Complement component 5 is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. This protein is composed of alpha and beta polypeptide chains that are linked by a disulfide bridge. An activation peptide, C5a, which is an anaphylatoxin that possesses potent spasmogenic and chemotactic activity, is derived from the alpha polypeptide via cleavage with a C5-convertase. The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components.[5]
Clinical significance
Mutations in this gene cause complement component 5 deficiency, a disease where patients show a propensity for severe recurrent infections. Defects in this gene have also been linked to a susceptibility to liver fibrosis and to rheumatoid arthritis.[5]
Therapeutic applications
The drug eculizumab (trade name Soliris) prevents cleavage of C5 into C5a and C5b.[7]
Complement system pathway
Membrane attack complex.
References
^ abcGRCh38: Ensembl release 89: ENSG00000106804 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000026874 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abc"C5 complement C5 (Homo sapiens (human)) Gene ID: 727". www.ncbi.nlm.nih.gov. 29 November 2020. Retrieved 9 December 2020.
^Dubois E, Cohen A (2009). "Eculizumab". Br J Clin Pharmacol. 68 (3): 318–319. doi:10.1111/j.1365-2125.2009.03491.x. PMC2766470. PMID 19740388.
Further reading
Tack BF, Morris SC, Prahl JW (1979). "Fifth component of human complement: purification from plasma and polypeptide chain structure". Biochemistry. 18 (8): 1490–7. doi:10.1021/bi00575a016. PMID 106884.
Fernandez HN, Hugli TE (1978). "Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a". J. Biol. Chem. 253 (19): 6955–64. doi:10.1016/S0021-9258(17)38013-4. PMID 690134.
DiScipio RG (1992). "Formation and structure of the C5b-7 complex of the lytic pathway of complement". J. Biol. Chem. 267 (24): 17087–94. doi:10.1016/S0021-9258(18)41897-2. PMID 1387399.
Haviland DL, Haviland JC, Fleischer DT, et al. (1991). "Complete cDNA sequence of human complement pro-C5. Evidence of truncated transcripts derived from a single copy gene". J. Immunol. 146 (1): 362–8. PMID 1984448.
Bohnsack JF, Mollison KW, Buko AM, et al. (1991). "Group B streptococci inactivate complement component C5a by enzymic cleavage at the C-terminus". Biochem. J. 273 (Pt 3): 635–40. doi:10.1042/bj2730635. PMC1149811. PMID 1996961.
Lundwall AB, Wetsel RA, Kristensen T, et al. (1985). "Isolation and sequence analysis of a cDNA clone encoding the fifth complement component". J. Biol. Chem. 260 (4): 2108–12. doi:10.1016/S0021-9258(18)89523-0. PMID 2579066.
Zuiderweg ER, Fesik SW (1989). "Heteronuclear three-dimensional NMR spectroscopy of the inflammatory protein C5a". Biochemistry. 28 (6): 2387–91. doi:10.1021/bi00432a008. PMID 2730871.
Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW (1989). "Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data". Biochemistry. 28 (1): 172–85. doi:10.1021/bi00427a025. PMID 2784981.
Haefliger JA, Tschopp J, Vial N, Jenne DE (1989). "Complete primary structure and functional characterization of the sixth component of the human complement system. Identification of the C5b-binding domain in complement C6". J. Biol. Chem. 264 (30): 18041–51. doi:10.1016/S0021-9258(19)84676-8. PMID 2808363.
Wetsel RA, Lemons RS, Le Beau MM, et al. (1988). "Molecular analysis of human complement component C5: localization of the structural gene to chromosome 9". Biochemistry. 27 (5): 1474–82. doi:10.1021/bi00405a012. PMID 3365401.
Zuiderweg ER, Mollison KW, Henkin J, Carter GW (1988). "Sequence-specific assignments in the 1H NMR spectrum of the human inflammatory protein C5a". Biochemistry. 27 (10): 3568–80. doi:10.1021/bi00410a007. PMID 3408713.
Stewart JL, Kolb WP, Sodetz JM (1987). "Evidence that C5b recognizes and mediates C8 incorporation into the cytolytic complex of complement". J. Immunol. 139 (6): 1960–4. PMID 3624872.
Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor". J. Biol. Chem. 270 (34): 19828–32. doi:10.1074/jbc.270.34.19828. PMID 7649993.
Babkina IN, Seregin SV, Daniliuk NK, et al. (1995). "[Chemico-enzymatic synthesis, cloning and expression of a gene for an analog of human anaphylatoxin C5a]". Bioorg. Khim. 21 (5): 359–64. PMID 7661861.
Wang X, Fleischer DT, Whitehead WT, et al. (1995). "Inherited human complement C5 deficiency. Nonsense mutations in exons 1 (Gln1 to Stop) and 36 (Arg1458 to Stop) and compound heterozygosity in three African-American families". J. Immunol. 154 (10): 5464–71. PMID 7730648.
Oppermann M, Götze O (1995). "Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors". Immunology. 82 (4): 516–21. PMC1414921. PMID 7835913.
Süsal C, Kirschfink M, Kröpelin M, et al. (1994). "Complement activation by recombinant HIV-1 glycoprotein gp120". J. Immunol. 152 (12): 6028–34. PMID 7911492.
Arribas J, Arizti P, Castaño JG (1994). "Antibodies against the C2 COOH-terminal region discriminate the active and latent forms of the multicatalytic proteinase complex". J. Biol. Chem. 269 (17): 12858–64. doi:10.1016/S0021-9258(18)99955-2. PMID 8175701.
Süsal C, Kirschfink M, Kröpelin M, et al. (1996). "Identification of complement activation sites in human immunodeficiency virus type-1 glycoprotein gp120". Blood. 87 (6): 2329–36. doi:10.1182/blood.V87.6.2329.bloodjournal8762329. PMID 8630395.
Ames RS, Li Y, Sarau HM, et al. (1996). "Molecular cloning and characterization of the human anaphylatoxin C3a receptor". J. Biol. Chem. 271 (34): 20231–4. doi:10.1074/jbc.271.34.20231. PMID 8702752.
Fredslund F, Laursen NS, Roversi P, et al. (2008). "Structure of and influence of a tick complement inhibitor on human complement component 5". Nat Immunol. 9 (7): 753–60. doi:10.1038/ni.1625. PMID 18536718. S2CID 205361576.
complement, component, protein, that, humans, encoded, gene, c5available, structurespdbortholog, search, pdbe, rcsblist, codes1cfa, 1kjs, 1xwe, 3cu7, 3hqa, 3hqb, 3kls, 3km9, 3prx, 3pvm, 4a5w, 4e0s, 4p39, 4uu9, 5i5k, 5hce, 5hcc, 5hcdidentifiersaliasesc5, cpamd4. Complement component 5 is a protein that in humans is encoded by the C5 gene 5 C5Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1CFA 1KJS 1XWE 3CU7 3HQA 3HQB 3KLS 3KM9 3PRX 3PVM 4A5W 4E0S 4P39 4UU9 5I5K 5HCE 5HCC 5HCDIdentifiersAliasesC5 C5D C5a C5b CPAMD4 ECLZB complement component 5 complement C5External IDsOMIM 120900 MGI 96031 HomoloGene 20412 GeneCards C5Gene location Human Chr Chromosome 9 human 1 Band9q33 2Start120 932 642 bp 1 End121 075 195 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 B 2 23 22 cMStart34 873 343 bp 2 End34 951 450 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inright lobe of liveroocytebody of pancreassecondary oocyteAchilles tendontibial nerveleft coronary arterypopliteal arterybody of stomachlower lobe of lungTop expressed inleft lobe of liverright lung lobeleft lungleft lung lobegallbladdersecondary oocytecarotid bodyhabenulathoracic diaphragmconjunctival fornixMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionchemokine activity protein binding endopeptidase inhibitor activity signaling receptor bindingCellular componentextracellular region extracellular exosome membrane attack complex extracellular spaceBiological processG protein coupled receptor signaling pathway cytolysis complement activation alternative pathway immune system process complement activation response to stress in utero embryonic development positive regulation of angiogenesis chemotaxis cell surface receptor signaling pathway complement activation classical pathway positive regulation of vascular endothelial growth factor production inflammatory response regulation of complement activation negative regulation of macrophage chemotaxis negative regulation of endopeptidase activity innate immune response cell chemotaxisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez72715139EnsemblENSG00000106804ENSMUSG00000026874UniProtP01031P06684RefSeq mRNA NM 001735NM 001317163NM 001317164NM 010406RefSeq protein NP 001304092NP 001304093NP 001726NP 034536Location UCSC Chr 9 120 93 121 08 MbChr 2 34 87 34 95 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseComplement component 5 is involved in the complement system It is cleaved into C5a and C5b C5a plays an important role in chemotaxis 6 C5b forms the first part of the complement membrane attack complex Deficiency is thought to cause Leiner s disease Contents 1 Function 2 Clinical significance 3 Therapeutic applications 4 Complement system pathway 5 References 6 Further reading 7 External linksFunction EditComplement component 5 is the fifth component of complement which plays an important role in inflammatory and cell killing processes This protein is composed of alpha and beta polypeptide chains that are linked by a disulfide bridge An activation peptide C5a which is an anaphylatoxin that possesses potent spasmogenic and chemotactic activity is derived from the alpha polypeptide via cleavage with a C5 convertase The C5b macromolecular cleavage product can form a complex with the C6 complement component and this complex is the basis for formation of the membrane attack complex which includes additional complement components 5 Clinical significance EditMutations in this gene cause complement component 5 deficiency a disease where patients show a propensity for severe recurrent infections Defects in this gene have also been linked to a susceptibility to liver fibrosis and to rheumatoid arthritis 5 Therapeutic applications EditThe drug eculizumab trade name Soliris prevents cleavage of C5 into C5a and C5b 7 Complement system pathway Edit Membrane attack complex References Edit a b c GRCh38 Ensembl release 89 ENSG00000106804 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000026874 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c C5 complement C5 Homo sapiens human Gene ID 727 www ncbi nlm nih gov 29 November 2020 Retrieved 9 December 2020 Immunology at MCG 1 phagocyt dead link Dubois E Cohen A 2009 Eculizumab Br J Clin Pharmacol 68 3 318 319 doi 10 1111 j 1365 2125 2009 03491 x PMC 2766470 PMID 19740388 Further reading EditTack BF Morris SC Prahl JW 1979 Fifth component of human complement purification from plasma and polypeptide chain structure Biochemistry 18 8 1490 7 doi 10 1021 bi00575a016 PMID 106884 Fernandez HN Hugli TE 1978 Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a J Biol Chem 253 19 6955 64 doi 10 1016 S0021 9258 17 38013 4 PMID 690134 DiScipio RG 1992 Formation and structure of the C5b 7 complex of the lytic pathway of complement J Biol Chem 267 24 17087 94 doi 10 1016 S0021 9258 18 41897 2 PMID 1387399 Haviland DL Haviland JC Fleischer DT et al 1991 Complete cDNA sequence of human complement pro C5 Evidence of truncated transcripts derived from a single copy gene J Immunol 146 1 362 8 PMID 1984448 Bohnsack JF Mollison KW Buko AM et al 1991 Group B streptococci inactivate complement component C5a by enzymic cleavage at the C terminus Biochem J 273 Pt 3 635 40 doi 10 1042 bj2730635 PMC 1149811 PMID 1996961 Lundwall AB Wetsel RA Kristensen T et al 1985 Isolation and sequence analysis of a cDNA clone encoding the fifth complement component J Biol Chem 260 4 2108 12 doi 10 1016 S0021 9258 18 89523 0 PMID 2579066 Zuiderweg ER Fesik SW 1989 Heteronuclear three dimensional NMR spectroscopy of the inflammatory protein C5a Biochemistry 28 6 2387 91 doi 10 1021 bi00432a008 PMID 2730871 Zuiderweg ER Nettesheim DG Mollison KW Carter GW 1989 Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data Biochemistry 28 1 172 85 doi 10 1021 bi00427a025 PMID 2784981 Haefliger JA Tschopp J Vial N Jenne DE 1989 Complete primary structure and functional characterization of the sixth component of the human complement system Identification of the C5b binding domain in complement C6 J Biol Chem 264 30 18041 51 doi 10 1016 S0021 9258 19 84676 8 PMID 2808363 Wetsel RA Lemons RS Le Beau MM et al 1988 Molecular analysis of human complement component C5 localization of the structural gene to chromosome 9 Biochemistry 27 5 1474 82 doi 10 1021 bi00405a012 PMID 3365401 Zuiderweg ER Mollison KW Henkin J Carter GW 1988 Sequence specific assignments in the 1H NMR spectrum of the human inflammatory protein C5a Biochemistry 27 10 3568 80 doi 10 1021 bi00410a007 PMID 3408713 Stewart JL Kolb WP Sodetz JM 1987 Evidence that C5b recognizes and mediates C8 incorporation into the cytolytic complex of complement J Immunol 139 6 1960 4 PMID 3624872 Buhl AM Osawa S Johnson GL 1995 Mitogen activated protein kinase activation requires two signal inputs from the human anaphylatoxin C5a receptor J Biol Chem 270 34 19828 32 doi 10 1074 jbc 270 34 19828 PMID 7649993 Babkina IN Seregin SV Daniliuk NK et al 1995 Chemico enzymatic synthesis cloning and expression of a gene for an analog of human anaphylatoxin C5a Bioorg Khim 21 5 359 64 PMID 7661861 Wang X Fleischer DT Whitehead WT et al 1995 Inherited human complement C5 deficiency Nonsense mutations in exons 1 Gln1 to Stop and 36 Arg1458 to Stop and compound heterozygosity in three African American families J Immunol 154 10 5464 71 PMID 7730648 Oppermann M Gotze O 1995 Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors Immunology 82 4 516 21 PMC 1414921 PMID 7835913 Susal C Kirschfink M Kropelin M et al 1994 Complement activation by recombinant HIV 1 glycoprotein gp120 J Immunol 152 12 6028 34 PMID 7911492 Arribas J Arizti P Castano JG 1994 Antibodies against the C2 COOH terminal region discriminate the active and latent forms of the multicatalytic proteinase complex J Biol Chem 269 17 12858 64 doi 10 1016 S0021 9258 18 99955 2 PMID 8175701 Susal C Kirschfink M Kropelin M et al 1996 Identification of complement activation sites in human immunodeficiency virus type 1 glycoprotein gp120 Blood 87 6 2329 36 doi 10 1182 blood V87 6 2329 bloodjournal8762329 PMID 8630395 Ames RS Li Y Sarau HM et al 1996 Molecular cloning and characterization of the human anaphylatoxin C3a receptor J Biol Chem 271 34 20231 4 doi 10 1074 jbc 271 34 20231 PMID 8702752 Fredslund F Laursen NS Roversi P et al 2008 Structure of and influence of a tick complement inhibitor on human complement component 5 Nat Immunol 9 7 753 60 doi 10 1038 ni 1625 PMID 18536718 S2CID 205361576 External links EditComplement 5 at the US National Library of Medicine Medical Subject Headings MeSH This article incorporates text from the United States National Library of Medicine which is in the public domain This article on a gene on human chromosome 9 is a stub You can help Wikipedia by expanding it vte 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