Complement cascade (Homo sapiens)

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4, 9, 20, 72, 7571735834, 5874, 90, 912020766170468, 931, 19, 37, 52, 79...33, 1038, 931820, 5432042, 56, 82212795358310162, 73, 74, 81566, 773520, 545110910243, 57, 5924, 30, 9538, 4110, 3522, 5325, 49, 64, 88, 9851, 765010, 352011510145, 60, 77146226, 34, 582, 7, 16, 23, 31...5412, 32, 549110, 1343, 57, 5911, 84, 891, 52, 55, 85-87, 11115, 1121101417, 47, 48, 91206930, 36, 65519214, 2967, 7796cytosolcytosolInnocent bystander cellTarget CellMASP2-1 C5a C4A(1454-1744) ActivatedC1S:SERPING1C8A IGKV3D-20 S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) C5AR2 ligandsCR1:C3bBb, C4bC2acomplexesC9(22-559)dNQ-C4A(757-1446) C3dg C3c alpha' chain fragment 2 Cell surface IGHG1 Ig kappa chain V-I region DEE Ig kappa chain V-I region Wes IGLV3-25(1-?) Ig heavy chain V-III region WEA dNQ-C4B(757-1446) C7 C4B(20-675) Cell surface C4A(20-675) IGLV7-43(1-?) IGLC6 C1R C-terminal fragment Bacterial mannose surface pattern C3c alpha' chain fragment 2 IGLV7-43(1-?) MBL2 Ig lambda chain V-IV region Kern Lipoteichoic acid IGLV7-46(1-?) MASP1(20-699) IGHV7-81(1-?) IGLV3-25(1-?) IGLV3-16(1-?) FCN2 ligands:FCN2dodecamer:MASP1dimer:MASP2-1dimer:4xCa2+IGLV3-22(1-?) S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) C3 beta chain Ig lambda chain V-II region BOH Sialic acid Ig kappa chain V-I region Gal Sialic acid C3b alpha' VTNMASP2-1 IGKV1-5(23-?) IGKV3D-20 dNQ-C4B(757-1446) MASP1(20-699) IGLV1-36(1-?) Ig lambda chain V-VI region AR C7 IGLV4-60(1-?) IGHV7-81(1-?) C3d Ig kappa chain V-I region AG MASP2-1(16-444) Sialic acid FCN3 dNQ-C4B(757-1446) IGLV3-25(1-?) CFHR2 Ig kappa chain V-I region Gal Ig kappa chain V-I region HK101 Cell surface IGLV8-61(1-?) CD55 Ig heavy chain V-II region WAH IGKV1-12 Ig heavy chain V-III region BUT Ig heavy chain V-III region BUT IGKV3D-20 CD55:C3bIGLV3-12(1-?) C3d, C3dg, iC3bIGHG3 C3 beta chain IGLV(23-?) CLU(228-449) Ig lambda chain V-IV region Kern IGLC6 CFH IGLV2-18(1-?) IGLV3-27(1-?) Ig lambda chain V-II region BOH Ig heavy chain V-I region EU IGLV1-40(1-?) Ig kappa chain V-I region Gal Antigen C5 beta chain dNQ-C4A(757-1446) IGKV1-12 IGKV1-12 C8G IGHV(1-?) IGKC C3a C2Cell surface C4b-bindingprotein:Factor IIg kappa chain V region EV15 Bacterial mannose surface pattern IGLV4-69(1-?) C5b alpha' MASP1(20-699) C4B(20-675) C5a-desArg CR1 C3(H2O):BbC4B(20-675) IGLV3-27(1-?) C3b alpha' D-fucose CLU(23-227) Ca2+ dNQ-C4A(757-1446) CR1:iC3bIGLV2-11(1-?) C9(22-559) C4A(1454-1744) C3b alpha' Cell surface C3a C4BPA Ca2+C3c alpha' chain fragment 1 precursor IGLV3-12(1-?) Ig lambda chain V-IV region Hil C3 convertasesSERPING1C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)Ig heavy chain V-II region WAH IGLV2-33(1-?) CFH Ig lambda chain V region 4A IGLV(23-?) Ig lambda chain V-I region HA Lipoteichoic acid C7CD19 C4B(20-675) C1R C-terminal fragment IGLV2-18(1-?) C3 beta chain Cell surface:C3bIGLC2 dNQ-C4A(757-1446) C3 beta chain Ig kappa chain V-III region B6 CD46, CR1Ig kappa chain V region EV15 C7 CFI(19-335) dNQ-C3(672-1663) Cell surface Ig lambda chain V-I region NEWM CFHR3 C3dg C4A(20-675) IGLV4-69(1-?) CFH, CFHR3CFB(260-764) C4aIGLV1-44(1-?) IGLV3-16(1-?) C1R C-terminal fragment C3c alpha' chain fragment 1 dNQ-C4B(757-1446) Ca2+ C5b alpha' S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) C1QC Ig heavy chain V-III region WEA C4A(1454-1744) Ig kappa chain V-I region BAN C1QA C3a C3c alpha' chain fragment 1 precursor Ig heavy chain V-II region MCE Ig heavy chain V-II region WAH C3b alpha' C6 C4B(20-675) C7 Ig heavy chain V-III region CAM Antigen IGKV3D-20 CD46 C1R C-terminal fragment IGLV4-3(1-?) C2aIGHV7-81(1-?) Ig heavy chain V-III region DOB FCN2 Ca2+ FCN1 IGHG3 CPN2 Ig kappa chain V-I region Daudi IGKV1-5(23-?) IGHG1 IGLV5-45(1-?) IGLV3-27(1-?) Ig kappa chain V-I region DEE IGKV4-1(21-?) IGLV1-40(1-?) C3b alpha' IGKV4-1(21-?) Ig kappa chain V-I region Gal IGHG2 Ig kappa chain V-III region VG CD19:CD81VTN:C5b:C6:C7:C8:C9C4B(1454-1744) C4d C5b alpha' C3b alpha' IGLV5-45(1-?) C3b alpha' IGKV1-5(23-?) C8B IGLV1-36(1-?) IGLV4-60(1-?) IGLC7 IGKV2D-30 dNQ-C4A(757-1446) Ig kappa chain V-I region HK101 IGLV1-36(1-?) Ig kappa chain V-III region POM IGKV1-5(23-?) IGKV1-12 IGLV2-23(1-?) C4A(1454-1744) C5 beta chain Ig heavy chain V-II region MCE C3 beta chain C4B(1454-1744) MASP1(20-699) IGLV8-61(1-?) IGLV11-55(1-?) C3b alpha' Ig lambda chain V-III region LOI C1S N-terminal fragment C2a Ig lambda chain V region 4A IGKC COLEC11 Antigen:IgGC1S N-terminal fragment CFH CFB(26-764)CFHIGKVA18(21-?) IGLV4-60(1-?) Ig lambda chain V-I region NEWM IGKV4-1(21-?) Bacterial mannose surface pattern C8A C3b:Bb:C3b:ProperdinC1QB Heparins Ig kappa chain V-III region POM Ig heavy chain V-III region WEA Ca2+ IGLV11-55(1-?) Ig kappa chain V-I region HK101 C4A(20-675) Ig heavy chain V-III region BUT IGKVA18(21-?) C4B(1454-1744) C4B(1454-1744) COLEC11 Ig lambda chain V region 4A C1R C-terminal fragment IGKV2D-30 IgH heavy chain V-III region VH26 precursor IGHG3 Ig lambda chain V-VI region AR IGKV1-12 Ig kappa chain V-I region AG Ig heavy chain V-II region NEWM C4A alpha3 Ig lambda chain V-I region NEWM Cell surface IGLV3-16(1-?) IGLV1-36(1-?) CFI(19-335) C3b alpha' Ig lambda chain V-VI region AR C5Cell surface Cell surface IGLV11-55(1-?) IGKV2-28 Cell surface C3 alpha chain C3b alpha' Ig lambda chain V-I region HA Ig lambda chain V-III region SH C5a IGLV1-36(1-?) C4B(1454-1744) C3 beta chain C5bTC1QA MBL2,FCN:MASPs:carbohydrate patternsC4BPB C5 convertasesdNQ-C4B(757-1446) C5 beta chain Ig kappa chain V-I region AU CFB(260-764) Ig lambda chain V-I region NEW CR1 IGLV3-22(1-?) CFB(260-764) Ig heavy chain V-I region EU Ig lambda chain V-II region BOH C6 N-acetylgalactosamine Ig heavy chain V-III region JON Ig kappa chain V-III region B6 IGLV3-12(1-?) Ig heavy chain V-I region HG3 C3c alpha' chain fragment 2 Ig lambda chain V-II region BOH Ig lambda chain V-IV region Kern Cell surface Ig heavy chain V-III region TRO FCN1 Ig heavy chain V-III region WEA Ig heavy chain V-II region OU C5aIg kappa chain V-I region AU Ig heavy chain V-III region JON Ig kappa chain V-I region DEE IGLV4-3(1-?) C3a, C5aCFI(340-583) Ig lambda chain V-VI region AR Cell surface C4B(20-675) IGHV7-81(1-?) C1QC C4A(1454-1744) C1S N-terminal fragment dNQ-C3(672-1663) MASP2-1 C1QA CFB(260-764) C5a Cell surface:C4bC4A alpha4 fragment IGHG4 C9(22-559) C3b alpha' FCN3 ligandsIg kappa chain V-II region Cum C5b alpha' Cell surface FCN1 ligands:FCN1dodecamer:MASP1dimer:MASP2-1dimer:4xCa2+Ig heavy chain V-II region ARH-77 C3bdNQ-C4A(757-1446) C3 beta chain Ig heavy chain V-I region HG3 CD46, CR1:C4b:C3bcomplexesIg lambda chain V-I region VOR C4B(1454-1744) Complement factor 3C3 beta chain COLEC10 C1QC Ig heavy chain V-II region OU dNQ-C3(672-1663) FCN2 ligandsC8B dNQ-C4B(757-1446) C5b:C6:C7IGLV7-43(1-?) IGHG4 MASP2-1 IgH heavy chain V-III region VH26 precursor CFB(260-764) IGKV4-1(21-?) D-fucose Ig lambda chain V-IV region Hil dNQ-C4A(757-1446) Cell surface:C3b:BbIg heavy chain V-II region OU C3 beta chain Ig kappa chain V-II region RPMI 6410 C5 alpha chain C4B(20-675) C4B alpha4 fragment CD55 IGKV2-28 Ig kappa chain V-I region Daudi IGLV4-69(1-?) dNQ-C4B(757-1446) Ig kappa chain V-I region AU Ig heavy chain V-I region EU IGLV7-46(1-?) Properdin oligomerC4A(20-675) C3 beta chain Ig lambda chain V-IV region Bau Ig lambda chain V-IV region Kern IGLV5-45(1-?) IGLV1-40(1-?) CFH IGLC3 Ig kappa chain V-I region AG C1S C-terminal fragment C4A(20-675) Ig kappa chain V-III region POM dNQ-C4B(757-1446) Ig heavy chain V-I region EU Ig heavy chain V-III region BUT Ig kappa chain V-I region AU IGLV(23-?) ActivatedC1R:SERPING1C4BPA C4A-derived C4a C4A(20-675) C2a Antigen CFB(260-764) Ig lambda chain V-VI region AR Ig kappa chain V-II region FR IGHV(1-?) IGKV1-5(23-?) C1QC Ig lambda chain V-I region NEW C3 beta chain MBL2 Ig lambda chain V-II region TOG CFD CFI(19-335) Ca2+Ig heavy chain V-III region BRO Ca2+C1S(16-688) C4A(20-675) C4BPB C5 beta chain C5(965-1676) Ig heavy chain V-I region HG3 C3a-desArg Ig heavy chain V-III region JON IGLV5-37(1-?) Ig heavy chain V-III region BRO Cellsurface:C3b:CFHRdimersMASP1(20-699) FCN2 IgH heavy chain V-III region VH26 precursor N-acetyl-D-glucosamine S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) C3 beta chain dNQ-C4B(757-1446) C2aCFHR4 C3d CFB(26-764) Ig heavy chain V-III region BRO CFB(260-764) IGLC6 CFHR5 Ig kappa chain V-I region AG C1S N-terminal fragment IGLV8-61(1-?) Ig heavy chain V-III region CAM CFI:CFH,FHR3:iC3bC5 beta chain Ig kappa chain V-I region Wes IGKV2D-30 IGLV4-60(1-?) N-acetyl-D-glucosamine C5AR2C4B(1454-1744) Ig kappa chain V-I region Wes IGLC3 Ig heavy chain V-II region MCE Ig kappa chain V-II region FR Ig lambda chain V-II region MGC C8A C4B(20-675) IGLV7-43(1-?) Ig heavy chain V-I region HG3 C1S N-terminal fragment IGLV5-45(1-?) Ig lambda chain V-I region VOR COLEC11 Ig heavy chain V-III region CAM IGLV1-40(1-?) IGKV4-1(21-?) IGLV1-36(1-?) C4B(1454-1744) MASP1(20-699) Ig kappa chain V-II region Cum Ig kappa chain V-I region HK101 CD55C1QC dNQ-C4A(757-1446) IGLV7-46(1-?) C3c alpha' chain fragment 1 precursor C3 beta chain IGLC1 Ig heavy chain V-III region KOL Cell surface CD46 CFB(26-764) C1S C-terminal fragment IGLV3-16(1-?) CFB(260-764) C3c alpha' chain fragment 2 CFI(340-583) CFI:CFH:C3bC4B(20-675) Ig kappa chain V-I region AU C4b-binding proteinIGLV2-18(1-?) C2a Ig heavy chain V-III region TRO C1QB CFB(260-764) Ig lambda chain V-I region NEW C4B(1454-1744) Ig lambda chain V-II region MGC Ig lambda chain V-II region MGC CFHR3 IGHG2 CD81 IGLV2-18(1-?) dNQ-C4A(757-1446) CD46:Cellsurface:C4bdNQ-C4B(757-1446) CFHR4 IGKC Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SHost cell surfaceFCN2 Ig lambda chain V-IV region Hil dNQ-C4A(757-1446) IGLC2 Ig lambda chain V-I region NEWM IGKV2D-30 iC3bIGLV4-3(1-?) C4A(20-675) Ig heavy chain V-III region KOL C3b alpha' IGLV3-27(1-?) H2OC2bCR2C5 beta chain IGLV10-54(1-?) IGLV1-44(1-?) C3cC1QB C6 C6 dNQ-C4B(757-1446) IGHG3 CLU(228-449) C5 beta chain C3b alpha' C3 beta chain dNQ-C4A(757-1446) MASP1(20-448) IGHV(1-?) C4B(1454-1744) C3 beta chain C4A(20-675) N-acetyl-D-glucosamine C3 beta chain IGHV(1-?) C3dg C1QC IGLC2 Ig lambda chain V-I region NEW 1,3-beta-D-glucan C4A(1454-1744) Ig heavy chain V-III region BUT C5b alpha' Ig lambda chain V region 4A MBL2,FCN:activated MASPs:carbohydrate patterns VTN N-acetylgalactosamine C4A(1454-1744) Ig lambda chain V-III region LOI Cell surface C4A(20-675) Ig lambda chain V-VI region AR IGLV4-69(1-?) IGKV4-1(21-?) IGLV2-33(1-?) Cell surface:C4b:C2aCFI(340-583) Ig heavy chain V-II region NEWM C5b:C6Ig heavy chain V-III region BRO Ig lambda chain V-I region VOR Ig heavy chain V-II region OU FCN2 C8B MASP2-1 Ig kappa chain V-I region HK101 1,3-beta-D-glucan CR1 C4A(1454-1744) Ig heavy chain V-III region KOL Ig lambda chain V-II region NEI Cell surface CL-LK:MASP1dimer:MASP2dimer:Bacterialmannose surfacepattern:4xCa2+C3bIg kappa chain V-III region B6 C2a IGHG2 MASP1(20-699) Ig lambda chain V-I region VOR Ig heavy chain V-II region ARH-77 dNQ-C4A(757-1446) C3 beta chain MASP2-1 CFI:CD46, CR1:C4b,C3b complexesC3b alpha' IGHG3 Ig lambda chain V-II region BOH Ig kappa chain V-III region B6 Ig heavy chain V-II region MCE C4A(1454-1744) Cell surface IGLV10-54(1-?) Ig kappa chain V-III region VG Ig lambda chain V-II region MGC COLEC10 CLU(23-227) FCN3 ligands:FCN3multimer:MASP1dimer:MASP2dimer:4xCa2+Ig kappa chain V-I region Daudi Properdin oligomer Cell surface:C4bIg lambda chain V-IV region Bau IGHG2 IGHV7-81(1-?) C8A C3b alpha' Ig heavy chain V-II region ARH-77 IGLV2-23(1-?) IGLV2-11(1-?) C4B(1454-1744) Ig kappa chain V region EV15 Ig lambda chain V-II region NEI Ig kappa chain V-I region AU C3aC8G C4B(1454-1744) Ig heavy chain V-II region OU C4B alpha3 C3 beta chain Ig heavy chain V-III region TRO IGLV5-37(1-?) IgH heavy chain V-III region VH26 precursor C8A IGKC Ig lambda chain V-IV region Hil Cell surface C1R N-terminal fragment IGLV2-11(1-?) C4B(20-675) Ig lambda chain V-IV region Kern C3 beta chain IGKV1-5(23-?) C4B(20-675) C3a-desArg IGHG2 11xCbxE-PROS1Ig lambda chain V-III region SH C5 beta chain Ig lambda chain V-II region BOH Ig kappa chain V-I region BAN C1S(16-688) CFHR3 C3b alpha' IGLV7-43(1-?) C4B(1454-1744) SERPING1 C3 beta chain C1QA IGLV2-33(1-?) Cell surface:C3bCFHR5 Ig lambda chain V-IV region Hil IGLV3-12(1-?) C4B(20-675) Ig kappa chain V-I region DEE Ig kappa chain V-II region RPMI 6410 Antigen:IgG:C1Q:2xActivated C1R:2xC1SCell surface CFHR3 C3AR1:C3aIg heavy chain V-III region DOB C5b alpha' C3b alpha' C4B(1454-1744) COLEC10 Ig kappa chain V-I region Daudi Bacterial mannosesurface patternMASP2-1(445-686) C4A(1454-1744) Ig lambda chain V-III region SH dNQ-C4A(757-1446) ELANE CR2 C4bC2a, C3bBbC5AR1Ig kappa chain V-I region BAN C5bC3c alpha' chain fragment 1 precursor Ig kappa chain V-I region Wes IGLV(23-?) MASP2-1 C4-bindingprotein:C4bC4B(20-675) C1QC C5 beta chain Ig heavy chain V-III region BUT CR2:C3d,C3dg,iC3b:CD19:CD81dNQ-C4B(757-1446) C5b:C6:C7:C8IGLV(23-?) Ig heavy chain V-III region KOL Ig heavy chain V-II region NEWM C8B C3 beta chain IGHG4 N-acetyl-D-glucosamine Ig lambda chain V-IV region Bau C4A(20-675) CFH:C3bC5 beta chain C8G IGLV2-33(1-?) Ig lambda chain V-II region NEI IGLV3-12(1-?) Ig heavy chain V-III region CAM C4A(956-1336) MASP1(20-699) IGLV2-11(1-?) IGLV2-33(1-?) Ig heavy chain V-I region EU C5b:C6:C7, C8, C9Properdin oligomer CR2 Ig heavy chain V-III region CAM Cell surface IGHV(1-?) Ig kappa chain V-I region Wes IGKV1-5(23-?) Ig lambda chain V-III region LOI MASP2-1 Bacterial mannose surface pattern IGLV2-18(1-?) CPB2 Ig lambda chain V-IV region Bau Ig lambda chain V-I region VOR Ig kappa chain V-III region B6 MASP1(20-699) IGLC6 Ig lambda chain V-II region NEI IGLC3 dNQ-C3(672-1663) Ig lambda chain V-I region NEW C8IGLV8-61(1-?) C5AR2:C5AR2 ligandsIGHG4 CLUC4B(20-675) Cell surface:C4bCFB(260-764) C3b alpha' C8B C5b alpha' Cell surface:C3bCR1 Properdin oligomer Ig heavy chain V-III region KOL CFIIg kappa chain V-III region VG IGLV4-60(1-?) IGLV2-23(1-?) IGLV4-60(1-?) C4B(1454-1744) Cell surface:C3b:BbIGLV11-55(1-?) N-acetyl-D-glucosamine C5b:C6:C7:C8C1QIg heavy chain V-II region NEWM C4A(20-675) IGLV5-37(1-?) CR1C5b alpha' Ig lambda chain V-III region SH IGLC6 C3 beta chain C4BPA C3 beta chain IGLV4-69(1-?) Ca2+ CPN1 MASP2-1 Ig heavy chain V-I region EU C1QC C4B(20-675) Ig kappa chain V-I region Gal Ig kappa chain V-III region B6 dNQ-C4A(757-1446) C4A(20-675) Cell surface FCN1 ligandsC8G C6 C4BPA N-acetyl-D-glucosamine Ca2+ C8B Ig lambda chain V-III region SH C2aCD59:C5b-C9Ig lambda chain V-II region MGC Ig kappa chain V-I region AG Ig kappa chain V-I region BAN Ig lambda chain V-I region HA C2a Ig lambda chain V-II region TOG C6 C4A(1454-1744) C4B(20-675) Ig kappa chain V-I region AU Ig lambda chain V-II region MGC CFB(260-764) Cell surface:C4b:C2aIGLV2-18(1-?) Ig lambda chain V-I region NEWM C1S C-terminal fragment Ig kappa chain V-I region AG Ig heavy chain V-III region JON C4b with hydrolysedthioesterC4B(1454-1744) IGLV10-54(1-?) IgH heavy chain V-III region VH26 precursor Ig kappa chain V-II region FR C5AR1 Ig kappa chain V-III region VG C4A(20-675) Membrane AttackComplexIg heavy chain V-II region NEWM IgH heavy chain V-III region VH26 precursor C3b alpha' CD46 Ig heavy chain V-III region WEA IGKV2D-30 Ig heavy chain V-III region BRO IGLV4-3(1-?) C8A C5 beta chain C7 IGHG1 thrombin heavy chain Cell surface IGLV4-69(1-?) C4cIg heavy chain V-II region ARH-77 Properdin oligomer C1QA C3aIGLV2-11(1-?) C4B(1454-1744) IGHV1-2 Cell surface Ig heavy chain V-III region BRO IGHG1 C1R N-terminal fragment C4A(1454-1744) IGKV3D-20 IGLC3 CFHR3 CFHR3 Ig heavy chain V-III region DOB CFH IGLV1-44(1-?) IGKV2-28 Ig lambda chain V-III region LOI C4B(20-675) 11xCbxE-PROS1 dNQ-C4A(757-1446) IGKVA18(21-?) CPN, CBP2Cell surface IGLV10-54(1-?) C1R N-terminal fragment IGLV2-23(1-?) IGLV8-61(1-?) MASP1(20-699) IGLV1-44(1-?) Ig lambda chain V-II region NEI Ig heavy chain V-III region DOB C7 IGLV4-69(1-?) Ig lambda chain V-III region LOI IGLV3-27(1-?) Ig lambda chain V-III region SH N-acetyl-D-glucosamine VTN:C5b:C6:C7C1QB Ig heavy chain V-III region JON Cell surface IGLV3-22(1-?) C4BPB C3 beta chain MBL2 dodecamer:MASP1dimer:MASP2-1 dimerMBL2 IGLV5-45(1-?) Antigen C4B-derived C4a C3b alpha' Ig heavy chain V-III region KOL CR1 Ig heavy chain V-III region TRO IGLV3-16(1-?) Cell surface C4dIg lambda chain V-I region NEW C3 beta chain C4A(1454-1744) IGKVA18(21-?) IGHG3 Ig kappa chain V-I region Daudi IGLV2-33(1-?) dNQ-C4B(757-1446) IGLV3-25(1-?) Sialic acid CL-LK:MASP1dimer:MASP2 dimerIGLV11-55(1-?) Ig kappa chain V-II region RPMI 6410 IGLC1 C3a-desArg Antigen:IgG:C1Q:2xActivated C1R:SERPING1:2xActivated C1S:SERPING1CFH Ig lambda chain V-I region VOR D-fucose CFI(19-335)IGKV2-28 C1QA C6 Ig heavy chain V-II region MCE C4A(1454-1744) C3 beta chain CD55 IGHV7-81(1-?) Cell surface CR2:C3d,C3dg,iC3bIGLV2-11(1-?) C4B(20-675) C4A(1454-1744) C4B(20-675) C4A(1454-1744) Ig kappa chain V region EV15 D-fucose C3 beta chain IGLV1-40(1-?) C3b alpha' Ig kappa chain V-I region Wes IGLV4-3(1-?) IGLV4-60(1-?) Ig heavy chain V-III region WEA IGLV3-16(1-?) C3 convertasesIg heavy chain V-II region OU FCN3 FCN3 oligomer:MASP1dimer:MASP2-1 dimerC4A(1454-1744) C4c Cell surface C5 beta chain CD46:Cellsurface:C3bIGLV5-37(1-?) IGKV1-12 C3c alpha' chain fragment 2 Cell surface C4A(1454-1744) Ig kappa chain V-II region FR Cell surface IGHG4 C4B(1454-1744) IGLC2 IGHG2 IGLC6 dNQ-C4B(757-1446) IGLV1-44(1-?) dNQ-C4A(757-1446) FCN3 CFHR1 IGLV4-3(1-?) IGLV1-44(1-?) C3c alpha' chain fragment 2 IGLV5-37(1-?) IGLV1-40(1-?) IGLV7-46(1-?) C1QB Ig kappa chain V-II region Cum C4A(1454-1744) C2a dNQ-C4B(757-1446) Ig lambda chain V-III region SH Ig heavy chain V-II region WAH C3 beta chain C4B(1454-1744) Cell surface C3 beta chain Cell surface:C3b:CFBC3c alpha' chain fragment 2 Ig kappa chain V region EV15 H2OC5b alpha' dNQ-C4B(757-1446) Ig kappa chain V-III region B6 Ig lambda chain V-I region NEWM CFB(260-764) Ig lambda chain V-IV region Hil IGLV5-45(1-?) dNQ-C4B(757-1446) C5aTProperdin oligomer Ca2+C3b alpha' CD46 Ig lambda chain V-IV region Kern dNQ-C4B(757-1446) Ig heavy chain V-II region ARH-77 IGHG4 GZMM Ig lambda chain V-IV region Hil C3 beta chain C8G C2aC3 beta chain Ca2+ Ig kappa chain V-I region Gal CD46 Ig heavy chain V-III region TRO IGLV3-16(1-?) IGHV1-2 IGHV7-81(1-?) CFH Ig lambda chain V-II region MGC C4 bindingprotein:protein SIg kappa chain V-II region FR Ig lambda chain V-I region HA C4A(1454-1744) Ig kappa chain V-II region RPMI 6410 SERPING1 Complement Factor 4C3a CR1:C3bIg kappa chain V-II region RPMI 6410 CFB(26-259)C3d CFI(340-583)IGLC7 Ig lambda chain V-VI region AR C4B(20-675) Ig heavy chain V-I region EU IGLV7-46(1-?) CD55:C3 convertasecomplexesC5a-desArg Ig kappa chain V-III region POM Cell surfaceC3AR1Ig kappa chain V-I region DEE C1QA C1S C-terminal fragment Ig heavy chain V-II region WAH C9(22-559) Lipoteichoic acid CR1:C4bIg lambda chain V-II region TOG IGLV11-55(1-?) Ig kappa chain V-III region POM C3 beta chain C1R(18-705) C3b alpha' IGKV3D-20 IGKV2-28 CD59CFI(19-335) FCN1 dodecamer:MASP1dimer:MASP2-1 dimerIg heavy chain V-II region ARH-77 C3b alpha' Ig kappa chain V-II region Cum C3b alpha' N-acetylgalactosamine Ca2+ C3dgCell surface:C3bC3a-desArg,C5a-desArgMBL2 dodecamer:MASP1dimer:MASP2-1dimer:Bacterialmannose surfacepattern:4xCa2+IGLC2 IGLV8-61(1-?) IGHG1 Ig lambda chain V-III region LOI IGKV1-12 IGLC7 C4B(1454-1744) Ig heavy chain V-II region NEWM C4A(20-675) Ig heavy chain V-II region NEWM IGKC Cell surface IGLV3-25(1-?) IGKC Sialic acid CFH:Host cellsurfaceAntigen:IgG:C1Q:2xC1R:2xC1SIg heavy chain V-II region WAH Ig kappa chain V-I region BAN Ig kappa chain V-I region Wes C4A(1454-1744) C3(H2O):CFBIg lambda chain V-II region TOG IGLV7-46(1-?) IGLC1 Ca2+ IGLV2-33(1-?) C3 beta chain Ig heavy chain V-II region OU C4 activatorsdNQ-C4A(757-1446) Complement factor DCell surface:CFH,CFHR3:C3bBbProperdin oligomerIGHV1-2 C4B(20-675) IGLV5-37(1-?) Ig kappa chain V-I region Daudi Cellsurface:FH,FHR3:C3bIg kappa chain V-I region AG C5 beta chain Ig kappa chain V-III region POM C4A(20-675) C3 beta chain C2aCFB(260-764) C3c alpha' chain fragment 1 precursor CFI(19-335) dNQ-C4A(757-1446) C1QB Ig heavy chain V-III region DOB Ig lambda chain V-II region TOG Ig lambda chain V-I region NEW SERPING1 C7 Ig heavy chain V-II region MCE C3 beta chain C3b alpha' IGKV2-28 C3c alpha' chain fragment 1 precursor Ig kappa chain V region EV15 IGLC1 CR1 MASP2-1 C4A(20-675) Ig heavy chain V-III region JON Ig kappa chain V-II region Cum Ig heavy chain V-II region ARH-77 IGHV(1-?) C1QB Ig heavy chain V-III region TRO C4A(1454-1744) C4A(20-675) C1QB C3fCell surface Ig kappa chain V-III region VG IGLV11-55(1-?) C3 beta chain C3(H2O)dNQ-C4A(757-1446) IGLC1 CD19 IGHV1-2 IGLC7 C4A(1454-1744) Ig heavy chain V-II region MCE IGLV5-45(1-?) C5b alpha' 1,3-beta-D-glucan C8G C4B(20-675) Ig kappa chain V-III region VG Antigen C4A(20-675) 1,3-beta-D-glucan C4B alpha IGLC7 PCho Ig lambda chain V-IV region Bau C9(22-559)CFI(340-583) IGLV(23-?) Ig lambda chain V-I region HA Heparins C8A IGLV10-54(1-?) Ig lambda chain V-I region VOR IGLV2-18(1-?) IGHG3 Ig heavy chain V-III region KOL C3b alpha' Ig kappa chain V-II region Cum IGHG4 Ig kappa chain V-I region Daudi CD46CD81 C4B(956-1336) C5AR2 Ig heavy chain V-III region JON Antigen C4BPA C4B(1454-1744) C5b:C6:C7Ig heavy chain V-I region HG3 IGLV7-46(1-?) S-(L-isoglutamyl)-L-cysteine-C4A(757-1446) C4A(1454-1744) CD55:C4bAntigen SERPING1 C8G IGLV2-11(1-?) MBL2 C6 IGLV2-23(1-?) Ig lambda chain V region 4A Ig kappa chain V region EV15 Lipoteichoic acid IGKC C4BPB C7 MASP2-1 IGHV1-2 C4A(20-675) C4b:C2a:C3bC4A(20-675) IGLV1-36(1-?) Ig lambda chain V-II region BOH CLU:C5b:C6:C7, C8,C9C2a IGHG1 IGLV3-22(1-?) IGHV1-2 C6 IGKVA18(21-?) C3 beta chain Antigen:IgG:C1Q:2xActivated C1R:2xActivated C1SIGKV2-28 IGKVA18(21-?) FCN2 dodecamer:MASP1dimer:MASP2-1 dimerIg heavy chain V-III region DOB IGLC6 Ig heavy chain V-III region DOB Ig lambda chain V-II region NEI IGLV5-37(1-?) Activated thrombin,(ELANE)thrombin light chain C3f C5AR1:C5aIg heavy chain V-II region WAH C8B C1R C-terminal fragment C3 beta chain C4B(1454-1744) C1QA Cell surface:C4b:C2aC4 alpha dNQ-C3(672-1663) Ig kappa chain V-I region HK101 C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)IGKVA18(21-?) IGLV3-27(1-?) IGHG1 C4B(1454-1744) IGHV(1-?) Ig heavy chain V-III region BUT CR1 Ig kappa chain V-II region FR Ig kappa chain V-II region FR Ig kappa chain V-I region BAN IGLV7-43(1-?) C2a IGLV3-22(1-?) N-acetylgalactosamine C6 C8B IGLC7 C4c, C3fIg lambda chain V-II region TOG IGLC2 IGLV7-43(1-?) Ig kappa chain V-I region DEE dNQ-C4A(757-1446) IGLV3-27(1-?) C4B(20-675) C1S C-terminal fragment Ig heavy chain V-III region BRO MASP1(20-699) Ig lambda chain V-I region HA C1R N-terminal fragment Cell surface Ig heavy chain V-I region HG3 C4BPB Ig kappa chain V-I region BAN Ig lambda chain V-II region TOG CFHR dimersIg kappa chain V-III region POM IGLC3 S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) IGLV1-44(1-?) C3 beta chain CFHR3 C4A(1454-1744) IGLV2-23(1-?) C4B(1454-1744) CFI(340-583) VTN Cell surfaceC2a IGLV3-25(1-?) C4 bindingprotein:C4bC2aS-(L-isoglutamyl)-L-cysteine-C4A(757-1446) C3 beta chain CFB(260-764)IGLV2-23(1-?) FCN3 Ig kappa chain V-II region Cum C4B(1454-1744) Ig heavy chain V-I region HG3 N-acetylgalactosamine C3b alpha' C2a C3c alpha' chain fragment 1 precursor C3 beta chain Ig lambda chain V-IV region Bau N-acetylgalactosamine CFI(340-583) C9(22-559) C7 IGLC7 CRP(19-224) CFHR1 Sialic acid C4d, iC3bIGHG2 Cell surface Ig heavy chain V-III region WEA Ig kappa chain V-II region RPMI 6410 C4A(20-675) C8A IGLV(23-?) C4A(20-675) dNQ-C4B(757-1446) Ig heavy chain V-III region CAM C7 CFHR2 C3(H2O)CD59 IGLC2 IGLV3-12(1-?) IGLC3 IGLC1 IgH heavy chain V-III region VH26 precursor IGLC1 S-(L-isoglutamyl)-L-cysteine-C4B(757-1446) Ig lambda chain V-I region HA C5b alpha' MASP2-1 Bacterial mannose surface pattern MASP1(449-699) Ig lambda chain V-IV region Bau Ig kappa chain V-I region HK101 CFI:CFH,FHR3:C3bC3AR1 MASP1(20-699) CFB(260-764) C4B(20-675) Ig lambda chain V region 4A C1R N-terminal fragment IGKV4-1(21-?) C3b alpha' IGLV10-54(1-?) Ig lambda chain V-III region LOI C5a C5a-desArg C2a Ig kappa chain V-II region RPMI 6410 C3bC3 beta chain C-reactiveproteinpentamer:phosphocholine:C1QC4A(20-675) IGLC3 C4B(20-675) Ig kappa chain V-III region VG Ig kappa chain V-I region Gal IGLV3-25(1-?) C5 beta chain Ig lambda chain V region 4A MBL2,FCN:activatedMASPs:carbohydratepatternsC4A(20-675) Ig heavy chain V-III region TRO IGHV1-2 C4B(1454-1744) C4A(1454-1744) IGLV8-61(1-?) Ig lambda chain V-II region NEI IGLV3-22(1-?) C8G Ig heavy chain V-III region CAM IGLV3-22(1-?) Cellsurface:C3b:Bb:ProperdinIGKV2D-30 C9(22-559) IGKV3D-20 dNQ-C3(672-1663) CFI(19-335) C5b alpha' N-acetyl-D-glucosamine C6 Ca2+ IGKV2D-30 C3c alpha' chain fragment 2 Cell surface Ig lambda chain V-I region NEWM FCN1 Ig lambda chain V-IV region Kern C4A(20-675) Ig kappa chain V-I region DEE IGLV4-3(1-?) C6FCN1 C3 beta chain IGLV3-12(1-?) dNQ-C4B(757-1446) IGLV1-40(1-?) C4B(20-675) C3b alpha' C1R N-terminal fragment CFH IGLV10-54(1-?) 56597891100, 11194971066, 9910610828, 40635280, 10428, 4039, 11444, 80, 1041061071136321111, 5242, 82113


Description

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

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

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

N.B. Originally the larger fragment of Complement Factor 2 (C2) was designated C2a. However, complement scientists decided that the smaller of all C fragments should be designated with an 'a', the larger with a 'b', changing the nomenclature for C2. Recent literature may use the updated nomenclature and refer to the larger C2 fragment as C2b, and refer to the classical C3 convertase as C4bC2b. Throughout this pathway Reactome adheres to the original convention to agree with the current (Sep 2013) Uniprot names for C2 fragments. View original pathway at:Reactome.</div>

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Reactome-Converter 
Pathway is converted from Reactome ID: 166658
Reactome-version 
Reactome version: 65
Reactome Author 
Reactome Author: de Bono, Bernard

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Bibliography

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

History

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CompareRevisionActionTimeUserComment
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(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)ComplexR-HSA-981700 (Reactome)
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)
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 ProteinP0CG05 (Uniprot-TrEMBL)
IGLC3 ProteinP0CG06 (Uniprot-TrEMBL)
IGLC6 ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7 ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV(23-?) ProteinA2NXD2 (Uniprot-TrEMBL)
IGLV1-36(1-?) ProteinQ5NV67 (Uniprot-TrEMBL)
IGLV1-40(1-?) ProteinQ5NV69 (Uniprot-TrEMBL)
IGLV1-44(1-?) ProteinQ5NV81 (Uniprot-TrEMBL)
IGLV10-54(1-?) ProteinQ5NV86 (Uniprot-TrEMBL)
IGLV11-55(1-?) ProteinQ5NV87 (Uniprot-TrEMBL)
IGLV2-11(1-?) ProteinQ5NV84 (Uniprot-TrEMBL)
IGLV2-18(1-?) ProteinQ5NV65 (Uniprot-TrEMBL)
IGLV2-23(1-?) ProteinQ5NV89 (Uniprot-TrEMBL)
IGLV2-33(1-?) ProteinQ5NV66 (Uniprot-TrEMBL)
IGLV3-12(1-?) ProteinQ5NV85 (Uniprot-TrEMBL)
IGLV3-16(1-?) ProteinQ5NV64 (Uniprot-TrEMBL)
IGLV3-22(1-?) ProteinQ5NV75 (Uniprot-TrEMBL)
IGLV3-25(1-?) ProteinQ5NV90 (Uniprot-TrEMBL)
IGLV3-27(1-?) ProteinQ5NV91 (Uniprot-TrEMBL)
IGLV4-3(1-?) ProteinQ5NV61 (Uniprot-TrEMBL)
IGLV4-60(1-?) ProteinQ5NV79 (Uniprot-TrEMBL)
IGLV4-69(1-?) ProteinQ5NV92 (Uniprot-TrEMBL)
IGLV5-37(1-?) ProteinQ5NV68 (Uniprot-TrEMBL)
IGLV5-45(1-?) ProteinQ5NV82 (Uniprot-TrEMBL)
IGLV7-43(1-?) ProteinQ5NV80 (Uniprot-TrEMBL)
IGLV7-46(1-?) ProteinQ5NV83 (Uniprot-TrEMBL)
IGLV8-61(1-?) ProteinQ5NV62 (Uniprot-TrEMBL)
Ig heavy chain V-I region EU ProteinP01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 ProteinP01743 (Uniprot-TrEMBL)
Ig heavy chain V-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-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)
C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)ArrowR-HSA-166753 (Reactome)
C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)R-HSA-2855047 (Reactome)
C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)R-HSA-977626 (Reactome)
C4A(20-675):C4A(1454-1744):S-(L-isoglutamyl)-L-cysteine-C4A(757-1446),C4B(1454-1744):C4B(20-675):S-(L-isoglutamyl)-L-cysteine-C4B(757-1446)R-HSA-981713 (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)
C4bC2a, C3bBbR-HSA-977375 (Reactome)
C4bC2a, C3bBbR-HSA-981535 (Reactome)
C4c, C3fArrowR-HSA-977615 (Reactome)
C4cArrowR-HSA-981637 (Reactome)
C4d, iC3bArrowR-HSA-977615 (Reactome)
C4dArrowR-HSA-981637 (Reactome)
C5 convertasesmim-catalysisR-HSA-173680 (Reactome)
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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