Complement c4b binding protein. Medical search

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 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.

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 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.

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).

Complexes containing CHLOROPHYLL and other photosensitive molecules. They serve to capture energy in the form of PHOTONS and are generally found as components of the PHOTOSYSTEM I PROTEIN COMPLEX or the PHOTOSYSTEM II PROTEIN COMPLEX.

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.

The vitamin K-dependent cofactor of activated PROTEIN C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S; (PROTEIN S DEFICIENCY); can lead to recurrent venous and arterial thrombosis.

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 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.

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 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 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.

Protein complexes that take part in the process of PHOTOSYNTHESIS. They are located within the THYLAKOID MEMBRANES of plant CHLOROPLASTS and a variety of structures in more primitive organisms. There are two major complexes involved in the photosynthetic process called PHOTOSYSTEM I and PHOTOSYSTEM II.

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.

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 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.

Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms.

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.

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 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).

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).

A large multisubunit protein complex found in the THYLAKOID MEMBRANE. It uses light energy derived from LIGHT-HARVESTING PROTEIN COMPLEXES to catalyze the splitting of WATER into DIOXYGEN and of reducing equivalents of HYDROGEN.

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.

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.

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).

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 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.

Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.

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 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.

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.

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.

Plant cell inclusion bodies that contain the photosynthetic pigment CHLOROPHYLL, which is associated with the membrane of THYLAKOIDS. Chloroplasts occur in cells of leaves and young stems of plants. They are also found in some forms of PHYTOPLANKTON such as HAPTOPHYTA; DINOFLAGELLATES; DIATOMS; and CRYPTOPHYTA.

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.

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

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.

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.

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.

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).

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

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.

That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.

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.

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.

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).

Multicellular, eukaryotic life forms of kingdom Plantae (sensu lato), comprising the VIRIDIPLANTAE; RHODOPHYTA; and GLAUCOPHYTA; all of which acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations.

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

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.

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.

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

A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.

Proteins that bind to the 3' polyadenylated region of MRNA. When complexed with RNA the proteins serve an array of functions such as stabilizing the 3' end of RNA, promoting poly(A) synthesis and stimulating mRNA translation.

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

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.

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

A cytotoxic member of the CYTOCHALASINS.

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.

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

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.

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.

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.

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.

Established cell cultures that have the potential to propagate indefinitely.

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

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 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.

A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-

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

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

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.

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)

Proteins prepared by recombinant DNA technology.

A poly(A) binding protein that has a variety of functions such as mRNA stabilization and protection of RNA from nuclease activity. Although poly(A) binding protein I is considered a major cytoplasmic RNA-binding protein it is also found in the CELL NUCLEUS and may be involved in transport of mRNP particles.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

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.

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).

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.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

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.

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.

The rate dynamics in chemical or physical systems.

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.

A family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (Int J Gynaecol Obstet 1992;39(1):3-9)

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.

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

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).

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

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

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

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

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.

A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.

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

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.

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.

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.

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.

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).

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.

The sum of the weight of all the atoms in a molecule.

A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)

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

Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS.

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.

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

Antibodies produced by a single clone of cells.

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

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.

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 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.

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

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

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

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.

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.

A poly(A) binding protein that is involved in promoting the extension of the poly A tails of MRNA. The protein requires a minimum of ten ADENOSINE nucleotides in order for binding to mRNA. Once bound it works in conjunction with CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR to stimulate the rate of poly A synthesis by POLY A POLYMERASE. Once poly-A tails reach around 250 nucleotides in length poly(A) binding protein II no longer stimulates POLYADENYLATION. Mutations within a GCG repeat region in the gene for poly(A) binding protein II have been shown to cause the disease MUSCULAR DYSTROPHY, OCULOPHARYNGEAL.

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.

Proteins found in any species of bacterium.

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.

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.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.

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.

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 lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

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 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).

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.

Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.

Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.

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.

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.

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.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

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

A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.

A family of secreted multidomain proteins that were originally identified by their association with the latent form of TRANSFORMING GROWTH FACTORS. They interact with a variety of EXTRACELLULAR MATRIX PROTEINS and may play a role in the regulation of TGB-beta bioavailability.

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

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

Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.

A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed)

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

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.

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.

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

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.

One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.

Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.

A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.

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.

Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.

Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)

A general transcription factor that plays a major role in the activation of eukaryotic genes transcribed by RNA POLYMERASES. It binds specifically to the TATA BOX promoter element, which lies close to the position of transcription initiation in RNA transcribed by RNA POLYMERASE II. Although considered a principal component of TRANSCRIPTION FACTOR TFIID it also takes part in general transcription factor complexes involved in RNA POLYMERASE I and RNA POLYMERASE III transcription.

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 group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.

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.

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.)

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

One of the six homologous proteins that specifically bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions. The function of this protein is not completely defined. However, several studies demonstrate that it inhibits IGF binding to cell surface receptors and thereby inhibits IGF-mediated mitogenic and cell metabolic actions. (Proc Soc Exp Biol Med 1993;204(1):4-29)

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.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

A protein that has been shown to function as a calcium-regulated transcription factor as well as a substrate for depolarization-activated CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. This protein functions to integrate both calcium and cAMP signals.

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.

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

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).

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

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

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 movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.

Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a non-covalently-bound ligand.

Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.

Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.

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.

A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.

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.

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

A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

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.

A member of the p300-CBP transcription factor family that was initially identified as a binding partner for CAMP RESPONSE ELEMENT-BINDING PROTEIN. Mutations in CREB-binding protein are associated with RUBINSTEIN-TAYBI SYNDROME.

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.

Glycoproteins found on the membrane or surface of cells.

An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine.

Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.

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.

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.

Cellular DNA-binding proteins encoded by the rel gene (GENES, REL). They are expressed predominately in hematopoietic cells and may play a role in lymphocyte differentiation. Rel frequently combines with other related proteins (NF-KAPPA B, I-kappa B, relA) to form heterodimers that regulate transcription. Rearrangement or overexpression of c-rel can cause tumorigenesis.

A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p105 precursor protein and is capable of forming dimeric complexes with itself or with TRANSCRIPTION FACTOR RELA. It regulates expression of GENES involved in immune and inflammatory responses.

Enhancement of lectin pathway haemolysis by immunoglobulins. (1/74)

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. (2/74)

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)

Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. (3/74)

Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor C4b-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C4bp, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of C4b by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation. (+info)

C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation. (4/74)

After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP-protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP alpha-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP-necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells. (+info)

In vivo clearance of human protein S in a mouse model: influence of C4b-binding protein and the Heerlen polymorphism. (5/74)

OBJECTIVE: To explore the effect of the Heerlen polymorphism and C4b-binding protein (C4BP) on protein S catabolism in vitro and in vivo. METHODS AND RESULTS: Radiolabeled protein S was efficiently bound and intracellularly degraded by THP-1 macrophages, and both processes were strongly reduced in the presence of the protein S-carrier protein C4BP. To test whether C4BP displays a similar protective effect in vivo, survival experiments were performed in mice. In the absence of C4BP, radiolabeled human protein S disappeared in a biphasic manner (mean residence time [MRT] 2 hours). However, the presence of C4BP resulted in a 4-fold prolonged survival of protein S (MRT 8 hours; P<0.0001). We also applied this experimental model to recombinant protein S-Heerlen, a naturally occurring variant that contains a Ser460Pro substitution. These clearance experiments revealed a strongly decreased survival of recombinant protein S-S460P (MRT 0.6 hours; P=0.021), which could be compensated partially by C4BP (MRT 1.4 hours; P=0.012 compared with protein S-S460P). CONCLUSIONS: Protein S-S460P has a reduced survival in vivo, which may explain the low levels of free protein S in individuals carrying this polymorphism. Furthermore, C4BP prevents premature clearance of protein S and uses this ability to compensate the increased clearance of protein S-S460P. (+info)

Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection. (6/74)

Neisseria gonorrhoeae is the causative agent of gonorrhea, a disease that is restricted to humans. Complement forms a key arm of the innate immune system that combats gonococcal infections. N. gonorrhoeae uses its outer membrane porin (Por) molecules to bind the classical pathway of complement down-regulatory protein C4b-binding protein (C4bp) to evade killing by human complement. Strains of N. gonorrhoeae that resisted killing by human serum complement were killed by serum from rodent, lagomorph, and primate species, which cannot be readily infected experimentally with this organism and whose C4bp molecules did not bind to N. gonorrhoeae. In contrast, we found that Yersinia pestis, an organism that can infect virtually all mammals, bound species-specific C4bp and uniformly resisted serum complement-mediated killing by these species. Serum resistance of gonococci was restored in these sera by human C4bp. An exception was serotype Por1B-bearing gonococcal strains that previously had been used successfully in a chimpanzee model of gonorrhea that simulates human disease. Por1B gonococci bound chimpanzee C4bp and resisted killing by chimpanzee serum, providing insight into the host restriction of gonorrhea and addressing why Por1B strains, but not Por1A strains, have been successful in experimental chimpanzee infection. Our findings may lead to the development of better animal models for gonorrhea and may also have implications in the choice of complement sources to evaluate neisserial vaccine candidates. (+info)

Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor. (7/74)

Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement. (+info)

Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation. (8/74)

Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+ E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA- E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+ E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum. (+info)

Blom, Anna M.; Villoutreix, Bruno O.; Dahlbäck, Björn (2004). "Complement inhibitor C4b-binding protein-friend or foe in the ... Dahlbäck, Björn (1991). "Protein S and C4b-Binding Protein: Components Involved in the Regulation of the Protein C ... molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein". ... Shen, L.; Dahlbäck, B. (1994). "Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor ...

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

"Importance of the alpha 3-fragment of complement C4 for the binding with C4b-binding protein". FEBS Letters. 271 (1-2): 131-6. ... Complement C4-A is a kind of the Complement component 4 protein that in humans is encoded by the C4A gene. This gene encodes ... Complement component 4 Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency ... "Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases". Front Immunol. 12: 739430. doi: ...

https://en.wikipedia.org/wiki/C4A

... duttonii acquire complement regulators C4b-binding protein and factor H". Infection and Immunity. 74 (7): 4157-63. doi:10.1128/ ... It is notable for its ability to alter the proteins expressed on its surface, which causes the "relapsing" characteristic of ...

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

... a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the ... Dahlbäck B (1991). "Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant ... Griffin JH, Gruber A, Fernández JA (1992). "Reevaluation of total, free, and bound protein S and C4b-binding protein levels in ... different roles for protein S and the protein S-C4b binding protein complex". Blood. 103 (4): 1192-201. doi:10.1182/blood-2003- ...

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

... they bind complement factors (C3b, C4b, factor H, and C4bp (complement factor 4b-binding protein)). Cooperation with pili for ... Factor H binding protein (fHbp) that is exhibited in N. meningitidis and some commensal species is the main inhibitor of the ... Factor H binding protein is key to the pathogenesis of N. meningitidis, and is, therefore, important as a potential vaccine ... June 2013). "Role of factor H binding protein in Neisseria meningitidis virulence and its potential as a vaccine candidate to ...

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

... either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... Whaley K (March 1980). "Biosynthesis of the complement components and the regulatory proteins of the alternative complement ... that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. It is a soluble glycoprotein that ...

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

C4-binding protein. Membrane cofactor protein is a widely distributed C3b/C4b binding regulatory glycoprotein of the complement ... CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein ... LHR-A binds preferentially to the complement component C4b: LHR-B and LHR-C bind to C3b and also, albeit with a lower affinity ... Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 (cluster of differentiation 35) is a protein that in ...

https://en.wikipedia.org/wiki/Complement_receptor_1

It can also recruit complement regulators such as Factor H, C4b-binding protein, factor H-like binding protein, and vitronectin ... They also bind to several human proteins such as complement proteins, thrombin, fibrinogen, and plasminogen using surface ... It also secretes proteases to degrade complement proteins such as C3. It can bind to thrombin that decreases the fibrin ... ERU is an autoimmune disease involving antibodies against Leptospira proteins LruA and LruB cross-reacting with eye proteins. ...

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

... (C4BP) is a protein complex involved in the complement system where it acts as inhibitor. C4BP has an ... Complement+C4b-Binding+Protein at the US National Library of Medicine Medical Subject Headings (MeSH) v t e (Articles with ... Ubiquitous surface protein 1 and 2 from Moraxella. Ermert D, Blom AM (January 2016). "C4b-binding protein: The good, the bad ... C4BP accelerates decay of C3-convertase and is a cofactor for serine protease factor I which cleaves C4b and C3b. C4BP binds ...

https://en.wikipedia.org/wiki/C4b-binding_protein

2005). "Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/ ... "Complement factor H and related proteins: an expanding family of complement-regulatory proteins?". Immunol. Today. 15 (3): 121- ... 2007). "Binding of human factor H-related protein 1 to serum-resistant Borrelia burgdorferi is mediated by borrelial complement ... Complement factor H-related protein 1 is a protein that in humans is encoded by the CFHR1 gene. GRCh38: Ensembl release 89: ...

https://en.wikipedia.org/wiki/CFHR1

... complement receptor 1 (CR1), C4b-binding protein and Factor H. Convertase assembly is suppressed by the proteolytic cleavage of ... C4b-binding protein inhibits the haemolytic function of cell-bound C4b. C4b-binding protein and C3b inactivator control the C3 ... Binding β1H to C3b increases C3bINA binding, while factor B binding prevents C3bINA binding and is competitive with β1H binding ... C3b (and C4b) as mediated by Factor I in the presence of membrane cofactor protein (MCP, CD46), C4b-binding protein, CR1, or a ...

https://en.wikipedia.org/wiki/C3-convertase

Protein S circulates in human plasma in two forms: approximately 60 percent is bound to complement component C4b β-chain while ... decreased protein S activity: decreased free protein S levels (normal total protein S levels) In terms of treatment for protein ... decreased protein S activity: decreased total protein S levels, as well as decreased free protein S levels Type II - decreased ... In regards to the mechanism of protein S deficiency, Protein S is made in liver cells and the Endothelium. Protein S is a ...

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

CRIg Soluble complement regulators Factor H C4-Binding Protein (C4bp) Other proteins with characteristic CCP domains have been ... Complement C3b/C4b Receptor 1, CR1 (CD35) Complement Regulator of the Immunoglobulin Superfamily, ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement control proteins also play a role in malignancy. Complement proteins protect against malignant cells- both by direct ...

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

C4b-binding protein, factor I, S protein or clusterin, the membrane-bound inhibitors are CR1, membrane cofactor protein (MCF), ... Besides complement particles C1q and C3b which help to opsonize the apoptotic cells, also thrombospondin, pentraxins (C- ... Collectins (e.g. mannose-binding lectin and surfactant protein A) bind the altered surface sugars on apoptotic cell and enable ... As an example, CD14 normally binds lipopolysaccharide (LPS) on the surface of gram-negative bacteria but can also recognize LPS ...

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

MASP-2 is activated to cleave complement components C4 and C2 into C4a, C4b, C2a, and C2b. MASP1 (protein) Mannan-binding ... Mannan-binding lectin serine protease 2 also known as mannose-binding protein-associated serine protease 2 (MASP-2) is an ... The encoded proteins are members of the trypsin family of peptidases. MASP-2 is involved in the complement system. MASP-2 is ... The Ra-reactive factor (RARF) is a complement-dependent bactericidal factor that binds to the Ra and R2 polysaccharides ...

https://en.wikipedia.org/wiki/MASP2_(protein)

... the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... Mannose-binding lectin (MBL), also called mannan-binding lectin or mannan-binding protein (MBP), is a lectin that is ... One way the most-recently discovered lectin pathway is activated is through mannose-binding lectin protein. MBL binds to ...

https://en.wikipedia.org/wiki/Mannan-binding_lectin

Complement proteins involved in innate opsonization include C4b, C3b and iC3b. In the alternative pathway of complement ... Therefore, Some opsonins (including some complement proteins) have evolved to bind Pathogen-associated molecular patterns, ... C1q association eventually leads to the recruitment of complement C4b and C3b, both of which are recognized by complement ... Both IgM and IgG undergo conformational change upon binding antigen that allows complement protein C1q to associate with the Fc ...

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

... is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding ... C4b, C2a, and C2b. In f, two smaller MBL-associated proteins (MAps) are found in complex with MBL. MBL-associated protein of 19 ... are bound by MBL. Mannan-binding lectin, also called mannose-binding protein, ... Classical complement pathway Alternative complement pathway Mannan-binding lectin Wallis R, Mitchell DA, Schmid R, Schwaeble WJ ...

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

Complement system Mannan-binding lectin MASP2 (protein) GRCh38: Ensembl release 89: ENSG00000127241 - Ensembl, May 2017 "Human ... MASP-2 is then able to cleave C4 into proteins C4a and C4b. MASP-1 is also responsible for creating C3 convertase by cleaving ... the mannose-binding lectin and the ficolins. This protein is directly involved in complement activation because MASP-1 ... Takada F, Takayama Y, Hatsuse H, Kawakami M (October 1993). "A new member of the C1s family of complement proteins found in a ...

https://en.wikipedia.org/wiki/MASP1_(protein)

C5 convertase is also formed by the classical pathway when C3b binds C4b and C2b. C5a is an important chemotactic protein, ... In the classical pathway, C4 binds to Ig-associated C1q and C1r2s2 enzyme cleaves C4 to C4b and 4a. C4b binds to C1q, antigen- ... About 50 proteins and protein fragments make up the complement system, including serum proteins, and cell membrane receptors. ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ...

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

... formation of the C3-convertase and C5-convertases requires binding of C2 to an activated surface-bound C4b in the presence of ... Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical ... It is thought that cleavage of C2 by C1s, while bound to C4b, results in a conformational rotation of C2b whereas the released ... Kam CM, McRae BJ, Harper JW, Niemann MA, Volanakis JE, Powers JC (Mar 1987). "Human complement proteins D, C2, and B. Active ...

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

The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... for example by binding to pentraxins such as C-reactive protein or directly to the surface of pathogens. Such binding of C1q ... Active C1s splits C4 and then C2, producing C4a, C4b, C2a and C2b. The classical pathway C3-convertase (C4bC2b complex) is ... Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody ...

https://en.wikipedia.org/wiki/C1_complex

The binding of C2 and C4b results in C2 being cleaved by C1s into C2a and C2b. C2a diffuses into the plasma as a protein ... The classical complement pathway can be initiated by the binding of antigen-antibody complexes to the C1q protein. The globular ... These globular regions of C1q can also bind to bacterial and viral surface proteins, apoptotic cells, and acute phase proteins ... Surface bound C4b acts as a receptor for the binding of C2. ... As a result of this C4b is restricted to only bind to pathogen ...

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

CR1 can bind to C4b and C3b complexes, whereas CR2 (murine and human) binds to C3dg-bound complexes. CR1, a surface protein ... is a protein that in humans is encoded by the CR2 gene. CR2 is involved in the complement system. It binds to iC3b (inactive ... 1987). "A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32". J. ... 1991). "Intracellular interaction of EBV/C3d receptor (CR2) with p68, a calcium-binding protein present in normal but not in ...

https://en.wikipedia.org/wiki/Complement_receptor_2

The classical pathway C5 convertase is composed of the fragments of complement proteins, C4b, C2a produced by cleavage mediated ... a binding site for a plasma protein called Factor B is also exposed. Factor B then binds to C3b and is cleaved by a plasma ... The binding of C5 is influenced by C6 and C7, components which are thought to act subsequent to it in the complement sequence. ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ...

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

In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This ... Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, ... certain proteins that normally attack bacteria (IgM antibodies) attach themselves to red blood cells and bind them together ...

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

... complement factor i MeSH D12.776.124.486.274.920.662 - complement c4b-binding protein MeSH D12.776.124.486.274.930 - complement ... complement c4 MeSH D12.776.124.486.274.350.250 - complement c4a MeSH D12.776.124.486.274.350.260 - complement c4b MeSH D12.776. ... complement c1 inactivator proteins MeSH D12.776.124.486.274.920.250.500 - complement c1 inhibitor protein MeSH D12.776.124.486. ... mannose-binding protein-associated serine proteases MeSH D12.776.124.486.274.860.450 - complement factor d MeSH D12.776.124.486 ...

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

... binding the C4b subunit and releasing C4a into the bloodstream; similarly, binding of C2 causes release of C2b. Together, MBL, ... Complement receptors, collectins, ficolins, pentraxins such as serum amyloid and C-reactive protein, lipid transferases, ... these proteins contain a nucleotide binding site (NBS) for nucleoside triphosphates. Interaction with other proteins (e.g. the ... 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

... of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. The protein ... As has been demonstrated for CD46 with other ligands, the CD46 protein structure is believed to linearize upon binding HHV-6. ... The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded ... CD46 complement regulatory protein also known as CD46 (cluster of differentiation 46) and Membrane Cofactor Protein is a ...

https://en.wikipedia.org/wiki/CD46

... cells from complement-mediated damage. CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for ... and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution". The Journal ... Factor I requires a C3b-binding protein cofactor such as complement factor H, CR1, or Membrane Cofactor of Proteolysis (MCP or ... "Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, ...

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

... in the major histocompatibility complex III close to the Complement component 4 genes C4A and C4B, the Tenascin X gene TNXB and ... The human enzyme binds one substrate at a time. In contrast, the well-characterized bovine enzyme can bind two substrates. The ... This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for ... In the chicken and quail, there is only a single CYP21 gene, which locus is located between complement component C4 and TNX ...

https://en.wikipedia.org/wiki/21-Hydroxylase

Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. DAF ... Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement ... regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during activation of ... DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2 ...

https://en.wikipedia.org/wiki/Decay-accelerating_factor

... or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex ( ... and functionally-related proteins, inactivate the complement component. Given the C3 is constantly being turned over in the ... The C1 complement complex binds to these antibodies resulting in its activation via cross proteolysis. This activated C1 ... Furthermore, if C3b does bind to a host-cell surface, regulators of complement activity (RCAs), a group of genetically-, ...

https://en.wikipedia.org/wiki/C3b

C4b and C3bi from plasma complement. The extracellular domain of the receptors contains a lectin-like complement-binding domain ... lactoferrin and antibiotic proteins. Degranulation of these into the phagosome, accompanied by high reactive oxygen species ... Among these are receptors that recognise the Fc part of bound IgG antibodies, deposited complement or receptors, that recognise ... Recognition by complement receptors is not enough to cause internalisation without additional signals. In macrophages, the CR1 ...

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

C3a is a 77 residue anaphylatoxin that binds to the C3a receptor (C3aR), a class A G protein-coupled receptor. It plays a large ... C1q mediates the classical pathway by activating the C1 complex, which cleaves C4 and C2 into smaller fragments (C4a, C4b, C2a ... This complex has the ability to catalyze the formation of C3a and C3b after it binds properdin, a globulin protein, and is ... C3a is one of the proteins formed by the cleavage of complement component 3; the other is C3b. ...

https://en.wikipedia.org/wiki/C3a_(complement)

3 of which are protein coding. One of these proteins, SKI2W, has 1246 amino acids and a helicase binding domain between amino ... "Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes ... The human protein was named SKI2W because of its similarity to yeast protein Ski2, which has highly homologous (nearly ... The ski2 (the SKI2W homolog in yeast) contains DEVH-box proteins which suggests it is the only protein in the ski complex to ...

https://en.wikipedia.org/wiki/SKIV2L

C4b and C2a, from their complex (whereupon C4b can bind another protein C2, and conduct these steps again). Because C4b is ... or C4B-C4B) and 31% trimodular configuration (equally split between LLL as C4A-C4A-C4B or LSS as C4A-C4B-C4B). Regarding C4 ... "The internal thioester and the covalent binding properties of the complement proteins C3 and C4". Protein Science. 6 (2): 263- ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar A, ...

https://en.wikipedia.org/wiki/Complement_component_4

2005). "Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic activity". Int. J. Cancer. 117 (6): ... "Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes ... Serine/threonine-protein kinase 19 is an enzyme that in humans is encoded by the STK19 gene. This gene encodes a serine/ ... 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins ...

https://en.wikipedia.org/wiki/STK19

Carrier Proteins / genetics * Coenzyme A Ligases / genetics * Complement C4b-Binding Protein / genetics ... Most of the novel genes are expressed in retinal tissue and could be involved in the pathogenesis of AMD (i.e., complement, ...

https://pubmed.ncbi.nlm.nih.gov/32277175/

Complement C4b-Binding Protein Medicin och livsvetenskap 54% * Islets of Langerhans Medicin och livsvetenskap 47% ... Non-traditional functions of the Complement System proteins Golec, E., Blom, A. & King, B. ... I am currently studying novel roles of complement proteins, with focuses on C3 and CD59 and how they affect cellular function ... Outside in: Roles of complement in autophagy. King, B. C., Kulak, K., Colineau, L. & Blom, A. M., 2021 juli 1, I: British ...

https://portal.research.lu.se/sv/persons/ben-king

The major function of protein S is as a cofactor to facilitate the action of activated protein C (APC) on its substrates, ... Protein S is a vitamin K-dependent anticoagulant protein that was first discovered in Seattle, Washington in 1979 and ... A portion of protein S is noncovalently bound with high affinity to the complement regulatory protein C4b-binding protein (C4BP ... This rise is in association with total increases in the complement binding protein, C4BP. Free protein S levels do not increase ...

https://www.medscape.com/answers/205582-158217/what-is-protein-s-deficiency

Approximately 60% is bound non-covalently to complement component C4b binding protein β-chain (C4BP), whereas the remaining 40 ... Dahlback B. Inhibition of protein C cofactor function of human and bovine protein S by C4b-binding protein. J Biol Chem 1986; ... Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation ... Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S-C4b binding protein complex. Blood ...

https://www.stoptheclot.org/news/article137/

C4b-Binding Protein C4b-C3b Inactivator Cofactor C4bC3bINA-Cofactor Complement 4b Binding Protein Complement C3b-C4b ... C4b-Binding Protein Term UI T126953. LexicalTag NON. ThesaurusID NLM (2006). Complement 4b Binding Protein Term UI T126954. ... Complement C3b Inactivator Proteins [D12.776.124.486.274.920.325] * Complement C4b-Binding Protein [D12.776.124.486.274.920.662 ... Complement C4b-Binding Protein Preferred Concept UI. M0096952. Registry Number. 0. Scope Note. A serum protein that regulates ...

https://meshb-prev.nlm.nih.gov/record/ui?ui=D050716

Complement C4b-Binding Protein Entry term(s). C4b Binding Protein C4b C3b Inactivator Cofactor C4b-Binding Protein C4b-Binding ... Complement C4b Binding Protein Complement Component 4b Binding Protein Complement Component 4b-Binding Protein Protein, C4b- ... C4b Binding Protein. C4b C3b Inactivator Cofactor. C4b-Binding Protein. C4b-Binding Protein, Complement. C4b-C3b Inactivator ... Complement C4b Binding Protein. Complement Component 4b Binding Protein. Complement Component 4b-Binding Protein. Protein, C4b- ...

https://decs.bvsalud.org/en/ths/resource/?id=50837

Complement C4b binding protein measurement (procedure). Code System Preferred Concept Name. Complement C4b binding protein ...

https://phinvads.cdc.gov/vads/ViewCodeSystemConcept.action?oid=2.16.840.1.113883.6.96&code=104357007

Complement C4b-Binding Protein 100% * Complement Factor H 82% * Moraxella catarrhalis 82% ... Complement-mediated clearance of neurotoxic species associated with Alzheimers disease: a novel approach to preventing ... Global analysis of evasive strategies developed by Staphylococcus aureus to inhibit complement. Laabei, M. ... Elucidating the immune signalling mediated by a novel white rust resistance protein. Cevik, V. ...

https://researchportal.bath.ac.uk/en/organisations/department-of-life-sciences/projects/?status=FINISHED

C4b-binding protein is a regulatory protein of the Complement Cascade that possesses decay-accelerating activity. Circulating ... Gel Scan of C4b-Binding Protein, (C4BP, C4bBP), Human Plasma. This information is representative of the product ART prepares, ... C4b-binding protein has been investigated for its role in Alzheimers Disease, Psoriasis, as well as autoimmune diseases ... Functional transformation of C-reactive protein by hydrogen peroxide. J Biol Chem. 2017 Feb 24;292(8):3129-3136. doi: 10.1074/ ...

https://www.athensresearch.com/products/all/c4b-binding-protein-c4bp-c4bbp-human-plasma-protein-s-free

It was also found to bind human complement regulatory proteins factor-H and C4b-binding protein (C4BP). CtPra1-factor-H and ... It contains several membrane-bound protein families, including some Tsh proteins bearing a SUR7/PalI motif. The presence of ... Interactions of Candida tropicalis pH-related antigen 1 with complement proteins C3, C3b, factor-H, C4BP and complement evasion ... a surface bound and secretory protein, has been found to interact strongly with the immune system and help in complement ...

https://pesquisa.bvsalud.org/brasil/?lang=pt&q=mh:Prote%C3%ADnas+F%C3%BAngicas/imunologia

Consumption and subsequent exhaustion of coagulation proteins and pl... ... as a cofactor for activated protein C is regulated by the degree it is bound to the complement protein C4B-binding protein. ... Protein C, along with protein S, also serves as a major anticoagulant compensatory mechanism. Under normal conditions, protein ... 18] Activated protein C combats coagulation via proteolytic cleavage of factors Va and VIIIa and proteolyzes PAR1 when bound to ...

https://emedicine.medscape.com/article/199627

Complement C4b-Binding Protein 19% * Complement Inactivating Agents 17% * Complement Receptors 15% ... I that is strongly associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement ... I that is strongly associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement ...

https://researchportal.hkr.se/sv/publications/a-mutation-in-factor-i-that-is-strongly-associated-with-atypical--2/fingerprints/

C4 Binding Protein, Plasma C4B is a complement binding protein that specifically binds 50% circulating protein S, a vitamin K ... Since C4B may be elevated in certain disease states, this may affect the available "free protein S" to engage in anticoagulant ... Because nearly half of the calcium in blood is bonded to protein, high or low protein levels might alter total calcium test ... Because nearly half of the calcium in blood is bonded to protein, high or low protein levels might alter total calcium test ...

https://www.ultalabtests.com/testing/categories/blood-disorder/all-tests

CRYSTAL STRUCTURE OF A COMPLEMENT PROTEIN THAT REGULATES BOTH PATHWAYS OF COMPLEMENT ACTIVATION AND BINDS HEPARAN SULFATE ... Solution structure of the two N-terminal CCP modules of C4b-binding protein (C4BP) alpha-chain. ... Vaccinia Complement Protein in Complex with Heparin. 1srz. Solution structure of the second complement control protein (CCP) ... CRYSTAL STRUCTURE OF A COMPLEMENT CONTROL PROTEIN THAT REGULATES BOTH PATHWAYS OF COMPLEMENT ACTIVATION AND BINDS HEPARAN ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=CCP&START=1462&END=1519&E_VALUE=4.81e-1&TYPE=SMART&BLAST=CGVPDSSLVNYANFSCLEGTDFLKQCSISCVPPAKLQGLNPWLTCLEDGLWSLPEVYC

Complement factor I binds C4BP (Homo sapiens) * C4-binding protein:C4b [plasma membrane] (Homo sapiens) * C4b-binding protein [ ... C4b-binding protein binds C4b (Homo sapiens) * C4-binding protein:C4b [plasma membrane] (Homo sapiens) * C4b-binding protein [ ... C4b binding protein binds Protein S (Homo sapiens) * C4 binding protein:protein S [plasma membrane] (Homo sapiens) * C4b- ... C4b binding protein binds C4bC2a (Homo sapiens) * C4 binding protein:C4bC2a [plasma membrane] (Homo sapiens) * C4b-binding ...

https://reactome.org/content/detail/R-HSA-981625

Complement C4b-Binding Protein Medicine & Life Sciences 51% * Antigens Medicine & Life Sciences 51% ... was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b- ... was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b- ... was directed to the calcium-free conformation of PS and had virtually identical affinity for free and C4b-binding protein (C4b- ...

https://moh-it.pure.elsevier.com/en/publications/monoclonal-antibody-based-enzyme-linked-immunosorbent-assays-elis

A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions ... A further complement protein, C2, binds to this membrane complex to give C4b2. The C1s subunit then enzymically cleaves the ... The activated C1s subunits cleave C4 into C4b and C4a; the latter can diffuse away and serve as a leucocyte activator. The C4b ... a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent ...

https://www.pharmacy180.com/article/activation-of-the-classical-complement-pathway-498/

Infection of mammalian cells occurs through the virus binding to cell surface proteins, with a critical interaction between the ... C3b and C4b. Nominally these complement fragments contribute to the elimination of pathogens through multiple biological ... IFN inducible protein-10, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, tumour necrosis factor-α, and IFN ... The complement system in COVID-19. The complement system is an essential component of the innate immune system [65, 75, 109, ...

https://openres.ersjournals.com/content/6/4/00405-2020

Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine ... Benito, E., Valor, L. M., Jimenez-Minchan, M., Huber, W. & Barco, A. cAMP response element-binding protein is a primary hub of ... Generally, complement cascade products of C3b, C5b, C4b are involved in opsonization for pathogens. And evidence suggests that ... activation of innate immune responses and microglial proteins involved in protein digestion, as well as of complement and ...

https://www.nature.com/articles/s41392-021-00867-y?error=cookies_not_supported&code=f3315543-a0fe-402e-8108-67dbd0f21d4e

However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... The C5b-C6 interface consists of three binding sites stabilized predominantly by van der Waals interactions, and several ... However, when proper regulation of the complement system is compromised, MAC also attacks host tissues and contributes to ... The C5b6 interface consists of three binding sites stabilized predominantly by van der Waals interactions, and several critical ...

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

10] All of these proteins interact with complement proteins, particularly C3b and C4b, dissociate the convertase complexes of ... In paroxysmal nocturnal hemoglobinuria (PNH), the absence of anchor proteins that bind complement-regulating proteins (eg, CD55 ... In paroxysmal nocturnal hemoglobinuria (PNH), the absence of anchor proteins that bind complement-regulating proteins (eg, CD55 ... 9] ; homologous restriction factor (HRF), or C8 binding protein; and membrane inhibitor of reactive lysis (MIRL), or CD59. [ ...

https://emedicine.medscape.com/article/207468-overview

Learn about the three pathways lead to complement activation and some of their key inhibitors. ... C3i then binds the plasma protein, Factor B. Bound Factor B is cleaved by Factor D to produce Ba and Bb. Ba is released and the ... C4b binds C2, which is subsequently cleaved by C1s. This results in the release of C2b and C2a. C2a remains associated with C4b ... C4b binds C2, which is subsequently cleaved by C1s. This results in the release of C2b and C2a. C2a remains associated with C4b ...

https://www.abcam.com/pathways/complement-cascade-and-its-inhibitors

... and C4b-binding protein β chain as new potential biomarkers for pulmonary tuberculosis. PLoS One. 2017;12(3): e0173304. ... Serum protein KNG1, APOC3, and PON1 as potential biomarkers for Yin-deficiency-heat syndrome. Evid Based Complement Alternat ... Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis. BMC ... Jiang TT, Shi LY, Wei LL, Li X, Yang S, Wang C, Liu CM, Chen ZL, Tu HH, Li ZJ, Ji-Cheng Li*. Serum amyloid A, protein Z, ...

https://en.z2hospital.com/contents/828/2910.html

BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the ... in Protein folding in silico : protein folding versus protein structure prediction (2012) ... BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the ... in Roterman-Konieczna, I. (Ed.) Protein Fold Silico Protein Fold Versus Protein Struct Predict (2012) ...

https://orbilu.uni.lu/browse?type=author&value=Jurkowski%2C+Wiktor+40021149

Mannose-binding lectin. CRP = C-reactive protein; HLA = human leukocyte antigen; IL = interleukin; TNF = tumor necrosis factor. ... Complement genes include the following:. * C1Q, C1R, and C1S deficiencies are associated with SLE, lupus nephritis, and ... C4A and C4B (possibly) gene deletions are associated with SLE. FcγR genes include the following:. * These mediate the binding ... FcγRIIa binds to IgG2 and is encoded by 2 codominant alleles, H131 (or high affinity) and R131 (or low affinity); the low- ...

https://www.staging.medscape.com/answers/330369-78283/which-complement-genes-have-an-etiologic-role-in-lupus-nephritis

Approximately 60% is bound non-covalently to complement component C4b binding protein β-chain (C4BP), whereas the remaining 40% is free [ 3 ]. (stoptheclot.org)
All C4BP molecules that contain a Beta chain circulate in plasma in a high-affinity, calcium-dependent complex with vitamin K-dependent, anticoagulant Protein S. (athensresearch.com)
It was also found to bind human complement regulatory proteins factor-H and C4b-binding protein (C4BP). (bvsalud.org)
CtPra1-factor-H and CtPra1-C4BP interactions were found to be ionic in nature as the binding intensity affected by high sodium chloride concentrations. (bvsalud.org)

and CR1L (complement C3b/C4b receptor 1 like). (wormbase.org)
Certain autoantibodies, such as anti-NMDAR antibodies (which bind both DNA and the N-methyl-d-aspartate receptor 3 ) and anti-phospholipid antibodies, 4 have been reported as mediators of NPSLE. (nature.com)
CR Complement receptor. (pediagenosis.com)
CD21, also known as CR2 (complement receptor 2) and C3d receptor, binds C3d and iC3b. (biolegend.com)
complement C3b/C4b receptor 1 (Knops b. (gsea-msigdb.org)
p51 process helps to digitize blood-brain entry, actively on Aquaporin-7 physiological complaints any backlog apoptosis or channel is here unfolded by metabotropic granules that are value of the conditions( CR1, CD55), transport as a lipid for the computer I( TAK1 translocation of C3b and C4b( CR1, CD46), or seek the receptor of MAC( CD59). (evakoch.com)
Two surfaces of download Stupid History: Tales of Stupidity, Strangeness, and Mythconceptions Through the produced in Reactome indicate cellular function kinase outside the T of plasma water, entering locus extension with the I H3 phosphorylated CenH3( not indexed CENP-A), and the embryo of junctions, complex proteins at the Patients of pro-apoptotic cells that belong intracellular for receptor sodium. (evakoch.com)
This antibody recognizes a c-erbB-2 protein, which is a receptor tyrosine kinase of the c- erbB family. (immbio.hu)
The anaphylatoxins engage their respective G protein-coupled receptors (GPCR), the C3a receptor (C3aR) and the C5a receptor (C5aR1) on innate immune cells to induce their migration and activation to and at the site of pathogen breach [2-4] . (hapres.com)
Fc gamma receptor glycosylation modulates the binding of IgG glycoforms: a requirement for stable antibody interactions. (expasy.org)
Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. (joplink.net)

HGFs may bind to specific cell receptors on the surface of the cells to directly induce their proliferation and differentiation or may stimulate the production of other cytokines that then act on the target cells. (jaypeedigital.com)
CD46( MCP) derived to the autophosphorylation membrane of a central vein translocates it from cytoplasmic server by planning cessation of C3b and C4b, and understood membrane of CD46 on arising receptors may include to Landmark pathway( Elward K et al. (evakoch.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)

C. albicans pH-related antigen 1 (CaPra1), a surface bound and secretory protein, has been found to interact strongly with the immune system and help in complement evasion. (bvsalud.org)
Thus, we characterised how pH-related antigen 1 of C. tropicalis (CtPra1) interacts with some of the key complement proteins of the innate immune system. (bvsalud.org)
Type I deficiencies correspond to reduced antigen levels of both Total and Free Protein S. (nicholsinstitute.com)
Type II deficiencies are characterized by a reduced Protein S Activity but with normal antigen levels of both Total and Free Protein S. (nicholsinstitute.com)
Type III deficiencies are defined by a reduced antigen level and activity of Free Protein S but the antigen level of Total Protein S remains normal. (nicholsinstitute.com)
To evaluate the influence of C4b-BP bound PS on PS antigen determinations, ELISA systems employing the four Mabs individually as capture antibody (Ab) and peroxidase-conjugated polyclonal anti-PS IgG as detecting Ab were developed and compared to immunoelectrophoresis (EIA) and to an ELISA employing polyclonal anti-PS IgG as capture and detecting Ab, in the determination of PS in purified systems and in plasma. (elsevier.com)
These results highlight the potential influence of high C4b-BP on plasma PS antigen determination. (elsevier.com)
A complement cascade similar to that of the alternative pathway can be activated through specific antibody-antigen interactions. (pharmacy180.com)
In the classical pathway the initiating step is the specific binding of IgG or IgM to antigen. (pharmacy180.com)
Once this occurs, a complement protein termed C1 (which comprises a single C1q subunit, two C1r subunits and two C1s subunits) binds to adjacent Fc domains in the antibody-antigen complex. (pharmacy180.com)
The C4b covalently associates with the antibody-antigen complex on the surface of a microbial membrane and can serve as an opsonin. (pharmacy180.com)
In the case of the IgG and IgM molecules the Fc domains will only align adjacent to each other when the corresponding Fab domains bind antigen. (pharmacy180.com)
Once C1 binds to adjacent Fc domains within an antibody-antigen complex C1-INH is displaced. (pharmacy180.com)
The classical pathway can additionally lead to complement protein deposition on insoluble antibody- antigen immune complexes circulating within blood, and in doing so promote the clearance of such potentially harmful complexes by Kupffer cells of the liver. (pharmacy180.com)
Ig IgM and some subclasses of IgG (in the human, IgG1-IgG3), when bound to antigen are recognized by Clq to initiate the classic pathway. (pediagenosis.com)
C4b then binds to C2, and also, via a very unusual type of reactive thioester bond, to any local macromolecule, such as the antigen- antibody complex itself, or to the membrane in the case of a cell-bound antigen. (pediagenosis.com)

The major function of protein S is as a cofactor to facilitate the action of activated protein C (APC) on its substrates, activated factor V (FVa) and activated factor VIII (FVIIIa). (medscape.com)
Protein S functions predominantly as a nonenzymatic cofactor for the action of another anticoagulant protein, activated protein C (APC). (medscape.com)
APC requires protein S as a cofactor in its enzymatic action on its 2 substrates, FVa and FVIIIa. (medscape.com)
Thus, this process is designed to dampen and shut off clotting by switching off the key cofactor proteins FVa and FVIIIa. (medscape.com)
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a). (nih.gov)
Circulating in plasma, it aids in the control of fluid-phase and surface-associated activation of C3 and C5 and serves as a cofactor to Factor 1 in the proteolytic degradation of C4b. (athensresearch.com)
It is the free form of Protein S that serves as the cofactor for activated protein C (APC). (nicholsinstitute.com)
A novel non-synonymous polymorphism (p.Arg240His) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity. (cdc.gov)
it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. (assaygenie.com)
This gene encodes a vitamin K-dependent plasma protein that functions as a cofactor for the anticoagulant protease, activated protein C (APC) to inhibit blood coagulation. (assaygenie.com)

C4b-binding protein is a regulatory protein of the Complement Cascade that possesses decay-accelerating activity. (athensresearch.com)
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)
Subsequently, continued propagation leads to the terminal cascade by cleavage of complement C5 to form C5b and C5a. (frontiersin.org)
C1 is the first molecule in the classical complement cascade and comprises C1q and two molecules of C1r and C1s respectively. (abcam.com)
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)
And stimulates the complement cascade and hence an inflammatory reaction. (theloganguards.com)

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)
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)

Protein S deficiency usually manifests clinically as venous thromboembolism (VTE). (medscape.com)
[ 1 ] Any association of protein S deficiency with arterial thrombosis appears coincidental or weak at best. (medscape.com)
Evidence for arterial thrombosis in other hereditary thrombophilias (eg, protein C deficiency, antithrombin III deficiency, or factor V Leiden gene mutation) also appears to be minimal. (medscape.com)
[ 3 ] Acquired protein S deficiency has been reported in patients infected with COVID-19 and is associated with increased risk of thrombotic events in these patients. (medscape.com)
Hereditary protein S deficiency is an autosomal dominant trait. (medscape.com)
To understand how thrombosis occurs in protein S deficiency, its physiological function should be briefly reviewed. (medscape.com)
Therefore, a deficiency in Protein S increases an individual's risk for thrombosis since the normal mechanism of thrombin inhibition is decreased. (nicholsinstitute.com)
Classification of inherited protein S deficiency requires both activity and antigenic testing for protein S. (nicholsinstitute.com)
These studies demonstrate that a Cys430-Phe mutation does not prevent the de novo synthesis of the b subunit, but alters the conformation of the mutant protein sufficiently to impair its intracellular transport, resulting in its deficiency in this patient. (embl.de)
A group of serum proteins as potential diagnostic biomarkers for Yin-deficiency-heat syndrome. (z2hospital.com)
Defects in PROS1 are the cause of thrombophilia due to protein S deficiency, autosomal dominant (THPH5). (assaygenie.com)

Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome. (cdc.gov)

Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. (cdc.gov)

Activation of the classical complement pathway starts with binding of an activating substance to the Cl molecule, which activates the Cl sub-units, resulting in cleavage of C4 to C4b releasing C4a in the process. (immbio.hu)
The short-lived C4b molecule can bind covalently to membranes. (immbio.hu)
Because of the short life of the C4b molecule much of the C4d is free and circulates in serum. (immbio.hu)

Protein S is a vitamin K-dependent anticoagulant protein that was first discovered in Seattle, Washington in 1979 and arbitrarily named after that city. (medscape.com)
Protein S is part of a system of anticoagulant proteins that regulate normal coagulation mechanisms in the body. (medscape.com)
[ 5 ] Under most normal circumstances, the anticoagulant proteins prevail and blood remains in a liquid nonthrombotic state. (medscape.com)
In one of many examples of nature's efficiency, the same enzyme that clots blood, thrombin, is converted from clotting to an anticoagulant mechanism on the surface of the endothelium and it then activates protein C to its active enzymatic form, APC. (medscape.com)
A plasma protein solution used to treat coagulation factor deficiencies, reverse anticoagulant effects, and shock from a loss of plasma fluids, and is also used in plasma exchange procedures. (drugbank.com)

CtPra1 inhibited functional complement activation with different effects on classical (â ¼20 %), lectin (â ¼25 %) and alternative (â ¼30 %) pathways. (bvsalud.org)
Further, when C1 is free in the circulation it is bound to a protein termed C1 inhibitor (C1-INH) which prevents any possible activation of C1 in the absence of antibody. (pharmacy180.com)
The functions of the classical complement pathway are similar to those described for the alternative pathway, i.e. opsonization, leucocyte activation and membrane lysis of target cells. (pharmacy180.com)
The presence of two complement pathways provides for rapid (alternative) and specific (classical) activation of a key defence mechanism, and offers greater protection against the development of microbial resistance mechanisms. (pharmacy180.com)
Activation of all three pathways converges on the cleavage of complement protein C3 into C3b and C3a [ 6 ]. (frontiersin.org)
Learn about the three pathways lead to complement activation and some of their key inhibitors. (abcam.com)
the classical pathway initiated by antibodies bound to the surface of foreign bodies and the alternative and lectin pathways that provide an antibody-independent mechanism for complement activation, induced by the presence of bacteria and other micro-organisms. (abcam.com)
C1q attaches to antibodies bound on the pathogen surface, leading to the activation of C1s. (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)
The binding of MBL to mannose and N-acetyl glucosamine in micro-organisms leads to the activation of MASPs, which subsequently cleave C4 and C2. (abcam.com)
Following these cleavage events, complement pathway activation continues as in the classical pathway. (abcam.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)
Succinate to inhibit complement activation. (theloganguards.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)

The complement system is a heat-labile component of blood that confers bactericidal properties. (abcam.com)
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)
Thirty-three gel slices were excised from each of three gel lanes (n = 99), digested with trypsin, and subjected to nanoflow liquid chromatography electrospray ionization tandem mass spectrometry (nano-LC-ESI-MS/MS). The protein component of hAH was also analyzed by antibody-based protein arrays, and selected proteins were quantified.A total of 676 proteins were identified in hAH. (omicsdi.org)

The C1s subunit then enzymically cleaves the bound C2a to generate on the membrane a new complex termed C4b2b, which is the C3 convertase of the classical pathway. (pharmacy180.com)

Two monoclonal antibodies (Mabs) specifically directed to human protein S (PS) - named 5E9E9 and 3B10.25 - were produced and their properties compared to those of 2 previously characterized anti-PS-Mabs (HPS-2 and S10). (elsevier.com)
The antibodies that activate the classical complement pathway are IgM and IgG. (pharmacy180.com)
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. (lookformedical.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)

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)

Recombinant CtPra1, was found to bind human C3 and C3b, central molecules of the complement pathways that are important components of the innate immune system. (bvsalud.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)
Among the viral proteins shown to be expressed during lytic replication are potent signaling molecules such as vGPCR, vIL6, vIRFs, vCCLs, K1 and K15, which have been implicated experimentally in the angiogenic and inflammatory phenotype observed in KS lesions. (genome.jp)
Characterization of the protein composition of hAH will identify molecules involved in maintaining a homeostatic environment for anterior segment tissues. (omicsdi.org)

The host proteins that serve key regulatory functions within the alternative pathway (DAF, CR1 factor I, CD59) also serve similar functions within the classical pathway. (pharmacy180.com)
18 Genetic or pharmacologic blockade of the complement pathway can prevent synaptic stripping and alleviate multiple age- and inflammation-related disorders. (nature.com)
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)
G protein pathway suppressor 2 [Source. (gsea-msigdb.org)

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)

However, for the inactivation of FVIIIa, APC and protein S require the help of the nonactivated clotting protein, factor V. This is another example of dual use of a protein in this same process. (medscape.com)
The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. (embl.de)
We demonstrate the presence of complement factor b (bf) and complement c3 in uterine luminal fluid collected from estrogen-stimulated immature and. (theloganguards.com)

TotalSeq™ is BioLegend's brand of antibody-oligonucleotide conjugates, to enable simultaneous analysis of proteins and mRNA in single cells. (biolegend.com)
This antibody reacts with a 145 kDa molecular weight protein, designated as CD117/c-kit. (immbio.hu)
Ten proteins were identified by both nano-LC-ESI-MS/MS and antibody protein arrays.Proteomic analysis of hAH identified 676 nonredundant proteins. (omicsdi.org)

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)
It activates complement, is opsonophagocytic, and protects animals from experimental challenge. (medscape.com)

Thrombosis is observed in both heterozygous and homozygous genetic deficiencies of protein S. (medscape.com)
The common denominator in the disease, a biochemical defect, appears to be a genetic mutation leading to the inability to synthesize the glycosyl-phosphatidylinositol (GPI) anchor that binds these proteins to cell membranes. (medscape.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)

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)
It was discovered over a century ago by Jules Bordet as a liver-derived and serum-circulating system of proteins key to the detection and destruction of pathogens that have successfully breached the body's protective epithelial borders [1] . (hapres.com)

This activity occurs via a coordinated system of proteins, termed the protein C system. (medscape.com)

Autoimmune-associated HLA-B8-DR3 haplotypes in Asian Indians are unique in C4 complement gene copy numbers and HSP-2 1267A/G. (cdc.gov)
Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. (cdc.gov)

Hippocampal extracellular matrix levels and stochasticity in synaptic protein expression increase with age and are associated with age-dependent cognitive decline. (uni.lu)
Extracellular matrix proteins were the only group of proteins that showed a robust and progressive upregulation over time. (uni.lu)
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)

HGFs are a group of proteins that (i) regulate proliferation, differentiation, and maturation of haematopoietic progenitor cells, (ii) influence the commitment of progenitors to specific lineages, and (iii) affect the function and survival of mature blood cells. (jaypeedigital.com)

Recent studies have identified that similar to SARS-CoV, SARS-CoV-2 binds to a specific human cell surface protein, angiotensin-converting enzyme 2 (ACE2). (ersjournals.com)
Several of these latent viral and lytic proteins are known to transform host cells, linking KSHV with the development of severe human malignancies. (genome.jp)
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)
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)
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)
And activity of steroid sulfatase complementing dehydroepiandrosterone sulfate uptake and intracrine steroid activations in human adipose tissue. (theloganguards.com)
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)
Human CS is composed of about 35 to 40 proteins and glycoproteins present in blood plasma or on cell surfaces [ 8 ]. (biomedcentral.com)
A purified form of human immunoglobulin G and other proteins used to treat immunodeficiency and a wide variety of autoimmune disorders. (drugbank.com)
Pili (or fimbriae), fibrils, and a protein called Hia mediate adherence of Hib to cells of the human respiratory tract. (medscape.com)

This map integrates pathways implicated in PD pathogenesis such as synaptic and mitochondrial dysfunction, impaired protein degradation, alpha-synuclein pathobiology and neuroinflammation. (uni.lu)

This classification was abandoned because of the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells. (medscape.com)

Most of the novel genes are expressed in retinal tissue and could be involved in the pathogenesis of AMD (i.e., complement, inflammation, and lipid pathways). (nih.gov)

Native CtPra1 was found to be expressed both as membrane-bound and secretory forms in the clinical isolates. (bvsalud.org)
A further complement protein, C2, binds to this membrane complex to give C4b2. (pharmacy180.com)
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)
Finally, surface bound C5b678 recruits multiple C9s, to a maximum of 18, to form the membrane attack complex (MAC or C5b6789 n where n = 1-18) [ 9 , 12 ]. (frontiersin.org)
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)
Two 'C3b inactivator' enzymes rapidly inactivate C3b, releasing the fragment C3c and leaving membrane bound C3d. (pediagenosis.com)
Finally, numerous outer membrane proteins have recently been identified as important components of pathogenesis and immunity. (medscape.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)

Thus, C. tropicalis appears to be a master of immune evasion by using Pra1 protein. (bvsalud.org)
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)
The complement system is generally considered among the evolutionary oldest parts of our immune system. (hapres.com)

The complete taxonomic breakdown of all proteins with CCP domain is also avaliable . (embl.de)

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) gains entry into the lung epithelial cells by binding to the surface protein angiotensin-converting enzyme 2. (ersjournals.com)

Further investigation using in-vivo models will help ascertain if these proteins can be novel therapeutic targets. (bvsalud.org)

By better understanding the mechanism of function of both of these proteins, we hope to develop potential future treatments for diabetes. (lu.se)
Whenever procoagulant forces are locally activated to form a physiologic or pathologic clot, protein S participates as part of one mechanism of controlling clot formation. (medscape.com)

Reveals complement-mediated inflammation in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (clippers). (theloganguards.com)

Anatomy18

Organisms10

Diseases8

Chemicals and Drugs144

Analytical, Diagnostic and Therapeutic Techniques and Equipment22

Phenomena and Processes52

Disciplines and Occupations1

Information Science3

Enhancement of lectin pathway haemolysis by immunoglobulins. (1/74)

Mechanism of complement-dependent haemolysis via the lectin pathway: role of the complement regulatory proteins. (2/74)

Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis. (3/74)

C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation. (4/74)

In vivo clearance of human protein S in a mouse model: influence of C4b-binding protein and the Heerlen polymorphism. (5/74)

Human C4b-binding protein selectively interacts with Neisseria gonorrhoeae and results in species-specific infection. (6/74)

Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor. (7/74)

Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation. (8/74)

Complement C4b

Complement C3

Complement Inactivator Proteins

Complement C4

Complement C4b-Binding Protein

Light-Harvesting Protein Complexes

Complement C4a

Protein S

Complement C3b

Complement C3a

Complement C1q

Complement Activation

Complement C5a

Photosynthetic Reaction Center Complex Proteins

Complement C5

Complement System Proteins

Complement C6

Chlorophyll

Complement C3c

Receptors, Complement

Complement C3d

Complement C2

Photosystem II Protein Complex

Complement C9

Molecular Sequence Data

Complement C1s

Complement C3-C5 Convertases

Complement Membrane Attack Complex

Plant Proteins

Complement C1r

Complement Factor B

Amino Acid Sequence

Complement Pathway, Alternative

Chloroplasts

Receptors, Complement 3b

Base Sequence

Complement C7

Complement Pathway, Classical

Complement C8

Complement Factor H

Glycoproteins

Complement C1

Light

Complement Factor I

Complement C5b

Complement C2a

Plants

Receptor, Anaphylatoxin C5a

Protein Binding

Complement Activating Enzymes

Carrier Proteins

Arabidopsis

Poly(A)-Binding Proteins

Complement Inactivating Agents

Complement Hemolytic Activity Assay

Complement C1 Inactivator Proteins

Cytochalasin B

Receptors, Complement 3d

Anaphylatoxins

Binding Sites

Complement C3b Inactivator Proteins

Complement Fixation Tests

Complement Factor D

RNA, Messenger

Cell Line

DNA-Binding Proteins

Antigens, CD55

Antigens, CD46

Tacrolimus Binding Proteins

Complement C3-C5 Convertases, Classical Pathway

Complement C2b

Gene Expression Regulation

Antigens, CD59

Recombinant Proteins

Poly(A)-Binding Protein I

NF-kappa B

Cloning, Molecular

DNA

Mutation

Transcription, Genetic