Complement activation (WP545)

Homo sapiens

The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system. The classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. [source: Wikipedia] The classical pathway begins with circulating C1Q binding to an antigen on the surface of a pathogen, which goes on to active and recruit 2 copies of each C1R and C1S, forming a C1 complex. The activated C1 complex cleaves C2 and C4. Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. The cleavage product C5B joins C6, C7, C8 and multiple copies of C9 to form the membrane attack complex, which forms a channel for water to flood into the target cell, leading to osmotic lysis. The decay accelerating factor (DAF) inhibits C3 convertase. The lectin pathway involves mannose-binding lectin (MBL) binding the surface of the pathogen instead of C1Q. MBL-associated serine proteases MASP1 and MASP1 can cleave C2 and C4 in place of the C1 complex, leading to the formation of C3 convertase and the subsequent cascade. The alternative pathway relies on the spontaneous hydrolysis of C3 and the cleavage of factor B (CFB) by factor D (CFD), which form an alternative C3 convertase stabilized by factor P (CFP). Additional copies of the cleavage product C3B are recruited to the complex, resulting in an alternative C5 convertase, which cleaves C5 and contributes C5B to the formation of the membrane attack complex. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP545 CPTAC Assay Portal]

Authors

Nathan Salomonis , Kristina Hanspers , Michiel Adriaens , Christine Chichester , Martina Summer-Kutmon , Alex Pico , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

classical complement pathway

Participants

Label Type Compact URI Comment
H2O Metabolite hmdb:HMDB0002111
C1S GeneProduct ncbigene:716
C1QB GeneProduct ncbigene:713
C1R GeneProduct ensembl:ENSG00000159403
C1QA GeneProduct ncbigene:712 update: C1QA HUMAN
C1QG GeneProduct ncbigene:714 update C1QC HUMAN
C8A GeneProduct ncbigene:731
MASP2 GeneProduct ncbigene:10747
C2A GeneProduct ncbigene:717
C3 GeneProduct ncbigene:718
C9 GeneProduct ncbigene:735
C8B GeneProduct ncbigene:732
C6 GeneProduct ncbigene:729
C4B GeneProduct ncbigene:721
DAF GeneProduct ncbigene:1604
C4A GeneProduct ncbigene:720
C7 GeneProduct ncbigene:730
C5 GeneProduct ncbigene:727
C2 GeneProduct ncbigene:717
C3B GeneProduct ncbigene:718
C5B GeneProduct ncbigene:727
C8G GeneProduct ncbigene:733
MASP1 GeneProduct ncbigene:5648
CFBb GeneProduct ncbigene:629
CFB GeneProduct ncbigene:629
CFD GeneProduct ncbigene:1675
CFP GeneProduct ncbigene:5199

References

  1. Opportunities for new therapies based on the natural regulators of complement activation. Brook E, Herbert AP, Jenkins HT, Soares DC, Barlow PN. Ann N Y Acad Sci. 2005 Nov;1056:176–88. PubMed Europe PMC Scholia