CleavesAlternative pathwayPathwaysCleavageBinds to factorC3BINAClassical pathwayBorreliaConvertaseSerineInactivationHumansCascadeRegulatorsCofactorSurface proteinsRegulatory proteinsMutationsInhibitorGroup of proteinsOpsoninDeficiencyActivationGeneHemolytic uremic sCDNASerum proteinsOpsonizationBind2000DecreasesComponentsMoleculesDegradationFactor I proteinUrinePhagocytosisComplexInteractionMolecular weightAtomic structure
Cleaves6
- Factor I cleaves C3b and C4b in a reaction, where fI is dependent on various cofactors, such as factor H, C4b-binding protein CR1 and membrane cofactor protein (MCP) [ 26 ]. (hindawi.com)
- mouse homolog is a regulatory serine proteinase of the complement cascade that cleaves C3b and C4b and inactivates them [RGD, Feb 2006]. (genscript.com)
- C2a in the convertase complex cleaves C3 releasing C3a and C3b. (abcam.com)
- This then acts similarly to C1 esterase and cleaves C2 and C4 to form C2aC4b, which is the C3 esterase that cleaves C3 to form C3b. (medscape.com)
- The alternative complement system pathway is spontaneously activated due to the absence of CD55, leading to activation of a C3 convertase that that cleaves C3 into C3a and C3b. (drugbank.com)
- C3b cleaves C5 into C5a and C5b. (drugbank.com)
Alternative pathway3
- The alternative pathway of complement activation is in a constant state of low-level activation (known as tickover). (abcam.com)
- Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
- The alternative pathway utilizes C3 and factors B and D to form the alternative pathway convertase C3b,Bb. (medscape.com)
Pathways7
- Activation of the complement system in response to an infection or foreign antigen is achieved via three complement pathways, the classical pathway, which is activated by antigen-antibody complexes, the lectin pathway, which is activated by the interaction of microbial carbohydrates with mannose-binding proteins in the plasma and tissue fluids, and the alternative complement pathway, which is activated by C3b binding to microbial surfaces and to antibody molecules. (hindawi.com)
- Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
- the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
- Each of these pathways uses different proteins. (medscape.com)
- Activation of the complement pathways. (medscape.com)
- The normal complement system consists of the classic and alternative pathways. (medscape.com)
- Several complement inhibitors currently under development target various steps in the complement activation pathways. (justia.com)
Cleavage4
- This domain contains the catalytic triad His-362, Asp-411, and Ser-507, which is responsible for specific cleavage of C3b and C4b. (wikipedia.org)
- Factor I-mediated cleavage of the α chain of C3b liberates 3 fragments with molecular weights of 68 kDa, 43 kDa, and 2 kDa. (hindawi.com)
- Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)
- The second phase for each involves cleavage of C3b, generating multiple biologically important fragments and large, potentially cytolytic complexes. (medscape.com)
Binds to factor2
- Here, C3b binds to factor B that is cleaved by factor D to Bb. (medscape.com)
- 1 C3b binds to factor B, which is cleaved by factor D into the smaller Ba and larger Bb. (drugbank.com)
C3BINA1
- It binds as a cofactor to C3b/C4b inactivator (C3bina), which then hydrolyzes the complement fragment C4b. (lu.se)
Classical pathway1
- C4BP controls the classical pathway of complement activation. (lu.se)
Borrelia3
- Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi. (ox.ac.uk)
- Mutational analyses of the BbCRASP-1 protein of Borrelia burgdorferi identify residues relevant for the architecture and binding of host complement regulators FHL-1 and factor H. (ox.ac.uk)
- The OspE-related proteins inhibit complement deposition and enhance serum resistance of Borrelia burgdorferi, the lyme disease spirochete. (ouhsc.edu)
Convertase7
- Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin in blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due to loss of iC3b and C3dg production. (wikipedia.org)
- It also accelerates the degradation of the C4bc2a complex (C3 convertase) by dissociating the complement fragment C2a. (lu.se)
- In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
- C3bBb complex then acts as the C3 convertase and generates more C3b through an amplification loop. (medscape.com)
- This interaction results in the formation of C4b2a, which is the classic pathway C3b convertase. (medscape.com)
- Small amounts of C3b are constantly being formed in the circulation, which are inactivated by factors H and I. The binding of C3b to a foreign antigen decreases its affinity for factor H and allows for the formation of increasing amounts of the alternate pathway convertase. (medscape.com)
- C3b is an opsonin itself, and C3 convertase facilitates the activation of the terminal pathway and the formation of the membrane attack complex C5b-9. (medscape.com)
Serine3
- Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. (hindawi.com)
- The plasma glycoprotein factor I (C3b/C4b inactivator) is a serine protease that acts as a regulator of the complement C3 cascade. (hindawi.com)
- Mannan-binding lectin (MBL) and MBL-associated serine proteases (MASPs) are involved in the initial step of the lectin pathway of complement activation. (abcam.com)
Inactivation5
- Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
- One central immune escape mechanism is the inactivation of the host complement attack by acquisition host complement regulators FHL-1 and factor H via complement regulator-acquiring surface proteins (BbCRASPs). (ox.ac.uk)
- Heat inactivation is used, for instance, to inactivate the serum's complement binding capacity. (seraglob.com)
- Heat inactivation is the most common procedure used to inactivate the complement binding capacity of the serum in order to ensure that cells are not being lysed by means of antibody binding. (seraglob.com)
- Nevertheless, complement inactivation may be of significance if the experiment set-up includes, for example, a screening of specific viruses or virus propagation. (seraglob.com)
Humans1
- Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
Cascade4
- C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
- The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
- Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. (uams.edu)
- This invention relates to activation of the complement cascade in the body. (justia.com)
Regulators3
- This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design. (ox.ac.uk)
- Previously, 3 regions including the C terminus were identified as putative contact sites for the two complement regulators by the pepspot analysis. (ox.ac.uk)
- Single changes at 4 positions in region 1 either reduced (Lys136, Lys141, Glu147) or completely eliminated (Leu146) binding of both complement regulators. (ox.ac.uk)
Cofactor1
- the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
Surface proteins1
- This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). (ox.ac.uk)
Regulatory proteins2
- The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
- OBJECTIVES: This study aimed to evaluate the expression pattern of complement regulatory proteins (CRPs) CD46, CD59, and CD55 in HPV-positive (HPV+) & negative (HPV-) cervical cancer cell lines in search of a reliable differential biomarker. (bvsalud.org)
Mutations6
- Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
- At least 10 mutations in the CFI gene have been identified in people with complement factor I deficiency, a disorder characterized by immune system dysfunction. (medlineplus.gov)
- The mutations result in abnormal, nonfunctional, or absent complement factor I. (medlineplus.gov)
- The CFI gene mutations identified in this disorder result in an abnormal or nonfunctional version of complement factor I. The defective protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. (medlineplus.gov)
- Mapping the mutations onto the atomic structure of BbCRASP-1 reveals that, in contrast to earlier assumption, the C-terminal mutations act indirectly on FHL-1 and factor H binding, whilst the region 1 mutations map the site of direct complement regulator interaction. (ox.ac.uk)
Inhibitor4
- The structure of C3c in complex with the complement inhibitor, compstatin, and use of this information for rational design or identification of complement-inhibiting drugs are disclosed. (justia.com)
- Pegcetacoplan is a complement inhibitor indicated in the treatment of adults with paroxysmal nocturnal hemoglobinuria. (drugbank.com)
- Pegcetacoplan is a complement inhibitor indicated in the treatment of paroxysmal nocturnal hemoglobinuria (PNH). (drugbank.com)
- Pegcetacoplan is a complement C3 inhibitor that prevents complement-mediated hemolysis of red blood cells in patients with paroxysomal nocturnal hemoglobinuria. (drugbank.com)
Group of proteins2
- The complement system comprises a group of proteins which, when activated, provide one of the first lines of defence by promoting lysis and the removal of invading microbes. (hindawi.com)
- The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
Opsonin1
- Complement C3b is the major opsonin of the complement system which facilitates the phagocytosis process by coating antigens (each of the phagocytes expresses a complement receptor such as CR1, CR3, or CR4 that binds C3b, C4b, or C3bi) [ 28 , 29 ]. (hindawi.com)
Deficiency5
- Immune system abnormalities may be caused partly by complement system factor I deficiency. (hindawi.com)
- Factor I deficiency can be conferred by a C3 deficiency, since this also increases susceptibility to pyogenic infections by Neisseria meningitides, Haemophilus influenza, and Streptococcus pneumonia and increases the incidence of immune complex diseases due to impaired complement-mediated function [ 30 ]. (hindawi.com)
- The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- This condition, which may also occur in people with complement factor I deficiency, is characterized by kidney malfunction that can be serious or life-threatening. (medlineplus.gov)
- We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. (bvsalud.org)
Activation13
- Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
- Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)
- C-reactive protein (CRP, not shown) leads to classic pathway activation analogous to lectin pathway activation by MBL and ficolins. (medscape.com)
- Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. (uams.edu)
- Clinical presentations are similar for the three types of MPGN, but they manifest somewhat different mechanisms of complement activation and predisposition to recur in kidney transplants. (medscape.com)
- The classic and alternate pathway convertases cause C3 activation, forming C3a and C3b. (medscape.com)
- Inappropriate activation of the complement system leads to tissue injury causing or aggravating various pathological conditions, such as autoimmune diseases, burn injuries, Alzheimer's disease, stroke and heart attack, among others (reviewed by Sahu and Lambris, 2000). (justia.com)
- describes the use of a phage-displayed combinatorial random peptide library to identify a 27-residue peptide that binds to C3 and inhibits complement activation. (justia.com)
- Compstatin inhibits complement response by preventing the proteolytic activation of C3 (Sahu et al. (justia.com)
- 1996). Activation of C3 by the C3 convertases is a central amplification step in complement activation. (justia.com)
- Proteolytic activation of C3 yields C3b, which covalently binds to pathogenic or self surfaces providing a strong signal for clearance of the tagged particles. (justia.com)
- Because compstatin blocks this critical step of complement activation and because it is a small non-immunogenic peptide, compstatin has the potential to be developed into a therapeutic agent. (justia.com)
- 2 The resulting C3bBb can bind to other C3 proteins, leading to a positive feedback loop of complement activation. (drugbank.com)
Gene2
- Association of single nucleotide polymorphism in complement factor I gene with age-related macular degeneration]. (genscript.com)
- The CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
Hemolytic uremic s1
- Atypical hemolytic uremic syndrome is caused by complement overactivation. (wikipedia.org)
CDNA2
- These sequences represent the protein coding region of the Cfi cDNA ORF which is encoded by the open reading frame (ORF) sequence. (genscript.com)
- E05 478 566 350 170 or Enzyme-Linked Immunosorbent Assays, E05 478 566 350 170 or Enzyme-Linked Immunosorbent Assays, Human proteins, cDNA and human recombinants are used in human reactive ELISA kits and to produce anti-human mono and polyclonal antibodies. (gentaur.com)
Serum proteins1
- The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
Opsonization1
- The functions of complement include the attraction of inflammatory cells, opsonization to promote phagocytosis, immune complex clearance and direct microbial killing through the formation of the membrane attack complex (MAC). (abcam.com)
Bind2
- Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. (ox.ac.uk)
- 2 C3b proteins can also bind directly to a target cell, marking it as a target for phagocytosis. (drugbank.com)
20001
- The complement facts book , San Diego, 2000. (medscape.com)
Decreases1
- The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. (medlineplus.gov)
Components3
- Transcriptome characterization by RNA-Seq reveals the involvement of the complement components in noise-traumatized rat cochleae. (genscript.com)
- Research has shown, however, that fetal calf serum contains only a few components of the complement system (1). (seraglob.com)
- 1. Triglia, R.P., Linscott, W.D.: Titers of nine Complement Components, Conglutinin and C3b-Inactivator in adult and fetal bovine Sera. (seraglob.com)
Molecules1
- Complement-dependent cytotoxicity (CDC), which eliminates aberrant target cells through the assembly and complex formation of serum complement molecules, is one of the major effector functions of anticancer therapeutic antibodies. (bvsalud.org)
Degradation1
- Degradation of C3b by fI abrogates the action of this protein in the C3 pathway [ 27 ]. (hindawi.com)
Factor I protein1
- Then, factor I is cleaved by furin to yield the mature factor I protein, which is a disulfide-linked dimer of heavy chain (residues 19-335, 51 kDalton) and light chain (residues 340-583, 37 kDalton). (wikipedia.org)
Urine2
- The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria). (medlineplus.gov)
- ELISA tests are enzyme linked immunoassays to detect human, mouse or other proteins in serum, plasma, urine or biological fluids. (gentaur.com)
Phagocytosis1
- In patients with PNH, extravascular hemolysis is mediated by C3b marking red blood cells for phagocytosis, and intravascular hemolysis is mediated by the MAC. (drugbank.com)
Complex1
- Aplha, transcription related growth factors and stimulating factors or repressing nuclear factors are complex subunits of proteins involved in cell differentiation. (gentaur.com)
Interaction1
- Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. (ox.ac.uk)
Molecular weight1
- Many of the substances under investigation possess the disadvantage of being a large molecular weight proteins that are difficult to manufacture and must be administered by infusion. (justia.com)