UCSD Molecule Pages
Published online: 19 Oct 2012 | doi:10.6072/H0.MP.A004240.01
Basis Sequence: Human
Anjana Chandrasekhar1, Ashok Reddy Dinasarapu1, David E. Isenman2, Shankar Subramaniam3
1Department of Bioengineering, University of California, San Diego, CA 92093, US. 2University of Toronto, M5S 1A8, CA. 3Department of Bioengineering, University of California at San Diego, CA 92093, US.
Correspondence should be addressed to Anjana Chandrasekhar: firstname.lastname@example.org
Complement C5 is a 189 kDa protein synthesized in liver as a single-chain precursor molecule. The precursor molecule is then cleaved to a disulfide linked two-chain glycoprotein consisting of a 115 kDa (C5α) and a 75 kDa N-terminal (C5β) chain. C5 is present in all the three known complement activation pathways: classical, alternative and lectin. C5α chain is cleaved by C5 convertases, which are formed during the complement activation process, to form C5a (74 a.a long) and C5α' chain (925 a.a long). C5α' chain and C5β chain (655 a.a. long) together form C5b. C5a is a major anaphylotoxin involved in chemotaxis of neutrophils and release of pro-inflammatory cytokines. These functions of C5a require binding to its receptor, C5aR. C5b sequentially recruits C6, C7, C8 and C9 in a non-enzymatic manner to form the terminal complement complex (TCC, also called membrane attack complex or MAC). TCC forms a lytic pore in the target membrane and kills the pathogen. While the functions of C5a and C5b aid in killing the pathogen, they can also be responsible for generating an excess inflammatory response, which can damage host cells. Therefore, C5 functions are tightly regulated by interaction with other proteins in host. The regulatory proteins can either be host generated or pathogenic factors. Unregulated C5 function can result in disease phenotypes. Therapeutic antibodies against C5 are being developed with a view to treat these conditions.
Alternative names for this molecule:
Anaphylatoxin C5a analog; C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4; C5; Complement C5; Complement component 5; CPAMD4
The UCSD Signaling Gateway Molecule Pages (SGMP) is funded by NIH/NIGMS Grant 1 R01 GM078005-01. The authors thank Dr. John D. Lambris, University of Pennsylvania, Philadelphia, UCSD-SGMP editorial board member, for extensive discussions.