Complement component 1r explained

Complement C1r subcomponent (activated complement C1r, C overbar 1r esterase, C1r) is a protein involved in the complement system of the innate immune system.^{[1] [2] [3]} In humans, C1r is encoded by the C1R gene.^[4]

C1r along with C1q and C1s form the C1 complex, which is the first component of the serum complement system. C1r is an enzyme that activates C1s to its active form, by proteolytic cleavage.

Clinical significance

• Ehlers–Danlos syndrome Periodontal type is associated with mutations in the CR1 gene

Function

C1r has been shown to interact with C1s. C1r cleaves C1s to form the active form of C1s.^{[5] [6]}

Further reading

• Lee SL, Wallace SL, Barone R, Blum L, Chase PH . Familial deficiency of two subunits of the first component of complement. C1r and C1s associated with a lupus erythematosus-like disease . Arthritis and Rheumatism . 21 . 8 . 958–67 . 1979 . 737019 . 10.1002/art.1780210813 .
• Ward SL, Ingham KC . A calcium-binding monoclonal antibody that recognizes a non-calcium-binding epitope in the short consensus repeat units (SCRs) of complement C1r . Molecular Immunology . 29 . 1 . 83–93 . January 1992 . 1370572 . 10.1016/0161-5890(92)90160-Y .
• Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, Zavodszky P, Arlaud GJ, Schumaker VN . Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex . Biochemistry . 31 . 17 . 4254–62 . May 1992 . 1533159 . 10.1021/bi00132a015 .
• Busby TF, Ingham KC . NH2-terminal calcium-binding domain of human complement C1s- mediates the interaction of C1r- with C1q . Biochemistry . 29 . 19 . 4613–8 . May 1990 . 2372546 . 10.1021/bi00471a016 .
• Lyons LA, Kamboh MI, Ferrell RE . Genetic studies of low-abundance human plasma proteins. XI. Linkage analysis and population genetics of the C1S subcomponent of the first complement component . Complement and Inflammation . 6 . 2 . 81–7 . 1989 . 2541966 . 10.1159/000463078.
• Arlaud GJ, Van Dorsselaer A, Bell A, Mancini M, Aude C, Gagnon J . Identification of erythro-beta-hydroxyasparagine in the EGF-like domain of human C1r . FEBS Letters . 222 . 1 . 129–34 . September 1987 . 2820791 . 10.1016/0014-5793(87)80205-3 . 36194093 . free . 1987FEBSL.222..129A .
• Nguyen VC, Tosi M, Gross MS, Cohen-Haguenauer O, Jegou-Foubert C, de Tand MF, Meo T, Frézal J . Assignment of the complement serine protease genes C1r and C1s to chromosome 12 region 12p13 . Human Genetics . 78 . 4 . 363–8 . April 1988 . 2834284 . 10.1007/BF00291737 . 30582112 .
• Leytus SP, Kurachi K, Sakariassen KS, Davie EW . Nucleotide sequence of the cDNA coding for human complement C1r . Biochemistry . 25 . 17 . 4855–63 . August 1986 . 3021205 . 10.1021/bi00365a020 .
• Journet A, Tosi M . Cloning and sequencing of full-length cDNA encoding the precursor of human complement component C1r . The Biochemical Journal . 240 . 3 . 783–7 . December 1986 . 3030286 . 1147487 . 10.1042/bj2400783.
• Arlaud GJ, Willis AC, Gagnon J . Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r . The Biochemical Journal . 241 . 3 . 711–20 . February 1987 . 3036070 . 1147622 . 10.1042/bj2410711.
• Chesne S, Villiers CL, Arlaud GJ, Lacroix MB, Colomb MG . Fluid-phase interaction of C1 inhibitor (C1 Inh) and the subcomponents C1r and C1s of the first component of complement, C1 . The Biochemical Journal . 201 . 1 . 61–70 . January 1982 . 6282262 . 1163609 . 10.1042/bj2010061.
• Arlaud GJ, Gagnon J . Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r . Biochemistry . 22 . 8 . 1758–64 . April 1983 . 6303394 . 10.1021/bi00277a003 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Nöthen MM, Dewald G . A common amino acid polymorphism in complement component C1R . Human Molecular Genetics . 3 . 1 . 217 . January 1994 . 8162045 . 10.1093/hmg/3.1.217-a .
• Gasque P, Ischenko A, Legoedec J, Mauger C, Schouft MT, Fontaine M . Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells . The Journal of Biological Chemistry . 268 . 33 . 25068–74 . November 1993 . 10.1016/S0021-9258(19)74572-4 . 8227070 . free .
• Pelloux S, Thielens NM, Hudry-Clergeon G, Pétillot Y, Filhol O, Arlaud GJ . Identification of a cryptic protein kinase CK2 phosphorylation site in human complement protease Clr, and its use to probe intramolecular interaction . FEBS Letters . 386 . 1 . 15–20 . May 1996 . 8635594 . 10.1016/0014-5793(96)00403-6 . 28372780 . free . 1996FEBSL.386...15P .
• Bradley K, North J, Saunders D, Schwaeble W, Jeziorska M, Woolley DE, Whaley K . Synthesis of classical pathway complement components by chondrocytes . Immunology . 88 . 4 . 648–56 . August 1996 . 8881771 . 1456645 .
• Lacroix M, Rossi V, Gaboriaud C, Chevallier S, Jaquinod M, Thielens NM, Gagnon J, Arlaud GJ . Structure and assembly of the catalytic region of human complement protease C1r: a three-dimensional model based on chemical cross-linking and homology modeling . Biochemistry . 36 . 21 . 6270–82 . May 1997 . 9174342 . 10.1021/bi962719i .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Bersch B, Hernandez JF, Marion D, Arlaud GJ . Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family . Biochemistry . 37 . 5 . 1204–14 . February 1998 . 9477945 . 10.1021/bi971851v .

Notes and References

1. Book: Sim RB . The human complement system serine proteases and their proenzymes . Proteolytic Enzymes, Part C . Methods in Enzymology . 80 Pt C . 26–42 . 1981 . 6281620 . 10.1016/s0076-6879(81)80006-7 . 9780121819804 .
2. Leytus SP, Kurachi K, Sakariassen KS, Davie EW . Nucleotide sequence of the cDNA coding for human complement C1r . Biochemistry . 25 . 17 . 4855–63 . August 1986 . 3021205 . 10.1021/bi00365a020 .
3. Müller-Eberhard HJ . Molecular organization and function of the complement system . Annual Review of Biochemistry . 57 . 321–47 . 1988 . 3052276 . 10.1146/annurev.bi.57.070188.001541 .
4. Web site: Entrez Gene: C1R complement component 1, r subcomponent.
5. Thielens NM, Enrie K, Lacroix M, Jaquinod M, Hernandez JF, Esser AF, Arlaud GJ . The N-terminal CUB-epidermal growth factor module pair of human complement protease C1r binds Ca2+ with high affinity and mediates Ca2+-dependent interaction with C1s . The Journal of Biological Chemistry . 274 . 14 . 9149–59 . April 1999 . 10092586 . 10.1074/jbc.274.14.9149 . free .
6. Thiel S, Petersen SV, Vorup-Jensen T, Matsushita M, Fujita T, Stover CM, Schwaeble WJ, Jensenius JC . Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19 . Journal of Immunology . 165 . 2 . 878–87 . July 2000 . 10878362 . 10.4049/jimmunol.165.2.878 . free .