Human Complement System (Homo sapiens)

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1-17ClusterinFXIaBaEndougenous (host) molecules Neutrophil inhibitory factor (NIF) Exogenous molecules (eg. pathogenic)DegradationC5b6-9 complexIgGPlasminIgMC3(H2O)BbFIXa FXaIgACompstatinThrombin Complement proteins (host)Fibrin BaC4bC2FGBMAp19HIV-gp41ITGA2C3(H2O)C3bBbSSL5C4bGpm1pKLKB1SPICEC5L2LAMA5ITGB3FXIIaNS1PKCCFBC3dSFTPA2ELANEC3a-desArgSAPPKAC1qRpCKClfACPNC3bB3bSbiICAM1SCINA2MEfbbeta-GlucanWASFnBPAOPNC4aCFIHSGNAI3ClfBC5ADMC5a-desArgITGA2BC4b2bC3aFGBTLR2SCPProtein-SDCNFGGSICC8C1qCFPVCP HeparinIBSPCD40PLGFGACD19 Leishmanial protein kinase-1C1sgC1qRC7FPR1LRP2SkpE-LDLC3SELLSSL7FCN1FGASELEFKBP13CFDARRB2C6cC1qRPor1ACR3CD59THBSfMLPGpm1pFXCRPStcEOMCIMCPC1INHLAMC1GNAI2TXNRgpAC4a-desArgSFTPA1C3aR1VTNCbpATFECP FnBPBCHIPSPLAUREhpC4-ALTASSL10C9FXIIIC3fOmpK36PTX3DAFCR1C3cFXIaCFHC1rC2LAMB1CD16aMAp44C4BPCFHR1Protein MCRIgCD23PrPAPOA1SELPFNC4b2b3bgp350GNA15HSV-gCRPS19CR2CLEC4MFCN2ICAM2CR4C5aR1ALBSfbSELPLGGNA1870C3bBbPADIPOQSSL11iC3bC3bProtein-ACFHR4MBL2LfhAMASP1191918, 191919KLKB1MASP1PTX3CRPIgMIgGDCNITGA2cC1qRPor1BVCP LAMA5LAMB1LAMC1C3PLRP2Fibrin CPNCPB2 C3(H2O)BbDegradationPlasminKLKB1CFDCFBHeparinC3bLAMA5LAMB1LAMC1VCP SPICEHSV-gCCFPC1INHMCPCR1DAFEfbEhpSbiFNC3SbiCFHC3bSbiCFHSbiCFH19CbpAPTX3CFHCRPPrPSSL5HeparinDegradationKLKB1C3dCFHCFHCFICFICFIMCPCFICFICFIVCP SPICESCINLfhACFHR1LAMA5LAMB1LAMC1CFICR1CRIgCR1HSV-gCHeparinSAPIgGFGBFGAFNTXNProtein MEfbClfAAPOA1C5b678 complexC5b67 complexC5b6 complexC5 Leishmanial protein kinase-1SSL7CFHR1C3bB3bPPlasminThrombin FXaFIXa FXIaDegradationC5aC5bC5L2CPB2 CPNSSL5 Leishmanial protein kinase-1C9HeparinPlasmin


Description

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 [1] and are controlled by regulators [2]. 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 [3]. 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 [4]. 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 [5][6]. 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) [7]. 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)[8] 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)[9] has published a curated data on each protein involved in human complement activation pathways (refs. [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] ).

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Ontology Terms

 

Bibliography

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  1. Dinasarapu AR, Saunders B, Ozerlat I, Azam K, Subramaniam S; ''Signaling gateway molecule pages--a data model perspective.''; Bioinformatics, 2011 PubMed Europe PMC
  2. Chandrasekhar A, Dinasarapu AR, Thiel S, Subramaniam S; '' L-Ficolin.''; UCSD Molecule Pages, 2 (1), 37-44., 2013
  3. Dinasarapu AR, Chandrasekhar A, Fujita T, Subramaniam S; ''Mannose/mannan-binding lectin.''; UCSD Molecule Pages, 2013
  4. Dinasarapu AR, Chandrasekhar A, Sahu A, Subramaniam S; ''Complement C3''; UCSD Molecule Pages, 1 (2), 34-48, 2012
  5. Ricklin D, Hajishengallis G, Yang K, Lambris JD; ''Complement: a key system for immune surveillance and homeostasis.''; Nat Immunol, 2010 PubMed Europe PMC
  6. Dinasarapu AR, Chandrasekhar A, Hajishengallis G, Subramaniam S; '' Integrin beta-2. ''; UCSD Molecule Pages., 2013
  7. Chandrasekhar A, Dinasarapu AR, Isenman D.E, Subramaniam S; ''Complement C5. ''; UCSD Molecule Pages , 1 (2), 61-70., 2012
  8. Chandrasekhar A, Dinasarapu AR, Cedzyaski M, Subramaniam S; '' H-Ficolin. ''; UCSD Molecule Pages., 2013
  9. Yang K, Dinasarapu AR, Reis ES, Deangelis RA, Ricklin D, Subramaniam S, Lambris JD; ''CMAP: Complement Map Database.''; Bioinformatics, 2013 PubMed Europe PMC
  10. Chandrasekhar A, Dinasarapu AR, Tenner AJ, Subramaniam S; ''Complement C1q subcomponent subunit A.''; UCSD Molecule Pages, 1 (2), 49-60, 2012
  11. Dinasarapu A, Chandrasekhar A, Jozsi M, Subramaniam S; ''Complement factor H.''; UCSD Molecule Pages, 1 (2), 71-86, 2012
  12. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S; '' MASP-3. ''; UCSD Molecule Pages., 2013
  13. Dinasarapu AR, Chandrasekhar A, Inal J, Subramaniam S; ''Complement C2. ''; UCSD Molecule Pages., 2013
  14. Min J,, Chandrasekhar A, Dinasarapu AR, Kemper C, Subramaniam S; ''Properdin.''; UCSD Molecule Pages., 2014
  15. Chandrasekhar A, Dinasarapu AR, Thielens N, Subramaniam S; ''MASP-2. ''; UCSD Molecule Pages., 2013
  16. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S; '' MAp44.''; UCSD Molecule Pages., 2013
  17. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S; ''''; UCSD Molecule Pages., 2013
  18. Kishore U, Reid KB; ''C1q: structure, function, and receptors.''; Immunopharmacology, 2000 PubMed Europe PMC
  19. Dinasarapu AR, Chandrasekhar A, Sahu A, Subramaniam S; ''Complement C3''; UCSD Molecule Pages, 1 (2), 34-48. (doi: 10.6072/H0.M, 2012

History

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CompareRevisionActionTimeUserComment
107137view14:21, 17 September 2019MaintBotChEBI identifier normalization
105407view15:52, 7 August 2019DeSlModified description
105406view15:51, 7 August 2019DeSlModified description
105405view15:50, 7 August 2019DeSlModified description
105404view15:47, 7 August 2019DeSlModified description
105403view15:45, 7 August 2019DeSlModified description
105402view15:43, 7 August 2019DeSlModified description
105401view15:41, 7 August 2019DeSlModified description
105400view15:40, 7 August 2019DeSlModified description
105399view15:39, 7 August 2019DeSlModified description
105398view15:38, 7 August 2019DeSlModified description
105397view15:37, 7 August 2019DeSlModified description
105396view15:35, 7 August 2019DeSlModified description
105395view15:33, 7 August 2019DeSlModified description
105394view15:32, 7 August 2019DeSlModified description
105393view15:31, 7 August 2019DeSlAdded all lit. refs from description to main GPML
105374view15:37, 5 August 2019DeSlConnected unconnected lines
105373view15:36, 5 August 2019DeSlUpdated UTF-8 encoding in description text
105372view15:32, 5 August 2019DeSlStarted updating lit. refs from description to main PW
105315view22:44, 29 July 2019AriuttaHGNC -> HGNC Accession number.
103008view15:14, 31 January 2019Mkutmonupdated outdated Ensembl identifier
97328view19:27, 9 May 2018Khanspersconnected interactions
96979view18:20, 24 April 2018AlexanderPicoReverted to version '09:30, 7 March 2018' by AlexanderPico
96977view15:58, 24 April 2018WpblockedModified title
96299view16:30, 7 March 2018Fehrhartfixed connections
96298view16:27, 7 March 2018Fehrhartfixed connections
90154view07:48, 19 October 2016ElisaQuick edit to datanode annotation or property
89913view13:28, 6 October 2016MkutmonModified description
86150view08:26, 2 July 2016EgonwFixed a weird char in a reference.
85633view13:45, 4 June 2016EgonwReplaced a mim-conversion with Arrow.
85193view10:22, 24 April 2016EgonwRemoved redundant BioPax content, which broke RDF generation.
83005view09:25, 17 November 2015FehrhartUpdate ensembl ID for C2
78589view14:51, 7 January 2015MaintBotadded missing graphIds
78075view21:59, 29 November 2014EgonwPlaced a non-numeric Entrez Gene ID
77666view12:00, 5 October 2014EgonwReplaced 'Uniprot-SwissProt' by 'Uniprot-TrEMBL'.
77344view15:44, 23 August 2014EgonwFixed the XRef for heparan sulfate.
77343view15:43, 23 August 2014EgonwAdded DataSource annotation for Xrefs for two Ensembl IDs.
77342view14:17, 23 August 2014EgonwMarked a few DataNodes with ChEBI ids as Metabolite.
77158view20:59, 29 July 2014KhanspersOntology Term : 'complement system pathway' added !
77120view16:07, 21 July 2014AdinasarapuModified description
77119view15:59, 21 July 2014AdinasarapuModified description
77118view15:58, 21 July 2014AdinasarapuModified description
77117view15:15, 21 July 2014AdinasarapuModified title
76810view19:32, 16 July 2014Khanspersaddded doi
76809view19:22, 16 July 2014KhanspersAnother litref
76808view19:17, 16 July 2014Khanspersmoved literature reference from description to Bibliography
76480view11:58, 10 July 2014ElisaPeriodical save, work in progress
76479view11:26, 10 July 2014AnweshaAdded a literature reference
76478view10:58, 10 July 2014ElisaPeriodical save, work in progress
76440view14:55, 7 July 2014ElisaPeriodical save, work in progress

External references

DataNodes

View all...
NameTypeDatabase referenceComment
Leishmanial protein kinase-1GeneProduct
A2MGeneProductENSG00000175899 (Ensembl)
ADIPOQGeneProductENSG00000181092 (Ensembl)
ADMGeneProductENSG00000148926 (Ensembl)
ALBGeneProductENSG00000163631 (Ensembl)
APOA1GeneProductENSG00000118137 (Ensembl)
ARRB2GeneProductENSG00000141480 (Ensembl)
C1INHGeneProductENSG00000149131 (Ensembl)
C1qComplexA004228:32716 (Other)
  • C1q is composed of 18 polypeptide chains: six A-chains, six B-chains, and six C-chains.
  • Type your comment here
C1qRpGeneProductENSG00000125810 (Ensembl)
C1rGeneProductP00736 (Uniprot-TrEMBL)
C1sGeneProductENSG00000182326 (Ensembl)
C2GeneProductENSG00000166278 (Ensembl)
C3(H2O)GeneProduct629 (Entrez Gene)
C3GeneProductENSG00000125730 (Ensembl)
C3a-desArgGeneProduct718 (Entrez Gene)
C3aGeneProduct718 (Entrez Gene)
C3aR1GeneProductENSG00000171860 (Ensembl)
C3bB3bComplexAlternative C5 convertase

Complex Components C3b

Bb
C3bB3bPComplexAlternative C5 convertase and CFP complex

Complex Components C3b Bb

CFP
C3bBbComplexComplex Components

C3b

Bb
C3bBbPComplexComplex Components

C3b Bb

CFP
C3bGeneProductP01024 (Uniprot-TrEMBL)
C3cGeneProduct718 (Entrez Gene) Peptide fragment from complement C3
C3dGeneProduct718 (Entrez Gene) Peptide fragment from complement C3
C3fGeneProduct718 (Entrez Gene) Peptide fragment from complement C3
C4-AGeneProduct720 (Entrez Gene) Complement C4 exists in two isoforms, C4-A and C4-B.
C4BPGeneProductENSG00000123838 (Ensembl) Two isoforms exists (C4BPA and C4BPB).
C4a-desArgGeneProduct720 (Entrez Gene)
C4aGeneProduct720 (Entrez Gene)
C4b2bComplexComplex Components

C4b

C2b
C4b2b3bComplexClassical C5 convertase

Complex Components C4b C2b

C3b
C4bGeneProduct720 (Entrez Gene)
C5GeneProduct727 (Entrez Gene)
C5L2GeneProductENSG00000134830 (Ensembl)
C5a-desArgGeneProduct727 (Entrez Gene)
C5aGeneProduct727 (Entrez Gene)
C5aR1GeneProductENSG00000197405 (Ensembl)
C5bGeneProduct727 (Entrez Gene)
C6GeneProductENSG00000039537 (Ensembl)
C7GeneProductENSG00000112936 (Ensembl)
C8GeneProductENSG00000157131 (Ensembl) Complement C8 exhists in 3 isoforms.
C9GeneProductENSG00000113600 (Ensembl)
CD16aGeneProductENSG00000203747 (Ensembl)
CD19GeneProductENSG00000177455 (Ensembl)
CD23GeneProductENSG00000104921 (Ensembl)
CD40GeneProductENSG00000101017 (Ensembl)
CD59GeneProductENSG00000085063 (Ensembl)
CFBGeneProduct1037 (HGNC Accession number)
CFDGeneProductENSG00000197766 (Ensembl)
CFHGeneProductENSG00000000971 (Ensembl)
CFHR1GeneProductENSG00000080910 (Ensembl)
CFHR4GeneProductENSG00000134365 (Ensembl)
CFIGeneProductENSG00000205403 (Ensembl)
CFPGeneProductENSG00000126759 (Ensembl)
CHIPSGeneProduct5332454 (Entrez Gene)
CKGeneProductENSG00000113712 (Ensembl)
CLEC4MGeneProductENSG00000104938 (Ensembl)
CPB2 GeneProductENSG00000120054 (Ensembl)
CPNGeneProductENSG00000120054 (Ensembl)
CR1GeneProductENSG00000203710 (Ensembl)
CR2GeneProductENSG00000117322 (Ensembl)
CR3ComplexENSG00000160255 (Ensembl) ITGAM and ITGB2
CR4ComplexENSG00000140678 (Ensembl) ITGB2 and ITGAX
CRIgGeneProductENSG00000155659 (Ensembl)
CRPGeneProductENSG00000132693 (Ensembl)
CbpAGeneProduct933487 (Entrez Gene)
ClfAGeneProduct2859231 (Entrez Gene)
ClfBGeneProduct5331889 (Entrez Gene)
DAFGeneProductENSG00000196352 (Ensembl)
DCNGeneProductENSG00000011465 (Ensembl)
E-LDLGeneProductENSG00000173486 (Ensembl)
ELANEGeneProductENSG00000197561 (Ensembl)
EfbGeneProduct3238454 (Entrez Gene)
EhpGeneProductYP_043213 (Entrez Gene)
FCN1GeneProductENSG00000085265 (Ensembl)
FCN2GeneProductENSG00000160339 (Ensembl)
FGAGeneProduct2243 (Entrez Gene)
FGAGeneProductENSG00000171560 (Ensembl)
FGBGeneProduct2244 (Entrez Gene)
FGBGeneProductENSG00000171564 (Ensembl)
FGGGeneProductENSG00000171557 (Ensembl)
FKBP13GeneProductENSG00000173486 (Ensembl)
FNGeneProductENSG0000011541 (Ensembl)
FPR1GeneProductENSG00000171051 (Ensembl)
FXGeneProductENSG00000126218 (Ensembl)
FXIIIGeneProductENSG00000124491 (Ensembl)
FXIIaGeneProductP00748 (Uniprot-TrEMBL)
FXIaGeneProductP03951 (Uniprot-TrEMBL)
FnBPAGeneProduct3913735 (Entrez Gene)
FnBPBGeneProduct3913823 (Entrez Gene)
GNA15GeneProductENSG00000060558 (Ensembl)
GNA1870GeneProduct12393750 (Entrez Gene)
GNAI2GeneProductENSG00000114353 (Ensembl)
GNAI3GeneProductENSG00000065135 (Ensembl)
Gpm1pGeneProduct A factor H-, FHL-1-, and plasminogen-binding surface protein of Candida albicans
Gpm1pGeneProductXP_721143 (Entrez Gene)
HIV-gp41GeneProduct155971 (Entrez Gene)
HSMetaboliteCHEBI:28815 (ChEBI)
HSV-gCGeneProduct2703410 (Entrez Gene)
HeparinMetaboliteCHEBI:28304 (ChEBI)
IBSPGeneProductENSG00000029559 (Ensembl)
ICAM1GeneProductENSG00000090339 (Ensembl)
ICAM2GeneProductENSG00000108622 (Ensembl)
ITGA2BGeneProductENSG00000005961 (Ensembl)
ITGA2GeneProductENSG00000164171 (Ensembl)
ITGB3GeneProductENSG00000259207 (Ensembl)
KLKB1GeneProductENSG00000164344 (Ensembl)
LAMA5GeneProductENSG00000130702 (Ensembl)
LAMB1GeneProductENSG00000091136 (Ensembl)
LAMC1GeneProductENSG00000135862 (Ensembl)
LRP2GeneProductENSG00000081479 (Ensembl)
LTAMetaboliteCHEBI:28640 (ChEBI)
LfhAGeneProductAAN47894 (Entrez Gene)
MASP1GeneProductENSG00000127241 (Ensembl)
MAp19GeneProduct10747 (Entrez Gene)
MAp44GeneProduct5648 (Entrez Gene)
MBL2GeneProductENSG00000165471 (Ensembl)
MCPGeneProductENSG00000117335 (Ensembl)
NS1GeneProductAAM51537|780
OMCIGeneProductAAT65682 (Entrez Gene)
OPNGeneProductENSG00000118785 (Ensembl)
OmpK36GeneProductAEW62399 (Entrez Gene)
PKAGeneProductENSG00000072062 (Ensembl)
PKCGeneProductENSG00000154229 (Ensembl)
PLAURGeneProductENSG00000011422 (Ensembl)
PLGGeneProductENSG00000122194 (Ensembl)
PTX3GeneProductENSG00000163661 (Ensembl)
Por1AGeneProduct
Por1BGeneProduct
PrPGeneProductENSG00000171867 (Ensembl)
Protein MGeneProduct2940887 (NCBI Protein)
Protein-AGeneProduct5332074 (Entrez Gene)
Protein-SGeneProductENSG00000184500 (Ensembl)
RPS19GeneProductENSG00000105372 (Ensembl)
RgpAGeneProduct6330747 (NCBI Protein) Gngipain-1
SAPGeneProductENSG00000132703 (Ensembl)
SCINGeneProductENSG00000106804 (Ensembl)
SCPGeneProduct1030336 (NCBI Protein) Streptococcal C5a peptidase
SELEGeneProductENSG00000007908 (Ensembl)
SELLGeneProductENSG00000188404 (Ensembl)
SELPGeneProductENSG00000174175 (Ensembl)
SELPLGGeneProductENSG00000110876 (Ensembl)
SFTPA1GeneProductENSG00000122852 (Ensembl)
SFTPA2GeneProductENSG00000185303 (Ensembl)
SICGeneProduct269972 (Entrez Gene)
SPICEGeneProductSmall inhbitor of complement enzymes
SSL10GeneProduct2859141 (Entrez Gene)
SSL11GeneProduct1123177 (Entrez Gene)
SSL5GeneProduct2859140 (Entrez Gene)
SSL7GeneProduct2859139 (Entrez Gene)
SbiGeneProduct5331420 (Entrez Gene)
SfbGeneProduct3573107 (Entrez Gene)
SkpGeneProductADD54834 (Entrez Gene)
StcEGeneProductAAU25886 (Entrez Gene)
TFECP GeneProductT. foetus extracellular cysteine proteinase
THBSGeneProductENSG00000137801 (Ensembl)
TLR2GeneProduct7097 (Entrez Gene)
TXNGeneProductENSG00000136810 (Ensembl)
VCP GeneProduct3707640 (Entrez Gene)
VTNGeneProductENSG00000109072 (Ensembl)
WASGeneProductENSG00000015285 (Ensembl)
beta-GlucanMetaboliteCHEBI:28793 (ChEBI)
cC1qRGeneProductENSG00000179218 (Ensembl)
fMLPMetaboliteCHEBI:53490 (ChEBI)
gC1qRGeneProductENSG00000108561 (Ensembl)
gp350GeneProductYP_001129462 (Entrez Gene)
iC3bGeneProductP01024 (Uniprot-TrEMBL) Peptide fragment from complement C3

Annotated Interactions

No annotated interactions

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