Complement system (WP2806)

The complement activation takes place through one or more of the well-established (alternative, classical or lectin) pathways consisting of plasma and membrane-bound proteins. All three pathways converge at the level of complement C3 [https://doi.org/10.6072/H0.MP.A004235.01] and are controlled by regulators [https://doi.org/10.1038/ni.1923]. Complement C3 belongs to the alpha-2-macroglobulin family of proteins, and consists of a alpha-chain and an beta-chain. Cleavage of C3 which can be initiated by one or more of the above three distinct pathways, into C3b[Proteolysis@23-667,749-1663] and C3a [Proteolysis@672-748] is an important step in the complement activation cascade. Classical and lectin pathways, when activated with recognition of pathogens (or immune complexes) use C3-convertase [C4b2a] to cleave complement C3 into C3a and C3b [https://doi.org/10.1084/jem.125.2.359]. However, in alternative pathway a small fraction of the C3 molecules are hydrolyzed to C3(H20) exposing new binding sites. This hydrated C3 [C3(H20)] recruits complement factor B [fB], which is then cleaved by complement factor D [fD] to result in formation of the minor form of C3-convertase [C3(H20)Bb] that cleaves C3 into C3a and C3b [https://doi.org/10.1084/jem.154.3.856]. Further, addition of C3b to C3 convertase [C3bBb or C4b2a] results in C5 convertase [C3bBb3b or C4b2a3b], that cleaves complement C5 to C5a and C5b, is the last enzymatic step of the complement activation cascade [https://doi.org/10.1074/jbc.273.27.16828][https://www.ncbi.nlm.nih.gov/pubmed/?term=2387864]. During complement activation C5b interacts with complement C6, C7, C8 and C9 in a sequential and non-catalyzed manner to result in the formation of Terminal Complement Complex (TCC) [https://doi.org/10.1074/jbc.M111.219766]. The entire network is considered as a simple recognition and elimination system of host-immune complexes and apoptotic and/or pathogens, and therefore promotes host immune homeostasis. The complement system is also involved in cross-talk with other processes related to coagulation, lipid metabolism and cancer. However, many pathogens counteract complement attack through a range of different mechanisms, such acquisition of host complement regulators to the surface of pathogen, or secretion of complement inactivation factors. In order to have a holistic view of the entire complement network, Dr. John D.Lambris group (University of Pennsylvania) developed the Complement Map Database (CMAP) which is a unique repository focused on documented molecular interactions described within the complement cascade and between complement and other biological systems. Information contained in CMAP (http://www.complement.us/cmap/index.php)[https://doi.org/10.1093/bioinformatics/btt269] is entirely based on published experimental data and is fully revised by experts in the field. Further, the Signaling Gateway Molecule Pages -SGMP-( https://escholarship.org/uc/molecule_pages)[https://doi.org/10.1093/bioinformatics/btr190] has published a curated data on each protein involved in human complement activation pathways (refs. [https://doi.org/10.6072/H0.MP.A004235.01] [https://doi.org/10.6072/H0.MP.A004228.01] [https://doi.org/10.6072/H0.MP.A004276.01] [https://doi.org/10.6072/H0.MP.A004256.01] [https://doi.org/10.6072/H0.MP.A004240.01] [https://doi.org/10.6072/H0.MP.A008392.01] [https://doi.org/10.6072/H0.MP.A008391.01] [https://doi.org/10.6072/H0.MP.A004274.01] [https://doi.org/10.6072/H0.MP.A004275.01] [https://doi.org/10.6072/H0.MP.A004266.01] [https://doi.org/10.6072/H0.MP.A004267.01] [https://doi.org/10.6072/H0.MP.A004263.01] [https://doi.org/10.6072/H0.MP.A004234.01] [https://doi.org/10.6072/H0.MP.A004258.01] ).
last edited

Authors

Elisa, Adinasarapu, Anwesha, Khanspers, Egonw, MaintBot, Fehrhart, Mkutmon, Wpblocked, AlexanderPico, Ariutta, DeSl, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: complement system pathway

Participants

Label Type Compact Identifier
HSV-gC GeneProduct ncbigene:2703410
FnBPA GeneProduct ncbigene:3913735
CD16a GeneProduct ensembl:ENSG00000203747
IBSP GeneProduct ensembl:ENSG00000029559
beta-Glucan Metabolite chebi:28793
C4a GeneProduct ncbigene:720
SELE GeneProduct ensembl:ENSG00000007908
C3b GeneProduct uniprot:P01024
RgpA GeneProduct ncbiprotein:6330747
C4BP GeneProduct ensembl:ENSG00000123838
ITGA2 GeneProduct ensembl:ENSG00000164171
C1q Complex :A004228:32716
CR2 GeneProduct ensembl:ENSG00000117322
DCN GeneProduct ensembl:ENSG00000011465
FPR1 GeneProduct ensembl:ENSG00000171051
ClfB GeneProduct ncbigene:5331889
KLKB1 GeneProduct ensembl:ENSG00000164344
SPICE GeneProduct None
Efb GeneProduct ncbigene:3238454
OmpK36 GeneProduct ncbigene:AEW62399
ARRB2 GeneProduct ensembl:ENSG00000141480
gC1qR GeneProduct ensembl:ENSG00000108561
Protein-A GeneProduct ncbigene:5332074
DAF GeneProduct ensembl:ENSG00000196352
FGB GeneProduct ncbigene:2244
Gpm1p GeneProduct ncbigene:XP_721143
FnBPB GeneProduct ncbigene:3913823
C5aR1 GeneProduct ensembl:ENSG00000197405
SSL7 GeneProduct ncbigene:2859139
C3aR1 GeneProduct ensembl:ENSG00000171860
LAMA5 GeneProduct ensembl:ENSG00000130702
LTA Metabolite chebi:28640
LfhA GeneProduct ncbigene:AAN47894
CK GeneProduct ensembl:ENSG00000113712
Ehp GeneProduct ncbigene:YP_043213
CFHR1 GeneProduct ensembl:ENSG00000080910
gp350 GeneProduct ncbigene:YP_001129462
C3a-desArg GeneProduct ncbigene:718
C5 GeneProduct ncbigene:727
C3d GeneProduct ncbigene:718
CPN GeneProduct ensembl:ENSG00000120054
TLR2 GeneProduct ncbigene:7097
SELP GeneProduct ensembl:ENSG00000174175
C7 GeneProduct ensembl:ENSG00000112936
FGA GeneProduct ncbigene:2243
PTX3 GeneProduct ensembl:ENSG00000163661
CbpA GeneProduct ncbigene:933487
Protein-S GeneProduct ensembl:ENSG00000184500
SFTPA2 GeneProduct ensembl:ENSG00000185303
C9 GeneProduct ensembl:ENSG00000113600
C1s GeneProduct ensembl:ENSG00000182326
C6 GeneProduct ensembl:ENSG00000039537
PrP GeneProduct ensembl:ENSG00000171867
CR3 Complex ensembl:ENSG00000160255
fMLP Metabolite chebi:53490
C1r GeneProduct uniprot:P00736
ClfA GeneProduct ncbigene:2859231
CD40 GeneProduct ensembl:ENSG00000101017
OPN GeneProduct ensembl:ENSG00000118785
Sfb GeneProduct ncbigene:3573107
cC1qR GeneProduct ensembl:ENSG00000179218
C3a GeneProduct ncbigene:718
C1INH GeneProduct ensembl:ENSG00000149131
CD59 GeneProduct ensembl:ENSG00000085063
MBL2 GeneProduct ensembl:ENSG00000165471
StcE GeneProduct ncbigene:AAU25886
C5a-desArg GeneProduct ncbigene:727
ICAM2 GeneProduct ensembl:ENSG00000108622
VCP GeneProduct ncbigene:3707640
GNA15 GeneProduct ensembl:ENSG00000060558
C3c GeneProduct ncbigene:718
WAS GeneProduct ensembl:ENSG00000015285
Por1A GeneProduct None
ALB GeneProduct ensembl:ENSG00000163631
THBS GeneProduct ensembl:ENSG00000137801
SIC GeneProduct ncbigene:269972
CD23 GeneProduct ensembl:ENSG00000104921
C4b GeneProduct ncbigene:720
SELPLG GeneProduct ensembl:ENSG00000110876
FGG GeneProduct ensembl:ENSG00000171557
SSL10 GeneProduct ncbigene:2859141
SCP GeneProduct ncbiprotein:1030336
CFHR4 GeneProduct ensembl:ENSG00000134365
GNAI2 GeneProduct ensembl:ENSG00000114353
MAp44 GeneProduct ncbigene:5648
NS1 GeneProduct None
PKC GeneProduct ensembl:ENSG00000154229
FXIIa GeneProduct uniprot:P00748
C5L2 GeneProduct ensembl:ENSG00000134830
CFP GeneProduct ensembl:ENSG00000126759
HIV-gp41 GeneProduct ncbigene:155971
C1qRp GeneProduct ensembl:ENSG00000125810
ITGB3 GeneProduct ensembl:ENSG00000259207
CD19 GeneProduct ensembl:ENSG00000177455
TXN GeneProduct ensembl:ENSG00000136810
SSL5 GeneProduct ncbigene:2859140
Leishmanial protein kinase-1 GeneProduct None
OMCI GeneProduct ncbigene:AAT65682
FCN2 GeneProduct ensembl:ENSG00000160339
ITGA2B GeneProduct ensembl:ENSG00000005961
Heparin Metabolite chebi:28304
ELANE GeneProduct ensembl:ENSG00000197561
iC3b GeneProduct uniprot:P01024
C4-A GeneProduct ncbigene:720
A2M GeneProduct ensembl:ENSG00000175899
Skp GeneProduct ncbigene:ADD54834
CFB GeneProduct :1037
HS Metabolite chebi:28815
FXIII GeneProduct ensembl:ENSG00000124491
PLAUR GeneProduct ensembl:ENSG00000011422
PKA GeneProduct ensembl:ENSG00000072062
GNA1870 GeneProduct ncbigene:12393750
C3f GeneProduct ncbigene:718
ICAM1 GeneProduct ensembl:ENSG00000090339
MASP1 GeneProduct ensembl:ENSG00000127241
C2 GeneProduct ensembl:ENSG00000166278
C3bB3b Complex None
Protein M GeneProduct ncbiprotein:2940887
VTN GeneProduct ensembl:ENSG00000109072
CFH GeneProduct ensembl:ENSG00000000971
FXIa GeneProduct uniprot:P03951
PLG GeneProduct ensembl:ENSG00000122194
Sbi GeneProduct ncbigene:5331420
FGA GeneProduct ensembl:ENSG00000171560
SAP GeneProduct ensembl:ENSG00000132703
TFECP GeneProduct None
ADM GeneProduct ensembl:ENSG00000148926
C8 GeneProduct ensembl:ENSG00000157131
CLEC4M GeneProduct ensembl:ENSG00000104938
CHIPS GeneProduct ncbigene:5332454
SSL11 GeneProduct ncbigene:1123177
FX GeneProduct ensembl:ENSG00000126218
RPS19 GeneProduct ensembl:ENSG00000105372
C3 GeneProduct ensembl:ENSG00000125730
MAp19 GeneProduct ncbigene:10747
SCIN GeneProduct ensembl:ENSG00000106804
GNAI3 GeneProduct ensembl:ENSG00000065135
C4b2b Complex None
APOA1 GeneProduct ensembl:ENSG00000118137
E-LDL GeneProduct ensembl:ENSG00000173486
CR1 GeneProduct ensembl:ENSG00000203710
C3(H2O) GeneProduct ncbigene:629
FCN1 GeneProduct ensembl:ENSG00000085265
C3bBbP Complex None
FGB GeneProduct ensembl:ENSG00000171564
SELL GeneProduct ensembl:ENSG00000188404
CFI GeneProduct ensembl:ENSG00000205403
LAMB1 GeneProduct ensembl:ENSG00000091136
FKBP13 GeneProduct ensembl:ENSG00000173486
SFTPA1 GeneProduct ensembl:ENSG00000122852
LAMC1 GeneProduct ensembl:ENSG00000135862
LRP2 GeneProduct ensembl:ENSG00000081479
C4a-desArg GeneProduct ncbigene:720
MCP GeneProduct ensembl:ENSG00000117335
CRP GeneProduct ensembl:ENSG00000132693
CR4 Complex ensembl:ENSG00000140678
Gpm1p GeneProduct None
CRIg GeneProduct ensembl:ENSG00000155659
FN GeneProduct ensembl:ENSG0000011541
C3bBb Complex None
C4b2b3b Complex None
CFD GeneProduct ensembl:ENSG00000197766
ADIPOQ GeneProduct ensembl:ENSG00000181092
KLKB1 GeneProduct ensembl:ENSG00000164344
MASP1 GeneProduct ensembl:ENSG00000127241
PTX3 GeneProduct ensembl:ENSG00000163661
CRP GeneProduct ensembl:ENSG00000132693
DCN GeneProduct ensembl:ENSG00000011465
ITGA2 GeneProduct ensembl:ENSG00000164171
cC1qR GeneProduct ensembl:ENSG00000179218
Por1B GeneProduct None
VCP GeneProduct ncbigene:3707640
LAMA5 GeneProduct ensembl:ENSG00000130702
LAMB1 GeneProduct ensembl:ENSG00000091136
LAMC1 GeneProduct ensembl:ENSG00000135862
C3 GeneProduct ensembl:ENSG00000125730
LRP2 GeneProduct ensembl:ENSG00000081479
CPN GeneProduct ensembl:ENSG00000120054
CPB2 GeneProduct ensembl:ENSG00000120054
KLKB1 GeneProduct ensembl:ENSG00000164344
CFD GeneProduct ensembl:ENSG00000197766
CFB GeneProduct :1037
Heparin Metabolite chebi:28304
C3b GeneProduct uniprot:P01024
LAMA5 GeneProduct ensembl:ENSG00000130702
LAMB1 GeneProduct ensembl:ENSG00000091136
LAMC1 GeneProduct ensembl:ENSG00000135862
VCP GeneProduct ncbigene:3707640
SPICE GeneProduct None
HSV-gC GeneProduct ncbigene:2703410
CFP GeneProduct ensembl:ENSG00000126759
C1INH GeneProduct ensembl:ENSG00000149131
MCP GeneProduct ensembl:ENSG00000117335
CR1 GeneProduct ensembl:ENSG00000203710
DAF GeneProduct ensembl:ENSG00000196352
Efb GeneProduct ncbigene:3238454
Ehp GeneProduct ncbigene:YP_043213
Sbi GeneProduct ncbigene:5331420
FN GeneProduct ensembl:ENSG0000011541
C3 GeneProduct ensembl:ENSG00000125730
Sbi GeneProduct ncbigene:5331420
CFH GeneProduct ensembl:ENSG00000000971
C3b GeneProduct uniprot:P01024
Sbi GeneProduct ncbigene:5331420
CFH GeneProduct ensembl:ENSG00000000971
Sbi GeneProduct ncbigene:5331420
CFH GeneProduct ensembl:ENSG00000000971
CbpA GeneProduct ncbigene:933487
PTX3 GeneProduct ensembl:ENSG00000163661
CFH GeneProduct ensembl:ENSG00000000971
CRP GeneProduct ensembl:ENSG00000132693
PrP GeneProduct ensembl:ENSG00000171867
SSL5 GeneProduct ncbigene:2859140
Heparin Metabolite chebi:28304
KLKB1 GeneProduct ensembl:ENSG00000164344
C3d GeneProduct ncbigene:718
CFH GeneProduct ensembl:ENSG00000000971
CFH GeneProduct ensembl:ENSG00000000971
CFI GeneProduct ensembl:ENSG00000205403
CFI GeneProduct ensembl:ENSG00000205403
CFI GeneProduct ensembl:ENSG00000205403
MCP GeneProduct ensembl:ENSG00000117335
CFI GeneProduct ensembl:ENSG00000205403
CFI GeneProduct ensembl:ENSG00000205403
CFI GeneProduct ensembl:ENSG00000205403
VCP GeneProduct ncbigene:3707640
SPICE GeneProduct None
SCIN GeneProduct ensembl:ENSG00000106804
LfhA GeneProduct ncbigene:AAN47894
CFHR1 GeneProduct ensembl:ENSG00000080910
LAMA5 GeneProduct ensembl:ENSG00000130702
LAMB1 GeneProduct ensembl:ENSG00000091136
LAMC1 GeneProduct ensembl:ENSG00000135862
CFI GeneProduct ensembl:ENSG00000205403
CR1 GeneProduct ensembl:ENSG00000203710
CRIg GeneProduct ensembl:ENSG00000155659
CR1 GeneProduct ensembl:ENSG00000203710
HSV-gC GeneProduct ncbigene:2703410
Heparin Metabolite chebi:28304
SAP GeneProduct ensembl:ENSG00000132703
FGB GeneProduct ncbigene:2244
FGA GeneProduct ncbigene:2243
FN GeneProduct ensembl:ENSG0000011541
TXN GeneProduct ensembl:ENSG00000136810
Protein M GeneProduct ncbiprotein:2940887
Efb GeneProduct ncbigene:3238454
ClfA GeneProduct ncbigene:2859231
APOA1 GeneProduct ensembl:ENSG00000118137
C5 GeneProduct ncbigene:727
Leishmanial protein kinase-1 GeneProduct None
SSL7 GeneProduct ncbigene:2859139
CFHR1 GeneProduct ensembl:ENSG00000080910
C3bB3bP Complex None
C5a GeneProduct ncbigene:727
C5b GeneProduct ncbigene:727
C5L2 GeneProduct ensembl:ENSG00000134830
CPB2 GeneProduct ensembl:ENSG00000120054
CPN GeneProduct ensembl:ENSG00000120054
SSL5 GeneProduct ncbigene:2859140
Leishmanial protein kinase-1 GeneProduct None
C9 GeneProduct ensembl:ENSG00000113600
Heparin Metabolite chebi:28304

References

  1. Kishore U, Reid KB. C1q: structure, function, and receptors. Immunopharmacology. 2000 Aug;49(1–2):159–70. PubMed Europe PMC Scholia
  2. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010 Sep;11(9):785–97. PubMed Europe PMC Scholia
  3. Dinasarapu AR, Saunders B, Ozerlat I, Azam K, Subramaniam S. Signaling gateway molecule pages--a data model perspective. Bioinformatics. 2011 Jun 15;27(12):1736–8. PubMed Europe PMC Scholia
  4. Yang K, Dinasarapu AR, Reis ES, Deangelis RA, Ricklin D, Subramaniam S, et al. CMAP: Complement Map Database. Bioinformatics. 2013 Jul 15;29(14):1832–3. PubMed Europe PMC Scholia