Complement system (WP2806)
Homo sapiens
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] ).
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 IkedaActivity
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Cited In
- Looking for pathways related to COVID-19: confirmation of pathogenic mechanisms by SARS-CoV-2–host interactome (2021).
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- Long Term Culture of the A549 Cancer Cell Line Promotes Multilamellar Body Formation and Differentiation towards an Alveolar Type II Pneumocyte Phenotype (2016).
- Acute and chronic blood serum proteome changes in patients with methanol poisoning (2022).
- Discovering Common Pathogenic Mechanisms of COVID-19 and Parkinson Disease: An Integrated Bioinformatics Analysis (2022).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
complement system pathwayReferences
- 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
- Complement C2 [Internet]. Dinasarapu AR. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004234 DOI Scholia
- Complement C3 [Internet]. Dinasarapu. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004235 DOI Scholia
- Complement C5 [Internet]. Chandrasekhar. UCSD Signaling Gateway Molecule Pages; 2012. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004240 DOI Scholia
- 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
- Properdin [Internet]. Min J. UCSD Signaling Gateway Molecule Pages; 2014. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004258 DOI Scholia
- 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
- L-Ficolin [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004266 DOI Scholia
- H-Ficolin [Internet]. Chandrasekhar A. UCSD Signaling Gateway; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004267 DOI Scholia
- MASP-1 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004274 DOI Scholia
- MASP-2 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A004275 DOI Scholia
- 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
- MASP-3 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A008391 DOI Scholia
- MAp44 [Internet]. Chandrasekhar A. UCSD Signaling Gateway Molecule Pages; 2013. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A008392 DOI Scholia
- C1q: structure, function, and receptors. Kishore U, Reid KB. Immunopharmacology. 2000 Aug;49(1–2):159–70. PubMed Europe PMC Scholia
- 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
- 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
- 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