uniprot-TrEMBL)
CFB(260-764) ProteinP00751 (Uniprot-TrEMBL)
CFB(260-764)ProteinP00751 (Uniprot-TrEMBL)
CFDProteinP00746 (Uniprot-TrEMBL)
CFH ProteinP08603 (Uniprot-TrEMBL)
CFH, FHR-3ProteinR-HSA-2109537 (Reactome)
CFH:C3bComplexR-HSA-976755 (Reactome)
CFH:Host cell surfaceComplexR-HSA-1006173 (Reactome)
CFHProteinP08603 (Uniprot-TrEMBL)
CFI(19-335) ProteinP05156 (Uniprot-TrEMBL)
CFI(19-335)ProteinP05156 (Uniprot-TrEMBL)
CFI(340-583) ProteinP05156 (Uniprot-TrEMBL)
CFI(340-583)ProteinP05156 (Uniprot-TrEMBL)
CFI:CFH,FHR3:C3bComplexR-HSA-977365 (Reactome)
CFI:CFH:C3bComplexR-HSA-976770 (Reactome)
CFIComplexR-HSA-976749 (Reactome)
CR1 ProteinP17927 (Uniprot-TrEMBL)
CR1:C3bBb, C4bC2a complexesComplexR-HSA-981676 (Reactome)
CR1:C3bComplexR-HSA-981635 (Reactome)
CR1:C4bComplexR-HSA-981675 (Reactome)
CR1:iC3bComplexR-HSA-3266508 (Reactome)
CR1ProteinP17927 (Uniprot-TrEMBL)
CRP(19-224) ProteinP02741 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Cell surface:C3b:Bb:ProperdinComplexR-HSA-173752 (Reactome)
Cell surface:CFH,FHR3:C3bBbComplexR-HSA-977373 (Reactome)
Cell surface:FH,FHR3:C3bComplexR-HSA-977596 (Reactome)
Cell surface:C3b:BbComplexR-HSA-173749 (Reactome)
Cell surface:C3b:CFBComplexR-HSA-173737 (Reactome)
Cell surface:C3bComplexR-HSA-981542 (Reactome)
Cell surface:C4b:C2aComplexR-HSA-166784 (Reactome)
Cell surface:C4bComplexR-HSA-981716 (Reactome)
Cell surfaceR-NUL-983438 (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 4ComplexR-HSA-981697 (Reactome)
Complement factor 3ComplexR-HSA-166822 (Reactome) Linked by disulphide bond between positions 559 and 816.
Complement factor 5ComplexR-HSA-173676 (Reactome)
Complement factor DProteinR-HSA-2975824 (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.
D-fucose MetaboliteCHEBI:28847 (ChEBI)
DAF:C3bComplexR-HSA-981684 (Reactome)
DAF:C4bComplexR-HSA-981639 (Reactome)
FCN1 ProteinO00602 (Uniprot-TrEMBL)
FCN1 ligandMetaboliteR-ALL-2855114 (Reactome)
FCN1:MASP2 dimer:MASP1 dimerComplexR-HSA-2855100 (Reactome)
FCN1:MASPs:Ca2+:FCN1 ligandComplexR-HSA-2855134 (Reactome)
FCN2 ProteinQ15485 (Uniprot-TrEMBL)
FCN2 ligandMetaboliteR-ALL-2855063 (Reactome)
FCN2:MASP2 dimer:MASP1 dimerComplexR-HSA-2855087 (Reactome)
FCN2:MASPs:Ca2+:FCN2 ligandComplexR-HSA-2855065 (Reactome)
FCN3 ProteinO75636 (Uniprot-TrEMBL)
FCN3 ligandMetaboliteR-ALL-2855098 (Reactome)
FCN3:MASP2 dimer:MASP1 dimerComplexR-HSA-2855122 (Reactome)
FCN3:MASPs:Ca2+:FCN3 ligandComplexR-HSA-2855093 (Reactome)
H2OMetaboliteCHEBI:15377 (ChEBI)
Heparins MetaboliteCHEBI:24505 (ChEBI)
Host cell surfaceComplexR-HSA-1006146 (Reactome)
IGHG1 ProteinP01857 (Uniprot-TrEMBL)
IGHG2 ProteinP01859 (Uniprot-TrEMBL)
IGHG3 ProteinP01860 (Uniprot-TrEMBL)
IGHG4 ProteinP01861 (Uniprot-TrEMBL)
IGHV(1-?) ProteinA2KUC3 (Uniprot-TrEMBL)
IGHV7-81(1-?) ProteinQ6PIL0 (Uniprot-TrEMBL)
IGKC ProteinP01834 (Uniprot-TrEMBL)
IGKV1-5(23-?) ProteinP01602 (Uniprot-TrEMBL)
IGKV4-1(21-?) ProteinP06312 (Uniprot-TrEMBL)
IGKVA18(21-?) ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1 ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2 ProteinP0CG05 (Uniprot-TrEMBL)
IGLC3 ProteinP0CG06 (Uniprot-TrEMBL)
IGLC6 ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7 ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV(23-?) ProteinA2NXD2 (Uniprot-TrEMBL)
IGLV1-36(1-?) ProteinQ5NV67 (Uniprot-TrEMBL)
IGLV1-40(1-?) ProteinQ5NV69 (Uniprot-TrEMBL)
IGLV1-44(1-?) ProteinQ5NV81 (Uniprot-TrEMBL)
IGLV10-54(1-?) ProteinQ5NV86 (Uniprot-TrEMBL)
IGLV11-55(1-?) ProteinQ5NV87 (Uniprot-TrEMBL)
IGLV2-11(1-?) ProteinQ5NV84 (Uniprot-TrEMBL)
IGLV2-18(1-?) ProteinQ5NV65 (Uniprot-TrEMBL)
IGLV2-23(1-?) ProteinQ5NV89 (Uniprot-TrEMBL)
IGLV2-33(1-?) ProteinQ5NV66 (Uniprot-TrEMBL)
IGLV3-12(1-?) ProteinQ5NV85 (Uniprot-TrEMBL)
IGLV3-16(1-?) ProteinQ5NV64 (Uniprot-TrEMBL)
IGLV3-22(1-?) ProteinQ5NV75 (Uniprot-TrEMBL)
IGLV3-25(1-?) ProteinQ5NV90 (Uniprot-TrEMBL)
IGLV3-27(1-?) ProteinQ5NV91 (Uniprot-TrEMBL)
IGLV4-3(1-?) ProteinQ5NV61 (Uniprot-TrEMBL)
IGLV4-60(1-?) ProteinQ5NV79 (Uniprot-TrEMBL)
IGLV4-69(1-?) ProteinQ5NV92 (Uniprot-TrEMBL)
IGLV5-37(1-?) ProteinQ5NV68 (Uniprot-TrEMBL)
IGLV5-45(1-?) ProteinQ5NV82 (Uniprot-TrEMBL)
IGLV7-43(1-?) ProteinQ5NV80 (Uniprot-TrEMBL)
IGLV7-46(1-?) ProteinQ5NV83 (Uniprot-TrEMBL)
IGLV8-61(1-?) ProteinQ5NV62 (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-III region LOI ProteinP80748 (Uniprot-TrEMBL)
Ig lambda chain V-III region SH ProteinP01714 (Uniprot-TrEMBL)
Ig lambda chain V-VII region MOT ProteinP01720 (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-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)
IgH heavy chain

V-III region VH26

precursor
ProteinP01764 (Uniprot-TrEMBL)
Lipoteichoic acid MetaboliteCHEBI:28640 (ChEBI)
MASP1(20-448) ProteinP48740 (Uniprot-TrEMBL)
MASP1(20-699) ProteinP48740 (Uniprot-TrEMBL)
MASP1(449-699) ProteinP48740 (Uniprot-TrEMBL)
MASP2-1 ProteinO00187-1 (Uniprot-TrEMBL)
MASP2-1(16-444) ProteinO00187-1 (Uniprot-TrEMBL)
MASP2-1(445-686) ProteinO00187-1 (Uniprot-TrEMBL)
MBL bound to

mannose-based carbohydrates on

bacterial surfaces
ComplexR-HSA-166719 (Reactome)
MBL-II:MASP-2

dimer:MASP-1 dimer

complex
ComplexR-HSA-166710 (Reactome)
MBL/FCN:activated

MASP:carbohydrate

patterns
ComplexR-HSA-3266545 (Reactome)
MBL/Ficolin:MASPs

bound to carbohydrate

patterns
ComplexR-HSA-3266540 (Reactome)
MBL2 ProteinP11226 (Uniprot-TrEMBL)
MBL:activated

MASPs:mannose-based

carbohydrates
ComplexR-HSA-166724 (Reactome)
Membrane Attack ComplexComplexR-HSA-173728 (Reactome)
N-acetyl-D-glucosamine MetaboliteCHEBI:28009 (ChEBI)
N-acetylgalactosamine MetaboliteCHEBI:40356 (ChEBI)
PCho MetaboliteCHEBI:36700 (ChEBI)
Properdin oligomerR-HSA-182548 (Reactome)
Sialic acid MetaboliteCHEBI:28879 (ChEBI)
VTN ProteinP04004 (Uniprot-TrEMBL)
VTN:C5b:C6:C7:C8:C9ComplexR-HSA-2530442 (Reactome)
VTN:C5b:C6:C7ComplexR-HSA-2530437 (Reactome)
VTNProteinP04004 (Uniprot-TrEMBL)
dNQ-C3(672-1663) ProteinP01024 (Uniprot-TrEMBL)
dNQ-C4A(757-1446) ProteinP0C0L4 (Uniprot-TrEMBL)
dNQ-C4B(757-1446) ProteinP0C0L5 (Uniprot-TrEMBL)
iC3bComplexR-HSA-976805 (Reactome)
iC3bComplexR-HSA-977380 (Reactome)
thioester-C1010-Q1013-C4bComplexR-HSA-981700 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11xCbxE-PROS1R-HSA-981665 (Reactome)
?FI:CD46, CR1:C4b, C3b complexesArrowR-HSA-977602 (Reactome)
?FI:CD46, CR1:C4b, C3b complexesR-HSA-977615 (Reactome)
?FI:CD46, CR1:C4b, C3b complexesmim-catalysisR-HSA-977615 (Reactome)
Antigen: antibody:

C1 (activated C1R

and C1S) complex
ArrowR-HSA-173631 (Reactome)
Antigen: antibody:

C1 (activated C1R)

complex
ArrowR-HSA-173626 (Reactome)
Antigen: antibody:

C1 (activated C1R)

complex
R-HSA-173631 (Reactome)
Antigen: antibody:

C1 (activated C1R)

complex
mim-catalysisR-HSA-173631 (Reactome)
Antigen: antibody: C1 complexR-HSA-173626 (Reactome)
Antigen: antibody: C1 complexmim-catalysisR-HSA-173626 (Reactome)
Bacterial

mannose-based carbohydrate

surface pattern
R-HSA-166721 (Reactome)
C-reactive

protein

pentamer:phosphocholine:C1Q
ArrowR-HSA-173626 (Reactome)
C2R-HSA-166792 (Reactome)
C2aArrowR-HSA-166792 (Reactome)
C2aArrowR-HSA-977619 (Reactome)
C2aArrowR-HSA-977629 (Reactome)
C2aArrowR-HSA-981621 (Reactome)
C2aArrowR-HSA-981680 (Reactome)
C2aR-HSA-166795 (Reactome)
C2bArrowR-HSA-166792 (Reactome)
C3 convertasesR-HSA-981621 (Reactome)
C3 convertasesmim-catalysisR-HSA-166817 (Reactome)
C3(H2O):BbArrowR-HSA-173745 (Reactome)
C3(H2O):Bbmim-catalysisR-HSA-183130 (Reactome)
C3(H2O):CFBArrowR-HSA-173740 (Reactome)
C3(H2O):CFBR-HSA-173745 (Reactome)
C3(H2O)ArrowR-HSA-173739 (Reactome)
C3(H2O)ArrowR-HSA-981621 (Reactome)
C3(H2O)R-HSA-173740 (Reactome)
C3aArrowR-HSA-166817 (Reactome)
C3aArrowR-HSA-174551 (Reactome)
C3aArrowR-HSA-183130 (Reactome)
C3b:Bb:C3b:ProperdinArrowR-HSA-174551 (Reactome)
C3bArrowR-HSA-166817 (Reactome)
C3bArrowR-HSA-183130 (Reactome)
C3bArrowR-HSA-981621 (Reactome)
C3bR-HSA-976768 (Reactome)
C3bR-HSA-981539 (Reactome)
C3cArrowR-HSA-3266557 (Reactome)
C3dgArrowR-HSA-3266557 (Reactome)
C3fArrowR-HSA-976743 (Reactome)
C3fArrowR-HSA-977371 (Reactome)
C4 activatormim-catalysisR-HSA-166753 (Reactome)
C4 activatormim-catalysisR-HSA-166792 (Reactome)
C4 binding protein:C4bC2aArrowR-HSA-981648 (Reactome)
C4 binding protein:C4bC2aR-HSA-981680 (Reactome)
C4 binding protein:protein SArrowR-HSA-981665 (Reactome)
C4-binding protein:C4bArrowR-HSA-977626 (Reactome)
C4-binding protein:C4bArrowR-HSA-981680 (Reactome)
C4-binding protein:C4bR-HSA-981658 (Reactome)
C4aArrowR-HSA-166753 (Reactome)
C4b with hydrolysed thioesterArrowR-HSA-2855047 (Reactome)
C4b, C3bR-HSA-1006143 (Reactome)
C4b-binding protein:Factor IArrowR-HSA-981658 (Reactome)
C4b-binding protein:Factor IR-HSA-981637 (Reactome)
C4b-binding proteinArrowR-HSA-981637 (Reactome)
C4b-binding proteinR-HSA-977626 (Reactome)
C4b-binding proteinR-HSA-981648 (Reactome)
C4b-binding proteinR-HSA-981665 (Reactome)
C4b:C2a:C3bArrowR-HSA-173636 (Reactome)
C4bC2a, C3bBbR-HSA-977375 (Reactome)
C4bC2a, C3bBbR-HSA-981535 (Reactome)
C4c, C3fArrowR-HSA-977615 (Reactome)
C4cArrowR-HSA-981637 (Reactome)
C4d, iC3bArrowR-HSA-977615 (Reactome)
C4dArrowR-HSA-981637 (Reactome)
C5 convertasesmim-catalysisR-HSA-173680 (Reactome)
C5aArrowR-HSA-173680 (Reactome)
C5b:C6 complexArrowR-HSA-173705 (Reactome)
C5b:C6 complexR-HSA-173709 (Reactome)
C5b:C6:C7 complexArrowR-HSA-173709 (Reactome)
C5b:C6:C7 complexArrowR-HSA-173720 (Reactome)
C5b:C6:C7 complexR-HSA-173720 (Reactome)
C5b:C6:C7 complexR-HSA-173723 (Reactome)
C5b:C6:C7 complexR-HSA-2530453 (Reactome)
C5b:C6:C7:C8 complexArrowR-HSA-173723 (Reactome)
C5b:C6:C7:C8 complexR-HSA-173725 (Reactome)
C5b:C6:C7:C8 complexR-HSA-2530445 (Reactome)
C5bArrowR-HSA-173680 (Reactome)
C5bR-HSA-173705 (Reactome)
C6R-HSA-173705 (Reactome)
C7R-HSA-173709 (Reactome)
C8R-HSA-173723 (Reactome)
C8R-HSA-2530429 (Reactome)
C9(22-559)R-HSA-173725 (Reactome)
C9(22-559)R-HSA-2530429 (Reactome)
C9(22-559)R-HSA-2530445 (Reactome)
CD46, CR1:C4b:C3b complexesR-HSA-977602 (Reactome)
CD46, CR1ArrowR-HSA-977615 (Reactome)
CD46:C3bArrowR-HSA-1006143 (Reactome)
CD46:C4bArrowR-HSA-1006143 (Reactome)
CD46R-HSA-1006143 (Reactome)
CD55:C3 convertase complexesArrowR-HSA-981535 (Reactome)
CD55:C3 convertase complexesR-HSA-977619 (Reactome)
CD55R-HSA-981535 (Reactome)
CD59:C5b-C9ArrowR-HSA-2530445 (Reactome)
CD59R-HSA-2530445 (Reactome)
CFB(26-259)ArrowR-HSA-173745 (Reactome)
CFB(26-259)ArrowR-HSA-183122 (Reactome)
CFB(26-764)R-HSA-173740 (Reactome)
CFB(26-764)R-HSA-183126 (Reactome)
CFB(260-764)ArrowR-HSA-977605 (Reactome)
CFB(260-764)ArrowR-HSA-977619 (Reactome)
CFB(260-764)ArrowR-HSA-977629 (Reactome)
CFB(260-764)ArrowR-HSA-981621 (Reactome)
CFH, FHR-3ArrowR-HSA-977371 (Reactome)
CFH, FHR-3R-HSA-977363 (Reactome)
CFH, FHR-3R-HSA-981728 (Reactome)
CFH:C3bArrowR-HSA-976768 (Reactome)
CFH:C3bR-HSA-976810 (Reactome)
CFH:Host cell surfaceArrowR-HSA-1006169 (Reactome)
CFH:Host cell surfaceArrowR-HSA-977363 (Reactome)
CFH:Host cell surfaceArrowR-HSA-981728 (Reactome)
CFHArrowR-HSA-976743 (Reactome)
CFHR-HSA-1006169 (Reactome)
CFHR-HSA-976768 (Reactome)
CFI(19-335)R-HSA-976801 (Reactome)
CFI(340-583)R-HSA-976801 (Reactome)
CFI:CFH,FHR3:C3bArrowR-HSA-977359 (Reactome)
CFI:CFH,FHR3:C3bR-HSA-977371 (Reactome)
CFI:CFH,FHR3:C3bmim-catalysisR-HSA-977371 (Reactome)
CFI:CFH:C3bArrowR-HSA-976810 (Reactome)
CFI:CFH:C3bR-HSA-976743 (Reactome)
CFI:CFH:C3bmim-catalysisR-HSA-976743 (Reactome)
CFIArrowR-HSA-976743 (Reactome)
CFIArrowR-HSA-976801 (Reactome)
CFIArrowR-HSA-977371 (Reactome)
CFIArrowR-HSA-977615 (Reactome)
CFIArrowR-HSA-981637 (Reactome)
CFIR-HSA-976810 (Reactome)
CFIR-HSA-977359 (Reactome)
CFIR-HSA-977602 (Reactome)
CFIR-HSA-981658 (Reactome)
CR1:C3bArrowR-HSA-977629 (Reactome)
CR1:C3bBb, C4bC2a complexesArrowR-HSA-977375 (Reactome)
CR1:C3bBb, C4bC2a complexesR-HSA-977629 (Reactome)
CR1:C4bArrowR-HSA-977629 (Reactome)
CR1:iC3bR-HSA-3266557 (Reactome)
CR1ArrowR-HSA-3266557 (Reactome)
CR1R-HSA-977375 (Reactome)
Ca2+R-HSA-166721 (Reactome)
Ca2+R-HSA-2855054 (Reactome)
Ca2+R-HSA-2855077 (Reactome)
Ca2+R-HSA-2855125 (Reactome)
Cell surface:C3b:Bb:ProperdinArrowR-HSA-173754 (Reactome)
Cell surface:C3b:Bb:ProperdinR-HSA-174551 (Reactome)
Cell surface:C3b:Bb:Properdinmim-catalysisR-HSA-174551 (Reactome)
Cell surface:CFH,FHR3:C3bBbArrowR-HSA-977363 (Reactome)
Cell surface:CFH,FHR3:C3bBbR-HSA-977605 (Reactome)
Cell surface:FH,FHR3:C3bArrowR-HSA-977605 (Reactome)
Cell surface:FH,FHR3:C3bArrowR-HSA-981728 (Reactome)
Cell surface:FH,FHR3:C3bR-HSA-977359 (Reactome)
Cell surface:C3b:BbArrowR-HSA-183122 (Reactome)
Cell surface:C3b:BbR-HSA-173754 (Reactome)
Cell surface:C3b:BbR-HSA-977363 (Reactome)
Cell surface:C3b:CFBArrowR-HSA-183126 (Reactome)
Cell surface:C3b:CFBR-HSA-183122 (Reactome)
Cell surface:C3bArrowR-HSA-981539 (Reactome)
Cell surface:C3bR-HSA-173636 (Reactome)
Cell surface:C3bR-HSA-183126 (Reactome)
Cell surface:C3bR-HSA-981728 (Reactome)
Cell surface:C4b:C2aArrowR-HSA-166795 (Reactome)
Cell surface:C4b:C2aArrowR-HSA-981621 (Reactome)
Cell surface:C4b:C2aR-HSA-173636 (Reactome)
Cell surface:C4b:C2aR-HSA-981648 (Reactome)
Cell surface:C4bArrowR-HSA-981621 (Reactome)
Cell surface:C4bArrowR-HSA-981713 (Reactome)
Cell surface:C4bR-HSA-166795 (Reactome)
Cell surfaceR-HSA-981539 (Reactome)
Cell surfaceR-HSA-981713 (Reactome)
Complement Factor 4R-HSA-166753 (Reactome)
Complement factor 3R-HSA-166817 (Reactome)
Complement factor 3R-HSA-173739 (Reactome)
Complement factor 3R-HSA-174551 (Reactome)
Complement factor 3R-HSA-183130 (Reactome)
Complement factor 5R-HSA-173680 (Reactome)
Complement factor Dmim-catalysisR-HSA-173745 (Reactome)
Complement factor Dmim-catalysisR-HSA-183122 (Reactome)
DAF:C3bArrowR-HSA-977619 (Reactome)
DAF:C4bArrowR-HSA-977619 (Reactome)
FCN1 ligandR-HSA-2855125 (Reactome)
FCN1:MASP2 dimer:MASP1 dimerR-HSA-2855125 (Reactome)
FCN1:MASPs:Ca2+:FCN1 ligandArrowR-HSA-2855125 (Reactome)
FCN2 ligandR-HSA-2855054 (Reactome)
FCN2:MASP2 dimer:MASP1 dimerR-HSA-2855054 (Reactome)
FCN2:MASPs:Ca2+:FCN2 ligandArrowR-HSA-2855054 (Reactome)
FCN3 ligandR-HSA-2855077 (Reactome)
FCN3:MASP2 dimer:MASP1 dimerR-HSA-2855077 (Reactome)
FCN3:MASPs:Ca2+:FCN3 ligandArrowR-HSA-2855077 (Reactome)
H2OR-HSA-173739 (Reactome)
H2OR-HSA-2855047 (Reactome)
Host cell surfaceR-HSA-1006169 (Reactome)
MBL bound to

mannose-based carbohydrates on

bacterial surfaces
ArrowR-HSA-166721 (Reactome)
MBL-II:MASP-2

dimer:MASP-1 dimer

complex
R-HSA-166721 (Reactome)
MBL/FCN:activated

MASP:carbohydrate

patterns
ArrowR-HSA-166726 (Reactome)
MBL/Ficolin:MASPs

bound to carbohydrate

patterns
R-HSA-166726 (Reactome)
Membrane Attack ComplexArrowR-HSA-173725 (Reactome)
Properdin oligomerArrowR-HSA-981621 (Reactome)
Properdin oligomerR-HSA-173754 (Reactome)
R-HSA-1006143 (Reactome) Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding cell surface glycoprotein which is a cofactor for Complement factor I.
R-HSA-1006169 (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.
R-HSA-166721 (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.
R-HSA-166726 (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).
R-HSA-166753 (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.
R-HSA-166792 (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.
R-HSA-166795 (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.
R-HSA-166817 (Reactome) C4b and C2a bind to form the classical pathway C3-convertase (C4bC2a), C3b and the Bb fragment of Factor B form the alternative pathway C3 convertase (C3bBb). The C3(H2O):Bb C3 convertase is sometimes called the initiating convertase, and the C5 convertases also have C3 convertase activity (Rawal & Pangburn 2001).

All three pathways merge at the proteolytic cleavage of component C3 by C3 convertases to form two fragments C3b and C3a. The cleavage of component C3 exposes a reactive thioester bond on C3b, leading to the covalent attachment of C3b to glycoproteins on the target cell surface (Law SK et al. 1979; Tack BF et al. 1980). The opsonization with C3b enables the recruitment of phagocytes (Newman SL et al. 1985; Gadjeva M et al. 1998). In addition, C3b anchors the assembly of C3/C5 convertases leading to an amplification of C3 cleavage and effecting C5 activation (Fearon DT 1979; Takata Y et al 1987; Kinoshita T et al. 1988). Moreover, the activation of C3b exposes binding sites for factors B, H and I, properdin, decay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 (CR1) and microbial molecules such as vaccinia virus complement-control protein and staphylococcal complement inhibitor (SCIN) from Staphylococcus aureus (Forneris F et al. 2010; Morgan HP et al. 2011; Nilsson SC et al. 2010; Lambris JD et al. 1984; Medof ME et al.1984; Barilla-LaBarca ML et al. 2002; Smith BO et al. 2002; Bernet J et al. 2004; Garcia Bl et al. 2010) . C3b associates with these molecules to mediate the activation, amplification and regulation of the complement response.

R-HSA-173626 (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.
R-HSA-173631 (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.
R-HSA-173636 (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).
R-HSA-173680 (Reactome) Cleavage of C5 by C5 convertases is the last enzymatic step in the complement activation. C5 convertases are formed when C3b molecule is covalently deposited in the immediate vicinity of pre-assembled C3 convertases switching them to C5 convertases C4bC2aC3b and C3bBbC3b (Takata Y et al 1987; Kinoshita T et al. 1988; Rawal N and Pangburn MK 2001, 2003). The additional 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. The proteolytic cleavage of C5 generates the small fragment C5a and the large fragment C5b.

C5b initiates an assembly of terminal complement components (C6-C9) leading to the formation of membrane attack complex (MAC) on the target surface (Aleshin AE et al. 2012; Hadders MA et al. 2012). MAC disrupts the cell membrane causing a subsequent cell death through osmotic lysis.

Anaphylatoxin C5a mediates pro-inflammatory and immunemodulatory signals via its receptors C5aR and C5L2. The anaphylatoxin receptors are found on surfaces of phagocytes as well as other cell types. In inflammation, they induce cytokine production, degranulation and chemotaxis of leukocytes (Monk PN et al. 2007).

R-HSA-173705 (Reactome)
R-HSA-173709 (Reactome)
R-HSA-173720 (Reactome)
R-HSA-173723 (Reactome)
R-HSA-173725 (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).
R-HSA-173739 (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
R-HSA-173740 (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).
R-HSA-173745 (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).
R-HSA-173754 (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; Alcorlo M et al. 2013). 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).
R-HSA-174551 (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.
R-HSA-183122 (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).
R-HSA-183126 (Reactome) C3b on a surface binds Factor B from solution to form a complex (Schreiber et al. 1978; Muller-Eberhard 1988).
R-HSA-183130 (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).
R-HSA-2530429 (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.
R-HSA-2530445 (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]
R-HSA-2530453 (Reactome) Vitronectin interacts with C5b:C6:C7 complex preventing it from the binding with the cell membrane
R-HSA-2855047 (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].
R-HSA-2855054 (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].
R-HSA-2855077 (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].
R-HSA-2855125 (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).

R-HSA-3266557 (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).

R-HSA-976743 (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.
R-HSA-976768 (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.
R-HSA-976801 (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).
R-HSA-976810 (Reactome) Complement factor I binds the factor H:C3b complex.
R-HSA-977359 (Reactome) Complement factor I binds to the Factor H:C3b complex.
R-HSA-977363 (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.
R-HSA-977371 (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.
R-HSA-977375 (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).
R-HSA-977602 (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.
R-HSA-977605 (Reactome) Factor H greatly accelerates the displacement (decay) of Complement factor Bb from C3b.
R-HSA-977615 (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).
R-HSA-977619 (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).
R-HSA-977626 (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.
R-HSA-977629 (Reactome) Complement Receptor 1 (CR1) displaces the activated enzyme components Bb and C2a from the conventional and alternative C3 convertases C4bC2a and C3bBb, respectivley.
R-HSA-981535 (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).
R-HSA-981539 (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).
R-HSA-981621 (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.
R-HSA-981637 (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.
R-HSA-981648 (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.
R-HSA-981658 (Reactome) C4b-binding protein is a cofactor for Complement Factor I, allowing it to bind and thereby mediating C4b proteolysis.
R-HSA-981665 (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).
R-HSA-981680 (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).
R-HSA-981713 (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.
R-HSA-981728 (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.
VTN:C5b:C6:C7:C8:C9ArrowR-HSA-2530429 (Reactome)
VTN:C5b:C6:C7ArrowR-HSA-2530453 (Reactome)
VTN:C5b:C6:C7R-HSA-2530429 (Reactome)
VTNR-HSA-2530453 (Reactome)
iC3bArrowR-HSA-976743 (Reactome)
iC3bArrowR-HSA-977371 (Reactome)
thioester-C1010-Q1013-C4bArrowR-HSA-166753 (Reactome)
thioester-C1010-Q1013-C4bR-HSA-2855047 (Reactome)
thioester-C1010-Q1013-C4bR-HSA-977626 (Reactome)
thioester-C1010-Q1013-C4bR-HSA-981713 (Reactome)

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