Complement system (WP2806)

Homo sapiens

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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 (doi:10.6072/H0.MP.A004235.01) and are controlled by regulators (doi: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 (doi: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 (doi: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 (doi:10.1074/jbc.273.27.16828). 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) (doi: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 (see doi: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 (doi:10.1093/bioinformatics/btr190) has published a curated data on each protein involved in human complement activation pathways (refs. Dinasarapu et al, Chandrasekhar et al, Dinasarapu et al, Dinasarapu et al, Chandrasekhar et al, Chandrasekhar et al, Chandrasekhar et al, Chandrasekhar et al, Chandrasekhar et al, Chandrasekhar et al, Chandrasekhar et al, Dinasarapu et al, Dinasarapu et al, Min et al).

Authors

Elisa Cirillo , Ashok R. Dinasarapu , Anwesha Bohler , Kristina Hanspers , Egon Willighagen , Friederike Ehrhart , Martina Summer-Kutmon , Alex Pico , Anders Riutta , Denise Slenter , Eric Weitz , Lars Willighagen , and Shuya Ikeda

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

complement system pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
beta-Glucan Metabolite chebi:28793
LTA Metabolite chebi:28640
fMLP Metabolite chebi:53490
Heparin Metabolite chebi:28304
HS Metabolite chebi:28815
HSV-gC GeneProduct ncbigene:2703410
FnBPA GeneProduct ncbigene:3913735
CD16a GeneProduct ensembl:ENSG00000203747
IBSP GeneProduct ensembl:ENSG00000029559
C4a GeneProduct ncbigene:720
SELE GeneProduct ensembl:ENSG00000007908
C3b GeneProduct uniprot:P01024
RgpA GeneProduct ncbiprotein:6330747 Gngipain-1
C4BP GeneProduct ensembl:ENSG00000123838 Two isoforms exists (C4BPA and C4BPB).
ITGA2 GeneProduct ensembl:ENSG00000164171
CR2 GeneProduct ensembl:ENSG00000117322
DCN GeneProduct ensembl:ENSG00000011465
FPR1 GeneProduct ensembl:ENSG00000171051
ClfB GeneProduct ncbigene:5331889
KLKB1 GeneProduct ensembl:ENSG00000164344
Efb GeneProduct ncbigene:3238454
OmpK36 GeneProduct uniprot:A0A0H3H0Y2
ARRB2 GeneProduct ensembl:ENSG00000141480
gC1qR GeneProduct ensembl:ENSG00000108561
Protein-A GeneProduct ncbigene:5332074
DAF GeneProduct ensembl:ENSG00000196352
FGB GeneProduct ncbigene:2244
FnBPB GeneProduct ncbigene:3913823
C5aR1 GeneProduct ensembl:ENSG00000197405
SSL7 GeneProduct ncbigene:2859139
C3aR1 GeneProduct ensembl:ENSG00000171860
LAMA5 GeneProduct ensembl:ENSG00000130702
LfhA GeneProduct ncbigene:AAN47894
CK GeneProduct ensembl:ENSG00000113712
Ehp GeneProduct uniprot:A0A0H3K2R1
CFHR1 GeneProduct ensembl:ENSG00000080910
gp350 GeneProduct uniprot:P68343
C3a-desArg GeneProduct ncbigene:718
C5 GeneProduct ncbigene:727 Complement C5
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
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 uniprot:O82882
C5a-desArg GeneProduct ncbigene:727
ICAM2 GeneProduct ensembl:ENSG00000108622
VCP GeneProduct ncbigene:3707640
GNA15 GeneProduct ensembl:ENSG00000060558
C3c GeneProduct ncbigene:718 Peptide fragment from complement C3
WAS GeneProduct ensembl:ENSG00000015285
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 Streptococcal C5a peptidase
CFHR4 GeneProduct ensembl:ENSG00000134365
GNAI2 GeneProduct ensembl:ENSG00000114353
MAp44 GeneProduct ncbigene:5648
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
OMCI GeneProduct uniprot:Q5YD59
FCN2 GeneProduct ensembl:ENSG00000160339
ITGA2B GeneProduct ensembl:ENSG00000005961
ELANE GeneProduct ensembl:ENSG00000197561
iC3b GeneProduct uniprot:P01024 Peptide fragment from complement C3
C4-A GeneProduct ncbigene:720 Complement C4 exists in two isoforms, C4-A and C4-B.
A2M GeneProduct ensembl:ENSG00000175899
Skp GeneProduct uniprot:P0AEU7
CFB GeneProduct hgnc:1037
FXIII GeneProduct ensembl:ENSG00000124491
PLAUR GeneProduct ensembl:ENSG00000011422
PKA GeneProduct ensembl:ENSG00000072062
GNA1870 GeneProduct ncbigene:12393750
C3f GeneProduct ncbigene:718 Peptide fragment from complement C3
ICAM1 GeneProduct ensembl:ENSG00000090339
MASP1 GeneProduct ensembl:ENSG00000127241
C2 GeneProduct ensembl:ENSG00000166278
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
ADM GeneProduct ensembl:ENSG00000148926
C8 GeneProduct ensembl:ENSG00000157131 Complement C8 exhists in 3 isoforms.
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
APOA1 GeneProduct ensembl:ENSG00000118137
E-LDL GeneProduct ensembl:ENSG00000173486
CR1 GeneProduct ensembl:ENSG00000203710
C3(H2O) GeneProduct ncbigene:629
FCN1 GeneProduct ensembl:ENSG00000085265
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
CRIg GeneProduct ensembl:ENSG00000155659
FN GeneProduct ensembl:ENSG0000011541
CFD GeneProduct ensembl:ENSG00000197766 Complement Factor D
ADIPOQ GeneProduct ensembl:ENSG00000181092
CPB2 GeneProduct ensembl:ENSG00000120054
CFD GeneProduct ensembl:ENSG00000197766
Ehp GeneProduct ncbigene:YP_043213
C3d GeneProduct ncbigene:718 Peptide fragment from complement C3
LfhA GeneProduct uniprot:Q47153
C5 GeneProduct ncbigene:727
C5a GeneProduct ncbigene:727
C5b GeneProduct ncbigene:727

References

  1. Complement C1q subcomponent subunit A [Internet]. Chandrasekhar. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004228 DOI Scholia
  2. Complement C2 [Internet]. Dinasarapu AR. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004234 DOI Scholia
  3. Complement C3 [Internet]. Dinasarapu. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004235 DOI Scholia
  4. Complement C5 [Internet]. Chandrasekhar. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004240 DOI Scholia
  5. Complement factor H [Internet]. Dinasarapu AR. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004256 DOI Scholia
  6. Properdin [Internet]. Min J. UCSD Signaling Gateway Molecule Pages; 2014. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004258 DOI Scholia
  7. Integrin beta-2 [Internet]. Dinasarapu AR. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004263 DOI Scholia
  8. L-Ficolin [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004266 DOI Scholia
  9. H-Ficolin [Internet]. Chandrasekhar A. UCSD Signaling Gateway; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004267 DOI Scholia
  10. MASP-1 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004274 DOI Scholia
  11. MASP-2 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004275 DOI Scholia
  12. Mannose/mannan-binding lectin [Internet]. Dinasarapu AR. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004276 DOI Scholia
  13. MASP-3 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A008391 DOI Scholia
  14. MAp44 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A008392 DOI Scholia
  15. C1q: structure, function, and receptors. Kishore U, Reid KB. Immunopharmacology. 2000 Aug;49(1–2):159–70. PubMed Europe PMC Scholia
  16. Complement: a key system for immune surveillance and homeostasis. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Nat Immunol. 2010 Sep;11(9):785–97. PubMed Europe PMC Scholia
  17. Signaling gateway molecule pages--a data model perspective. Dinasarapu AR, Saunders B, Ozerlat I, Azam K, Subramaniam S. Bioinformatics. 2011 Jun 15;27(12):1736–8. PubMed Europe PMC Scholia
  18. CMAP: Complement Map Database. Yang K, Dinasarapu AR, Reis ES, Deangelis RA, Ricklin D, Subramaniam S, et al. Bioinformatics. 2013 Jul 15;29(14):1832–3. PubMed Europe PMC Scholia