Complement c3 c5 convertases. Medical search

Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.

A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.

Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.

A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.

The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.

A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.

A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.

C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.

The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.

The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.

The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-

A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.

The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.

The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.

A CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.

A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).

A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.

A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.

A 206-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.

A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).

Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.

A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.

Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.

A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).

A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.

A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.

The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.

A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.

Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.

A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.

The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.

A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.

Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.

An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).

The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.

GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.

A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.

Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.

A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.

A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.

Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.

A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.

Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.

Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.

An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.

Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.

Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.

A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.

Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.

Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.

Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.

A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.

A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).

A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).

Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.

Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.

Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.

The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.

Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)

Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.

Proteins prepared by recombinant DNA technology.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.

An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).

Established cell cultures that have the potential to propagate indefinitely.

An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.

The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.

The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.

A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.

A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).

The parts of a macromolecule that directly participate in its specific combination with another molecule.

A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.

Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

A type of chromogranin which was initially characterized in the ANTERIOR PITUITARY GLAND. It is found in several species including human, rat, mouse, and others. Secretogranin II is an acidic protein of 559 to 586 amino acid residues that can stimulate DOPAMINE release from neurons and release of pituitary GONADOTROPINS.

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.

The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.

A group of acidic proteins that are major components of SECRETORY GRANULES in the endocrine and neuroendocrine cells. They play important roles in the aggregation, packaging, sorting, and processing of secretory protein prior to secretion. They are cleaved to release biologically active peptides. There are various types of granins, usually classified by their sources.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

An envelope protein of the human immunodeficiency virus that is encoded by the HIV env gene. It has a molecular weight of 160,000 kDa and contains numerous glycosylation sites. It serves as a precursor for both the HIV ENVELOPE PROTEIN GP120 and the HIV ENVELOPE PROTEIN GP41.

Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).

A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.

The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.

Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.

A 13-amino acid peptide derived from proteolytic cleavage of ADRENOCORTICOTROPIC HORMONE, the N-terminal segment of ACTH. ACTH (1-13) is amidated at the C-terminal to form ACTH (1-13)NH2 which in turn is acetylated to form alpha-MSH in the secretory granules. Alpha-MSH stimulates the synthesis and distribution of MELANIN in MELANOCYTES in mammals and MELANOPHORES in lower vertebrates.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

The rate dynamics in chemical or physical systems.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.

Physiologically inactive substances that can be converted to active enzymes.

The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.

Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.

A family of structurally-related angiogenic proteins of approximately 70 kDa in size. They have high specificity for members of the TIE RECEPTOR FAMILY.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.

A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.

A 31-amino acid peptide that is the C-terminal fragment of BETA-LIPOTROPIN. It acts on OPIOID RECEPTORS and is an analgesic. Its first four amino acids at the N-terminal are identical to the tetrapeptide sequence of METHIONINE ENKEPHALIN and LEUCINE ENKEPHALIN.

A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.

An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.

Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.

Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Antibodies produced by a single clone of cells.

The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Glycoproteins found on the membrane or surface of cells.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.

The process of cleaving a chemical compound by the addition of a molecule of water.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

Elements of limited time intervals, contributing to particular results or situations.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.

The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)

A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ.

The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.

Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.

Matrix metalloproteinases that are associated with the CELL MEMBRANE, either through transmembrane domains or GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS. Membrane-type matrix metalloproteinases may act within the pericellular environment to influence the process of CELL MIGRATION.

Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.

One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.

ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.

Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.

Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.

Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.

Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.

Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.

CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.

Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).

Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.

A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.

Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.

Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.

Plasmids containing at least one cos (cohesive-end site) of PHAGE LAMBDA. They are used as cloning vehicles.

A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Proteins found in any species of bacterium.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.

A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.

Transport proteins that carry specific substances in the blood or across cell membranes.

Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.

A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. Defects in STEROID 21-HYDROXYLASE; STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES); TESTOSTERONE 5-ALPHA-REDUCTASE; or steroidogenic acute regulatory protein; among others, underlie these disorders.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.

An individual in which both alleles at a given locus are identical.

Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Biologically active substances whose activities affect or play a role in the functioning of the immune system.

The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.

The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.

Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.

Peptides composed of between two and twelve amino acids.

A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.

A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.

Channel catfish virus gene 50 encodes a secreted, mucin-like glycoprotein. (1/215)

Cells infected with the wild-type (WT) strain of channel catfish virus (CCV) secreted a glycoprotein with an apparent molecular mass (MM) superior to 200 kDa into the culture medium. This protein, designated gp250, was the sole viral glycoprotein detected in the culture medium after [3H]mannose labeling of the infected cells. When cells were infected with the attenuated V60 strain, a glycoprotein of 135 kDa (designated gp135) was detected instead of gp250. Because WT gene 50 is predicted to encode a secreted, mucin-type glycoprotein, we expressed this gene transiently and detected a glycoprotein of the same apparent MM as gp250 in the culture medium of transfected catfish cells. The increased mobility in SDS-PAGE of the secreted V60 glycoprotein correlated with the presence of a major deletion in V60 gene 50. Therefore, we concluded that gp250 in the WT and gp135 in the V60 strains are both likely encoded by gene 50. An important shift in the relative mobility of gp250 in SDS-PAGE was observed after tunicamycin treatment of infected cells labeled with [3H]glucosamine, confirming the presence of N-linked sugars on gp250. We observed variations in the size of PCR products derived from gene 50 amplification in three different field isolates. Such genetic variations are a characteristic feature of mucin genes and are linked to crossing-over events between internal repeated sequences, such as those present in gene 50. (+info)

Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. (2/215)

We recently suggested that sites of length polymorphisms in protein families (indels) might serve as useful guides for locating protein:protein interaction sites. This report describes additional site-specific mutagenesis and synthetic peptide inhibition studies aimed at testing this idea for the paralogous complement C3, C4, and C5 proteins. A series of C5 mutants was constructed by altering the C5 sequence at each of the 27 indels in this protein family. Mutants were expressed in COS cells and were assayed for hemolytic activity and protease sensitivity. Mutants at five indels showed relatively normal expression but substantially reduced sp. act., indicating that the mutations damaged sites important for C5 function. Twenty-three synthetic peptides with C5 sequences and 10 with C3 sequences were also tested for the ability to inhibit C hemolytic activity. Three of the C5 peptides and one of the C3 peptides showed 50% inhibition of both C hemolytic and bactericidal activities at a concentration of 100 microM. In several cases both the mutational and peptide methods implicated the same indel site. Overall, the results suggest that regions important for function of both C3 and C5 lie proximal to residues 150-200 and 1600-1620 in the precursor sequences. Additional sites potentially important for C5 function are near residue 500 in the beta-chain and at two or three sites between the N-terminus of the alpha'-chain and the C5d fragment. One of the latter sites, near residue 865, appears to be important for proteolytic activation of C5. (+info)

Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. (3/215)

A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes. (+info)

Enhancement of lectin pathway haemolysis by immunoglobulins. (4/215)

We recently reported that indicator sheep erythrocytes (E) coated with mannan and sensitized with mannan-binding lectin (MBL) (E-M-MBL) are lysed by human serum in the absence of calcium via the lectin pathway of complement activation by a process which requires alternative pathway amplification and is associated with increased binding of and control by complement regulatory proteins C4 bp and factor H. In the present study, we investigated the effect of immunoglobulin (Ig) on this haemolysis. Co-sensitization of indicator E with anti-E haemolysin led to threefold enhancement of lectin pathway haemolysis in the absence of calcium, associated with increased binding of C3 and C5. Lysis was enhanced approximately twofold when E-M-MBL were chemically or immunologically coated with IgM or IgA, and fourfold when coated with IgG, prior to lysis in human serum-Mg-ethyleneglycol tetraacetic acid. The presence of haemolysin did not reduce the binding or inhibitory activity of C4 bp, and the enhancing activity of haemolysin was retained in serum depleted of C4 bp. By contrast, binding of factor H was greatly reduced in the presence of haemolysin, which had no enhancing effect in serum depleted of factor H. These experiments demonstrate the ability of IgG, IgM and IgA to enhance lectin pathway cytolysis, and that this enhancement occurs by neutralization of the inhibitory activity of factor H. Immunoglobulin enhancement of lectin pathway cytolysis represents another interaction between the innate and adaptive systems of immunity. (+info)

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (5/215)

Mannan-binding lectin (MBL) is an acute phase protein which activates the classical complement pathway at the level of C4 and C2 via two novel serine proteases homologous to C1r and C1s. We recently reported that haemolysis via this lectin pathway requires alternative pathway amplification. The present experiments sought to establish the basis for this requirement, and hence focused on the activity and regulation of the C3 convertases. Complement activation was normalized between the lectin and classical pathways such that identical amounts of bound C4 and of haemolytically active C4,2 sites were present on the indicator cells. Under these conditions, there was markedly less haemolysis, associated with markedly less C3 and C5 deposited, via the lectin pathway than via the classical pathway, particularly when alternative pathway recruitment was blocked by depletion of factor D. Lectin pathway activation was associated with enhanced binding in the presence of MBL of complement control proteins C4bp and factor H to C4b and C3b, respectively, with decreased stability of the C3-converting enzyme C4b,2a attributable to C4bp. Immunodepletion of C4bp and/or factor H increased lectin pathway haemolysis and allowed lysis to occur in absence of the alternative pathway. Thus, the lectin pathway of humans is particularly susceptible to the regulatory effects of C4bp and factor H, due at least in part to MBL enhancement of C4bp binding to C4b and factor H binding to C3b. (+info)

Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases. (6/215)

The goal of this study was to identify the site(s) in CR1 that mediate the dissociation of the C3 and C5 convertases. To that end, truncated derivatives of CR1 whose extracellular part is composed of 30 tandem repeating modules, termed complement control protein repeats (CCPs), were generated. Site 1 (CCPs 1-3) alone mediated the decay acceleration of the classical and alternative pathway C3 convertases. Site 2 (CCPs 8-10 or the nearly identical CCPs 15-17) had one-fifth the activity of site 1. In contrast, for the C5 convertase, site 1 had only 0.5% of the decay accelerating activity, while site 2 had no detectable activity. Efficient C5 decay accelerating activity was detected in recombinants that carried both site 1 and site 2. The activity was reduced if the intervening repeats between site 1 and site 2 were deleted. The results indicate that, for the C5 convertases, decay accelerating activity is mediated primarily by site 1. A properly spaced site 2 has an important auxiliary role, which may involve its C3b binding capacity. Moreover, using homologous substitution mutagenesis, residues important in site 1 for dissociating activity were identified. Based on these results, we generated proteins one-fourth the size of CR1 but with enhanced decay accelerating activity for the C3 convertases. (+info)

Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding. (7/215)

Factor B is a serine protease, which despite its trypsin-like specificity has Asn instead of the typical Asp at the bottom of the S(1) pocket (position 189, chymotrypsinogen numbering). Asp residues are present at positions 187 and 226 and either one could conceivably provide the negative charge for binding the P(1)-Arg of the substrate. Determination of the crystal structure of the factor B serine protease domain has revealed that the side chain of Asp(226) is within the S(1) pocket, whereas Asp(187) is located outside the pocket. To investigate the possible role of these atypical structural features in substrate binding and catalysis, we constructed a panel of mutants of these residues. Replacement of Asp(187) caused moderate (50-60%) decrease in hemolytic activity, compared with wild type factor B, whereas replacement of Asn(189) resulted in more profound reductions (71-95%). Substitutions at these two positions did not significantly affect assembly of the alternative pathway C3 convertase. In contrast, elimination of the negative charge from Asp(226) completely abrogated hemolytic activity and also affected formation of the C3 convertase. Kinetic analyses of the hydrolysis of a P(1)-Arg containing thioester by selected mutants confirmed that residue Asp(226) is a primary structural determinant for P(1)-Arg binding and catalysis. (+info)

Functional role of the noncatalytic subunit of complement C5 convertase. (8/215)

The C5 convertase is a serine protease that consists of two subunits: a catalytic subunit which is bound in a Mg2+-dependent complex to a noncatalytic subunit. To understand the functional role of the noncatalytic subunit, we have determined the C5-cleaving properties of the cobra venom factor-dependent C5 convertase (CVF, Bb) made with CVF purified from the venom of Naja naja (CVFn) and Naja haje (CVFh) and compared them to those for two C3b-dependent C5 convertases (ZymC3b,Bb and C3b,Bb). A comparison of the kinetic parameters indicated that although the four C5 convertases (CVFn,Bb, ZymC3b,Bb, CVFh,Bb, and C3b,Bb) had similar catalytic rate constants (kcat = 0.004-0.012 s-1) they differed 700-fold in their affinity for the substrate as indicated by the Km values (CVFn,Bb = 0.036 microM, ZymC3b,Bb = 1.24 microM, CVFh,Bb = 14.0 microM, and C3b,Bb = 24 microM). Analysis of binding interactions between C5 and the noncatalytic subunits (CVFh or C3b, or CVFn) using the BIAcore, revealed dissociation binding constants (Kd) that were similar to the Km values of the respective enzymes. The kinetic and binding data demonstrate that the binding site for C5 resides in the noncatalytic subunit of the enzyme, the affinity for the substrate is solely determined by the noncatalytic subunit and the catalytic efficiency of the enzyme appears not to be influenced by the nature of this subunit. (+info)

... has a cleavage activity and it is essential for forming lectin C3 and C5 convertases and for activation of the complement. For ... Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize ... Collectins are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of ...

https://en.wikipedia.org/wiki/Collectin

C3b binds to the C3 convertase (C4b2b), to form C5 convertase (C4b2b3b). C5 convertase then cleaves C5 into C5a and C5b. Like ... The C3b component of the cleaved C3 binds to C3 convertase (C4b2b) to generate C5 convertase (C4b2b3b), which cleaves the C5 ... In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ...

https://en.wikipedia.org/wiki/Classical_complement_pathway

Bb remains bound to C3(H2O) to form C3(H2O)Bb. This complex is also known as a fluid-phase C3-convertase. This convertase, the ... a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. The C5-convertase of the ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b; accelerate ... C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form ...

https://en.wikipedia.org/wiki/Alternative_complement_pathway

The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...

https://en.wikipedia.org/wiki/C3_convertase

In the classical and lectin pathways of complement activation, formation of the C3-convertase and C5-convertases requires ... making the C3 convertase C4b2b, whereas older sources refer to the larger fragment of C2 as C2a, making the C3 convertase C4b2a ... a fragment of complement component C2 produced during C3 convertase formation". Acta Crystallographica D. 65 (Pt 3): 266-274. ... C2b is the smallest , enzymatically active, fragment of C3 convertase in this pathway, C4b2b (NB: some sources now refer to the ...

https://en.wikipedia.org/wiki/Complement_component_2

... classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC ... classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC ... 3.4.21.45: complement factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ... 3.4.21.45: complement factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ...

https://en.wikipedia.org/wiki/List_of_EC_numbers_(EC_3)

... which promotes cleavage of C3 into C3a and C3b. C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex). The ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the classical pathway ...

https://en.wikipedia.org/wiki/Complement_system

... iC3b C5 - C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1 ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ... see complement proteins section) Collectins Mannan-binding lectin (MBL) Surfactant protein A (SP-A) Surfactant protein D (SP-D ...

https://en.wikipedia.org/wiki/Outline_of_immunology

The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... CVFBb does not require C3 for cleavage of C5, whereas C4b2boxy need native C3 for cleavage of C5 protein. The modified C5 ...

https://en.wikipedia.org/wiki/C5-convertase

This protein binds to bacterial cell walls and dying human cells to stabilize the C3 and C5-convertase enzyme complexes to form ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... Properdin is protein that in humans is encoded by the CFP (complement factor properdin) gene. Properdin is plasma glycoprotein ...

https://en.wikipedia.org/wiki/Properdin

Rawal N, Pangburn MK (March 2001). "Structure/function of C5 convertases of complement". International Immunopharmacology. 1 (3 ... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... Complement factor B is a protein that in humans is encoded by the CFB gene. This gene encodes complement factor B, a component ...

https://en.wikipedia.org/wiki/Complement_factor_B

C3 is cleaved into its a and b subunits, and C3b binds the convertase. These together are called the C5 convertase. Similarly ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... Together, MBL, C4b and C2a are known as the C3 convertase. ... C5, C6, C7, C8 and C9 form the membrane attack complex (MAC). ... Once bound to the ligands MBL and Ficolin oligomers recruit MASP1 and MASP2 and initiate the lectin pathway of complement ...

https://en.wikipedia.org/wiki/Pattern_recognition_receptor

... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 - complement c3-c5 convertases, alternative pathway MeSH ... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... complement c3 MeSH D12.776.124.486.274.250.250 - complement c3a MeSH D12.776.124.486.274.250.260 - complement c3b MeSH D12.776. ...

https://en.wikipedia.org/wiki/List_of_MeSH_codes_(D12.776.124)

... which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and ... Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell ... The drug interferes with the formation of the membrane attack complex in erythrocytes by binding to C5, compensating for the ... The complement system is part of the innate immune system and has a variety of functions, from destroying invading ...

https://en.wikipedia.org/wiki/Paroxysmal_nocturnal_hemoglobinuria

... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ... January 2011). "The development of atypical hemolytic uremic syndrome depends on complement C5". Journal of the American ... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... Moreover, the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to ...

https://en.wikipedia.org/wiki/Factor_H

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs.bvs.br/I/del_i2006.htm

Name: complement component 2 (within H-2S). Synonyms: classical-complement pathway C3/C5 convertase ...

https://www.mmrrc.org/catalog/sds.php?mmrrc_id=38808

However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ... MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on ...

https://www.frontiersin.org/articles/10.3389/fphy.2018.00130/full

... and C5-convertase of human complement. 2odq. Complement component C2a, the catalytic fragment of C3- and C5-convertase of human ... Complement component C2a, the catalytic fragment of C3- ... C3 convertase (C3bBb) stabilized by SCIN. 2ww8. Structure of ... Complement component C2a. 2ica. CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5- ... Integrin I domain of complement receptor 3 in complex with C3d. 4mmx. Integrin AlphaVBeta3 ectodomain bound to the tenth domain ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=VWA&START=227&END=403&E_VALUE=4.21e-39&TYPE=SMART&BLAST=KRDILFLFDGSVNVLGQFPAVRDFLYRIIEELDVKPDGTRVAIAQFSDDVRLESRFSEHQTKAEILNLVKKMKLKTGKALNLGYALDYALRNIFVRSAGSRIEDNVQQFLVLLVAGRSSDAVAGPASSLKQRGVVPFIFQAKNANPSELEQIVLSPAFILAAESLPKIGDLQSQIVS

C5-9).The IgG antibody, C3NeF, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... Corvillo F, Lopez-Trascasa M. Acquired partial lipodystrophy and C3 glomerulopathy: dysregulation of the complement system as a ... C3 nephritic factor and SLE: report of four cases and review of the literature. QJM. 1994 Oct. 87(10):609-15. [QxMD MEDLINE ...

https://emedicine.medscape.com/article/123039-medication

complement factor B Previous and unofficial names. alternative-complement pathway C3/C5 convertase , B-factor, properdin , BFD ... complement C1r Previous and unofficial names. complement C1r-A subcomponent , complement component 1, r subcomponent A , ... C1sb , complement component C1SB , r-gsp , Gm5077 , predicted gene 5077 , complement component 1 , complement component 1, s ... C2 , Factor B , H2-Bf , histocompatibility 2, complement component factor B , properdin factor B ...

https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=751

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2017.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2015.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2020.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2019.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2009.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2011.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2013.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2014.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2010.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2012.bvsalud.org/I/del_i2006.htm

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2008.bvsalud.org/I/del_i2006.htm

C3-C5 Convertase C3-C5 Convertases, Complement Complement C3 C5 Convertases Convertase, C3-C5 Convertases, Complement C3-C5 ... C3 Activator. C3 C5 Convertase. C3 Convertase. C3 Convertases, Complement. C3-C5 Convertase. C3-C5 Convertases, Complement. C5 ... Complement C3 C5 Convertases. Complement C3 Convertases. Complement C5 Convertases. Convertase, C 3. Convertase, C3. Convertase ... C3-C5. Convertase, Complement 3. Convertases, Complement C3. Convertases, Complement C3-C5. Convertases, Complement C5. ...

https://decs.bvsalud.org/en/ths/resource/?id=50828

Complement 3 Convertase. Complement C3-C5 Convertases. Growth Substances, Pigments, and Vitamins. Growth Substances. ...

https://decs2018.bvsalud.org/I/del_i2006.htm

Watch a video to learn how C1 is activated initiating the classical complement pathway creating chronic hemolysis and ... Once active, C3 convertase initiates the complement response. Cleaved active products of C3 and C5 drive the effector responses ... It also leads to activation of the classical complement pathway. Now we are going to talk about complement and complement ... The classical and lectin pathways cleave C2 and C4 to form C3 convertase. The alternative pathway relies on separate factors to ...

https://www.understandingcad.com/mechanism-cold-agglutinin-disease

Alternative Complement Pathway C3 C5 Convertase Neuroscience 60% * Complement Factor B Immunology and Microbiology 60% ...

https://tohoku.pure.elsevier.com/en/publications/negative-regulation-of-protein-phosphatase-2c%CE%B2-by-isg15-conjugati

CFB; BF; BFD; Complement factor B; C3/C5 convertase; Glycine-rich beta glycoprotein; GBG; PBF2; Properdin factor B. ...

https://www.proteogenix.science/product/cleaved-factor-b-bb-k260-polyclonal-antibody/

Many of these reagents inhibit the C3 convertases during the early stages of the cascade. However, a drawback of total systemic ... When given intravenously to rodents, OmCI totally ablated complement hemolytic activity, which gradually restored as C5 was ... Using C5-sufficient and C5-deficient mice we showed that prolonged half-life was due to binding to plasma C5. Surface plasmon ... The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated ...

https://nora.nerc.ac.uk/id/eprint/1597/

Alternative Complement Pathway C3 C5 Convertase Medicine and Dentistry 66% * Non Insulin Dependent Diabetes Mellitus ...

https://publires.unicatt.it/it/publications/blockade-of-receptor-activator-of-nuclear-factor-%CE%BAb-rankl-signali-7

Thus, the absence of CD55 and CD59 on PNH red cells allows C3 and C5 convertases to proceed unchecked and ultimately leads to ... CD59 and CD55 act at different levels of the complement cascade. CD55 blocks C3 convertases, and CD59 blocks the addition of C9 ... CD59 and CD55 are GPI-APs that serve as important regulators of the complement cascade. ... Hemolytic anemia in PNH results from the increased susceptibility of PNH erythrocytes to complement. ...

https://diseasesdic.com/paroxysmal-nocturnal-hemoglobinuria-pnh-definition-symptoms-and-treatment/

... administered a C3 complement inhibitor (CR2-Crry) in MRL/lpr mice from 16 to 24 weeks of age.[58] CR2 binds to C3 deposited ... C1r and C1s serine proteases are then activated and fragment C2 and C4 to form C3 convertase. This enzymatic complex becomes ... A monoclonal antibody to C5 component inhibited the cleavage of C5 to C5a and C5b, blocking the formation of the membrane ... Anti-complement Therapy. Complement appears to play a dual role in the progression of SLE, serving a beneficial role in ...

https://www.medscape.com/viewarticle/817430_4

The complements are activated in the following order: Ag-Ab complex-C1 C4 C2 C3 C5 C6 C7 C8 C9. This process occurs on the ... Some C3b joins C4b2a to form C4b2a3b (C5 convertase). C5 convertase cleaves C5 into C5a and C5b. C5a is released in circulation ... C3 convertase) is formed. The C4b2a complex attached to cell membrane has enzymatic activity and can cleave several hundred C3 ... In alternate pathway, C3 is activated directly with no role of earlier complement components. It does not require antigen- ...

https://www.jaypeedigital.com/eReader/chapter/9789350901847/ch1

The complement convertases probably recognises their substrates C3 and C5 in a manner similar to this, see Laursen et al (2011 ... Figure. Models of the very large proteolytic complexes cleaving C3, C4 and C5. Left, A model of C5 (blue) bound to the cobra ... We have determined structures of the key proteins C3, C4, and C5 in a variety of functional states, and hereby been able to ... protect our own cells from complement, and contributes to clearance of pathogens and host cells targeted by complement ...

https://mbg.au.dk/en/research/research-areas/protein-science/gregers-rom-andersen?tx_pure_pure5%5Basc%5D=0&tx_pure_pure5%5Bcontroller%5D=Publications&tx_pure_pure5%5Border%5D=publicationYear&cHash=51a654cf836efac94dce728aca743630

3c). Interestingly, complement 8 alpha chain, complement 9 and C3/C5 convertase from the alternative pathway showed the same ... Complement 1-4 and C3/C5 convertase of the classical pathway together with clusterin and vitronectin were associated with a ... C3, C4 and C7) showed the same abundance behavior as described above, whereas further complement components (C5, C8, C9 and ... whereas complement 5a anaphylatoxin (C5) showed a significant decrease in abundance (Fig. 3c). During CARL, the inflammation- ...

https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03441-4

... is an integral membrane protein that inhibits complement activation by blocking the convertases that activate C3 and C5. We ... nearly all of which systemically inhibit complement. There are benefits of targeting complement inhibition to sites of ... The complement system has long been recognized as a potential druggable target for a variety of inflammatory conditions. Very ... The complement system is a potent mediator of ischemia-reperfusion injury (IRI), which detrimentally affects the function and ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:Traumatismo+por+Reperfus%C3%A3o/imunologia

The complex between complement system proteins C5b and C6 is the cornerstone for the assembly of the membrane attack complex (MAC, also known as C5b6789 n ). (frontiersin.org)
Without PIG-A, important proteins cannot connect to the cell surface and protect the cell from substances in the blood called complement. (diseasesdic.com)
An important component in the innate immune system is the complement system, formed by more than 50 soluble and membrane bound proteins. (au.dk)
The soluble proteins are present in extracellular fluids, while the membrane proteins are located in membranes surrounding many of our cells, where they transmit the extracellular danger signal into intracellular signaling, protect our own cells from complement, and contributes to clearance of pathogens and host cells targeted by complement opsonization. (au.dk)
We have determined structures of the key proteins C3, C4, and C5 in a variety of functional states, and hereby been able to propose how these proteins are proteolytically cleaved by enzymes assembled and activated in response to danger signals (see figure). (au.dk)
Complement consists of over 50 proteins that either circulate in blood, the lymph and interstitial fluids, or are expressed on cells in mostly pro-enzyme and non-activated states. (hapres.com)
In IgA nephropathy, complement proteins in the circulation have also been studied and found to have predictive relevance. (alliedacademies.org)
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)

Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
C3 activation involves cleavage by C3 convertase into C3a and C3b. (mayocliniclabs.com)
This culminates in the cleavage of the core complement effector molecules C3 and C5 into the bio-active anaphylatoxins C3a and C5a and the opsonins C3b and C5b. (hapres.com)
Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.com)
Each pathway converges on C3 cleavage to produce the anaphylatoxin C3a and active fragment C3b once activated [ 1 ][ 2 ]. (alliedacademies.org)

As part of the innate immunity, the complement system orchestrates a cascade of biochemical reactions that result in pathogen elimination and in activation of the adaptive immune response [ 1 , 2 ]. (frontiersin.org)
Many of these reagents inhibit the C3 convertases during the early stages of the cascade. (nerc.ac.uk)
CD59 and CD55 are GPI-APs that serve as important regulators of the complement cascade. (diseasesdic.com)
CD59 and CD55 act at different levels of the complement cascade. (diseasesdic.com)
Once triggered, a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the insoluble C3b, which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction, and also a C5 convertase. (downhouse.software)
Sensing of pathogens or danger by one or more of the three activation pathways, the classical, the lectin, or the alternative complement pathway, triggers activation of the system in a cascade-like fashion. (hapres.com)
C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
It is well known that the complement system functions as a 'complement' of the immune system, playing an important role in immune response, pathogen clearance, and inflammation," according to a scientist at Creative Biolabs, "and the complement cascade cannot be activated without the catalysis of several enzymes, among which C3 convertase and C5 convertase are considered the most important ones. (madurai-news.in)
Several genes not involved in the complement cascade have also been implicated. (medscape.com)
These findings point to the complement cascade as a viable therapy target for chronic renal disease. (alliedacademies.org)
Deficiencies in the complement cascade can lead to overwhelming infection and sepsis. (medscape.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)
The complement cascade consists of 3 separate pathways that converge in a final common pathway. (medscape.com)

OmCI ablated clinical disease, reduced C3 and C9 deposition at the neuro-muscular junction, and effected a marked reduction in cellular infiltration at this site. (nerc.ac.uk)
Thus, the absence of CD55 and CD59 on PNH red cells allows C3 and C5 convertases to proceed unchecked and ultimately leads to increased deposition of membrane attack complexes on the red cell membrane. (diseasesdic.com)
CD55 induces the decay of the C3 and C5 convertases, preventing C3b deposition and downstream assembly of the MAC complex ( 1 , 2 ). (aai.org)
The presence of C3 distinguishes IgA nephropathy from glomerular IgA deposition in the asymptomatic stage. (alliedacademies.org)
C3GN is a type of glomerulonephritis characterized by dominant C3 deposition resulting from overactivation of the alternative pathway of complement (APC) from acquired or hereditary causes. (renalfellow.org)
Overactivation of the APC leads to deposition of C3 in the glomeruli, which can lead to an inflammatory reaction and resulting glomerular injury. (renalfellow.org)
Interestingly, it has been noted that some patients with post-infectious glomerulonephritis show persistent C3 deposition instead of fully recovering, and this so-called "resolving/atypical" post-infectious glomerulonephritis is thought to represent the development of C3GN in patients with APC abnormalities. (renalfellow.org)

The versatile response of the complement system emerges from its three pathways known as alternative, classical, and lectin, that are either constitutively active in the fluid phase (alternative and classical pathway [ 3 - 5 ]) or initiate upon sensing danger-associated molecular patterns on pathogens (classical and lectin pathways). (frontiersin.org)
In cold agglutinin disease, certain abnormal bone marrow cells produce antibodies called cold agglutinins, which activate a part of the immune system known as the complement pathway. (understandingcad.com)
Recent identification of a C5-binding protein in the salivary gland of the soft tick Ornithodoros moubata has enabled development of a terminal pathway-specific reagent, OmCI, with potential to ameliorate disease while leaving key physiological processes unaffected. (nerc.ac.uk)
The complement system can be activated via immune complexes, and the alternative pathway (properdin pathway), which is activated primarily by foreign bodies such as microorganisms. (mayocliniclabs.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)
C2a remains associated with C4b to form the classical pathway C3 convertase (C4b2a). (abcam.com)
The latter binds to the C3 convertase complex to form C4b2a3b, the classical pathway C5 convertase. (abcam.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)
Complement can be activated in three different ways, one of which is the classical pathway. (madurai-news.in)
The classical pathway for complement activation is a major contributor to the defense against infections, the removal of necrotic cells, and the maintenance of homeostasis. (madurai-news.in)
Creative Biolabs can provide custom services based on targets of the classical pathway and a full range of therapeutical antibodies, inhibitors, and soluble complement regulators, such as C1 inhibitors, C3 inhibitors, C5 inhibitors, and C5aR inhibitors. (madurai-news.in)
Complement alternative pathway (AP) dysregulation has been implicated in geographic atrophy, an advanced form of age-related macular degeneration. (arvojournals.org)
[ 3 ] The existence of multiple, complement-related AMD risk alleles has lent further support to this theory and has shed light on the role of uncontrolled alternative complement pathway activation in this disease. (medscape.com)
Lectins activate the lectin pathway in a manner similar to the antibody interaction with complement in the classical pathway. (medscape.com)
The most common mechanism of APC overactivation is development of autoantibodies to C3 convertase, called C3 nephritis factor (C3NeF), which stabilize the convertase and lead to pathway overactivation. (renalfellow.org)
Genetic testing may uncover mutations in components of the alternative pathway of complement such as CFH, CFI, MCP/CD46, and CFHR. (renalfellow.org)
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. (nih.gov)

When given intravenously to rodents, OmCI totally ablated complement hemolytic activity, which gradually restored as C5 was resynthesized. (nerc.ac.uk)
Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. (biomedcentral.com)
The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system. (biomedcentral.com)

These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION . (bvsalud.org)
Serine proteases that cleaves C3 at the carboxyl of Arg-77 of the alpha-chain to yield COMPLEMENT 3A and COMPLEMENT 3B in either the classical or the alternative pathways of COMPLEMENT ACTIVATION. (bvsalud.org)
C1 amplifies the activation of C3, resulting in extravascular hemolysis and chronic inflammation. (understandingcad.com)
1. Berentsen S. Complement activation and inhibition in autoimmune hemolytic anemia: focus on cold agglutinin disease. (understandingcad.com)
Noris M, Remuzzi G. Overview of complement activation and regulation. (understandingcad.com)
The involvement of complement (C) in inflammatory diseases has driven the search for agents capable of inhibiting dysregulated complement activation. (nerc.ac.uk)
When immune complexes are not involved, the alternate method of complement activation initiates the reactant sequence at C3, bypassing C1, C4, and C2. (mayocliniclabs.com)
A decrease in C3 levels to the abnormal range is consistent with disease activation in systemic lupus erythematosus (SLE). (mayocliniclabs.com)
Activation of complement can be started either via adaptive or innate immune recognition. (pediagenosis.com)
Nevertheless, excessive complement activation can cause unpleasant side-effects (see Fig. 36). (pediagenosis.com)
Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
In this study, we show that direct stimulation of CD55 on CD4 + T cells with CD97 can modulate T cell activation but does not interfere with CD55-mediated complement regulation. (aai.org)
This finding emphasises the importance of AP in complement activation amplification. (alliedacademies.org)
These structural changes allow Factors B (FB) and D (FD) to bind to the bioactive form of C3, C3(H2 O), resulting in the formation of fluid phase C3 convertase and therefore enhancing complement activation. (alliedacademies.org)
at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check. (medscape.com)
Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked by Bothrops snakes. (biomedcentral.com)
To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber model. (biomedcentral.com)
Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system by B. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. (biomedcentral.com)

This C3 convertase is stabilised by Properdin. (alliedacademies.org)

C3 nephritic factor and SLE: report of four cases and review of the literature. (medscape.com)

Furthermore, Creative Biolabs offers custom solutions and services based on the C5 convertase to meet specific demands from global clients, which mainly include verification of C5 convertase activity, C5 convertase deficiency identification, and C5 convertase inhibitor development. (madurai-news.in)

MAC is the terminal product of three converging pathways of the complement system and functions as a pore forming complex on cell surfaces, as a response of the immune system in fighting pathogens. (frontiersin.org)

Left, A model of C5 (blue) bound to the cobra venom factor (orange) and the catalytically active serine protase Bb (grey). (au.dk)
Decay-accelerating factor (CD55) is a complement regulatory protein, which is expressed by most cells to protect them from complement-mediated attack. (aai.org)
Decay accelerating factor (CD55) is a 70-kDa single chain complement regulatory protein, that consists of four extracellular short consensus repeat (SCR) 3 domains, linked to the membrane by a GPI anchor ( 1 ). (aai.org)
The common coding variant Y402H in the complement factor H ( CFH ) gene was the first identified. (medscape.com)
[ 21 ] Such rare variants have been described in the complement factor H ( CFH ), complement factor I ( CFI ), complement factor 9 ( C9 ), and complement factor 3 ( C3) genes. (medscape.com)
It is primarily regulated by complement Factor H (CFH), which, in cooperation with Factor I, degrades C3 to an inactive version known as iC3b (FI). (alliedacademies.org)
A North African study of molecular basis of complement factor I deficiency in atypical hemolytic and uremic syndrome patients suggested that the Ile357Met mutation may be a founding effect. (medscape.com)

The long term aim of our research is therefore also to develop selective inhibitors of the complement and other branches of innate immunity. (au.dk)

Severe recurrent bacterial infections occur in patients with homozygous C3 deficiency and in those patients with low levels of C3 secondary to the absence of C3b activator. (mayocliniclabs.com)
Cases of complement deficiency have helped defined the role of complement in host defense. (medscape.com)

Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)
The classical complement system is engrained in the mind of scientists and clinicians as a blood-operative key arm of innate immunity, critically required for the protection against invading pathogens. (hapres.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)

Although complement was initially considered only a key constituent of innate immunity, due to its critical role in delivering co-stimulatory signals via engagement of complement receptors on antigen presenting cells (APCs) or directly on B and T cells, it is now also widely recognized as a required functional bridge between innate and adaptive immunity [5-7] . (hapres.com)
The complement system is a key player in innate immunity as well as a powerful link between innate and adaptive immunity. (alliedacademies.org)

Corvillo F, Lopez-Trascasa M. Acquired partial lipodystrophy and C3 glomerulopathy: dysregulation of the complement system as a common pathogenic mechanism. (medscape.com)
These mutations also cause complement dysregulation in the setting of atypical hemolytic uremic syndrome. (renalfellow.org)

New York, USA - November 21, 2022 - Complement-based drug discovery and development has received significant interest and attention from global scientists dedicated to studying complement therapeutics, which have dramatically expedited the development of complement therapeutics. (madurai-news.in)

C3 (MW 180 000), the central component of all complement reac- tions, split by its convertase into a small (C3a) and a large (C3b) fragment. (pediagenosis.com)
Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)
The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
These 3 pathways converge at the component C3. (medscape.com)

Genes encoding products involved in complement control and interaction with immune complexes are found within these regions. (alliedacademies.org)

C2a in the convertase complex cleaves C3 releasing C3a and C3b. (abcam.com)
This complex cleaves C5 leading to the release of C5a and C5b. (abcam.com)

Complement C6 then binds to C5b to form the complex C5b6 [ 7 ]. (frontiersin.org)
The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX . (nih.gov)

Recent case reports demonstrating the efficacy of the humanised anti-C5 monoclonal antibody eculizumab support this notion, but more research into the involvement of complement in IgA nephropathy is needed to guide future treatment strategies. (alliedacademies.org)

Note that, in the absence of antibody, many of the molecules that activate the complement system are carbohydrate or lipid in nature (e.g. lipopolysaccharides, mannose), suggesting that the system evolved mainly to recognize bacterial surfaces via their non-protein features. (pediagenosis.com)

It is widely expressed on human cells, including PBLs, and protects them from complement-mediated lysis. (aai.org)

The present study aimed to assess whether Bothrops jararacussu and Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways. (biomedcentral.com)

Likely the most exciting observation though about intracellular complement-coined the complosome to set it apart from the liver-derived and serum-circulating complement system [13] -is the finding that it unexpectedly serves key roles in single cell metabolism [12, 14,15] . (hapres.com)

C5 is then digested into an additional, more powerful soluble anaphylatoxin, C5a, and the insoluble C5b, which cooperates with other components to lead to the formation of the Membrane Attack Complex (MAC) comprised of C9 molecules inserted into the plasma membrane. (downhouse.software)

These data offer exciting prospects for targeted treatment of complement-mediated diseases without the detrimental inhibition of the opsonic roles of complement. (nerc.ac.uk)
For complement-driven C3GN, a variety of treatments have been attempted but inhibition of complement with anti-C5 therapy has been effective in a subset of patients, and plasmapheresis has been used for autoantibody-mediated disease. (renalfellow.org)

However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to several complement-mediated autoimmune diseases. (frontiersin.org)
Recent work, however, has defined a novel and unexpected role for an intracellular complement system-the complosome-in the regulation of key metabolic events that underlie peripheral human T cell survival as well as the induction and cessation of their effector functions. (hapres.com)
Indeed, C3 convertase and C5 convertase are both potential complement therapeutic targets in the treatment of related diseases, such as hemolytic uremic syndrome (HUS), which is induced by the down-regulation of C5 convertase blocking. (madurai-news.in)
Recently, an increase in T cell responsiveness in CD55 −/− mice was shown to be mediated by a lack of complement regulation. (aai.org)

Work on better defining the instructive role of complement on adaptive immune cells led to the somewhat surprising finding that these complement effects were mostly independent of liver-derived complement but rather mediated by locally produced and activated complement-for example, C3 and C5 secreted by APCs and then activated in the extracellular space [8-10] . (hapres.com)

CR Complement receptor. (pediagenosis.com)
complement C3b/C4b receptor 1 (Knops b. (gsea-msigdb.org)

CH50 activity reflects C5 blockade in PNH patients treated with eculizumab and is directly related to circulating free eculizumab levels. (ashpublications.org)
Both CH50 and free eculizumab level markers look promising for the monitoring of complement blockade in patients with PNH receiving eculizumab. (ashpublications.org)

CD55 blocks C3 convertases, and CD59 blocks the addition of C9 into the terminal membrane attack complex. (diseasesdic.com)

The tick-over mechanism is the result of spontaneous and continuous hydrolysis of C3, which causes conformational changes in C3. (alliedacademies.org)

The complement system is an integral part of the body's immune defenses. (mayocliniclabs.com)
This review summarizes the current knowledge about the emerging vital role of the complosome in T cell metabolism and discusses how viewing the evolution of the complement system from an "unconventional" vantage point could logically account for the development of its metabolic activities. (hapres.com)
The complement system is generally considered among the evolutionary oldest parts of our immune system. (hapres.com)
The growing notion that compartmentalization of complement-mediated activity in immunity may exist was then supported by the discovery of an intracellularly generated and functioning complement system in human CD4 + and CD8 + T cells [11,12] . (hapres.com)
Further, and based on those new aspects of complement activity, we move into more uncharted areas and discuss a hypothetical alternative to the currently accepted model on how the complement system may have evolved and finally outline some of the key questions and challenges in this exciting new research area. (hapres.com)
Rare genetic variants in the complement system have also been found to play an important role in AMD. (medscape.com)
In physiological situations, the AP is always active at low levels and is responsible for complement system functioning. (alliedacademies.org)
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)
An intricate system regulates complement activity. (medscape.com)

Specific complement deficiencies are also associated with an increased risk of developing autoimmune disease, such as SLE. (medscape.com)

For decades, the company has kept its minds focused on becoming a dependable and high-tech biotech firm that contributes to the advancement of complement-based drug discovery. (madurai-news.in)

The instigation of an immune response via C5b6 is also detrimental to host-cells unless complement is properly regulated at the terminal stage [ 14 ]. (frontiersin.org)
C5 (MW 180 000), split by its convertase into C5a, a small peptide that, together with C3a (anaphylatoxins), acts on mast cells, polymorphs and smooth muscle to promote the inflammatory response, and C5b, which initiates the assembly of C6, 7, 8 and 9 into the membrane damaging or 'lytic' unit. (pediagenosis.com)
In this brief feature article, we give a succinct overview of our current understanding about the mechanistic roles of intracellular complement during the immunometabolic adaptions underlying the life cycle of human T cells. (hapres.com)
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)

Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization and (2) defects in lytic activity (defects in MAC). (medscape.com)

The essential feature is the requirement for a specific antigen-antibody interaction, leading via components C1, C2 and C4 to the formation of a 'convertase' which splits C3. (pediagenosis.com)

Complement activity can activate C5, leading to intravascular hemolysis and chronic inflammation. (understandingcad.com)
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)

Complement is found in the bloodstream in a physiologically inactive state and can be triggered by three mechanisms: the classical (CP), lectin (LP), and alternative (AP) pathways (AP). (alliedacademies.org)

Complement plays a key role in the aetiology of IgA nephropathy, according to mounting clinical, genetic, and biochemical evidence. (alliedacademies.org)

[ 4 ] 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)

Some new clinical entities are linked with partial complement defects. (medscape.com)
This article outlines some of the disease states associated with complement deficiencies and their clinical implications. (medscape.com)

Hemolytic anemia in PNH results from the increased susceptibility of PNH erythrocytes to complement. (diseasesdic.com)
[ 2 ] , whereas C5 to C9 may have enhanced susceptibility to meningococcal disease. (medscape.com)

Decreased C3 may be associated with acute glomerulonephritis, membranoproliferative glomerulonephritis, immune complex disease, active systemic lupus erythematosus, septic shock, and end-stage liver disease. (mayocliniclabs.com)

Anatomy22

Organisms17

Diseases13

Chemicals and Drugs126

Analytical, Diagnostic and Therapeutic Techniques and Equipment28

Phenomena and Processes47

Disciplines and Occupations2

Information Science3

Health Care1

Channel catfish virus gene 50 encodes a secreted, mucin-like glycoprotein. (1/215)

Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. (2/215)

Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. (3/215)

Enhancement of lectin pathway haemolysis by immunoglobulins. (4/215)

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (5/215)

Decay accelerating activity of complement receptor type 1 (CD35). Two active sites are required for dissociating C5 convertases. (6/215)

Mutational analysis of the primary substrate specificity pocket of complement factor B. Asp(226) is a major structural determinant for p(1)-Arg binding. (7/215)

Functional role of the noncatalytic subunit of complement C5 convertase. (8/215)

Proprotein Convertases

Complement C3

Complement C3-C5 Convertases

Complement C4

Complement C4a

Furin

Proprotein Convertase 2

Complement C5

Complement C3a

Complement Activation

Complement C4b

Subtilisins

Complement C1q

Complement C3b

Complement C5a

Proprotein Convertase 1

Complement C2

Complement System Proteins

Proprotein Convertase 5

Complement C6

Complement C3c

Complement C3d

Receptors, Complement

Complement C9

Complement Pathway, Classical

Complement Pathway, Alternative

Complement Inactivator Proteins

Complement C1s

Complement Factor B

Complement Membrane Attack Complex

Complement C2a

Complement C1r

Complement C7

Complement Activating Enzymes

Complement C8

Complement C1

Complement Hemolytic Activity Assay

Complement C3-C5 Convertases, Classical Pathway

Receptors, Complement 3b

Complement Factor H

Complement C5b

Antigens, CD55

Receptor, Anaphylatoxin C5a

Complement C3-C5 Convertases, Alternative Pathway

Complement Factor D

Complement Factor I

Complement Inactivating Agents

Aspartic Acid Endopeptidases

Complement C1 Inactivator Proteins

Serine Endopeptidases

Protein Precursors

Neuroendocrine Secretory Protein 7B2

Receptors, Complement 3d

Anaphylatoxins

Complement C3 Convertase, Alternative Pathway

Molecular Sequence Data

Amino Acid Sequence

Properdin

Protein Processing, Post-Translational

Complement Fixation Tests

Cobra Venoms

Carboxypeptidase H

Complement C4b-Binding Protein

Pro-Opiomelanocortin

alpha 1-Antitrypsin

Complement C3b Inactivator Proteins

Complement Pathway, Mannose-Binding Lectin

Complement C2b

Antigens, CD59

Pituitary Hormones

Recombinant Proteins

Protein Binding

Antigen-Antibody Complex

Steroid 21-Hydroxylase

Cell Line

Complement C1 Inhibitor Protein

Immunoglobulin G

Hemolysis

Complement C5 Convertase, Classical Pathway

Complement C3 Convertase, Classical Pathway