Complement cascade (Homo sapiens)

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47, 48, 52, 71, 11247, 725320103908814, 18, 305, 13, 19, 22, 54...8745, 63, 76, 7826, 6573, 9331, 6723, 11426, 50, 6511527, 86, 88, 9758, 72, 747, 42, 70158082, 944710382, 944, 244029, 36, 957, 83, 1002644, 49, 64421025647, 7238279835, 9984, 1047976, 85, 97341110, 93927210533, 66, 68, 75, 1114720, 674779, 103342, 21, 32, 39, 59...9, 4311320, 6755, 93, 108344, 49, 642424477689465, 6, 13, 17, 54...2047cytosolcytosolTarget CellInnocent bystander cellIg kappa chain V-II region RPMI 6410 C4A(20-675) C7 C4B alpha3 IGLV2-33(1-?) Complement Factor 4Ig heavy chain V-III region JON Ig kappa chain V-I region Gal N-acetylgalactosamine Ig kappa chain V-I region Daudi C9(22-559)Ig heavy chain V-II region OU C4A(956-1336) C3d Ig lambda chain V-VI region AR Ig heavy chain V-II region WAH C4A(20-675) Cell surface:C3b:BbCell surface CFB(260-764) C8B dNQ-C4A(757-1446) C7 CR1 Ig kappa chain V-I region Daudi IGLV2-23(1-?) C4BPB Ig lambda chain V-I region NEWM IGLV2-23(1-?) C5a-desArg Ig kappa chain V-II region FR IGLC6 IGLV4-60(1-?) C3 beta chain C1QC C4B(20-675) C3c alpha' chain fragment 1 precursor C5b alpha' FCN2 FCN1 Ig heavy chain V-III region BRO CD55 Ig heavy chain V-III region WEA MASP2-1 C6 VTN:C5b:C6:C7:C8:C9IGKV2-28 Cell surface:C3bCD55:C4bAntigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1dNQ-C3(672-1663) IGKC C4A(20-675) Ig heavy chain V-III region WEA Cellsurface:FH,FHR3:C3bC4bCell surface Cell surface Ig kappa chain V-I region AU IGLV3-12(1-?) CFI(19-335) Cell surface CD59:C5b-C9C1S C-terminal fragment FCN1 Ig kappa chain V-II region RPMI 6410 C6 IGHG3 S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) IGLC2 C4A(1454-1744) S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) CFI(19-335) C4B alpha4 fragment IGLV4-60(1-?) IGHG4 C5a-desArg C4A(20-675) Ig lambda chain V-I region VOR Ig kappa chain V-II region Cum C9(22-559) IGKV1-12 C4A(1454-1744) SERPING1 C3 beta chain C5b:C6:C7IGLV4-3(1-?) IGLV5-45(1-?) CD19 C3a IGLV3-16(1-?) IGKV1-12 IgH heavy chain V-III region VH26 precursor C1QB IGLV3-27(1-?) Cell surface IGLV5-37(1-?) CD46Ig lambda chain V-IV region Kern S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) CD46 C3d, C3dg, iC3bIGKV1-12 dNQ, ester crosslinked-C4B(757-1446) Cell surface C5b alpha' Ig heavy chain V-I region EU CFI(19-335)Ig kappa chain V-I region BAN IGLV1-44(1-?) Ig kappa chain V-II region Cum C5aTIGLC6 N-acetyl-D-glucosamine IGLV3-12(1-?) Ig lambda chain V-IV region Kern IGLC1 IGHV1-2 IGLV2-18(1-?) IGKVA18(21-?) dNQ, ester crosslinked-C4B(757-1446) C3 beta chain C6 C3c alpha' chain fragment 1 precursor C1QA IGLC3 N-acetyl-D-glucosamine C4b:C2a:C3bSialic acid dNQ-C4A(757-1446) D-fucose Antigen C3(H2O):CFBC3 beta chain CPN1 C3b alpha' IGLC1 CR1 dNQ-C4A(757-1446) C4A(1454-1744) IGLV4-3(1-?) C3c alpha' chain fragment 2 IGKV3D-20 IGLV4-69(1-?) Ig heavy chain V-III region DOB C3bMASP2-1(445-686) Ig lambda chain V-II region MGC C7 Cell surface:C4bIg heavy chain V-III region CAM C3 beta chain IGLV7-46(1-?) IGLC7 CFH Ig lambda chain V-II region BOH Ig lambda chain V-I region NEW IGLV4-60(1-?) 11xCbxE-PROS1IGLV4-3(1-?) C6 dNQ-C4A(757-1446) IGKV1-12 Ca2+ CR1:C3bC3 beta chain IGLV4-3(1-?) IGLV3-25(1-?) C5b alpha' C2a dNQ, ester crosslinked-C4B(757-1446) Cell surface C1QC Antigen:IgGC5 beta chain C3 beta chain IGKV3D-20 MASP1(449-699) Ig kappa chain V-III region B6 C4A(20-675) Ig heavy chain V-II region MCE CFB(260-764) C8B VTNCD55IGHV7-81(1-?) Ig lambda chain V-I region VOR CFH C4d, iC3bIg kappa chain V-I region Wes C3b alpha' dNQ-C4A(757-1446) IGLV7-46(1-?) IGLV2-23(1-?) MASP1(20-699) Ig heavy chain V-III region WEA dNQ, ester crosslinked-C4B(757-1446) C8G C3cIg lambda chain V-VI region AR C1R C-terminal fragment IGLV2-18(1-?) CFH:Host cellsurfaceIGKV3D-20 IGLV4-69(1-?) IGLV4-3(1-?) C4B(1454-1744) Ig lambda chain V-III region LOI CFB(260-764) Ig kappa chain V region EV15 CR1:C4bMBL2 Host cell surfaceIg kappa chain V-I region Daudi CFH C7 IGLC2 IGLC2 IGHG2 Ig lambda chain V-II region MGC C1R(18-705) Ig heavy chain V-III region BRO C4 bindingprotein:protein SCFI:CFH:C3bIGKC IGHG1 CFH CFH S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) IGHG4 dNQ-C4A(757-1446) MASP1(20-699) CR1:C3bBb, C4bC2acomplexesC8G Cell surfaceCFHR3 Ig heavy chain V-III region BRO CR1 Ig heavy chain V-III region BUT C4A(1454-1744) COLEC11 Ig lambda chain V-II region NEI IGKC Ig lambda chain V-VI region AR N-acetyl-D-glucosamine N-acetylgalactosamine IGLV11-55(1-?) C3bC4B(20-675) Ig kappa chain V-II region RPMI 6410 IGKV1-5(23-?) D-fucose Ig lambda chain V-VI region AR Cell surface:C3b:CFBIg lambda chain V-IV region Bau C4A(1454-1744) IGLC7 IGLV3-16(1-?) C4B(20-675) C1QB C3 beta chain Ig kappa chain V-I region Daudi Ig lambda chain V-I region NEW CFB(260-764) Antigen C9(22-559) C4B(20-675) C4A(1454-1744) Ig lambda chain V-I region HA Ig heavy chain V-III region WEA C4A(20-675) C5 alpha chain CLU(23-227) Ig heavy chain V-III region BRO IGLV10-54(1-?) IGHV7-81(1-?) C4b with hydrolysedthioesterIGKV3D-20 IGLV1-36(1-?) FCN2 C4A(20-675) IGLV2-33(1-?) Ig kappa chain V region EV15 Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region WEA dNQ, ester crosslinked-C4B(757-1446) C4A(20-675) IGLV3-27(1-?) IGLV(23-?) C4B(1454-1744) Sialic acid IGLV10-54(1-?) IGHG1 IGLC3 C8G C5 beta chain IGLV3-25(1-?) N-acetyl-D-glucosamine C4cthrombin heavy chain IGLC2 Ig lambda chain V-III region LOI C3 beta chain H2OCa2+ C4BPB C3b alpha' IGLV(23-?) 1,3-beta-D-glucan IGLV10-54(1-?) C1QB IGLV5-37(1-?) C3 beta chain IGLC6 MASP1(20-699) C4B(20-675) IGLV5-45(1-?) IGHV7-81(1-?) IGLV4-60(1-?) C1S C-terminal fragment Ig kappa chain V-I region HK101 Ig kappa chain V-I region AG IGHG3 Ig kappa chain V-II region FR Antigen Ig lambda chain V region 4A IGHG2 Antigen:IgG:C1Q:2xActivated C1R:2xC1SIg heavy chain V-I region HG3 MASP2-1 CR1 IGLV1-40(1-?) C3b alpha' Ig lambda chain V-III region SH Ig lambda chain V-II region NEI IGLV1-36(1-?) C3 beta chain IGLC1 IGKV4-1(21-?) Antigen:IgG:C1Q:2xC1R:2xC1SC4c C1S N-terminal fragment C4A(20-675) IGKVA18(21-?) C5a Ca2+ Ig kappa chain V-I region DEE IGHG4 C4B(1454-1744) Ig heavy chain V-III region BUT C3c alpha' chain fragment 1 precursor C4A(1454-1744) Ig lambda chain V-II region TOG C4B(20-675) C5a IGLV2-33(1-?) dNQ-C4A(757-1446) MASP1(20-699) Ig lambda chain V-IV region Kern IGKC C4A(1454-1744) Ig kappa chain V-I region BAN C3 beta chain IGLV11-55(1-?) C4A(20-675) C4B(20-675) C4B(1454-1744) Ig lambda chain V region 4A Cell surface IGLV4-69(1-?) IGLC1 Ig lambda chain V-II region MGC C4A(1454-1744) IGLV3-16(1-?) IGLV3-22(1-?) C3 beta chain Ig heavy chain V-II region WAH IGLV3-12(1-?) IGLV3-27(1-?) CD46:Cellsurface:C4bAntigen:IgG:C1Q:2xActivated C1R:2xActivated C1SCa2+IGLV2-23(1-?) Ig heavy chain V-III region BRO IGKV4-1(21-?) Ig kappa chain V-I region HK101 CL-LK:MASP1dimer:MASP2 dimerIGKV1-5(23-?) C3b alpha' C7 Ig lambda chain V-IV region Hil C5 beta chain C3 beta chain Lipoteichoic acid dNQ-C3(672-1663) C3c alpha' chain fragment 1 precursor Ig kappa chain V-II region Cum C5AR1:C5aCell surface:CFH,CFHR3:C3bBbIg heavy chain V-III region JON Ig kappa chain V-II region FR C3b:Bb:C3b:ProperdinIGLV11-55(1-?) Ig lambda chain V-I region NEWM C5AR2:C5AR2 ligandsC1QA IGHV(1-?) FCN3 C6 MASP1(20-699) C3c alpha' chain fragment 2 C8G Ig heavy chain V-II region WAH C4A(1454-1744) IGLV1-36(1-?) C3 beta chain Ig heavy chain V-III region BRO dNQ, ester crosslinked-C4B(757-1446) IGLC7 C1R C-terminal fragment CFHR3 Ig lambda chain V region 4A C2a Cell surface IGLC6 FCN3 IGLC3 CFB(260-764) Ca2+ CLUIGLV1-44(1-?) C4A(1454-1744) IGHG2 CFHR5 Ig lambda chain V region 4A MBL2 C6 Ig lambda chain V-III region SH Ig kappa chain V-I region Daudi IGLV1-40(1-?) IGLV4-69(1-?) Ig heavy chain V-II region NEWM CFI(19-335) C4B(1454-1744) C4d C4A(20-675) C3b alpha' CFH:C3bN-acetylgalactosamine dNQ-C3(672-1663) IGLV3-25(1-?) C5 beta chain Sialic acid CFHR1 Ig kappa chain V-II region Cum Ig kappa chain V-I region DEE Ig kappa chain V-I region BAN Membrane AttackComplexC4B(20-675) Ig heavy chain V-II region ARH-77 C3d Ig kappa chain V-II region FR Ig heavy chain V-II region MCE IGLV3-12(1-?) VTN IGLV5-45(1-?) CR2 IGHG3 CD81 CFB(260-764) Ig lambda chain V-III region SH C4B-derived C4a Ig kappa chain V-I region Daudi CR2 IGKVA18(21-?) IGLV10-54(1-?) C3 convertasesC5bSERPING1 C4A(1454-1744) C2a IGKV3D-20 IGLV8-61(1-?) IGHV1-2 VTN:C5b:C6:C7C4B alpha Ig kappa chain V region EV15 C4A(1454-1744) Ig heavy chain V-II region OU C3c alpha' chain fragment 2 IGLV7-43(1-?) C5b:C6:C7, C8, C9C4A(1454-1744) C5 beta chain MASP2-1 CFB(260-764) IGHG3 Ig heavy chain V-I region EU Antigen C3 beta chain IGKV2-28 C4A(1454-1744) Ig lambda chain V-I region HA Ig lambda chain V-I region NEW CFI(19-335) Sialic acid FCN1 ligands:FCN1dodecamer:MASP1dimer:MASP2-1dimer:4xCa2+MBL2 dodecamer:MASP1dimer:MASP2-1dimer:Bacterialmannose surfacepattern:4xCa2+Ig kappa chain V-I region AG Ig heavy chain V-III region WEA MASP2-1 Ig lambda chain V-I region VOR Sialic acid C4aC1S(16-688) N-acetyl-D-glucosamine CFHR3 C4B(1454-1744) C2a Ig lambda chain V-I region NEW CFI(340-583) IGLV1-36(1-?) IGHG2 FCN2 MASP2-1 Cell surface:C3bMASP1(20-699) FCN3 ligands:FCN3multimer:MASP1dimer:MASP2dimer:4xCa2+CPB2 CD81 Ig heavy chain V-III region BUT IGLV8-61(1-?) Ig heavy chain V-II region ARH-77 iC3bC1QB C3 convertasesIg kappa chain V-I region DEE Ig lambda chain V-I region VOR Ig kappa chain V-I region Gal Ig kappa chain V region EV15 C3c alpha' chain fragment 2 IGLV5-45(1-?) Cell surface C3 beta chain Ig lambda chain V-I region HA C8G C3a C4B(20-675) Antigen Ig kappa chain V-III region VG C4A(1454-1744) Ig kappa chain V-I region AG IGHG3 Ig kappa chain V-I region Wes Ig lambda chain V-IV region Hil CD46, CR1CD19 Ig kappa chain V-II region RPMI 6410 Ca2+C5b alpha' C8A Ig lambda chain V-IV region Bau IGLV3-22(1-?) MASP2-1 C3 beta chain IGKV2D-30 C3a-desArg Ig kappa chain V-I region HK101 C5b alpha' C3a-desArg IGHG4 C2aIGLV1-44(1-?) IGKV1-12 Ig heavy chain V-I region HG3 C3b alpha' C1R N-terminal fragment C3b alpha' Ig heavy chain V-III region DOB C7 Ig lambda chain V-II region MGC C1R C-terminal fragment C1QA dNQ-C4A(757-1446) C3b alpha' C3dg Ig heavy chain V-III region DOB MASP2-1 FCN2 ligands:FCN2dodecamer:MASP1dimer:MASP2-1dimer:4xCa2+C4B(956-1336) C3b alpha' dNQ-C4A(757-1446) Ig lambda chain V-I region VOR C4B(20-675) Cell surface C8G CFI(340-583) C4A(20-675) IGHG4 Ig heavy chain V-II region WAH FCN1 IGKV1-12 C3 beta chain Complement factor 3C5b alpha' IGLV8-61(1-?) MASP1(20-699) dNQ, ester crosslinked-C4B(757-1446) IGHV1-2 Ig kappa chain V-III region VG Heparins Ig kappa chain V-I region DEE Ig lambda chain V-III region LOI CD55 C3b alpha' Ig heavy chain V-II region OU C4B(20-675) C1R N-terminal fragment C2aC3b alpha' IGKC C3 beta chain IGLV2-11(1-?) IGLV3-22(1-?) C2a SERPING1 IGKV1-5(23-?) Ig lambda chain V-I region NEWM dNQ, ester crosslinked-C4B(757-1446) C5 beta chain Ig kappa chain V-II region RPMI 6410 IGLV1-40(1-?) Ig heavy chain V-I region EU dNQ-C3(672-1663) C1QC CR1:iC3bIGKV4-1(21-?) IGLV3-12(1-?) N-acetyl-D-glucosamine Ig lambda chain V-IV region Hil Ig lambda chain V-I region NEWM C3(H2O)C1R C-terminal fragment C1S N-terminal fragment Ig lambda chain V-II region TOG C3a-desArg Ig lambda chain V-II region TOG Ig kappa chain V-II region Cum Ig kappa chain V-I region AU IGKV3D-20 C4A(20-675) IGLV1-44(1-?) C1S N-terminal fragment Ca2+ C5AR1Ig lambda chain V-III region LOI Ig heavy chain V-III region CAM C5a-desArg C2a Ig kappa chain V-II region Cum Ig heavy chain V-III region KOL C4c, C3fC3b alpha' IGLV2-18(1-?) C4B(1454-1744) C3b alpha' CR1C3dgIGLV5-45(1-?) Ig heavy chain V-I region EU Ig kappa chain V-I region Gal C4bCell surface C4b-binding proteinCFB(260-764) C8B Ig lambda chain V region 4A MBL2 IGLV5-37(1-?) C8A C3c alpha' chain fragment 2 C3 beta chain C2a Ig kappa chain V-I region AU FCN2 C3b alpha' CFHR3 IGHV(1-?) C1R N-terminal fragment C5a C3aIg lambda chain V-II region MGC COLEC10 Ig lambda chain V region 4A MASP2-1 Ig lambda chain V-IV region Bau IGKV2D-30 Ig heavy chain V-III region CAM Ig kappa chain V-I region Wes Ig heavy chain V-I region EU MASP1(20-448) C4B(1454-1744) C4B(1454-1744) IGLV4-60(1-?) Ig lambda chain V-III region SH C3(H2O):BbC3 beta chain IGHG1 IGKVA18(21-?) C1QB C3 beta chain IGKVA18(21-?) N-acetylgalactosamine IGLV4-3(1-?) C5b:C6:C7:C8Ig kappa chain V region EV15 Ig lambda chain V-II region NEI CFB(26-764)Cell surface:C3b:BbCD59 C3b alpha' C6Cell surface Ig lambda chain V-IV region Hil Cell surface C4B(20-675) C2a Ig lambda chain V-IV region Bau C6 Cell surface:C3bC3b alpha' C4A(20-675) C1R N-terminal fragment Ig lambda chain V-II region BOH C4dCell surface:C4bC3c alpha' chain fragment 1 precursor Ig kappa chain V-I region AG IgH heavy chain V-III region VH26 precursor IGLV4-3(1-?) CFB(26-764) C1QA C5AR2C8G C3 beta chain C4A(1454-1744) C8A CFHR2 CFI(340-583) MASP1(20-699) IGKV2-28 IGLV3-22(1-?) C4bC2a, C3bBbC6 CD46 MBL2,FCN:activatedMASPs:carbohydratepatternsC3c alpha' chain fragment 2 dNQ, ester crosslinked-C4B(757-1446) Ig lambda chain V-II region BOH dNQ-C4A(757-1446) Bacterial mannose surface pattern CLU:C5b:C6:C7, C8,C9C5 beta chain C5IGLC6 IGLV1-40(1-?) IGKV2D-30 IgH heavy chain V-III region VH26 precursor C3b alpha' C4A-derived C4a IGLV5-37(1-?) Ig kappa chain V-III region VG IGHG1 Ig heavy chain V-II region NEWM IGLV2-18(1-?) C3 beta chain IGLV3-27(1-?) IGHV7-81(1-?) Ig kappa chain V-I region AG Ig kappa chain V-I region BAN IGLV1-40(1-?) C7 IGLV5-37(1-?) Ig lambda chain V-II region BOH IGKV2D-30 Ig heavy chain V-III region BUT Ig lambda chain V-I region VOR IGLV8-61(1-?) Ig kappa chain V-III region B6 C4A(20-675) IGLV2-33(1-?) CD46 Ig lambda chain V-III region LOI IGLV3-25(1-?) MASP1(20-699) C8A IGLV2-18(1-?) IGHG2 Ig kappa chain V-I region BAN IGLC6 IGHG3 Ig kappa chain V-I region HK101 IGLV2-23(1-?) IGKV4-1(21-?) C4A(1454-1744) C4A(1454-1744) C4A(20-675) Ig heavy chain V-III region BRO IGHG1 Ig kappa chain V-III region B6 FCN1 dodecamer:MASP1dimer:MASP2-1 dimerCLU(23-227) Ig heavy chain V-III region CAM CR2Cell surface C3b alpha' C4B(1454-1744) Ig heavy chain V-III region DOB IGLV7-43(1-?) C3b alpha' C8B Ig heavy chain V-I region HG3 IGLV5-45(1-?) Ig lambda chain V-IV region Hil C3f C3a-desArg,C5a-desArgIGLV3-27(1-?) IGLV7-43(1-?) IGHV1-2 IGLV1-44(1-?) IGKV3D-20 MBL2,FCN:MASPs:carbohydrate patternsProperdin oligomer Properdin oligomer IGKV2D-30 IGKV2-28 Cell surface CFHR dimersC1QC C5b alpha' Cell surface C4B(20-675) C4A(20-675) Cell surface IGHG1 C8A IGHV(1-?) Ig heavy chain V-II region WAH C5a C2a dNQ-C4A(757-1446) Cell surface Ig heavy chain V-II region NEWM Ig kappa chain V-I region DEE C4A(1454-1744) CD55:C3 convertasecomplexesIGHV(1-?) Cell surface D-fucose C4B(20-675) IGLV7-43(1-?) Ig heavy chain V-III region TRO Ig lambda chain V-II region BOH IGLV2-11(1-?) Ig heavy chain V-II region MCE Ig kappa chain V-I region Gal C8A ActivatedC1S:SERPING1C4A(20-675) C4A(20-675) C3 beta chain Ig lambda chain V-VI region AR C4B(1454-1744) Ig lambda chain V-I region HA IGLV10-54(1-?) IGLV(23-?) C7 Ig kappa chain V-II region FR Antigen C6 C3 beta chain C8B IGLV4-60(1-?) Sialic acid C4A(20-675) C3 alpha chain dNQ-C4B(757-1446) C3 beta chain Ig heavy chain V-III region KOL CR2:C3d,C3dg,iC3bFCN3 Ig lambda chain V-II region TOG Ig kappa chain V-I region HK101 Ig heavy chain V-III region BUT C2aC3a dNQ-C4A(757-1446) IGLV10-54(1-?) C5b:C6:C7:C8N-acetyl-D-glucosamine C8B Cell surface:C4b:C2aIg heavy chain V-III region JON IGLC3 Cell surface CFB(260-764)Ig kappa chain V-I region DEE S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) C5b alpha' Ig kappa chain V-I region AG Ig lambda chain V-IV region Hil Ig kappa chain V-I region BAN C3b alpha' IGKV4-1(21-?) C3d FCN3 oligomer:MASP1dimer:MASP2-1 dimerIGLV10-54(1-?) C3 beta chain Ig heavy chain V-III region KOL IGLV7-46(1-?) CFHR1 Ig heavy chain V-II region NEWM CD46 Cellsurface:C3b:Bb:ProperdinC3 beta chain IGLV3-22(1-?) IGLC3 IGHV7-81(1-?) Ig kappa chain V-I region Gal FCN3 IGKV1-5(23-?) Cell surface IGLV3-25(1-?) C4B(20-675) Ig kappa chain V-III region POM IGHG4 Ig heavy chain V-III region JON C1R N-terminal fragment CFB(260-764) C5 beta chain Ig kappa chain V-III region POM IGKV1-5(23-?) C4 alpha Ig heavy chain V-III region JON MASP1(20-699) C4B(1454-1744) C3b alpha' Ig lambda chain V-III region SH Ig lambda chain V-IV region Bau C4BPA C5b alpha' Cell surface Ig heavy chain V-III region TRO C4A(20-675) ELANE MBL2,FCN:activated MASPs:carbohydrate patterns IgH heavy chain V-III region VH26 precursor FCN2 dodecamer:MASP1dimer:MASP2-1 dimerIg heavy chain V-II region OU CR2:C3d,C3dg,iC3b:CD19:CD81Ig lambda chain V-IV region Bau FCN1 ligandsIGLV7-43(1-?) C1QC1S N-terminal fragment IGLV2-11(1-?) C8B IGLV3-25(1-?) CFHR5 IGKV1-5(23-?) C1QC Ig heavy chain V-III region CAM Ig lambda chain V-II region NEI MBL2 Cellsurface:C3b:CFHRdimersC1QB C5bTC4BPA IGHV(1-?) Ig heavy chain V-I region EU CFB(260-764) IGLV2-11(1-?) CFH Cell surface C4A alpha3 CPN2 C4BPB CFI(340-583)C4A(1454-1744) C4B(1454-1744) IGLV2-23(1-?) Ig lambda chain V-II region NEI Ig heavy chain V-II region NEWM Ig kappa chain V-I region Daudi C4B(1454-1744) C4B(20-675) IGHG4 IGLC7 IGLV(23-?) Ig heavy chain V-III region BUT Bacterial mannose surface pattern Ig lambda chain V-VI region AR C8A IGLV4-60(1-?) Ig heavy chain V-III region KOL C7 CFI(19-335) CR1 CD55:C3bC4B(20-675) C9(22-559) IGLV2-33(1-?) C4B(1454-1744) Cell surface Properdin oligomer Ig heavy chain V-III region WEA IGHV7-81(1-?) Ig heavy chain V-I region EU ActivatedC1R:SERPING1Activated thrombin,(ELANE)H2OMASP2-1 IGLC1 Ig lambda chain V-VI region AR C4B(1454-1744) Complement factor DIg kappa chain V-I region HK101 C4b-bindingprotein:Factor IC4B(1454-1744) CD55 IGHV(1-?) Ig lambda chain V-I region NEWM Ig lambda chain V-II region MGC dNQ-C4A(757-1446) C1QA C3c alpha' chain fragment 2 dNQ, ester crosslinked-C4B(757-1446) Ig kappa chain V-I region Gal C3 beta chain Ig lambda chain V-III region SH IGLC3 dNQ, ester crosslinked-C4B(757-1446) C4B(1454-1744) C4-bindingprotein:C4bIg lambda chain V-I region NEWM dNQ-C4A(757-1446) C1S N-terminal fragment IGLV2-11(1-?) Ig heavy chain V-II region OU C7dNQ-C4A(757-1446) Cell surfaceCFB(260-764) CFHCell surface C3AR1:C3aS-(L-isoglutamyl)-L-cysteine-C4B(757-1446) IGLC1 D-fucose C3 beta chain Ig heavy chain V-II region ARH-77 CD59C3a C1QA IGLV2-33(1-?) Ig heavy chain V-III region JON CFHR3 CLU(228-449) COLEC10 C4B(1454-1744) Ig heavy chain V-II region MCE IGLV2-11(1-?) Ig heavy chain V-III region CAM Ig kappa chain V region EV15 C1S(16-688) Ig lambda chain V-II region NEI C1QB Ig kappa chain V-III region VG IgH heavy chain V-III region VH26 precursor Cell surface dNQ, ester crosslinked-C4B(757-1446) IGLC7 C5 beta chain C9(22-559)Ig lambda chain V-IV region Kern C3b alpha' C4A(20-675) Ig kappa chain V-I region HK101 C8A IGLV7-46(1-?) Properdin oligomerIg heavy chain V-III region TRO C3 beta chain MASP2-1 C3 beta chain IGHG1 C3 beta chain CFHR3 IGLV1-40(1-?) C3 beta chain IGLV(23-?) Ig lambda chain V-IV region Kern IGLV3-27(1-?) IGLV1-36(1-?) VTN C4A(1454-1744) IGLV5-45(1-?) IGLV1-36(1-?) IGLV5-37(1-?) IGLV2-23(1-?) Ig kappa chain V-I region Gal C3b alpha' Ig heavy chain V-I region HG3 Bacterial mannosesurface patternIGLV(23-?) Ig lambda chain V-II region MGC C3a, C5aIGLV7-43(1-?) IGLV1-36(1-?) IGLV2-18(1-?) S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) Lipoteichoic acid Ig lambda chain V-III region LOI IGLV8-61(1-?) 1,3-beta-D-glucan C4A(20-675) Ig lambda chain V-II region TOG COLEC11 C3 beta chain IGKV4-1(21-?) Cell surface Ig lambda chain V-I region NEW IGLV11-55(1-?) IGKV2D-30 Ig heavy chain V-II region ARH-77 Ig kappa chain V-III region B6 Ig heavy chain V-II region ARH-77 C5 beta chain CFB(26-764) Cell surface IGLV4-69(1-?) C5 beta chain IGLV1-44(1-?) IGLV3-22(1-?) Ig kappa chain V-III region POM C5 beta chain C4BPB Cell surface CFI(340-583) IGLC6 Ig heavy chain V-III region KOL Properdin oligomer Ig kappa chain V-I region BAN C4A(1454-1744) CD46 IGKV1-5(23-?) C1QB C4A(20-675) C5b:C6Cell surface Ig kappa chain V-III region POM dNQ, ester crosslinked-C4B(757-1446) C3bC1QC CPN, CBP2COLEC11 Ig heavy chain V-III region TRO C9(22-559) CFHR4 N-acetylgalactosamine C5b:C6:C7IGKV2D-30 Ig kappa chain V-III region VG CFHR3 IGHV1-2 C4BPA Ig lambda chain V-III region LOI C5b alpha' Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SIGLC3 Properdin oligomer C3c alpha' chain fragment 1 IGLC1 C2bCa2+ Ig lambda chain V-III region SH C1QA CFI:CFH,FHR3:C3bC3aIGLV11-55(1-?) Cell surface:C4bIg heavy chain V-III region TRO IGKC C5 beta chain Ig heavy chain V-II region OU Ig kappa chain V-I region DEE C4B(20-675) Antigen IGLV3-12(1-?) IGLV7-43(1-?) C7 Cell surface Ig heavy chain V-I region HG3 IGLC2 Lipoteichoic acid C5AR1 CFH, CFHR3Ig kappa chain V-I region AU CRP(19-224) C4B(1454-1744) CL-LK:MASP1dimer:MASP2dimer:Bacterialmannose surfacepattern:4xCa2+Ig heavy chain V-II region NEWM C-reactiveproteinpentamer:phosphocholine:C1QIg lambda chain V-IV region Kern dNQ-C4A(757-1446) Ig heavy chain V-II region WAH 11xCbxE-PROS1 Ig lambda chain V-IV region Hil Ig heavy chain V-III region TRO IGKV2-28 Ig kappa chain V-III region B6 dNQ, ester crosslinked-C4B(757-1446) Ig kappa chain V-III region VG C5(965-1676) MASP1(20-699) C4A(1454-1744) IGKC Cell surface:C4b:C2aIg lambda chain V-I region HA C4B(20-675) IGLV3-12(1-?) IGLV1-40(1-?) C3b alpha' FCN2 ligandsC3AR1 Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region TRO IGLV8-61(1-?) Ig lambda chain V-II region TOG Ig kappa chain V-I region Wes C4A(20-675) Cell surface C4A alpha4 fragment Ig kappa chain V-II region Cum Cell surface Ig heavy chain V-II region WAH CFH C4B(20-675) FCN1 C4B(20-675) Ig heavy chain V-II region NEWM Ca2+Ig kappa chain V-III region VG 1,3-beta-D-glucan Ig lambda chain V-I region NEW IGLV3-16(1-?) Ig lambda chain V region 4A IGLV11-55(1-?) CFI(340-583) C3 beta chain Bacterial mannose surface pattern C2a C3 beta chain C4B(1454-1744) S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) Ig kappa chain V-II region RPMI 6410 COLEC10 IGLV11-55(1-?) Ca2+ C3c alpha' chain fragment 2 Cell surface C2aIg kappa chain V-II region FR IGLV(23-?) Ig heavy chain V-I region HG3 dNQ-C3(672-1663) CD46:Cellsurface:C3bIGHG3 C4B(1454-1744) IGLV7-46(1-?) Ig lambda chain V-I region NEW Ig lambda chain V-II region TOG CFHR2 IGLV3-16(1-?) IGKV2-28 C3fC5 beta chain CFB(260-764) Ca2+ C9(22-559) Ig lambda chain V-IV region Bau dNQ, ester crosslinked-C4B(757-1446) C1R C-terminal fragment SERPING1Cell surface C3b alpha' Heparins C2aIgH heavy chain V-III region VH26 precursor IGLC2 MASP1(20-699) MASP2-1 IGLV1-44(1-?) CFD N-acetyl-D-glucosamine Ig kappa chain V-I region Wes dNQ-C4A(757-1446) C4BPA dNQ, ester crosslinked-C4B(757-1446) IGLV4-69(1-?) C3AR1IGLV2-18(1-?) IGLV3-16(1-?) C5b alpha' Ig lambda chain V-II region BOH Ig heavy chain V-II region MCE C8Ig kappa chain V-III region POM IGLV8-61(1-?) IGLV3-27(1-?) IGKV2-28 C3c alpha' chain fragment 1 precursor 1,3-beta-D-glucan Properdin oligomerIg heavy chain V-III region BUT IGLV5-37(1-?) CLU(228-449) dNQ, ester crosslinked-C4B(757-1446) C3dg CFB(260-764) CFB(260-764) GZMM C5 convertasesCell surface:C3bCell surface:C4b:C2aIg kappa chain V-III region POM Ig heavy chain V-III region DOB Ig lambda chain V-IV region Kern Ig heavy chain V-III region KOL Ig kappa chain V-I region AG C3 beta chain CFI:CD46, CR1:C4b,C3b complexesC5AR2 ligandsC4A(1454-1744) IGLC7 C4B(20-675) Ig heavy chain V-III region DOB Ig kappa chain V-III region B6 MBL2 dodecamer:MASP1dimer:MASP2-1 dimerC2IGHG2 IGHG2 IGKVA18(21-?) IGLC2 C8G Ig heavy chain V-III region CAM C4B(1454-1744) CR1 CFI(340-583) Bacterial mannose surface pattern C4B(20-675) Ig heavy chain V-II region MCE C3b alpha' IGKV1-12 CFH Ig lambda chain V-I region NEWM Ig lambda chain V-II region BOH Ig lambda chain V-I region VOR C4A(20-675) IGLC7 IGKVA18(21-?) C3b alpha' Ig kappa chain V-I region Wes IGHV(1-?) dNQ, ester crosslinked-C4B(757-1446) Ig lambda chain V-II region NEI C4 bindingprotein:C4bC2aIGKV4-1(21-?) Ig heavy chain V-III region JON C5b alpha' IGLV2-11(1-?) PCho Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region DOB dNQ-C4A(757-1446) C4B(1454-1744) C4B(20-675) IgH heavy chain V-III region VH26 precursor CFHR4 C3 beta chain Ca2+ Ig kappa chain V region EV15 C3 beta chain MASP2-1 SERPING1 IGLV3-16(1-?) Ig heavy chain V-II region OU C3b alpha' C1QC C3b alpha' C4B(20-675) CFIIGLV3-22(1-?) IGLV7-46(1-?) CFB(26-259)C4BPA C1S C-terminal fragment FCN3 ligandsC6 Ig heavy chain V-III region KOL C1R C-terminal fragment Ig kappa chain V-II region FR IGLV3-25(1-?) Ig kappa chain V-III region B6 thrombin light chain Ig lambda chain V-I region HA N-acetylgalactosamine IGHV7-81(1-?) CD46, CR1:C4b:C3bcomplexesIg kappa chain V-I region AU C4B(1454-1744) Bacterial mannose surface pattern C1R N-terminal fragment C3 beta chain C3dg Ig kappa chain V-I region AU Lipoteichoic acid C5aC1S C-terminal fragment Ig kappa chain V-III region POM C1QA C8B MASP2-1(16-444) C4A(1454-1744) Ca2+C6 C4 activatorsdNQ-C4A(757-1446) dNQ-C3(672-1663) CFI(19-335) IGHV1-2 Ig kappa chain V-I region Wes C3c alpha' chain fragment 1 precursor dNQ, ester crosslinked-C4B(757-1446) CD19:CD81C5AR2 IGLV4-69(1-?) dNQ-C4A(757-1446) IGLV2-33(1-?) Ig heavy chain V-II region MCE C2a C4B(20-675) IGLV7-46(1-?) C1QC C4BPB C3(H2O)CR1 Ig lambda chain V-I region HA C4B(1454-1744) C1S C-terminal fragment Ig kappa chain V-I region AU CFI:CFH,FHR3:iC3bIGHV1-2 Ig heavy chain V-I region HG3 Ca2+ 17729, 95251241, 10641, 1061625101213, 962557, 8113911072854, 101367737, 517637, 51, 608, 696416


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). 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). 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. 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. 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). 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. 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. The complement cascade pathway is organised into the following sections: initial triggering, activation of C3 and C5, terminal pathway and regulation. View original pathway at Reactome.

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Pathway is converted from Reactome ID: 166658
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Reactome version: 75
Reactome Author 
Reactome Author: de Bono, Bernard

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Bibliography

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  34. Sim RB, Reboul A, Arlaud GJ, Villiers CL, Colomb MG.; ''Interaction of 125I-labelled complement subcomponents C-1r and C-1s with protease inhibitors in plasma.''; PubMed Europe PMC Scholia
  35. Kalant D, Cain SA, Maslowska M, Sniderman AD, Cianflone K, Monk PN.; ''The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein.''; PubMed Europe PMC Scholia
  36. Davis AE, Harrison RA, Lachmann PJ.; ''Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d,g (alpha 2D), and C3g.''; PubMed Europe PMC Scholia
  37. Kishore U, Ghai R, Greenhough TJ, Shrive AK, Bonifati DM, Gadjeva MG, Waters P, Kojouharova MS, Chakraborty T, Agrawal A.; ''Structural and functional anatomy of the globular domain of complement protein C1q.''; PubMed Europe PMC Scholia
  38. Ziccardi RJ, Cooper NR.; ''Activation of C1r by proteolytic cleavage.''; PubMed Europe PMC Scholia
  39. Teh C, Le Y, Lee SH, Lu J.; ''M-ficolin is expressed on monocytes and is a lectin binding to N-acetyl-D-glucosamine and mediates monocyte adhesion and phagocytosis of Escherichia coli.''; PubMed Europe PMC Scholia
  40. Jokiranta TS, Cheng ZZ, Seeberger H, Jòzsi M, Heinen S, Noris M, Remuzzi G, Ormsby R, Gordon DL, Meri S, Hellwage J, Zipfel PF.; ''Binding of complement factor H to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site.''; PubMed Europe PMC Scholia
  41. Butkowski RJ, Elion J, Downing MR, Mann KG.; ''Primary structure of human prethrombin 2 and alpha-thrombin.''; PubMed Europe PMC Scholia
  42. Fearon DT.; ''Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane.''; PubMed Europe PMC Scholia
  43. Bokisch VA, Müller-Eberhard HJ.; ''Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase.''; PubMed Europe PMC Scholia
  44. Bhakdi S, Käflein R, Halstensen TS, Hugo F, Preissner KT, Mollnes TE.; ''Complement S-protein (vitronectin) is associated with cytolytic membrane-bound C5b-9 complexes.''; PubMed Europe PMC Scholia
  45. Teillet F, Dublet B, Andrieu JP, Gaboriaud C, Arlaud GJ, Thielens NM.; ''The two major oligomeric forms of human mannan-binding lectin: chemical characterization, carbohydrate-binding properties, and interaction with MBL-associated serine proteases.''; PubMed Europe PMC Scholia
  46. Dahlbäck B, Stenflo J.; ''High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein.''; PubMed Europe PMC Scholia
  47. Müller-Eberhard HJ.; ''Molecular organization and function of the complement system.''; PubMed Europe PMC Scholia
  48. Gasque P.; ''Complement: a unique innate immune sensor for danger signals.''; PubMed Europe PMC Scholia
  49. Sheehan M, Morris CA, Pussell BA, Charlesworth JA.; ''Complement inhibition by human vitronectin involves non-heparin binding domains.''; PubMed Europe PMC Scholia
  50. Nagasawa S, Ichihara C, Stroud RM.; ''Cleavage of C4b by C3b inactivator: production of a nicked form of C4b, C4b', as an intermediate cleavage product of C4b by C3b inactivator.''; PubMed Europe PMC Scholia
  51. Kishore U, Reid KB.; ''C1q: structure, function, and receptors.''; PubMed Europe PMC Scholia
  52. Nonaka M, Yoshizaki F.; ''Evolution of the complement system.''; PubMed Europe PMC Scholia
  53. Matsumoto AK, Martin DR, Carter RH, Klickstein LB, Ahearn JM, Fearon DT.; ''Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.''; PubMed Europe PMC Scholia
  54. Garlatti V, Martin L, Lacroix M, Gout E, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural insights into the recognition properties of human ficolins.''; PubMed Europe PMC Scholia
  55. Farries TC, Lachmann PJ, Harrison RA.; ''Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products.''; PubMed Europe PMC Scholia
  56. Tschopp J, Chonn A, Hertig S, French LE.; ''Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9.''; PubMed Europe PMC Scholia
  57. Wu J, Wu YQ, Ricklin D, Janssen BJ, Lambris JD, Gros P.; ''Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.''; PubMed Europe PMC Scholia
  58. Fearon DT, Austen KF.; ''Initiation of C3 cleavage in the alternative complement pathway.''; PubMed Europe PMC Scholia
  59. Wittenborn T, Thiel S, Jensen L, Nielsen HJ, Jensenius JC.; ''Characteristics and biological variations of M-ficolin, a pattern recognition molecule, in plasma.''; PubMed Europe PMC Scholia
  60. Budayova-Spano M, Lacroix M, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C.; ''The crystal structure of the zymogen catalytic domain of complement protease C1r reveals that a disruptive mechanical stress is required to trigger activation of the C1 complex.''; PubMed Europe PMC Scholia
  61. Ma YG, Cho MY, Zhao M, Park JW, Matsushita M, Fujita T, Lee BL.; ''Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement.''; PubMed Europe PMC Scholia
  62. Matsushita M, Kuraya M, Hamasaki N, Tsujimura M, Shiraki H, Fujita T.; ''Activation of the lectin complement pathway by H-ficolin (Hakata antigen).''; PubMed Europe PMC Scholia
  63. Petersen SV, Thiel S, Jensenius JC.; ''The mannan-binding lectin pathway of complement activation: biology and disease association.''; PubMed Europe PMC Scholia
  64. Preissner KP, Podack ER, Müller-Eberhard HJ.; ''SC5b-7, SC5b-8 and SC5b-9 complexes of complement: ultrastructure and localization of the S-protein (vitronectin) within the macromolecules.''; PubMed Europe PMC Scholia
  65. Ross GD, Lambris JD, Cain JA, Newman SL.; ''Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs CR1 cofactor activity.''; PubMed Europe PMC Scholia
  66. Huang Y, Fedarovich A, Tomlinson S, Davies C.; ''Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex.''; PubMed Europe PMC Scholia
  67. Pangburn MK, Schreiber RD, Müller-Eberhard HJ.; ''Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution.''; PubMed Europe PMC Scholia
  68. Lehto T, Meri S.; ''Interactions of soluble CD59 with the terminal complement complexes. CD59 and C9 compete for a nascent epitope on C8.''; PubMed Europe PMC Scholia
  69. Hadders MA, Bubeck D, Roversi P, Hakobyan S, Forneris F, Morgan BP, Pangburn MK, Llorca O, Lea SM, Gros P.; ''Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9.''; PubMed Europe PMC Scholia
  70. Krych-Goldberg M, Hauhart RE, Subramanian VB, Yurcisin BM, Crimmins DL, Hourcade DE, Atkinson JP.; ''Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases.''; PubMed Europe PMC Scholia
  71. Schmidt BZ, Colten HR.; ''Complement: a critical test of its biological importance.''; PubMed Europe PMC Scholia
  72. Schreiber RD, Pangburn MK, Lesavre PH, Müller-Eberhard HJ.; ''Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.''; PubMed Europe PMC Scholia
  73. Kerr MA.; ''The human complement system: assembly of the classical pathway C3 convertase.''; PubMed Europe PMC Scholia
  74. Lesavre PH, Müller-Eberhard HJ.; ''Mechanism of action of factor D of the alternative complement pathway.''; PubMed Europe PMC Scholia
  75. Huang Y, Smith CA, Song H, Morgan BP, Abagyan R, Tomlinson S.; ''Insights into the human CD59 complement binding interface toward engineering new therapeutics.''; PubMed Europe PMC Scholia
  76. Fujita T, Matsushita M, Endo Y.; ''The lectin-complement pathway--its role in innate immunity and evolution.''; PubMed Europe PMC Scholia
  77. Ponnuraj K, Xu Y, Macon K, Moore D, Volanakis JE, Narayana SV.; ''Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase.''; PubMed Europe PMC Scholia
  78. Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW.; ''Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition.''; PubMed Europe PMC Scholia
  79. Mold C, Medof ME.; ''C3 nephritic factor protects bound C3bBb from cleavage by factor I and human erythrocytes.''; PubMed Europe PMC Scholia
  80. Podack ER, Tschoop J, Müller-Eberhard HJ.; ''Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b-8 assembly.''; PubMed Europe PMC Scholia
  81. Morgan HP, Schmidt CQ, Guariento M, Blaum BS, Gillespie D, Herbert AP, Kavanagh D, Mertens HD, Svergun DI, Johansson CM, Uhrín D, Barlow PN, Hannan JP.; ''Structural basis for engagement by complement factor H of C3b on a self surface.''; PubMed Europe PMC Scholia
  82. Seya T, Atkinson JP.; ''Functional properties of membrane cofactor protein of complement.''; PubMed Europe PMC Scholia
  83. Harris CL, Pettigrew DM, Lea SM, Morgan BP.; ''Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay.''; PubMed Europe PMC Scholia
  84. Brodbeck WG, Liu D, Sperry J, Mold C, Medof ME.; ''Localization of classical and alternative pathway regulatory activity within the decay-accelerating factor.''; PubMed Europe PMC Scholia
  85. MUELLER-EBERHARD HJ, LEPOW IH.; ''C'1 ESTERASE EFFECT ON ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF THE FOURTH COMPONENT OF COMPLEMENT.''; PubMed Europe PMC Scholia
  86. Nagasawa S, Stroud RM.; ''Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b.''; PubMed Europe PMC Scholia
  87. Troegeler A, Lugo-Villarino G, Hansen S, Rasolofo V, Henriksen ML, Mori K, Ohtani K, Duval C, Mercier I, Bénard A, Nigou J, Hudrisier D, Wakamiya N, Neyrolles O.; ''Collectin CL-LK Is a Novel Soluble Pattern Recognition Receptor for Mycobacterium tuberculosis.''; PubMed Europe PMC Scholia
  88. Müller-Eberhard HJ, Polley MJ, Calcott MA.; ''Formation and functional significance of a molecular complex derived from the second and the fourth component of human complement.''; PubMed Europe PMC Scholia
  89. Pangburn MK, Schreiber RD, Müller-Eberhard HJ.; ''Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3.''; PubMed Europe PMC Scholia
  90. Gerard NP, Gerard C.; ''The chemotactic receptor for human C5a anaphylatoxin.''; PubMed Europe PMC Scholia
  91. Garlatti V, Martin L, Gout E, Reiser JB, Fujita T, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch.''; PubMed Europe PMC Scholia
  92. Weis JJ, Tedder TF, Fearon DT.; ''Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes.''; PubMed Europe PMC Scholia
  93. Medicus RG, Götze O, Müller-Eberhard HJ.; ''Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway.''; PubMed Europe PMC Scholia
  94. Barilla-LaBarca ML, Liszewski MK, Lambris JD, Hourcade D, Atkinson JP.; ''Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells.''; PubMed Europe PMC Scholia
  95. Becherer JD, Lambris JD.; ''Identification of the C3b receptor-binding domain in third component of complement.''; PubMed Europe PMC Scholia
  96. Matsushita M, Endo Y, Fujita T.; ''Cutting edge: complement-activating complex of ficolin and mannose-binding lectin-associated serine protease.''; PubMed Europe PMC Scholia
  97. Hajela K, Kojima M, Ambrus G, Wong KH, Moffatt BE, Ferluga J, Hajela S, Gál P, Sim RB.; ''The biological functions of MBL-associated serine proteases (MASPs).''; PubMed Europe PMC Scholia
  98. Sepp A, Dodds AW, Anderson MJ, Campbell RD, Willis AC, Law SK.; ''Covalent binding properties of the human complement protein C4 and hydrolysis rate of the internal thioester upon activation.''; PubMed Europe PMC Scholia
  99. Cain SA, Monk PN.; ''The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74).''; PubMed Europe PMC Scholia
  100. Kinoshita T, Medof ME, Nussenzweig V.; ''Endogenous association of decay-accelerating factor (DAF) with C4b and C3b on cell membranes.''; PubMed Europe PMC Scholia
  101. Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, Fujita T, Fontecilla-Camps JC, Arlaud GJ, Thielens NM, Gaboriaud C.; ''Structural insights into the innate immune recognition specificities of L- and H-ficolins.''; PubMed Europe PMC Scholia
  102. Ziccardi RJ, Cooper NR.; ''Physicochemical and functional characterization of the C1r subunit of the first complement component.''; PubMed Europe PMC Scholia
  103. Pangburn MK, Müller-Eberhard HJ.; ''Kinetic and thermodynamic analysis of the control of C3b by the complement regulatory proteins factors H and I.''; PubMed Europe PMC Scholia
  104. Medof ME, Kinoshita T, Nussenzweig V.; ''Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.''; PubMed Europe PMC Scholia
  105. Goicoechea de Jorge E, Caesar JJ, Malik TH, Patel M, Colledge M, Johnson S, Hakobyan S, Morgan BP, Harris CL, Pickering MC, Lea SM.; ''Dimerization of complement factor H-related proteins modulates complement activation in vivo.''; PubMed Europe PMC Scholia
  106. Degen SJ, Davie EW.; ''Nucleotide sequence of the gene for human prothrombin.''; PubMed Europe PMC Scholia
  107. Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P.; ''Structures of C3b in complex with factors B and D give insight into complement convertase formation.''; PubMed Europe PMC Scholia
  108. Smith CA, Pangburn MK, Vogel CW, Müller-Eberhard HJ.; ''Molecular architecture of human properdin, a positive regulator of the alternative pathway of complement.''; PubMed Europe PMC Scholia
  109. Gout E, Garlatti V, Smith DF, Lacroix M, Dumestre-Pérard C, Lunardi T, Martin L, Cesbron JY, Arlaud GJ, Gaboriaud C, Thielens NM.; ''Carbohydrate recognition properties of human ficolins: glycan array screening reveals the sialic acid binding specificity of M-ficolin.''; PubMed Europe PMC Scholia
  110. Honoré C, Rørvig S, Munthe-Fog L, Hummelshøj T, Madsen HO, Borregaard N, Garred P.; ''The innate pattern recognition molecule Ficolin-1 is secreted by monocytes/macrophages and is circulating in human plasma.''; PubMed Europe PMC Scholia
  111. Christmas SE, Christmas SE, de la Mata Espinosa CT, Halliday D, Buxton CA, Cummerson JA, Johnson PM.; ''Levels of expression of complement regulatory proteins CD46, CD55 and CD59 on resting and activated human peripheral blood leucocytes.''; PubMed Europe PMC Scholia
  112. Sim RB, Laich A.; ''Serine proteases of the complement system.''; PubMed Europe PMC Scholia
  113. Ames RS, Li Y, Sarau HM, Nuthulaganti P, Foley JJ, Ellis C, Zeng Z, Su K, Jurewicz AJ, Hertzberg RP, Bergsma DJ, Kumar C.; ''Molecular cloning and characterization of the human anaphylatoxin C3a receptor.''; PubMed Europe PMC Scholia
  114. Dodds AW, Ren XD, Willis AC, Law SK.; ''The reaction mechanism of the internal thioester in the human complement component C4.''; PubMed Europe PMC Scholia
  115. Arlaud GJ, Reboul A, Sim RB, Colomb MG.; ''Interaction of C1-inhibitor with the C1r and C1s subcomponents in human C1.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
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)
Activated C1R:SERPING1ComplexR-HSA-8959919 (Reactome)
Activated C1S:SERPING1ComplexR-HSA-8959917 (Reactome)
Activated thrombin, (ELANE)ComplexR-HSA-8852723 (Reactome)
Antigen R-ALL-173548 (Reactome)
Antigen:IgG:C1Q:2x

Activated C1R:2x

Activated C1S
ComplexR-HSA-173618 (Reactome)
Antigen:IgG:C1Q:2x Activated C1R:2xC1SComplexR-HSA-173619 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SComplexR-HSA-8959916 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1ComplexR-HSA-8959915 (Reactome) C1 is a calcium-dependent complex of C1q, R and S in the molar ratio of 1:2:2. C1q subcomponent is composed of nine subunits, six of which are disulfide-linked dimers of the A and B chains, and three of which are disulfide-linked dimers of the C chain.
Antigen:IgG:C1Q:2xC1R:2xC1SComplexR-HSA-173582 (Reactome)
Antigen:IgGComplexR-HSA-173552 (Reactome)
Bacterial mannose surface patternR-ALL-166718 (Reactome)
Bacterial mannose surface pattern R-ALL-166718 (Reactome)
C-reactive

protein

pentamer:phosphocholine:C1Q
ComplexR-HSA-976769 (Reactome)
C1QA ProteinP02745 (Uniprot-TrEMBL)
C1QB ProteinP02746 (Uniprot-TrEMBL)
C1QC ProteinP02747 (Uniprot-TrEMBL)
C1QComplexR-HSA-173579 (Reactome)
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 convertasesComplexR-HSA-173750 (Reactome)
C3(H2O):BbComplexR-HSA-182451 (Reactome)
C3(H2O):CFBComplexR-HSA-182529 (Reactome)
C3(H2O)ComplexR-HSA-182450 (Reactome)
C3AR1 ProteinQ16581 (Uniprot-TrEMBL)
C3AR1:C3aComplexR-HSA-444688 (Reactome)
C3AR1ProteinQ16581 (Uniprot-TrEMBL)
C3a ProteinP01024 (Uniprot-TrEMBL)
C3a, C5aComplexR-HSA-8852810 (Reactome)
C3a-desArg ProteinP01024 (Uniprot-TrEMBL)
C3a-desArg, C5a-desArgComplexR-HSA-8852831 (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)
C3d ProteinP01024 (Uniprot-TrEMBL)
C3d, C3dg, iC3bComplexR-HSA-8852897 (Reactome)
C3dg ProteinP01024 (Uniprot-TrEMBL)
C3dgProteinP01024 (Uniprot-TrEMBL)
C3f ProteinP01024 (Uniprot-TrEMBL)
C3fProteinP01024 (Uniprot-TrEMBL)
C4 activatorsComplexR-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 alpha3 ProteinP0C0L4 (Uniprot-TrEMBL)
C4A alpha4 fragment ProteinP0C0L4 (Uniprot-TrEMBL)
C4A(1454-1744) ProteinP0C0L4 (Uniprot-TrEMBL)
C4A(20-675) ProteinP0C0L4 (Uniprot-TrEMBL)
C4A(956-1336) ProteinP0C0L4 (Uniprot-TrEMBL)
C4A-derived C4a ProteinP0C0L4 (Uniprot-TrEMBL) C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
C4B alpha ProteinP0C0L5 (Uniprot-TrEMBL)
C4B alpha3 ProteinP0C0L5 (Uniprot-TrEMBL)
C4B alpha4 fragment ProteinP0C0L5 (Uniprot-TrEMBL)
C4B(1454-1744) ProteinP0C0L5 (Uniprot-TrEMBL)
C4B(20-675) ProteinP0C0L5 (Uniprot-TrEMBL)
C4B(956-1336) ProteinP0C0L5 (Uniprot-TrEMBL)
C4B-derived C4a ProteinP0C0L5 (Uniprot-TrEMBL)
C4BPA ProteinP04003 (Uniprot-TrEMBL)
C4BPB ProteinP20851 (Uniprot-TrEMBL)
C4aComplexR-HSA-981725 (Reactome)
C4b with hydrolysed thioesterComplexR-HSA-2855046 (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)
C4bComplexR-HSA-981700 (Reactome)
C4c R-HSA-981715 (Reactome)
C4c, C3fComplexR-HSA-977621 (Reactome)
C4cComplexR-HSA-981715 (Reactome)
C4d R-HSA-981702 (Reactome)
C4d, iC3bComplexR-HSA-977624 (Reactome)
C4dComplexR-HSA-981702 (Reactome)
C5 alpha chain ProteinP01031 (Uniprot-TrEMBL)
C5 beta chain ProteinP01031 (Uniprot-TrEMBL)
C5 convertasesComplexR-HSA-173759 (Reactome)
C5(965-1676) ProteinP01031 (Uniprot-TrEMBL)
C5AR1 ProteinP21730 (Uniprot-TrEMBL)
C5AR1:C5aComplexR-HSA-375354 (Reactome)
C5AR1ProteinP21730 (Uniprot-TrEMBL)
C5AR2 ProteinQ9P296 (Uniprot-TrEMBL)
C5AR2 ligandsComplexR-HSA-964782 (Reactome)
C5AR2:C5AR2 ligandsComplexR-HSA-964812 (Reactome)
C5AR2ProteinQ9P296 (Uniprot-TrEMBL)
C5ComplexR-HSA-173676 (Reactome)
C5a ProteinP01031 (Uniprot-TrEMBL)
C5a-desArg ProteinP01031 (Uniprot-TrEMBL)
C5aProteinP01031 (Uniprot-TrEMBL)
C5aTProteinP01031 (Uniprot-TrEMBL)
C5b alpha' ProteinP01031 (Uniprot-TrEMBL)
C5b:C6:C7, C8, C9ComplexR-HSA-8852568 (Reactome)
C5b:C6:C7:C8ComplexR-HSA-173722 (Reactome)
C5b:C6:C7ComplexR-HSA-173708 (Reactome)
C5b:C6:C7ComplexR-HSA-173719 (Reactome)
C5b:C6ComplexR-HSA-173711 (Reactome)
C5bComplexR-HSA-173671 (Reactome) Linked by disulphide bond between positions 559 and 816.
C5bTComplexR-HSA-8852717 (Reactome)
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)
CD19 ProteinP15391 (Uniprot-TrEMBL)
CD19:CD81ComplexR-HSA-8853249 (Reactome)
CD46 ProteinP15529 (Uniprot-TrEMBL)
CD46, CR1:C4b:C3b complexesComplexR-HSA-981661 (Reactome)
CD46, CR1ComplexR-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:Cell surface:C3bComplexR-HSA-981623 (Reactome)
CD46:Cell surface:C4bComplexR-HSA-981669 (Reactome)
CD46ProteinP15529 (Uniprot-TrEMBL)
CD55 ProteinP08174 (Uniprot-TrEMBL)
CD55:C3 convertase complexesComplexR-HSA-981657 (Reactome)
CD55:C3bComplexR-HSA-981684 (Reactome)
CD55:C4bComplexR-HSA-981639 (Reactome)
CD55ProteinP08174 (Uniprot-TrEMBL)
CD59 ProteinP13987 (Uniprot-TrEMBL)
CD59:C5b-C9ComplexR-HSA-2530426 (Reactome)
CD59ProteinP13987 (Uniprot-TrEMBL)
CD81 ProteinP60033 (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)
CFD ProteinP00746 (Uniprot-TrEMBL)
CFH ProteinP08603 (Uniprot-TrEMBL)
CFH, CFHR3ComplexR-HSA-2109537 (Reactome)
CFH:C3bComplexR-HSA-976755 (Reactome)
CFH:Host cell surfaceComplexR-HSA-1006173 (Reactome)
CFHProteinP08603 (Uniprot-TrEMBL)
CFHR dimersComplexR-HSA-8851439 (Reactome)
CFHR1 ProteinQ03591 (Uniprot-TrEMBL)
CFHR2 ProteinP36980 (Uniprot-TrEMBL)
CFHR3 ProteinQ02985 (Uniprot-TrEMBL)
CFHR4 ProteinQ92496 (Uniprot-TrEMBL)
CFHR5 ProteinQ9BXR6 (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:CD46, CR1:C4b, C3b complexesComplexR-HSA-977599 (Reactome)
CFI:CFH,FHR3:C3bComplexR-HSA-977365 (Reactome)
CFI:CFH,FHR3:iC3bComplexR-HSA-8852842 (Reactome)
CFI:CFH:C3bComplexR-HSA-976770 (Reactome)
CFIComplexR-HSA-976749 (Reactome)
CL-LK:MASP1

dimer:MASP2 dimer:Bacterial mannose surface

pattern:4xCa2+
ComplexR-HSA-8852493 (Reactome)
CL-LK:MASP1 dimer:MASP2 dimerComplexR-HSA-8852513 (Reactome)
CLU(228-449) ProteinP10909 (Uniprot-TrEMBL)
CLU(23-227) ProteinP10909 (Uniprot-TrEMBL)
CLU:C5b:C6:C7, C8, C9ComplexR-HSA-8852569 (Reactome)
CLUComplexR-HSA-6810665 (Reactome)
COLEC10 ProteinQ9Y6Z7 (Uniprot-TrEMBL)
COLEC11 ProteinQ9BWP8 (Uniprot-TrEMBL)
CPB2 ProteinQ96IY4 (Uniprot-TrEMBL)
CPN, CBP2ComplexR-HSA-8852827 (Reactome)
CPN1 ProteinP15169 (Uniprot-TrEMBL)
CPN2 ProteinP22792 (Uniprot-TrEMBL)
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)
CR2 ProteinP20023 (Uniprot-TrEMBL)
CR2:C3d,C3dg,iC3b:CD19:CD81ComplexR-HSA-8853254 (Reactome)
CR2:C3d,C3dg,iC3bComplexR-HSA-8853246 (Reactome)
CR2ProteinP20023 (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:C3b:CFHR

dimers
ComplexR-HSA-8851427 (Reactome)
Cell surface:FH,FHR3:C3bComplexR-HSA-977596 (Reactome)
Cell surface R-ALL-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 surface:CFH, CFHR3:C3bBbComplexR-HSA-977373 (Reactome)
Cell surfaceR-ALL-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 DComplexR-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)
ELANE ProteinP08246 (Uniprot-TrEMBL)
FCN1 ProteinO00602 (Uniprot-TrEMBL)
FCN1 dodecamer:MASP1 dimer:MASP2-1 dimerComplexR-HSA-2855100 (Reactome)
FCN1 ligands:FCN1

dodecamer:MASP1 dimer:MASP2-1

dimer:4xCa2+
ComplexR-HSA-2855134 (Reactome)
FCN1 ligandsComplexR-ALL-2855114 (Reactome)
FCN2 ProteinQ15485 (Uniprot-TrEMBL)
FCN2 dodecamer:MASP1 dimer:MASP2-1 dimerComplexR-HSA-2855087 (Reactome)
FCN2 ligands:FCN2

dodecamer:MASP1 dimer:MASP2-1

dimer:4xCa2+
ComplexR-HSA-2855065 (Reactome)
FCN2 ligandsComplexR-ALL-2855063 (Reactome)
FCN3 ProteinO75636 (Uniprot-TrEMBL)
FCN3 ligands:FCN3

multimer:MASP1 dimer:MASP2

dimer:4xCa2+
ComplexR-HSA-2855093 (Reactome)
FCN3 ligandsComplexR-ALL-2855098 (Reactome)
FCN3 oligomer:MASP1 dimer:MASP2-1 dimerComplexR-HSA-2855122 (Reactome)
GZMM ProteinP51124 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
Heparins MetaboliteCHEBI:24505 (ChEBI)
Host cell surfaceComplexR-ALL-1006146 (Reactome)
IGHG1 ProteinP01857 (Uniprot-TrEMBL)
IGHG2 ProteinP01859 (Uniprot-TrEMBL)
IGHG3 ProteinP01860 (Uniprot-TrEMBL)
IGHG4 ProteinP01861 (Uniprot-TrEMBL)
IGHV(1-?) ProteinA2KUC3 (Uniprot-TrEMBL)
IGHV1-2 ProteinP23083 (Uniprot-TrEMBL)
IGHV7-81(1-?) ProteinQ6PIL0 (Uniprot-TrEMBL)
IGKC ProteinP01834 (Uniprot-TrEMBL)
IGKV1-12 ProteinA0A0C4DH73 (Uniprot-TrEMBL)
IGKV1-5(23-?) ProteinP01602 (Uniprot-TrEMBL)
IGKV2-28 ProteinA0A075B6P5 (Uniprot-TrEMBL)
IGKV2D-30 ProteinA0A075B6S6 (Uniprot-TrEMBL)
IGKV3D-20 ProteinA0A0C4DH25 (Uniprot-TrEMBL)
IGKV4-1(21-?) ProteinP06312 (Uniprot-TrEMBL)
IGKVA18(21-?) ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1 ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2 ProteinP0DOY2 (Uniprot-TrEMBL)
IGLC3 ProteinP0DOY3 (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-II region ARH-77 ProteinP06331 (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 WAH ProteinP01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO ProteinP01766 (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 JON ProteinP01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL ProteinP01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO ProteinP01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA ProteinP01763 (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 DEE ProteinP01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi ProteinP04432 (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 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 RPMI 6410 ProteinP06310 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 ProteinP01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM ProteinP01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG ProteinP04433 (Uniprot-TrEMBL)
Ig lambda chain V region 4A ProteinP04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA ProteinP01700 (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 VOR ProteinP01699 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH ProteinP01706 (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 TOG ProteinP01704 (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-VI region AR ProteinP01721 (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)
MBL2 ProteinP11226 (Uniprot-TrEMBL)
MBL2 dodecamer:MASP1

dimer:MASP2-1 dimer:Bacterial mannose surface

pattern:4xCa2+
ComplexR-HSA-166719 (Reactome)
MBL2 dodecamer:MASP1 dimer:MASP2-1 dimerComplexR-HSA-166710 (Reactome)
MBL2,FCN:MASPs:carbohydrate patternsComplexR-HSA-3266540 (Reactome)
MBL2,FCN:activated

MASPs:carbohydrate

patterns
ComplexR-HSA-3266545 (Reactome)
MBL2,FCN:activated MASPs:carbohydrate patterns R-HSA-3266545 (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)
S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) ProteinP0C0L4 (Uniprot-TrEMBL) C4 alpha chain has a thioester bond between Cys 1010 and Gln 1013
S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) ProteinP0C0L5 (Uniprot-TrEMBL)
SERPING1 ProteinP05155 (Uniprot-TrEMBL)
SERPING1ProteinP05155 (Uniprot-TrEMBL)
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, ester crosslinked-C4B(757-1446) ProteinP0C0L5 (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)
thrombin heavy chain ProteinP00734 (Uniprot-TrEMBL)
thrombin light chain ProteinP00734 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
11xCbxE-PROS1R-HSA-981665 (Reactome)
Activated C1R:SERPING1ArrowR-HSA-8852481 (Reactome)
Activated C1S:SERPING1ArrowR-HSA-8852481 (Reactome)
Activated thrombin, (ELANE)mim-catalysisR-HSA-8852716 (Reactome)
Antigen:IgG:C1Q:2x

Activated C1R:2x

Activated C1S
ArrowR-HSA-173631 (Reactome)
Antigen:IgG:C1Q:2x

Activated C1R:2x

Activated C1S
R-HSA-8852266 (Reactome)
Antigen:IgG:C1Q:2x Activated C1R:2xC1SArrowR-HSA-173626 (Reactome)
Antigen:IgG:C1Q:2x Activated C1R:2xC1SR-HSA-173631 (Reactome)
Antigen:IgG:C1Q:2x Activated C1R:2xC1Smim-catalysisR-HSA-173631 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SArrowR-HSA-8852266 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SR-HSA-9021306 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1ArrowR-HSA-9021306 (Reactome)
Antigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1R-HSA-8852481 (Reactome)
Antigen:IgG:C1Q:2xC1R:2xC1SR-HSA-173626 (Reactome)
Antigen:IgG:C1Q:2xC1R:2xC1Smim-catalysisR-HSA-173626 (Reactome)
Antigen:IgGArrowR-HSA-8852481 (Reactome)
Bacterial mannose surface patternR-HSA-166721 (Reactome)
Bacterial mannose surface patternR-HSA-8852509 (Reactome)
C-reactive

protein

pentamer:phosphocholine:C1Q
ArrowR-HSA-173626 (Reactome)
C1QArrowR-HSA-8852481 (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)
C3AR1:C3aArrowR-HSA-444647 (Reactome)
C3AR1R-HSA-444647 (Reactome)
C3a, C5aR-HSA-8852809 (Reactome)
C3a-desArg, C5a-desArgArrowR-HSA-8852809 (Reactome)
C3aArrowR-HSA-166817 (Reactome)
C3aArrowR-HSA-174551 (Reactome)
C3aArrowR-HSA-183130 (Reactome)
C3aR-HSA-444647 (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)
C3d, C3dg, iC3bR-HSA-8852874 (Reactome)
C3dgArrowR-HSA-3266557 (Reactome)
C3fArrowR-HSA-976743 (Reactome)
C3fArrowR-HSA-977371 (Reactome)
C4 activatorsmim-catalysisR-HSA-166753 (Reactome)
C4 activatorsmim-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-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)
C4bArrowR-HSA-166753 (Reactome)
C4bC2a, C3bBbR-HSA-977375 (Reactome)
C4bC2a, C3bBbR-HSA-981535 (Reactome)
C4bR-HSA-2855047 (Reactome)
C4bR-HSA-977626 (Reactome)
C4bR-HSA-981713 (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)
C5AR1:C5aArrowR-HSA-375395 (Reactome)
C5AR1R-HSA-375395 (Reactome)
C5AR2 ligandsR-HSA-964811 (Reactome)
C5AR2:C5AR2 ligandsArrowR-HSA-964811 (Reactome)
C5AR2R-HSA-964811 (Reactome)
C5R-HSA-173680 (Reactome)
C5R-HSA-8852716 (Reactome)
C5aArrowR-HSA-173680 (Reactome)
C5aR-HSA-375395 (Reactome)
C5aTArrowR-HSA-8852716 (Reactome)
C5b:C6:C7, C8, C9R-HSA-8852580 (Reactome)
C5b:C6:C7:C8ArrowR-HSA-173723 (Reactome)
C5b:C6:C7:C8R-HSA-173725 (Reactome)
C5b:C6:C7:C8R-HSA-2530445 (Reactome)
C5b:C6:C7ArrowR-HSA-173709 (Reactome)
C5b:C6:C7ArrowR-HSA-173720 (Reactome)
C5b:C6:C7R-HSA-173720 (Reactome)
C5b:C6:C7R-HSA-173723 (Reactome)
C5b:C6:C7R-HSA-2530453 (Reactome)
C5b:C6ArrowR-HSA-173705 (Reactome)
C5b:C6R-HSA-173709 (Reactome)
C5bArrowR-HSA-173680 (Reactome)
C5bR-HSA-173705 (Reactome)
C5bTArrowR-HSA-8852716 (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)
CD19:CD81R-HSA-8853252 (Reactome)
CD46, CR1:C4b:C3b complexesR-HSA-977602 (Reactome)
CD46, CR1ArrowR-HSA-977615 (Reactome)
CD46:Cell surface:C3bArrowR-HSA-1006143 (Reactome)
CD46:Cell surface:C4bArrowR-HSA-8951486 (Reactome)
CD46R-HSA-1006143 (Reactome)
CD46R-HSA-8951486 (Reactome)
CD55:C3 convertase complexesArrowR-HSA-981535 (Reactome)
CD55:C3 convertase complexesR-HSA-977619 (Reactome)
CD55:C3bArrowR-HSA-977619 (Reactome)
CD55:C4bArrowR-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, CFHR3R-HSA-977363 (Reactome)
CFH, CFHR3R-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 dimersR-HSA-8851436 (Reactome)
CFHR-HSA-1006169 (Reactome)
CFHR-HSA-976768 (Reactome)
CFI(19-335)R-HSA-976801 (Reactome)
CFI(340-583)R-HSA-976801 (Reactome)
CFI:CD46, CR1:C4b, C3b complexesArrowR-HSA-977602 (Reactome)
CFI:CD46, CR1:C4b, C3b complexesR-HSA-977615 (Reactome)
CFI:CD46, CR1:C4b, C3b complexesmim-catalysisR-HSA-977615 (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,FHR3:iC3bArrowR-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-977615 (Reactome)
CFIArrowR-HSA-981637 (Reactome)
CFIR-HSA-976810 (Reactome)
CFIR-HSA-977359 (Reactome)
CFIR-HSA-977602 (Reactome)
CFIR-HSA-981658 (Reactome)
CFImim-catalysisR-HSA-3266557 (Reactome)
CL-LK:MASP1

dimer:MASP2 dimer:Bacterial mannose surface

pattern:4xCa2+
ArrowR-HSA-8852509 (Reactome)
CL-LK:MASP1 dimer:MASP2 dimerR-HSA-8852509 (Reactome)
CLU:C5b:C6:C7, C8, C9ArrowR-HSA-8852580 (Reactome)
CLU:C5b:C6:C7, C8, C9TBarR-HSA-173709 (Reactome)
CLU:C5b:C6:C7, C8, C9TBarR-HSA-173720 (Reactome)
CLU:C5b:C6:C7, C8, C9TBarR-HSA-173723 (Reactome)
CLU:C5b:C6:C7, C8, C9TBarR-HSA-173725 (Reactome)
CLUR-HSA-8852580 (Reactome)
CPN, CBP2mim-catalysisR-HSA-8852809 (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)
CR2:C3d,C3dg,iC3b:CD19:CD81ArrowR-HSA-8853252 (Reactome)
CR2:C3d,C3dg,iC3bArrowR-HSA-8852874 (Reactome)
CR2:C3d,C3dg,iC3bR-HSA-8853252 (Reactome)
CR2R-HSA-8852874 (Reactome)
Ca2+R-HSA-166721 (Reactome)
Ca2+R-HSA-2855054 (Reactome)
Ca2+R-HSA-2855077 (Reactome)
Ca2+R-HSA-2855125 (Reactome)
Ca2+R-HSA-8852509 (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:C3b:CFHR

dimers
ArrowR-HSA-8851436 (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-1006143 (Reactome)
Cell surface:C3bR-HSA-173636 (Reactome)
Cell surface:C3bR-HSA-183126 (Reactome)
Cell surface:C3bR-HSA-8851436 (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 surface:C4bR-HSA-8951486 (Reactome)
Cell surface:CFH, CFHR3:C3bBbArrowR-HSA-977363 (Reactome)
Cell surface:CFH, CFHR3:C3bBbR-HSA-977605 (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 Dmim-catalysisR-HSA-173745 (Reactome)
Complement factor Dmim-catalysisR-HSA-183122 (Reactome)
FCN1 dodecamer:MASP1 dimer:MASP2-1 dimerR-HSA-2855125 (Reactome)
FCN1 ligands:FCN1

dodecamer:MASP1 dimer:MASP2-1

dimer:4xCa2+
ArrowR-HSA-2855125 (Reactome)
FCN1 ligandsR-HSA-2855125 (Reactome)
FCN2 dodecamer:MASP1 dimer:MASP2-1 dimerR-HSA-2855054 (Reactome)
FCN2 ligands:FCN2

dodecamer:MASP1 dimer:MASP2-1

dimer:4xCa2+
ArrowR-HSA-2855054 (Reactome)
FCN2 ligandsR-HSA-2855054 (Reactome)
FCN3 ligands:FCN3

multimer:MASP1 dimer:MASP2

dimer:4xCa2+
ArrowR-HSA-2855077 (Reactome)
FCN3 ligandsR-HSA-2855077 (Reactome)
FCN3 oligomer:MASP1 dimer:MASP2-1 dimerR-HSA-2855077 (Reactome)
H2OR-HSA-173739 (Reactome)
H2OR-HSA-2855047 (Reactome)
Host cell surfaceR-HSA-1006169 (Reactome)
MBL2 dodecamer:MASP1

dimer:MASP2-1 dimer:Bacterial mannose surface

pattern:4xCa2+
ArrowR-HSA-166721 (Reactome)
MBL2 dodecamer:MASP1 dimer:MASP2-1 dimerR-HSA-166721 (Reactome)
MBL2,FCN:MASPs:carbohydrate patternsR-HSA-166726 (Reactome)
MBL2,FCN:activated

MASPs:carbohydrate

patterns
ArrowR-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 (CFH) 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 as complexes with MASP1/2. In the presence of Ca2+, 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. 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 repetitive carbohydrate motifs on a target cell 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) The C5b fragment binds C6.
R-HSA-173709 (Reactome) The C5b:C6 complex binds C7. Normally the C5b:C6 complex remains bound to the C3/C5 convertase until it binds a single C7 molecule.
R-HSA-173720 (Reactome) C7 recruitment of C7 results in a weak association of C5b:C6:C7 with the target cell membrane, through a poorly characterized molecular mechanism (Muller -Eberhard et al. 1986).

C5b and C6 remains loosely bound to C3b until C5b binds to C7 and induces it to undergo a hydrophilic-amphiphilic transition. Hydrophobic binding regions for phospholipid are thereby exposed, and the trimolecular complex is endowed with a metastable membrane binding site. Membranebound

C5b-7 inflicts no harm on a cell but marks it for further assault.
R-HSA-173723 (Reactome) Recruitment of the C8 trimeric complex is mediated by the C8 beta chain (Monahan & Sodetz 1981). Binding enables C8 to undergo necessary conformational rearrangements that allow the C8 alpha chain to penetrate into the hydrophobic core of the lipid bilayer (Stecket et al. 1983, Weiland et al. 2014), firmly anchoring the C5b:C6:C7:C8 complex to the target cell membrane. A functional membrane pore can be formed by the C5b:C6:C7:C8 complex (Boyle et al. 1976, Tegla et al. 2011). These pores are small and unstable but can cause cell lysis if present in sufficient number (Martin et al. 1987). They also increase cytosolic free Ca2+ concentration and thereby stimulate signalling pathways (Koski et al. 1983, Niculescu & Rus 2001).
R-HSA-173725 (Reactome) The membrane attack complex (MAC) is the cytolytic end product of the complement cascade, composed of one C5:C6:C7:C8 complex and 12 to 15 C9 molecules (Podack et al. 1982, Biesecker et al. 1993). 12 C9 molecules are represented in this reaction. C9 peptides polymerize to form a ring-shaped transmembrane channel, which causes osmotic lysis of the target cell (Kondos et al. 2010). While formation of a pore is typically associated with necrotic cell death, there is evidence of membrane permeabilization from MACs containing one C9 molecule per C5b–8 complex (Sims et al. 1983).
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, 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 et al. 2004, Aoyagi et al. 2008, Ma et al. 2004, Garlatti et al. 2007, Gout et al. 2010). Ficolin-2 also binds to apoptotic HL60, U937 and Jurkat cells (Kuraya et al. 2005).
R-HSA-2855077 (Reactome) Ficolin-3 (H-ficolin, FCN3, Hakata antigen) consists of a collagen-like strand and three C-terminal recognition domains, which bind to carbohydrates on the target surface. Circulating FCN3 is associated with mannan-binding lectin-associated serine proteases (MASP). Upon ligand binding the FCN3:MASP complex triggers activation of the lectin pathway (Matsushita et al. 2002, Teillet et al. 2008, Zacho et al. 2012). FCN3 can specifically recognize Aerococcus viridans (Tsujimura et al. 2002, Zacho et al. 2012) and binds patterns of bacterial polysaccharides such as d-fucose and galactose (Garlatti et al. 2007). In adition to pathogenic ligands, FCN3 was reported to bind apoptotic Jurkat cells (Kuraya et al. 2005).
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 (CFI) cleaves iC3b into two molecules, C3c, which is released into solution, and C3dg, which remains attached to the membrane. This cleavage requires Complement receptor type 1 (CR1), which serves a cofactor for CFI (Medof et al. 1982). iC3b and C3dg can bind CR2 (CD21) to enhance B-cell immunity (Tuveson et al.1991, Sarrias et al. 2001).
R-HSA-375395 (Reactome) C5a (Fernandez HN and Hugli TE, 1978) is a protein fragment released from complement component C5. C5a is a potent anaphylatoxin, causing the release of histamine from mast cells and also being an effective leukocyte attractant. The C5a receptor (complement component 5a receptor 1, C5AR1; Cluster of Differentiation 88, CD88) (Gerard NP and Gerard C, 1991) mediates the pro-inflammatory and chemotactic actions of C5a.
R-HSA-444647 (Reactome) The complement component 3a receptor (C3AR) binds C3a, a 77-amino acid anaphylatoxin generated after proteolytic cleavage of C3 and C5 in response to complement activation. C3a is involved in a variety of inflammatory responses including chemotaxis and activation of granulocytes, mast cells and macrophages (Peng et al. 200, Klos et al. 2009).
R-HSA-8851436 (Reactome) CFHR dimers bind C3b, acting as competitive antagonists of Factor H (CFH) binding (de Jorge et al. 2013, Tortajada et al. 2013). CFHR1, CFHR2, and CFHR5 have a dimerization motif within their amino-terminal domains that enables formation of three homodimers (CFHR1:CFHR1, CFHR2:CFHR2, CFHR5:CFHR5) and three heterodimers (CFHR1:CFHR2, CFHR1:CFHR5, and CFHR2:CFHR5). Multiple binding interactions and avidity enable these dimers to out-compete CFH at physiologically relevant concentrations. CFHR2 homodimers bind C3b while allowing C3 convertase formation, but the CFHR2 bound convertases does not cleave C3 (Eberhardt et al. 2013).

CFHR3 and CFHR4 do not contain the dimerization motif seen in CFHR1, 2 and 5 but compete with factor H for binding to C3b (Hellwage et al. 1999, Fritsche et al. 2010). CFHR4 exists predominantly as a dimer in plasma (Hellwage et al. 1999).

As the main function of CFH is down-regulation of C3 activation through the alternative pathway amplification loop, CFHR dimers interfere with the C3b inhibitory actions of CFH, a process termed deregulation (de Jorge et al. 2013, Tortajada et al. 2013).
R-HSA-8852266 (Reactome) The plasma protease C1 inhibitor (C1Inh, SERPING1) can bind the activated C1r and C1s proteases in the activated C1 complex, rendering them proteolytically inactive (Sim et al. 1979a) and leading to the disassembly of the C1 complex, releasing inactive C1r:C1Inh and C1s:C1Inh complexes (Arlaud et al. 1979, Sim et al. 1979b, Ziccardi & Cooper 1979). C1Inh also inhibits and controls certain non-antibody-induced as well as spontaneous C1 activation. Thus C1Inh plays an important role in regulating nonspecific complement activation (Ziccardi et al. 1983). C1Inh is also a major physiological inhibitor of kallikrein (Ratnoff et al. 1969), coagulation factors XIa and XIIa (Forbes et al. 1970), and the enzymatically active fragments derived from factor XIIa (factor XIIf) (Schreiber et al. 1973).
R-HSA-8852481 (Reactome) Binding of the plasma protease C1 inhibitor (C1Inh, SERPING1) to the C1s and C1r subunits of the C1 complex leads to C1 disassembly, releasing inactive C1r:C1Inh and C1s:C1Inh complexes (Arlaud et al. 1979, Sim et al. 1979, Ziccardi & Cooper 1979). Thus C1Inh plays an important role in regulating nonspecific complement activation (Ziccardi et al. 1983).
R-HSA-8852509 (Reactome) Collectin kidney 1 (CL-K1, CL-11, COLEC11) (Keshi et al. 2006) forms disulfide-bridged stable heteromers with collectin liver 1 (CL-L1, COLEC10) (Otahani et al. 1999), with a ratio of one COLEC10 to two COLEC11 polypeptide chains. The majority of plasma COLEC11 was found in complex with COLEC10 (Henriksen et al. 2013). The resulting COLEC10:2xCOLEC11 heterocomplex, termred CL-LK, contains multiple Ca2+ -dependent carbohydrate-recognition domains (CRDs) and collagen-like regions, which allow high-avidity binding (KD ~10-9 M) to target cell surface carbohydrate patterns (Bajic et al. 2015); COLEC11 recognizes L-fucose and D-mannose and the disaccharide D-mannose(alpha1-2)-D-mannose (Keshi et al. 2006, Hansen et al. 2010, Selman & Hansen 2012, ). CL-LK can bind mannose-rich patterns on M. tuberculosis (Troegeler et al. 2015). The CL-LK complex was able to bind mannan-binding lectin-associated serine proteases (MASPs) in vitro with affinities in the nM range, and was associated with MASP1/3 and MASP2 in plasma. Upon binding to mannan or DNA in the presence of MASP2, the COLEC10:COLEC11 complex mediated deposition of C4b (Henriksen et al. 2013). Polymorphisms in the COLEC11 gene cause 3MC syndrome (Rooryck et al. 2011).
R-HSA-8852580 (Reactome) Clusterin is a dimer of two fragments of the same translation product, which are disulfide bonded by five cysteines on each peptide (Tobe et al. 1991). It is able to modulate the terminal complement cascade in vitro and prevent cellular lysis by the membrane attack complex (MAC), C5b-9. Clusterin forms complexes with C5b:C6:C7, or C5b:C6:C7:C8 or C5b:C6:C7:C8:C9, as the proteins assemble into the amphiphilic MAC. Clusterin binding renders the complexes soluble and lytically inactive (Jenne & Tschopp 1989, Choi et al. 1989, Murphy et al. 1989, Tschopp et al. 1993).
R-HSA-8852716 (Reactome) Thrombin, coagulation factors XIa, Xa, IXa and plasmin (Amara et al. 2010) can cleave C3 and C5 to generate C3a and C5a. Neutrophil elastase (ELANE) can cleave C5 generating an active C5a-like fragment (Vogt 2000).

Under normal conditions, thrombin cleavage of C5 may not be a physiologically significant reaction (Bagic et al. 2015) but the combined action of thrombin and convertases appears to enhance the efficiency of the lytic pathway (Krisinger et al. 2012). Clotting-induced production of thrombin leads to cleavage of C5 at the atypical site R947 in the CUB domain. C5a can be released from the atypical C5a fragment (termed C5aT) by conventional C5 convertases; the truncated C5b fragment, termed C5bT, can form a C5bT-9 membrane attack complex that has significantly increased lytic activity (Krisinger et al. 2012).
R-HSA-8852809 (Reactome) Carboxypeptidase N (CPN) is able to inactivate the complement anaphylatoxins C3a, C4a, and C5a (Bokisch & Müller-Eberhard 1970), 74-77 amino acid peptides that are released during complement activation. They mediate smooth muscle contraction, vasodilation, release of histamine from mast cells, and chemotaxis of selective bone marrow derived myeloid cells. C3a and C5a mediate their activities by binding the C3a receptor (C3AR1) and C5a receptor (C5AR1), respectively. CPN regulates these anaphylatoxins by removing their carboxy-terminal arginines, which reduces their biological activities 10-100-fold (Ember et al. 1998).
Carboxypeptidase B2 (Plasma carboxypeptidase B, Thrombin-activable fibrinolysis inhibitor, TAF1, CPB2) also can convert C3a and C5a to C3a-desArg and C5a-desArg (Campbell et al. 2002). C3a-desArg cannot bind C3AR1, and C5a-desArg has a 90% decrease in pro-inflammatory activity compared to C5a (Sayah et al. 2003).

CPN is a tetramer comprised of two heterodimers each consisting of a CPN1 and CPN2 subunit (Levin et al. 1982, Keil et al. 2007). The catalytic CPN1 subunit ranges in size from 48 kDa to 55 kDa. This reflects processing by trypsin or plasmin, which can remove a C-terminal segment to produce the 48 kDa form, and cleave at Arg218-Arg219 to produce two peptide chains held together in an active conformation by non-covalent bonds (Levin et al. 1982, Quagraine et al. 2005). This step increases the catalytic activity of CPN towards chromogenic substrates.
R-HSA-8852874 (Reactome) Complement receptor CR2 (CD21) is predominantly expressed on the surface of B-cells and follicular dendritic cells (FDCs). It binds the C3 fragments C3dg, C3d, and with lower affinity, inactive C3b (iC3b) on the antigen surface, where it forms the B cell co-receptor complex with CD19 and CD81 (Matsumoto et al. 1993). Co-ligation of receptors due to C3dg opsonisation lowers the threshold for B cell activation by 1000 to 10,000 times (Dempsey et al. 1996, Mongini et al. 1997); the C3d:CR2 complex induces an increase of B cell receptor (BCR) signaling in the presence of C3d-opsonized antigen on the B cell surface (Cherukuri et al. 2001). C3 is required for the induction and maintenance of B-cell lineage memory cells in germinal centers (GCs), where B cells encounter antigen-antibody-C3 fragment complexes on the surface of FDCs (Klaus & Humphrey 1986). C3d-opsonized antigen binds to CR2 on FDCs, which can present the antigen and induce effector and memory B cells (Fang et al. 1998).


Complement fragments, iC3b and C3dg, are produced in vivo due to the actions of the complement serine protease, factor I. This enzyme cleaves C3b in the presence of cofactors (factor H, MCP/CD46, complement receptor 1/CR1/CD35) to generate iC3b. CR1 acts as a cofactor for further factor I-mediated cleavage to C3dg.
R-HSA-8853252 (Reactome) Complement receptor CR2 (CD21), having bound to C3d, Cdg or 1C3b, forms the B cell co-receptor complex with CD19 and CD81 (Matsumoto et al. 1993).
R-HSA-8951486 (Reactome) Membrane cofactor protein (MCP; CD46) is a widely distributed cell surface glycoprotein that can bind C3b and C4b, which are cofactors for Complement factor I.
R-HSA-9021306 (Reactome) The plasma protease C1 inhibitor (C1Inh, SERPING1) forms proteolytically inactive stoichiometric covalent complexes with the C1r and C1s proteases (Sim et al. 1979a). This effectively disassembles the C1 complex, releasing inactive C1r:C1Inh and C1s:C1Inh complexes (Arlaud et al. 1979, Sim et al. 1979b, Ziccardi & Cooper 1979). C1Inh also inhibits and controls certain non-antibody-induced as well as spontaneous C1 activation. Thus C1Inh plays an important role in regulating nonspecific complement activation (Ziccardi et al. 1983). C1Inh is also a major physiological inhibitor of kallikrein (Ratnoff et al. 1969), coagulation factors XIa and XIIa (Forbes et al. 1970), and the enzymatically active fragments derived from factor XIIa (factor XIIf) (Schreiber et al. 1973).
R-HSA-964811 (Reactome) C5AR2 (GPR77, C5L2) has been described as a receptor for the chemotactic and inflammatory peptides anaphylatoxin C5a, C4a and C3a and even their des-arginated derivatives. Highest binding affinity was for C3a-desArg, also called Acylation Stimulating Protein (ASP), produced from C3a following arginine removal by carboxypeptidases. Binding of C3a and its derivatives has been disputed (Johswich et al. 2006) leading to suggestions that this receptor may be a C5a scavenger. It is weakly coupled to G(i)-mediated signaling pathways and believed to function primarily as a decoy receptor though it can interact with beta arrestin (Van Lith et al. 2009).
R-HSA-976743 (Reactome) Complement factor I (CFI) 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 (CFH) 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 (CFI) binds the factor H:C3b (CFH:C3b) complex.
R-HSA-977359 (Reactome) Complement factor I (CFI) binds to the membrane-associated Factor H:C3b complex.
R-HSA-977363 (Reactome) Factor H (CFH) binds to C3bBb, leading to displacement of Bb. Complement factor H-related protein 3 (FHR3) has also been reported to bind C3Bb leading to inhibition of C3Bb C3 convertase activity (Fritsche et al. 2010). CFH 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 (CFI) 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, CD46) and Complement Receptor 1 (CR1) act as cofactors for the protease activity of complement factor I (CFI) which binds MCP or CR1 complexes with C3b or C4b, inactivating C3b/C4b.
R-HSA-977605 (Reactome) Factor H (CFH) greatly accelerates the displacement (decay) of Complement factor Bb from C3b.
R-HSA-977615 (Reactome) Factor I (CFI) 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 (CFI), 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 (CFH) regulates the alternative pathway C3 convertase C3bBb and its C3b component both in plasma and at host cell surfaces. CFH 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.
SERPING1R-HSA-8852266 (Reactome)
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)
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