Complement cascade (Homo sapiens)

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5, 16, 22, 65, 8428462, 77, 8211, 7061, 638415, 28, 31, 34, 46...26624, 87234904362, 8415, 33, 46, 50, 58...40, 66, 92, 9312, 18, 433, 8, 19, 31, 48...36, 72, 93173642, 866732, 3920, 27, 35, 47, 837, 24, 5341, 448470426, 3962, 84626654, 94, 95738479, 85, 888429, 802, 7510, 12, 687542759145406, 3911, 52, 7025, 36, 38, 5524, 6461, 37, 691, 37, 69Innocent bystander cellcytosolcytosolTarget CellIg lambda chain V-I region NEWM IGHV(1-?) Ig heavy chain V-III region BUR C6 Cell surface C4d, iC3bC8A CR1 C3c alpha' chain fragment 1 precursor dNQ-C4A(757-1446) FCN2:MASPs:Ca2+:FCN2ligandC4A gamma IGLV4-69(1-?) MBL/Ficolin:MASPsbound tocarbohydratepatternsC8A Ig lambda chain V-II region TRO Ig kappa chain V-III region SIE IGLV2-18(1-?) IGHG2 C4B gamma C4B alpha3 MASP2-1(445-686) Ig heavy chain V-III region ZAP IGLC2 IGLC6 Ig lambda chain V-VII region MOT C3c alpha' chain fragment 2 FCN1:MASPs:Ca2+:FCN1ligandBacterial mannose-based carbohydrate surface pattern MBL bound tomannose-basedcarbohydrates onbacterial surfacesCFB(260-764) dNQ-C3(672-1663) C3 beta chain C4B gamma CD55 Ig heavy chain V-III region POM N-acetyl-D-glucosamine IGLV7-46(1-?) C4c, C3fC4A beta C3b alpha' C3 beta chain C4B gamma C5b alpha' Ig heavy chain V-II region COR IGLV1-44(1-?) MBL2 CD59:C5b-C9Ig kappa chain V-I region Rei Ig heavy chain V-III region BRO Ig heavy chain V-III region NIE C3 beta chain C2aIg lambda chain V-II region TOG Ig kappa chain V-I region AG C5b alpha' C4A gamma Ig kappa chain V-I region Roy Ig lambda chain V-I region NEWM C3b alpha' MASP1(20-699) Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-IV region MOL CR1:iC3bC2a Ca2+ Ig kappa chain V-IV region Len Ig kappa chain V-I region OU Ig lambda chain V-VI region EB4 C4A alpha b C3f IGKC Ig heavy chain V-III region TIL C4A gamma Ig lambda chain V-II region BUR C8G Ig heavy chain V-II region NEWM Ig heavy chain V-III region WEA Ig lambda chain V-VI region NIG-48 CFB(260-764) CFB(26-259)C4B gamma Ig heavy chain V-III region TIL IGLV3-12(1-?) Ig lambda chain V-I region HA C1QC C5 alpha Host cell surfaceC3b alpha' Ig heavy chain V-III region WAS C3 beta chain CFI(340-583)Ig heavy chain V-II region ARH-77 CFI(19-335) Antigen Ig heavy chain V-III region WEA dNQ-C4B(757-1446) IGHG4 Ig kappa chain V-III region WOL C3b alpha' Ig kappa chain V-III region POM Ig lambda chain V-III region LOI Sialic acid Cell surface VTN:C5b:C6:C7:C8:C9Ig kappa chain V-I region Ka Ca2+ Ig heavy chain V-II region WAH C2a IGLV3-16(1-?) Ig kappa chain V-III region Ti C3 beta chain Ig kappa chain V-III region NG9 C4A alpha b Cell surface:C3b:CFBSialic acid MASP1(20-699) Ig heavy chain V-III region HIL Cell surface:C4bD-fucose Ig kappa chain V-II region GM607 dNQ-C4A(757-1446) C3 alpha chain Ig heavy chain V-III region HIL IGKVA18(21-?) IGLV11-55(1-?) Ig kappa chain V-III region NG9 Cell surface IGLC1 Cell surface C1QA CD46 FCN1 1,3-beta-D-glucan Ig lambda chain V-IV region X Ig lambda chain V-II region NIG-84 C7 Ig heavy chain V-II region NEWM IGLV7-43(1-?) Ig kappa chain V-I region DEE C4A beta IGLV2-33(1-?) CD46 C8C5 beta Ig heavy chain V-II region COR thioester-C1010-Q1013-C4bC4B gamma CFI(340-583) C5b:C6:C7 complexN-acetyl-D-glucosamine IGLV7-43(1-?) Ig lambda chain V-VI region SUT C5b alpha' Antigen C3b alpha' Ig kappa chain V-II region GM607 C3 beta chain C5 beta C1QB C4BPA IGLV2-18(1-?) IGLV1-40(1-?) thioester-C1010-Q1013-C4bVTN:C5b:C6:C7C4B alpha chain fragment b C8A Ig kappa chain V-II region Cum dNQ-C4B(757-1446) Ig kappa chain V-III region GOL Sialic acid Cell surface Ig kappa chain V-I region Wes Ig lambda chain V-II region NIG-84 IGLV4-60(1-?) C4A alpha3 IGLV3-12(1-?) IGLV5-45(1-?) FCN3 MASP1(20-699) IgH heavy chain V-III region VH26 precursor IGLV3-16(1-?) CD55C4 activatorC4B beta Ig kappa chain V-III region B6 MBL:activatedMASPs:mannose-basedcarbohydratesC5b alpha' C4B beta CFH C4A beta Ig lambda chain V-I region MEM Ig kappa chain V-III region SIE Ig kappa chain V-IV region B17 Properdin oligomer IGKV4-1(21-?) MASP1(20-699) Ig lambda chain V-VI region WLT Ig kappa chain V-I region Lay Ig lambda chain V-II region BOH C2dNQ-C4B(757-1446) Ig lambda chain V-I region NIG-64 IGLV(23-?) C3 beta chain IGLV4-69(1-?) dNQ-C4B(757-1446) Ig heavy chain V-I region WOL C4B gamma C6 C4B alpha IGLV(23-?) C2a IGLC2 C1S N-terminal fragment CFHR3 C4 bindingprotein:protein SIg kappa chain V-III region HAH C4A gamma C5 convertasesIGHG2 C6 Ig kappa chain V-IV region STH Ig kappa chain V-I region Rei IGLV(23-?) CFI(340-583) FCN2 Ig kappa chain V-I region Hau C4B beta C3 beta chain Cell surface:C3bIg lambda chain V region 4A Ig heavy chain V-II region HE Cell surface FCN1 FCN3 Ig heavy chain V-III region KOL IGLV5-45(1-?) C5aIg lambda chain V-VII region MOT Ca2+ C4A gamma C5 beta Ig lambda chain V-II region BO C8A Ig lambda chain V-II region WIN H2OMASP2-1 dNQ-C4A(757-1446) C4B beta Ig heavy chain V-III region HIL MBL/FCN:activatedMASP:carbohydratepatternsIg lambda chain V-VI region EB4 C1QB Antigen: antibody:C1 (activated C1Rand C1S) complexIg kappa chain V-I region Ni Ig kappa chain V-IV region Len Ig heavy chain V-III region LAY Cellsurface:FH,FHR3:C3bCFB(260-764) IGKC CD55 Ig lambda chain V-I region EPS Ig kappa chain V-I region OU CFB(26-764) Ig heavy chain V-II region MCE IGLV4-3(1-?) C3 beta chain C4B beta Cell surface Ig kappa chain V region EV15 ?FI:CD46, CR1:C4b,C3b complexesMASP1(449-699) FCN3 Ig lambda chain V-I region WAH IGKC Cell surface:C3b:BbIg kappa chain V-IV region JI CR1:C3bBb, C4bC2acomplexesCell surface C4cC3b alpha' C4b-bindingprotein:Factor ICell surface C3bSialic acid C4B beta C4B gamma C4B beta C5 beta Ig heavy chain V-II region ARH-77 C4BPA Ig lambda chain V-I region NEW Cell surface CFI(19-335)Ig kappa chain V-III region CLL C3c alpha' chain fragment 1 precursor C1QA Ig lambda chain V-I region HA Ig kappa chain V-III region VH C3 beta chain Lipoteichoic acid Ig kappa chain V region EV15 Ig kappa chain V-I region Gal IGHG3 Ig heavy chain V-III region TUR Ig kappa chain V-I region DEE Ig lambda chain V-IV region MOL Bacterial mannose-based carbohydrate surface pattern IGLV3-27(1-?) Ig kappa chain V-IV region Len dNQ-C4B(757-1446) IGLV10-54(1-?) FCN2 C5b alpha' Ig heavy chain V-I region SIE Ig lambda chain V-II region TOG C3b alpha' IGLV8-61(1-?) Ig kappa chain V-I region Wes Ig lambda chain V-VI region AR C4B alpha chain fragment b IGLV10-54(1-?) Properdin oligomerC4A gamma C9(22-559) Ig lambda chain V-II region TOG C5b alpha' C2aCell surface Ig lambda chain V-II region NIG-58 dNQ-C4B(757-1446) Ig kappa chain V-III region GOL N-acetylgalactosamine Ig kappa chain V-III region CLL C3 beta chain CD59 Ig lambda chain V-I region WAH Ig kappa chain V-I region Daudi Ig kappa chain V-I region Bi Cellsurface:CFH,FHR3:C3bBbCFB(26-764) C3b alpha' C4B gamma Ig heavy chain V-I region EU C-reactiveproteinpentamer:phosphocholine:C1QIGLC3 C1QC Ig kappa chain V-III region HAH IGHG1 Ig heavy chain V-III region LAY C4A gamma CD46 C3b alpha' IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Walker C1QB Ca2+ Cell surface C4 bindingprotein:C4bC2aCell surface Ig kappa chain V-I region WEA C3 beta chain CD46, CR1:C4b:C3bcomplexesC4b with hydrolysedthioesterIg heavy chain V-III region WEA Ig kappa chain V-I region AU C3aIGLV1-40(1-?) C2aIGLV5-37(1-?) Ig heavy chain V-III region CAM Ig kappa chain V-I region Bi CFH:C3bAntigen: antibody:C1 (activated C1R)complexIg kappa chain V-III region GOL IGKV1-5(23-?) IGLV10-54(1-?) Ig heavy chain V-III region GAL Ig kappa chain V-II region FR Ig heavy chain V-III region NIE dNQ-C4B(757-1446) C2bIg kappa chain V-I region HK101 Ig heavy chain V-I region Mot VTN Ig heavy chain V-III region GAL Ig lambda chain V-II region WIN CFI(340-583) Ig heavy chain V-I region WOL Ig heavy chain V-I region Mot Cell surface C4A beta C3cIg lambda chain V-II region NEI IGHV(1-?) C1R C-terminal fragment C8B Cell surface Ig lambda chain V-II region TRO Ig kappa chain V-III region POM Cell surface:C4b:C2adNQ-C4A(757-1446) C4A beta Ig kappa chain V-III region CLL IGLV2-11(1-?) 1,3-beta-D-glucan Ig kappa chain V-I region Mev C4A beta Ig heavy chain V-II region OU C4A beta dNQ-C4B(757-1446) Bacterialmannose-basedcarbohydratesurface patternIg lambda chain V-II region MGC CR1 Ig lambda chain V-I region VOR Ig heavy chain V-III region KOL C4A beta C3b alpha' Ig kappa chain V-I region CAR Ig kappa chain V-I region WAT Cell surface C4B gamma C4A gamma Ig lambda chain V-IV region MOL C3 beta chain CFI(19-335) C5 beta Ig lambda chain V-I region BL2 C3c alpha' chain fragment 1 precursor C1R N-terminal fragment Ig heavy chain V-III region TUR C2a C3b alpha' Ig kappa chain V-I region Lay Ig lambda chain V-II region VIL Ig lambda chain V-IV region Kern IGKV4-1(21-?) Ig lambda chain V-VI region AR C8G MBL2 C4B beta C4BPA Cell surfaceIGLC6 Ig kappa chain V-III region IARC/BL41 Cell surface Cell surface:C4b:C2aC4B gamma Ig lambda chain V-II region VIL Ig kappa chain V-I region AG Cell surface:C4b:C2aC3b alpha' C4B gamma FCN1 liganddNQ-C4A(757-1446) Ig kappa chain V-I region AU MASP2-1 IGLV2-23(1-?) Ig kappa chain V-I region OU C4A gamma Cell surface Ig heavy chain V-III region TEI Ig kappa chain V-I region WEA IGLV3-16(1-?) C8B C4A beta CFI(19-335) CFI(19-335) IGLV1-44(1-?) CD46 C2a dNQ-C4B(757-1446) Membrane AttackComplexIg heavy chain V-III region TUR Ig kappa chain V-II region RPMI 6410 Lipoteichoic acid C4b, C3bIGLC3 Ig heavy chain V-III region TEI C3(H2O):CFBIGLV5-37(1-?) N-acetyl-D-glucosamine Ig lambda chain V-IV region Bau IGLV1-36(1-?) Ig lambda chain V-V region DEL Ig lambda chain V-III region SH Cellsurface:C3b:Bb:ProperdinC6 Ig heavy chain V-III region TRO Ig lambda chain V-IV region X Ig lambda chain V-II region NIG-58 Ig kappa chain V-I region HK101 C4A gamma C4B beta C3 beta chain dNQ-C4A(757-1446) Ig kappa chain V-I region Gal CFI(340-583) C3 beta chain Ig lambda chain V-II region MGC CFI:CFH,FHR3:C3bC4B beta dNQ-C4A(757-1446) CD46:C4bD-fucose Ca2+ Ig heavy chain V-III region WAS Ig heavy chain V-II region WAH IGHV7-81(1-?) Ig lambda chain V-III region LOI Ig heavy chain V-III region TRO C4BPB C3c alpha' chain fragment 2 Ig heavy chain V-III region TIL Ig kappa chain V-II region Cum C1S(16-688) C2a Ig kappa chain V-II region TEW IGLV3-22(1-?) C1QC Ig heavy chain V-III region NIE C3 beta chain CR1Ig lambda chain V-VI region EB4 Ig kappa chain V-I region Scw C1QC CFB(260-764) Ig kappa chain V-I region Roy C4A gamma C3 beta chain IGHV7-81(1-?) CFB(260-764) Ig lambda chain V-II region NEI C4A beta Ig heavy chain V-II region NEWM Cell surface dNQ-C4A(757-1446) C4B gamma Cell surface:C3b:BbFCN1 Ig kappa chain V-III region B6 C4A beta CR1 Ig kappa chain V-I region Hau Ig heavy chain V-II region WAH C5bIGHG3 Cell surface:C3bIg kappa chain V-I region Ka FCN2:MASP2dimer:MASP1 dimerCD55:C3 convertasecomplexesC7dNQ-C4A(757-1446) Ig heavy chain V-II region SESS Ig kappa chain V-I region BAN Ig heavy chain V-III region POM C4A beta C4B beta Ig heavy chain V-II region MCE Ig lambda chain V-II region NIG-58 iC3bC3c alpha' chain fragment 1 IGHV7-81(1-?) Antigen IGLV3-27(1-?) C5 beta Ig kappa chain V-I region Kue Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-I region NEWM C3 beta chain Ig kappa chain V-I region Daudi Ig heavy chain V-II region HE C5b alpha' C3(H2O)Ig lambda chain V-II region TRO Ig lambda chain V-I region MEM Ig kappa chain V-I region Scw dNQ-C4B(757-1446) Ig heavy chain V-II region SESS C8G Ig heavy chain V-I region SIE dNQ-C4B(757-1446) Ig lambda chain V-I region NIG-64 C4BPB VTN Ig kappa chain V-I region EU C3 beta chain C3b alpha' Ca2+ C3 beta chain Ig lambda chain V-IV region Kern Ig lambda chain V-VI region AR C3c alpha' chain fragment 2 Ig heavy chain V-II region ARH-77 11xCbxE-PROS1 Ig kappa chain V-II region MIL C4B beta Cell surface Ig kappa chain V-I region Walker FCN3:MASP2dimer:MASP1 dimerCD55 MASP1(20-699) CR1:C4bIg kappa chain V-III region POM C3(H2O):BbCFH, FHR-3Ig kappa chain V-I region BAN C6C4B beta IGLV3-25(1-?) CFI(340-583) Ig kappa chain V-I region WAT Ig kappa chain V-I region Daudi Ig heavy chain V-III region DOB MASP2-1 Ig kappa chain V-II region TEW IGKV4-1(21-?) Ig kappa chain V-I region Ka C1R(18-705) Ig lambda chain V-VI region SUT C4A gamma Ig kappa chain V-II region GM607 Ig heavy chain V-III region JON DAF:C3bdNQ-C4B(757-1446) IGLV8-61(1-?) Lipoteichoic acid MASP2-1 Ig lambda chain V-IV region Hil Cell surface C3b:Bb:C3b:ProperdinC5b:C6 complexC9(22-559)Ig heavy chain V-II region MCE dNQ-C4A(757-1446) C4B gamma CD46C8G Ig kappa chain V-I region Lay MASP2-1 Ig kappa chain V region EV15 C4BPA C2a C9(22-559)IGLC7 Ig lambda chain V-V region DEL C4A beta Ig heavy chain V-III region LAY C8B Ig kappa chain V-III region HIC Ig lambda chain V-II region BO Ig kappa chain V-I region Gal C4A gamma N-acetylgalactosamine CFI:CFH:C3bN-acetylgalactosamine C2aIGLV7-43(1-?) IGLC2 CFH Ig lambda chain V-II region BOH C3fC6 dNQ-C3(672-1663) C4A gamma C4B beta C3 beta chain C6 C3 beta chain Ig kappa chain V-I region Bi CFH Cell surface N-acetylgalactosamine Complement Factor 4IGLV4-60(1-?) IGHG2 IGLV5-45(1-?) Cell surface IGHG4 C7 CD46:C3bIGLV8-61(1-?) Ig heavy chain V-III region GA C4B gamma C4A gamma MASP2-1(445-686) Ig lambda chain V-VI region WLT Ig kappa chain V-I region WAT Ig kappa chain V-I region Kue Cell surface C3b alpha' Ig lambda chain V-I region BL2 CFB(260-764) IGLV2-33(1-?) Ig kappa chain V-IV region STH IGLV2-11(1-?) Ig kappa chain V-IV region STH Ig heavy chain V-II region OU Ig kappa chain V-I region CAR C4B gamma MASP1(449-699) C3bIGLV4-60(1-?) C4B gamma N-acetyl-D-glucosamine C3b alpha' C4B gamma Antigen: antibody:C1 complexCell surface Cell surfaceC5 beta CRP(19-224) Ig lambda chain V-VI region NIG-48 CR1 Ig heavy chain V-III region POM C3b alpha' dNQ-C4A(757-1446) IGHG3 dNQ-C3(672-1663) IGLV2-23(1-?) Ca2+ C4B beta Ig heavy chain V-III region CAM Ig kappa chain V-II region MIL C3 beta chain Ig kappa chain V-II region Cum C8B dNQ-C4B(757-1446) 1,3-beta-D-glucan FCN3 C4A gamma Cell surface C8B MASP1(20-699) C4BPB Ig kappa chain V-I region Roy C7 Ig lambda chain V-IV region Bau Ig lambda chain V region 4A C4B alpha4 fragment dNQ-C4A(757-1446) C4BPA Ig heavy chain V-III region JON Cell surface MBL2 C5 beta Ig lambda chain V-VII region MOT C4A gamma C7 MBL-II:MASP-2dimer:MASP-1 dimercomplexIg kappa chain V-I region Walker IGKVA18(21-?) C4A beta Properdin oligomerC5b:C6:C7:C8 complexIg heavy chain V-II region SESS C6 Ig kappa chain V-III region NG9 Ig heavy chain V-III region BUT Ig heavy chain V-III region GA C5 beta C4B beta C3 beta chain C3 beta chain C4B gamma Ig heavy chain V-III region BUT Ig lambda chain V-IV region Hil CFB(260-764) PCho Ig kappa chain V-III region VG C4A beta Ig heavy chain V-I region ND C8A Ig lambda chain V-III region SH FCN3:MASPs:Ca2+:FCN3ligandIg kappa chain V-I region Mev Cell surface:C3bC4A gamma FCN2 Ig kappa chain V-II region FR MASP2-1(16-444) C4A beta Ig kappa chain V-I region AU Ig lambda chain V-II region BUR D-fucose Ig lambda chain V-I region EPS IGLV7-46(1-?) Ig kappa chain V-II region TEW C4BPB Ig kappa chain V-IV region JI C8G Complement factor 5C8A dNQ-C4A(757-1446) MASP2-1 C4B gamma Ig heavy chain V-III region WAS C3 beta chain dNQ-C4A(757-1446) Ig heavy chain V-I region HG3 C3 beta chain Ig kappa chain V-III region Ti Ig kappa chain V-II region RPMI 6410 C4B beta Ig lambda chain V-III region LOI C4A gamma C4B alpha chain fragment b Ig kappa chain V-I region Kue C3 beta chain Ig kappa chain V-I region EU dNQ-C4A(757-1446) MASP1(20-448) Ig kappa chain V-I region Ni Ig lambda chain V-I region NIG-64 CFB(260-764)IGLV11-55(1-?) IGLC7 C4B gamma Ig heavy chain V-III region DOB CR1:C3bIg heavy chain V-III region GAL IGLV1-36(1-?) C4A gamma C1R C-terminal fragment C4b-binding proteinC3 beta chain IGHV(1-?) C4B gamma Ig lambda chain V-IV region Hil C4A beta Complement factor DIg kappa chain V-III region HIC Ig kappa chain V-I region WEA C3b alpha' Ig heavy chain V-I region ND Ig heavy chain V-II region OU Ig lambda chain V-II region WIN C3 beta chain C4B gamma Cell surface Ig lambda chain V-I region NEW C3 beta chain Ig heavy chain V-III region TEI Ig lambda chain V-I region VOR C1R N-terminal fragment Ig heavy chain V-II region DAW dNQ-C4B(757-1446) Ig lambda chain V-II region MGC CFB(260-764) Ig heavy chain V-III region CAM dNQ-C4A(757-1446) IGLV2-23(1-?) Ig heavy chain V-III region ZAP dNQ-C4B(757-1446) Ig kappa chain V-III region WOL Ig kappa chain V-II region FR C4B alpha chain fragment b VTNN-acetyl-D-glucosamine C6 Ig lambda chain V-VI region SUT C4bC2a, C3bBbC3 convertasesIg lambda chain V-I region VOR C3b alpha' C3b alpha' C5b:C6:C7:C8 complexC4B beta MASP1(20-448) Ig lambda chain V-II region NIG-84 Ig kappa chain V-I region Wes C4A gamma CFI(19-335) C4A beta C3(H2O)IGLV1-36(1-?) Ig kappa chain V-III region VH Ig lambda chain V-II region BO Ig lambda chain V-II region BOH C5b alpha' Ig heavy chain V-I region EU IgH heavy chain V-III region VH26 precursor C4A beta CFHC2aC3b alpha' FCN1 C4B beta CFHR3 dNQ-C3(672-1663) IGLV4-69(1-?) FCN1:MASP2dimer:MASP1 dimerIg heavy chain V-II region DAW C5 beta C3b alpha' C4c C3bIg heavy chain V-III region KOL Ig kappa chain V-III region VG FCN2 ligandCR1 C7 Ig kappa chain V-I region CAR C3b alpha' C7 IGLV1-44(1-?) C4-bindingprotein:C4bIg heavy chain V-II region DAW Ig lambda chain V-IV region Bau CFH dNQ-C4B(757-1446) IGLV2-11(1-?) Ig heavy chain V-III region BUT C5b:C6:C7 complexIg kappa chain V-III region WOL CR1 Ig lambda chain V-I region NEW Ca2+Ig kappa chain V-III region SIE Ig kappa chain V-III region VH C4BPB MASP1(20-699) IGLV4-3(1-?) Ig lambda chain V-II region VIL H2OIg heavy chain V-I region Mot Ig lambda chain V-IV region Kern CFIC4A beta CFB(260-764) Ig heavy chain V-I region SIE Ig kappa chain V-II region MIL C4B beta C4B beta C3b alpha' Ig kappa chain V-I region Ni CD46, CR1C3 beta chain Ig kappa chain V-III region HAH Cell surface IGLV5-37(1-?) Ig lambda chain V-I region BL2 Ig lambda chain V-I region EPS C5 beta CFDC7 C4A beta IGHG4 Ig heavy chain V-III region JON C1QA MASP2-1(16-444) MBL2 C3 convertasesIg heavy chain V-III region BRO Ig kappa chain V-I region Scw MASP2-1 C3b alpha' C3b alpha' Ig kappa chain V-I region Hau IGLV3-27(1-?) C4b:C2a:C3bC4B beta 11xCbxE-PROS1CFH Ig heavy chain V-II region COR C4B beta IGLC6 Ig lambda chain V-III region SH C4A beta Properdin oligomer IGLV4-3(1-?) iC3bIGHG1 Ig kappa chain V-IV region JI Ig heavy chain V-III region BRO CFH:Host cellsurfaceC6 IGLV3-22(1-?) MASP1(20-699) Ig heavy chain V-III region BUR Ca2+ Ig kappa chain V-I region Mev C3 beta chain MASP2-1 IGLV2-18(1-?) Ig kappa chain V-I region AG Ig kappa chain V-III region VG Ig heavy chain V-I region WOL C9(22-559) Ig lambda chain V-V region DEL IGLV3-25(1-?) C4A alpha4 fragment C4A alpha b C5b alpha' IGHG1 Ig kappa chain V-III region B6 Ig lambda chain V-I region MEM IGLC1 C3b alpha' Bacterial mannose-based carbohydrate surface pattern C4A beta C7 CFB(26-764)C2a C1S(16-688) Ig kappa chain V-I region HK101 C8G CFH Ig kappa chain V-III region HIC Sialic acid C5b alpha' Ig lambda chain V-II region NEI CD59Ig lambda chain V-VI region NIG-48 Ig kappa chain V-I region BAN C4B gamma Ig kappa chain V-IV region B17 IGLC1 IGLV3-22(1-?) C4A alpha b C4dIg heavy chain V-II region HE Complement factor 3Ig lambda chain V-IV region X IGLV3-25(1-?) Ig heavy chain V-I region EU MASP1(20-699) Ig heavy chain V-III region TRO C4A gamma Heparins C8B Ig kappa chain V-III region IARC/BL41 C4A gamma C1QA C3 beta chain C4 alpha Ig heavy chain V-III region GA Ig lambda chain V region 4A FCN3 ligandC3aMBL2 IGKV1-5(23-?) IGLV7-46(1-?) dNQ-C4B(757-1446) Ig kappa chain V-I region EU Ig lambda chain V-II region BUR C1QB Ig heavy chain V-III region BUR Ig kappa chain V-I region Rei Ig heavy chain V-I region ND Cell surface:C4bCFHR3 IGLC3 Heparins Ig kappa chain V-III region Ti Ig lambda chain V-I region HA IGLC7 C9(22-559) IGKVA18(21-?) FCN2 Ig heavy chain V-I region HG3 Bacterial mannose-based carbohydrate surface pattern C3dgIGLV1-40(1-?) Ig heavy chain V-III region DOB Ig heavy chain V-I region HG3 Ig kappa chain V-IV region B17 IGLV11-55(1-?) IGLV2-33(1-?) MASP2-1 dNQ-C4A(757-1446) DAF:C4bIGKV1-5(23-?) Ig kappa chain V-I region DEE C3c alpha' chain fragment 2 Ig lambda chain V-I region WAH IGLV3-12(1-?) C3 beta chain C4aIg heavy chain V-III region ZAP C1S C-terminal fragment Ig lambda chain V-VI region WLT 598515, 78815814307451, 7658, 601487857368179, 8813613, 219


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. View original pathway at:Reactome.</div>

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  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

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 R-NUL-173548 (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)
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 ProteinP01024 (Uniprot-TrEMBL)
C3c alpha' chain fragment 1 precursor 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 R-HSA-981715 (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)
CFHR3 ProteinQ02985 (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 R-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.
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 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)
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 oligomer R-HSA-182548 (Reactome)
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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