Complement Factor I

Complement C3b

Complement Factor H

Complement Factor B

Complement Factor D

Complement factor I

Complement factor B

C3a (complement)

Complement component 3

Complement component 4B

Complement control protein

List of OMIM disorder codes

Complement (group theory)

Properdin deficiency

CFHR5

CFHR4

CFHR2

Nucleolin

IC3b

Genome-wide association study

Complement component 2

Total complement activity

Synovial fluid

James Markusen

Single-nucleotide polymorphism

L-selectin

Iptacopan

Personalized medicine

BioCryst Pharmaceuticals

Tuxedo Computers

Phagoptosis

CD59

Atypical hemolytic uremic syndrome

ARF5

CFHR3

Proteins14

• Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)
• Binding sites, especially for complement receptor (CR3), malondialdehyde (MDA)-modified proteins, and apolipoprotein E (apoE), are dispersed throughout its 20 CCP modules (CCPs), also known as short consensus repeats, to facilitate additional 'non-canonical' FH activities. (imedpub.com)
• 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)
• 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)
• Cell surface proteins have evolved which prevent EC damage by the cytotoxic defence system, decay-accelerating factor (DAF), protectin (CD59) and membrane cofactor protein (MCP). (biomedcentral.com)
• We now show that complement factor H-related protein 1 (FHR-1) and factor H-like protein 1 (FHL-1), proteins of the FH protein family that show amino acid sequence and regulatory function similarities with FH, also bind to Stx2. (leibniz-hki.de)
• C3 and factor B proteins were measured in culture supernatant by enzyme-linked immunosorbent assay and C3 and factor B transcripts in harvested cells by reverse transcriptase - polymerase chain reaction . (bvsalud.org)
• Cytokine induced upregulation of C3 and factor B proteins was always associated with the upregulation of levels of C3 and factor B mRNA . (bvsalud.org)
• thus, PIGA mutations lead to a deficiency of GPI-anchored proteins, such as complement decay-accelerating factor (also known as CD55) and CD59 glycoprotein (CD59), which are both complement inhibitors. (medscape.com)
• How do distinct transcriptional regulatory proteins coordinate their job with extrinsic factors and the microenvironment? (nih.gov)
• The active ingredient comprises plasma proteins such as albumin , immunoglobulins, other globulins, coagulation factors, complement proteins and protease inhibitors. (rxlist.com)
• Genes that encode the proteins of complement components or their isotypes are distributed throughout different chromosomes, with 19 genes comprising 3 significant complement gene clusters in the human genome. (medscape.com)
• The important components of this system are various cell membrane-associated proteins such as complement receptor 1 (CR1), complement receptor 2 (CR2), and decay accelerating factor (DAF). (medscape.com)
• for example, the proteins factor H and factor I inhibit the formation of the enzyme C3 convertase of the alternative pathway. (medscape.com)

Deficiency10

• 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)
• Complement factor I deficiency is a disorder that affects the immune system. (medlineplus.gov)
• Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. (medlineplus.gov)
• Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). (medlineplus.gov)
• Complement factor I deficiency is caused by mutations in the CFI gene. (medlineplus.gov)
• Mutations in the CFI gene that cause complement factor I deficiency result in abnormal, nonfunctional, or absent complement factor I. The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
• Baracho GV, Nudelman V, Isaac L. Molecular characterization of homozygous hereditary factor I deficiency. (medlineplus.gov)
• Grumach AS, Leitao MF, Arruk VG, Kirschfink M, Condino-Neto A. Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family. (medlineplus.gov)
• Ponce-Castro IM, Gonzalez-Rubio C, Delgado-Cervino EM, Abarrategui-Garrido C, Fontan G, Sanchez-Corral P, Lopez-Trascasa M. Molecular characterization of Complement Factor I deficiency in two Spanish families. (medlineplus.gov)
• Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)

Alternative pathway5

• Factor H binds to C3b, accelerates the decay of the alternative pathway C3-convertase and acts as a cofactor for the factor Imediated proteolyticinac-tivation of C3b. (biovendor.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)
• Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6-8 and 18-20 and to delay and reduce FH cofactor activity on the cell surface. (leibniz-hki.de)
• Atypical hemolytic uremic syndrome (aHUS) is a disease associated with dysregulation of the immune complement system, especially of the alternative pathway (AP). (elsevierpure.com)
• In vitro activation of the alternative pathway of complement by settled grain dust. (cdc.gov)

Antibody3

• To study the effect of MAC on HMEC expression of DAF, EC monolayers were opsonised with IgG2a anti-endoglin monoclonal antibody, thus optimising complement fixation ability. (biomedcentral.com)
• Mouse anti Human Complement Factor H antibody, clone 028B-244.2.10X (10-10) recognizes human complement factor H which exists in 2 forms. (bio-rad-antibodies.com)
• Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)

Pathways5

• Activation of the complement pathways. (medscape.com)
• This prevents these components of the classical and of alternative complement pathways from forming a positive feedback loop. (bio-rad-antibodies.com)
• We are now focused on delineating the transcription factors and signaling pathways that are responsible for generating photoreceptors from retinal progenitor cells. (nih.gov)
• The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)
• Complement pathways and deficiencies. (medscape.com)

Inhibitors2

• Conventional protease inhibitors do not completely inactivate Factor I but they can do so if the enzyme is pre-incubated with its substrate: this supports the proposed rearrangement of the molecule upon binding to the substrate. (wikipedia.org)
• In conclusion, multiple interactions of key complement inhibitors FH, FHR-1 and FHL-1 with Stx2 corroborate our hypothesis of a direct role of complement in EHEC-associated HUS. (leibniz-hki.de)

Receptor3

• The factor I heavy chain has four domains: an FI membrane attack complex (FIMAC) domain, CD5 domain, and low density lipoprotein receptor 1 and 2 (LDLr1 and LDLr2) domains. (wikipedia.org)
• 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)
• Similarly, sEng is a truncated form of receptor for two subtypes of transforming growth factor beta (TGF β ) specifically, TGF β 1 and TGF β 2 which are highly expressed by vascular endothelial cells and syncytiotrophoblasts. (hindawi.com)

Excessive complement activation2

• Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). (lu.se)
• Complement factor H (CFH), consisting of 20 domains called complement control protein (CCP1-20), downregulates the AP as a cofactor for mediating C3 inactivation by complement factor I. However, anomalies related to CFH are known to cause excessive complement activation and cytotoxicity. (elsevierpure.com)

Regulates complement2

• 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)
• An intricate system regulates complement activity. (medscape.com)

Mutations2

• 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)
• These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations. (lu.se)

Protein11

• Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
• 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)
• This 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)
• 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)
• Complement factor H, a 155 kDaplasma glycoprotein, is an essential regulatory protein that plays a critical role in the homeostasis of the complement system in plasma and in the protection of bystander host cells and tissues from damage by complement activation. (biovendor.com)
• In addition, factor H has multiple physiological activities acts as an extracellularmatrix component, binds to cellular receptors of the integrintype, and interacts with a wide selection of ligands, such as the C-reactive protein, thrombospondin, bone sialoprotein, osteopontin, and heparin. (biovendor.com)
• Complement factor H is a soluble AP suppressor that recognizes self-surfaces on autologous surfaces, either directly via particular glycosaminoglycan and sialic acid or indirectly via C-reactive protein (CRP), and operates in fluid phase. (imedpub.com)
• Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
• Poolpol K, Orth-Höller D, Speth C, Zipfel PF, Skerka C, de Córdoba SR, Brockmeyer J, Bielaszewska M, Würzner R (2014) Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. (leibniz-hki.de)
• NRL interacts with homeodomain protein CRX and numerous other regulatory factors to control expression of most rod-expressed genes. (nih.gov)
• These bacteria use the surface protein Usp2 to capture and incapacitate the major complement factor C3. (lu.se)

Damage by complement1

• How do endothelial cells (ECs) protect themselves against damage by complement, particularly when they are present at the interface between blood and inflamed tissue? (biomedcentral.com)

Accelerates the decay1

• DAF prevents the formation and accelerates the decay of complement 3 (C3) convertases, MCP binds to C3b and C4b promoting their degradation and CD59 inhibits the membrane-attack complex (MAC). (biomedcentral.com)

Serum7

• The most widely studied serum markers for PE, to date, are vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). (hindawi.com)
• Factor H is secreted by the liver into the blood serum. (bio-rad-antibodies.com)
• Crain, SM, Bornstein, MB & Lennon, VA 1975, ' Depression of complex bioelectric discharges in cerebral tissue cultures by thermolabile complement-dependent serum factors ', Experimental Neurology , vol. 49, no. 1, pp. 330-335. (elsevierpure.com)
• Abolition of depression by preheating the sera, and restoration, in some cases,b y addition of fresh (unheated) guinea pig serum (10%) suggested that the effect was complement-dependent (see below). (elsevierpure.com)
• More direct demonstration of complement-dependence was difficult since many of the sera blocked bioelectric discharges even without addition of guinea pig serum. (elsevierpure.com)
• CspA-mediated binding of human factor H inhibits complement deposition and confers serum resistance in Borrelia burgdorferi. (ouhsc.edu)
• The effects of settled grain dust on the human serum complement cascade were investigated. (cdc.gov)

Deficiencies8

• Clinical significance of complement deficiencies. (medlineplus.gov)
• The dosage of Octaplas for replacement of multiple coagulation factors in patients with acquired deficiencies is 10 to 15 milliliters per kg. (rxlist.com)
• Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.com)
• Complement deficiencies are said to comprise between 1 and 10% of all primary immunodeficiencies. (medscape.com)
• [ 3 ] A registry of complement deficiencies has been established as a means to promote joint projects on treatment and prevention of diseases associated with defective complement function. (medscape.com)
• This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)
• Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)
• Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)

Inflammation4

• It is important in regulating the complement pathway, preventing unnecessary inflammation which can damage the host tissue. (bio-rad-antibodies.com)
• The complement system plays an important part in host defense and inflammation . (bvsalud.org)
• 4 , 6 - 9 Several factors, including inflammation, oxidative stress, and dyslipidemia, are considered decisive for the progression of atherosclerosis in ESRD. (lww.com)
• at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)

Form a unique fingerprint1

• Dive into the research topics of 'Functional anatomy of complement Factor H'. Together they form a unique fingerprint. (ed.ac.uk)

Partial complement1

• Some new clinical entities are linked with partial complement defects. (medscape.com)

Inactivation2

• 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)
• Complement factor H functions as a cofactor in the inactivation of C3b by factor I. It makes C3b susceptible to cleavage by factor I, resulting in iC3b. (bio-rad-antibodies.com)

Overactivation1

• Atypical hemolytic uremic syndrome is caused by complement overactivation. (wikipedia.org)

Bind complement1

• We showed that one common strategy is to bind complement inhibitor C4BP, which leads to decreased opsonisation of bacteria with C3b impairing phagocytosis and allowing bacterial survival. (lu.se)

Hemolytic activity1

• Aliquots were analyzed for factor-B conversion and hemolytic activity. (cdc.gov)

Properdin1

• Exceptions are C1, factor D, and properdin. (medscape.com)

System10

• The complement system is a crucial component of the innate immunity against microbial infection. (biovendor.com)
• Due to the constant monitoring of its alternate channel, the complement system reacts promptly to threat (AP). (imedpub.com)
• The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
• The complement system has recently been found to be involved in the pathogenesis of EHEC-associated HUS. (leibniz-hki.de)
• The complement system is part of the innate immune system. (medscape.com)
• The complement system plays an important part in defense against pyogenic organisms. (medscape.com)
• In addition to playing an important role in host defense against infection, the complement system is a mediator in both the pathogenesis and prevention of immune complex diseases, such as systemic lupus erythematosus (SLE). (medscape.com)
• These findings underscore the duality of the complement system. (medscape.com)
• Knowledge about the complement system is expanding. (medscape.com)
• Although the complement system is part of the body's innate, relatively nonspecific defense against pathogens, its role is hardly primitive or easily understood. (medscape.com)

Gene2

• The gene for Factor I in humans is located on chromosome 4. (wikipedia.org)
• rs800292, rs1061170, rs1410996) in the complement factor H ( CFH ) gene, rs 11200638-SNP in the high temperature requirement A-1 ( HTRA1 ) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor ( VEGF ) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor ( PEDF ) gene were evaluated. (dovepress.com)

Abnormal1

• The term "nocturnal" refers to the belief that hemolysis is triggered by acidosis during sleep and activates complement to hemolyze an unprotected and abnormal RBC membrane. (medscape.com)

Cytokines5

• This in turn results in an exponential production of multiple factors such as cytokines and growth factors leading to the clinical manifestations of PE [ 11 ]. (hindawi.com)
• To test the hypothesis that inflammatory cytokines and complement(C) MACs play a role in the expression of DAF, CD59 and MCP, and to investigate the intracellular signalling pathway involved in DAF expression. (biomedcentral.com)
• Synthesis of complement components C3 and factor B in human keratinocytes is differentially regulated by cytokines. (bvsalud.org)
• In skin the keratinocyte is the major cell type, it is known to produce two soluble complement components, C3 and factor B . In this study we investigated the regulation of synthesis of these components in foreskin keratinocytes by cytokines . (bvsalud.org)
• In conclusion, synthesis of C3 and factor B in keratinocytes is regulated by some cytokines , known to be produced by inflammatory cells and keratinocytes . (bvsalud.org)

Binds1

• Here, C3b binds to factor B that is cleaved by factor D to Bb. (medscape.com)

Innate1

• As a first line of defense against pathogens and a mediator between innate and adaptive immunity, complement is a particular focus of evasion strategies developed by pathogens. (lu.se)

Glycoprotein1

• Factor I is a glycoprotein heterodimer consisting of a disulfide linked heavy chain and light chain. (wikipedia.org)

Convertase3

• Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated. (lu.se)
• In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
• Factor H also inhibits the formation of the C3bBb complex (C3 convertase) and increases the rate of dissociation of both C3 convertase and the (C3b)NBB complex (C5 convertase). (bio-rad-antibodies.com)

Renal diseases2

• Complement factor H has revealed an association with two different renal diseases, glomerulonephri-tisand atypical hemolytic uremicsyndrome (aHUS). (biovendor.com)
• Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. (lu.se)

Diseases1

• In addition to the following diseases, low factor I is associated with recurrent bacterial infections in children. (wikipedia.org)

Cascade2

• How the immune response can activate the cascade process is still unknown but it is proposed to act in synergy with additional exacerbating factors such as predisposing maternal and ambient factors [ 12 ]. (hindawi.com)
• New studies point to the complex interplay between the complement cascade and adaptive immune response, and complement is also being studied in association with ischemic injury as a target of therapy. (medscape.com)

Intracellular1

• This indicated that, as expected, cytokine -induced enhancement in C3 and factor B levels was due to an increase in synthesis rather than their possible release from intracellular stores. (bvsalud.org)

Activation1

• The accumulation of anaphylatoxins (such as C5a) from complement activation might also have a role. (medscape.com)

Tissue1

• Locally synthesized complement may perform these functions at tissue and organ level. (bvsalud.org)

Receptors1

• Angiogenic factors and their receptors are important regulators of placental vascular development [ 13 ]. (hindawi.com)

Functional1

• We previously discovered that that Maf-family bZIP transcription factor NRL is critical for rod photoreceptor fate and functional differentiation, and that loss of NRL leads to S-cones instead of rods. (nih.gov)

Human3

• Crystal structure the crystal structure of human Factor I has been deposited as PDB: 2XRC. (wikipedia.org)
• Human keratinocytes were cultured in the presence of supernatant of activated peripheral blood mononuclear cells , interleukin-1alpha , interleukin-2 , interleukin-6 , transforming growth factor-beta1 , tumor necrosis factor-alpha , or interferon-gamma . (bvsalud.org)
• Another important mechanism by which bacteria resist human complement is the production of proteases that efficiently degrade complement components. (lu.se)

Soluble1

• Like sFlt1, soluble endoglin (sEng) is an antiangiogenic factor capable of inhibiting capillary tube formation in vitro [ 17 ]. (hindawi.com)

Resist1

• Pathogenic microorganisms, on the other hand, frequently resist complement assault and so escape destruction. (imedpub.com)

Disease2

• 1 It is a multifactorial disease with several identified genetic and environmental risk factors, including age, smoking, body mass index, hypertension, and others. (dovepress.com)
• So that suspect case of Ebola disease or suspect case of Ebola disease definition is a person with signs and symptoms compatible with Ebola disease and an epidemiological risk factor within 21 days before the onset of symptoms. (cdc.gov)

Clinical implications1

• Dysregulated factor I activity has clinical implications. (wikipedia.org)

Guinea2

• Complement consumption also was tested in dust treated sera from C4 deficient guinea pigs. (cdc.gov)
• Complement reductions also were seen in the treated sera from C4 deficient guinea-pigs. (cdc.gov)

Catalog1

• The Interaction With Host Pathway complements our catalog of research reagents including antibodies and ELISA kits against TNF, IL6, IL2, TLR2, TLR4. (novusbio.com)

Endothelial1

• Treatment is with dietary supplements, intravitreal injection of antivascular endothelial growth factor drugs, laser photocoagulation, photodynamic therapy, and low-vision devices. (msdmanuals.com)

Photodynamic therapy1

• This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). (dovepress.com)