| Description | C1r enzyme is the activated form of C1r proenzyme. C1r is a subunit of the C1 complex which is the first complement component in the classical pathway of complement. C1r proenzyme is an inactive zymogen until C1 is activated. C1r is activated when C1 binds to and is activated by antibodies bound to C1r enzyme is the activated form of C1r proenzyme. C1r is a subunit of the C1 complex which is the first complement component in the classical pathway of complement. C1r proenzyme is an inactive zymogen until C1 is activated. C1r is activated when C1 binds to and is activated by antibodies bound to antigens (immune complexes) yielding C1r enzyme, the first protease that initiates the cascade. C1 is a non-covalent calcium-dependent complex of one C1q, two C1r and two C1s molecules. Each C1q binds through two or more of its six arms to the Fc domains of IgG or IgM. The binding of multiple arms to immune complexes causes the two C1r proteins in the complex (protease zymogens) to activate producing two proteases that cleave and activate the two C1s protease zymogens in the complex. The activation of C1r results from cleavage of C1r into two fragments of 57,000 and 35,000 daltons. Activation of the bound C1s molecule is the only known function of C1r enzyme. Activated C1s cleaves complement component C4 releasing C4a and initiating covalent attachment of C4b to the activating surface. Activated C1s also cleaves C2 and the larger fragment of C2 binds to the surface-attached C4b forming C4b,C2a the C3/C5 convertase of the classical pathway.Extinction Coeff.: A280 nm = 1.15 at 1.0 mg/ml for pure C1rPurity: >90 % by SDS PAGE (Note: C1r enzyme is 92,000 unreduced, but upon reduction runs as 57,000 and 35,000 chains on SDS PAGE)Preservative: None, 0.22 µm filtered. Source: Normal human serum (shown by certified tests to be negative for HBsAg, HTLV-I/II, STS, and for antibodies to HCV, HIV-1 and HIV-II). Precautions: Use normal precautions for handling human blood products.Physical Characteristics & StructureC1r enzyme is a 92,000 dalton, two chain, trypsin-like enzyme. C1r is present in plasma at 31 µg/mL. C1r proenzyme is an unstable zymogen and it spontaneouslyactivates by cleaving a peptide bond in C1r producing a 57,000 dalton heavy chain and a 35,000 dalton light chain. This is the form sold as C1r enzyme. This self-activation occurs rapidly in the C1 complex upon binding to an immune complex and it occurs slowly with pure C1r. Two C1r form a C1r-C1r complex in the presence of calcium which in turn forms a stable complex with two C1s molecules in the presence of calcium. This tetramer can exist in solution, but in the presence of C1q it binds to C1q forming the C1 complex, which is stable in the presence of calcium. C1r self-activation is controlled in part by a weak association with C1esterase inhibitor (C1-INH) when it is in the C1 complex and similar stabilization occurs with purified C1r. C1r enzyme, however, is irreversibly inactivated by binding to C1-INH.FunctionC1r enzyme can be used to activate C1s proenzyme. In the presence of calcium it is still capable of binding another C1r enzyme and two C1s molecules and this complex is capable of binding to C1q. The activated C1r enzyme will rapidly activate the two C1s proenzymes to form C1s enzymes and the resulting C1q-C1r2-C1s2 complex is a fully active C1 molecule which will activate C4 and C2 in the fluid phase or on a cell bearing antibodies, such as EA. EA are sheep erythrocytes with rabbit IgM anti-sheep erythrocytes antibodies bound to their surface.AssaysThe activity of C1r enzyme is checked by measuring its ability to bind to the protease inhibitor C1 esterase inhibitor and remain covalently bound in the presence of SDS. It may also be used to activate C1s proenzyme and to form the activated C1 complex composed of one C1q, two C1r and two C1s molecules.ApplicationsSee sections titled Function and Assays above.RegulationActivated C1r is rapidly inactivated by C1-INH. The spontaneous activation of C1r observed with pure C1 and pure C1r proenzyme is minimized by the presence of C1-INH which rapidly inactivates spontaneously activated C1r enzyme. Stabilization of the proenzyme is also due to existence of a weak complex between C1-INH and C1r proenzyme. This association apparently stabilizes C1 thus preventing spontaneous activation in serum. Separation of C1-INH from C1 during purification is one of the reasons that isolated C1 and C1r proenzyme is unstable and prone to spontaneous activation. GeneticsThe EMBL/Genbank cDNA accession number for C1r is M14058. The genes for C1r and C1s are closely linked and located on chromosome 12p13.DeficienciesDeficiencies of each of the three components of C1 have been found. C1r and C1s deficient patients are prone to systemic lupus erythematosus (SLE).and recurrent pyogenic infections. They lack classical pathway function and may or may not exhibit C1r antigen in blood. DiseasesSee section titled Deficiencies above.Precautions/Toxicity/HazardsThis protein is purified from human serum and therefore precautions appropriate for handling any blood-derived product must be used even though the source was shown by certified tests to be negative for HBsAg, HTLV-I/II, STS, and for antibodies to HCV, HIV-1 and HIV-II.
Extinction Coeff.A280 nm = 1.15 at 1.0 mg/ml for pure C1rMolecular Weight92,000 Da (2 chains)Protein Purity>90 % by SDS PAGE (Note: C1r enzyme is 92,000 unreduced, but upon reduction runs as 57,000 and 35,000 chains on SDS PAGE)General DescriptionC1r enzyme is the activated form of C1r proenzyme. C1r is a subunit of the C1 complex which is the first complement component in the classical pathway of complement. C1r proenzyme is an inactive zymogen until C1 is activated. C1r is activated when C1 binds to and is activated by antibodies bound to antigens (immune complexes) yielding C1r enzyme, the first protease that initiates the cascade. C1 is a non-covalent calcium-dependent complex of one C1q, two C1r and two C1s molecules. Each C1q binds through two or more of its six arms to the Fc domains of IgG or IgM. The binding of multiple arms to immune complexes causes the two C1r proteins in the complex (protease zymogens) to activate producing two proteases that cleave and activate the two C1s protease zymogens in the complex. The activation of C1r results from cleavage of C1r into two fragments of 57,000 and 35,000 daltons. Activation of the bound C1s molecule is the only known function of C1r enzyme. Activated C1s cleaves complement component C4 releasing C4a and initiating covalent attachment of C4b to the activating surface. Activated C1s also cleaves C2 and the larger fragment of C2 binds to the surface-attached C4b forming C4b,C2a the C3/C5 convertase of the classical pathway.Physical Characteristics & StructureC1r enzyme is a 92,000 dalton, two chain, trypsin-like enzyme. C1r is present in plasma at 31 ug/mL. C1r proenzyme is an unstable zymogen and it spontaneously activates (Dodds, A.W. and Sim, R.B. editors (1997); Morikis, D. and Lambris, J.D. editors. (2005)) by cleaving a peptide bond in C1r producing a 57,000 dalton heavy chain and a 35,000 dalton light chain. This is the form sold as C1r enzyme. This self-activation occurs rapidly in the C1 complex upon binding to an immune complex and it occurs slowly with pure C1r. Two C1r form a C1r-C1r complex in the presence of calcium which in turn forms a stable complex with two C1s molecules in the presence of calcium. This tetramer can exist in solution, but in the presence of C1q it binds to C1q forming the C1 complex, which is stable in the presence of calcium. C1r self-activation is controlled in part by a weak association with C1esterase inhibitor (C1-INH) when it is in the C1 complex and similar stabilization occurs with purified C1r (Ziccardi, R.J. (1982)). C1r enzyme, however, is irreversibly inactivated by binding to C1-INH.FunctionC1r enzyme can be used to activate C1s proenzyme. In the presence of calcium it is still capable of binding another C1r enzyme and two C1s molecules and this complex is capable of binding to C1q. The activated C1r enzyme will rapidly activate the two C1s proenzymes to form C1s enzymes and the resulting C1q-C1r2-C1s2 complex is a fully active C1 molecule which will activate C4 and C2 in the fluid phase or on a cell bearing antibodies, such as EA (Dodds, A.W. and Sim, R.B. editors (1997); Morgan, B.P. ed. (2000)). EA are sheep erythrocytes with rabbit IgM anti-sheep erythrocytes antibodies bound to their surface (Morgan, B.P. ed. (2000)).AssaysThe activity of C1r enzyme is checked by measuring its ability to bind to the protease inhibitor C1 esterase inhibitor and remain covalently bound in the presence of SDS. It may also be used to activate C1s proenzyme and to form the activated C1 complex composed of one C1q, two C1r and two C1s molecules.ApplicationsSee sections titled Function and Assays above.RegulationActivated C1r is rapidly inactivated by C1-INH. The spontaneous activation of C1r observed with pure C1 and pure C1r proenzyme is minimized by the presence of C1-INH which rapidly inactivates spontaneously activated C1r enzyme. Stabilization of the proenzyme is also due to existence of a weak complex between C1-INH and C1r proenzyme. This association apparently stabilizes C1 thus preventing spontaneous activation in serum (Ziccardi, R.J. (1982)). Separation of C1-INH from C1 during purification is one of the reasons that isolated C1 and C1r proenzyme is unstable and prone to spontaneous activation. GeneticsThe EMBL/Genbank cDNA accession number for C1r is M14058. The genes for C1r and C1s are closely linked and located on chromosome 12p13.DeficienciesDeficiencies of each of the three components of C1 have been found (Ross, G.D. (1986)). C1r and C1s deficient patients are prone to systemic lupus erythematosus (SLE)and recurrent pyogenic infections (Rother, K., et al. (1998)). They lack classical pathway function and may or may not exhibit C1r antigen in blood. DiseasesSee section titled Deficiencies above.Precautions/Toxicity/HazardsThis protein is purified from human serum and therefore precautions appropriate for handling any blood-derived product must be used even though the source was shown by certified tests to be negative for HBsAg, HTLV-I/II, STS, and for antibodies to HCV, HIV-1 and HIV-II... Read More | Protein Purity≥85% by SDS PAGEExtinction CoeffA280 nm = 0.974 at 1.0 mg/ml for pure C3bMolecular Weight185,000 Da (2 chains)General DescriptionCynomolgus monkey C3 (cyno C3) is purified from pooled normal cynomolgus monkey serum. C3 is central to the activation of all three pathways of Protein Purity≥85% by SDS PAGEExtinction CoeffA280 nm = 0.974 at 1.0 mg/ml for pure C3bMolecular Weight185,000 Da (2 chains)General DescriptionCynomolgus monkey C3 (cyno C3) is purified from pooled normal cynomolgus monkey serum. C3 is central to the activation of all three pathways of complement activation (Law, S.K.A. and Reid, K.B.M. (1995)). Initiation of each pathway generates proteolytic enzyme complexes (C3 convertases) which are bound to the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. For a brief time (~60 µs) this nascent C3b is capable of reacting with and covalently coupling to hydroxyl groups on the target surface. Carbohydrates are the favored target, but protein hydroxyls and amino groups also react. This process of tagging the target surface with C3b is called opsonization. The reactive site in nascent C3b is a thioester (Tack B.J., et al. (1980); Pangburn M.K. and MüllerEberhard H.J. (1980)) and C3b is linked to the target through a covalent ester bond (an amide bond is formed if C3b is attached to amino groups). Most of the C3 activated during complement activation never attaches to the surface because its thioester reacts with water forming fluid phase C3b which is rapidly inactivated by factors H and I forming iC3b. Surface-bound C3b is necessary in all three pathways for efficient activation of C5 and formation of C5b-9 complexes that lyse the target cell membrane. Surface-bound C3b and its breakdown products iC3b and C3d are recognized by numerous receptors on lymphoid and phagocytic cells which use the C3b ligand to stimulate antigen presentation to cells of the adaptive immune system. The end result is an expansion of target-specific B-cell and T-cell populations.Physical Characteristics & StructureCynomolgus monkey C3 is an uncharacterized protein. The calculated molecular weight based on its amino acid sequence is 184,926 daltons similar to that of human C3 (185,000 daltons). Like human C3, cyno C3 is composed of two disulfide-linked chains. Analysis of purified cyno C3 by SDS/polyacrylamide gel electrophoresis under non-reduced conditions shows the mobility of cyno C3 to be similar to that of human C3. Under reduced conditions, the migration of the alpha chain of cyno C3 is comparable to that of human C3 alpha chain (110,000 daltons) while the beta chain migrates slightly ahead of the human C3 beta chain (75,000daltons).The extinction coefficient of cyno C3 is calculated from its amino acid sequence using ProtParam and assumes all pairs of Cys residues form cystines (i.e. a pair of cystine molecules are joined by a disulfide bond). The theoretical pI value for cyno monkey C3 is 6.03. Employing immunoturbidimetric method the serum concentration of cyno C3 has been reported to be 1.27 mg/ml in males and 1.1 mg/ml in female monkeys (Park H-K et al., (2016)). FunctionThe biological functions of C3 are described above in the General Description and Physical Characteristics sections.GeneticsCynomolgus monkey C3 chromosome location 19. The NCBI Gene ID number for Cynomolgus monkey C3 is 102131458 and UniProt accession number is A0A2K5VPN1.Precautions/Toxicity/HazardsThis protein is purified from animal serum and therefore precautions appropriate for handling any animal blood-derived product must be used.ReferencesLaw, S.K.A. and Reid, K.B.M. (1995) Complement 2nd Edition (ISBN 0199633568) Oxford University Press, Oxford.Tack BF, Harrison RA, Janatova J, Thomas ML, Prahl JW. (1980) Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci U S A. 77:5764-8.Pangburn M.K. and Müller-Eberhard H.J. (1980) Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med. 152:1102-14.Park H-K, Cho J-W, Lee B-S, Park H, Han J-S, Yang M-J, Im W-J, Park D-Y, Kim W-J, Han SC, Kim Y-B. (2016) Reference values of clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis) used in preclinical studies. Lab Anim Res. 32(2):79-86... Read More | Protein Purity≥85% by SDS PAGEExtinction CoeffA280 nm = 10.16 at 1.0 mg/ml for pure C3Molecular Weight187,000 Da (2 chains)General DescriptionRat C3 is purified from pooled normal rat serum. C3 is central to the activation of all three pathways of complement activation (Law, S.K.A. and Reid, KProtein Purity≥85% by SDS PAGEExtinction CoeffA280 nm = 10.16 at 1.0 mg/ml for pure C3Molecular Weight187,000 Da (2 chains)General DescriptionRat C3 is purified from pooled normal rat serum. C3 is central to the activation of all three pathways of complement activation (Law, S.K.A. and Reid, K.B.M. (1995)). Initiation of each pathway generates proteolytic enzyme complexes (C3 convertases) which are bound to the target surface. These enzymes cleave a peptide bond in C3 releasing the anaphylatoxin C3a and activating C3b. For a brief time (~60 µs) this nascent C3b is capable of reacting with and covalently coupling to hydroxyl groups on the target surface. Carbohydrates are the favored target, but protein hydroxyls and amino groups also react. This process of tagging the target surface with C3b is called opsonization. The reactive site in nascent C3b is a thioester (Tack B.J., et al. (1980); Pangburn M.K. and MüllerEberhard H.J. (1980)) and C3b is linked to the target through a covalent ester bond (an amide bond is formed if C3b is attached to amino groups). Most of the C3 activated during complement activation never attaches to the surface because its thioester reacts with water forming fluid phase C3b which is rapidly inactivated by factors H and I forming iC3b. Surface-bound C3b is necessary in all three pathways for efficient activation of C5 and formation of C5b-9 complexes that lyse the target cell membrane. Surface-bound C3b and its breakdown products iC3b and C3d are recognized by numerous receptors on lymphoid and phagocytic cells which use the C3b ligand to stimulate antigen presentation to cells of the adaptive immune system. The end result is an expansion of target-specific B-cell and T-cell populations.Physical Characteristics & StructureThe calculated molecular weight of rat C3 based on its amino acid sequence is 184,111daltons (without the signal peptide) and is similar to that of human C3 (185,000 daltons).The molecular weight of rat C3 as determined by SDS/polyacrylamide gel electrophoresis has been reported by Daha, M.R. et al., (1979) to be 187,000 daltons composed of two disulfide linked chains, alpha chain (123,000 daltons) and beta chain (76,000 daltons). The extinction coefficient of rat C3 (E1%/280nm = 10.16) is calculated based on its amino acid sequence using ProtParam and assumes all pairs of Cys residues form cystines (i.e. a pair of cysteine molecules are joined by a disulfide bond). The theoretical pI of rat C3 is 6.12. The normal plasma concentration of C3 inWistar rats has been reported to be 0.581mg/ml (Daha, M.R. et al., (1979)).FunctionThe biological functions of C3 are described above in the General Description section.GeneticsRat C3 chromosome location 9. The NCBI Gene ID number for rat C3 is 24232 and UniProt accession number is P01026.Precautions/Toxicity/HazardsThis protein is purified from animal plasma/serum and therefore precautions appropriate for handling any animal blood-derived product must be used.ReferencesLaw, S.K.A. and Reid, K.B.M. (1995) Complement 2nd Edition (ISBN 0199633568) Oxford University Press, Oxford.Tack BF, Harrison RA, Janatova J, Thomas ML, Prahl JW. (1980) Evidence for presence of an internal thiolester bond in third component of human complement. Proc Natl Acad Sci U S A. 77:5764-8.Pangburn M.K. and Müller-Eberhard H.J. (1980) Relation of putative thioester bond in C3 to activation of the alternative pathway and the binding of C3b to biological targets of complement. J Exp Med. 152:1102-14.Daha MR, Stuffers-Heiman M, Kijlstra A and Van ES LA. (1979) Isolation and characterization of the third component of rat complement. Immunology 36:63-70... Read More | Bovine pancreatic deoxyribonuclease is an endonuclease which splits phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide yielding polynucleotides with free hydroxyl group at the 3' position and phosphate group at the 5' position. The average chain length of a limit digest is aBovine pancreatic deoxyribonuclease is an endonuclease which splits phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide yielding polynucleotides with free hydroxyl group at the 3' position and phosphate group at the 5' position. The average chain length of a limit digest is a tetranucleotide.Used for the removal of DNA from protein samples. Deoxyribonuclease I from bovine pancreas has been used in a study to compare several procedures for reducing RNase contamination in preparations of DNase. Deoxyribonuclease I from bovine pancreas has also been used in a study to investigate the effect of the composition of sodium dodecyl sulfate preparations on the renaturation of enzymes after polyacrylamide gel electrophoresis... Read More | SHP2 protein degrader-2 (SHP2-D26) is a SHP2 protein PROTAC degrader. SHP2 protein degrader-2 reduces expression level of SHP2 in various cancer cells.In VitroSHP2 protein degrader-2 (SHP2-D26) achieves excellent degradation of SHP2 with the DC 50 (the concentration where 50% of the protein has beenSHP2 protein degrader-2 (SHP2-D26) is a SHP2 protein PROTAC degrader. SHP2 protein degrader-2 reduces expression level of SHP2 in various cancer cells.In VitroSHP2 protein degrader-2 (SHP2-D26) achieves excellent degradation of SHP2 with the DC 50 (the concentration where 50% of the protein has been degraded) values of 2.6 nM and 6.0 nM for MV4;11 and KYSE520 cells, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:Solid... Read More |