612 Results for: "western blot detection systems"

Supplier: Prosci

Monoclonal antibody RIP2 / CARDIAK / RICK Host: Rat Clone no: Nick-1 Species reactivity: rat isotype: IgG2a immunogen: RIP2 (monoclonal Nick-1) antibody was raised against recombinant human RIP2. Tested application: WB, ICC

Supplier: Prosci

The WAP four-disulfide core domain protein 2 (WFDC2), also known as epididymal protein 4, is a member of the WFDC domain family, a family of proteins that is characterized by the presence of Whey Acidic Protein (WAP) domain, and is highly expressed in the lung and salivary gland (1,2). Members of this family include SLPI and elafin, antiproteinases involved in the innate immune system. WFDC2 has been proposed to play a critical role in tumor formation and growth in ovarian cancer cells through the regulation of growth- and apoptosis-associated genes and may thus be a potential therapeutic target for epithelial ovarian cancer.

Supplier: Bioss

Ro autoantigens are of clinical significance because directed against them are found in most patients with primary Sjqgren syndrome, subacute cutaneous lupus erythematosus (SLE), neonatal lupus erythematosus, ANA-negative lupus erythematosus, and systemic lupus erythematosus-like disease secondary to homozygous C2 or C4 complement deficiency (1). Ro/SSA is a ribonucleoprotein that binds to auto in 35 to 50% of patients with SLE and in up to 97% of patients with Sjqgren syndrome (2). The Ro/SSA particle consists of a single immunoreactive protein noncovalently bound with one of four small RNA molecules (2). Most anti-Ro/SSA-positive sera detect not only the main protein, but also a smaller Ro/SSA protein (2). The genes which encode the smaller and larger proteins map to human chromosomes 11p15.5 and 1q31, respectively (3?). La/SSB is an autoimmune RNA-binding protein that plays a role in the transcription of RNA polymerase III was originally defined by its reactivity with auto from patients with Sjé°ƒren syndrome and SLE (6).

Supplier: Prosci

DOPA decarboxylase (DDC) belongs to the group II decarboxylase family of proteins. It is an important protein in the catecholamine biosynthesis pathway. DDC catalyzes the second reaction in the biosynthesis of catecholamines, trace amines and serotonin (1,2). It can form a homodimer and is expressed in the central nervous system. DDC can be used as markers for dopaminergic, noradrenergic and serotonergic neurons in a variety of applications including depression, schizophrenia, Parkinson's disease, neuroendocrine tumors and drug abuse. Defects in DDC gene may cause the autosomal recessive disorder AADC deficiency.

Supplier: Prosci

WT1 is a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilm's tumors. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilm's tumors. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated.

Supplier: Prosci

CLEC4M is a transmembrane receptor and is often referred to as L-SIGN because of its expression in the endothelial cells of the lymph nodes and liver. It is involved in the innate immune system and recognizes numerous evolutionarily divergent pathogens ranging from parasites to viruses, with a large impact on public health. The protein is organized into three distinct domains: an N-terminal transmembrane domain, a tandem-repeat neck domain and C-type lectin carbohydrate recognition domain. The extracellular region consisting of the C-type lectin and neck domains has a dual function as a pathogen recognition receptor and a cell adhesion receptor by binding carbohydrate ligands on the surface of microbes and endogenous cells. The neck region is important for homo-oligomerization which allows the receptor to bind multivalent ligands with high avidity. Variations in the number of 23 amino acid repeats in the neck domain of this protein are common and have a significant impact on ligand binding ability. This gene is closely related in terms of both sequence and function to a neighboring gene (GeneID 30835; often referred to as DC-SIGN or CD209). DC-SIGN and L-SIGN differ in their ligand-binding properties and distribution. Alternative splicing results in multiple variants.This gene encodes a type II integral membrane protein that is 77% identical to CD209 antigen, a HIV gp120-binding protein. This protein, like CD209, efficiently binds both intercellular adhesion molecule 3 (ICAM3) and HIV-1 gp120, and enhances HIV-1 infection of T cells. This gene is mapped to 19p13.3, in a cluster with the CD209 and CD23/FCER2 genes. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.

Supplier: Prosci

4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities.4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.

Supplier: Bioss

Ro autoantigens are of clinical significance because directed against them are found in most patients with primary Sjqgren syndrome, subacute cutaneous lupus erythematosus (SLE), neonatal lupus erythematosus, ANA-negative lupus erythematosus, and systemic lupus erythematosus-like disease secondary to homozygous C2 or C4 complement deficiency (1). Ro/SSA is a ribonucleoprotein that binds to auto in 35 to 50% of patients with SLE and in up to 97% of patients with Sjqgren syndrome (2). The Ro/SSA particle consists of a single immunoreactive protein noncovalently bound with one of four small RNA molecules (2). Most anti-Ro/SSA-positive sera detect not only the main protein, but also a smaller Ro/SSA protein (2). The genes which encode the smaller and larger proteins map to human chromosomes 11p15.5 and 1q31, respectively (3?). La/SSB is an autoimmune RNA-binding protein that plays a role in the transcription of RNA polymerase III was originally defined by its reactivity with auto from patients with Sjé°ƒren syndrome and SLE (6).

Supplier: Bioss

A mutation of the DYT1 gene, which codes for TorsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia. TorsinA comprises 332 amino acids. TorsinA is widely expressed throughout the mouse central nervous system and is detected in the majority of neurons in nearly all regions. The proteins display cytoplasmic distribution, although in some types of neurons localization is perinuclear. TorsinA often performs chaperone-like functions that assist in the assembly, operation, or dis-assembly of protein complexes. The gene which encodes TorsinA has high homology to three additional mammalian genes and a nematode gene and distal similarity to the family of heat-shock proteins and the Clp protease family. The gene which encodes TorsinA maps to human chromosome 9q34.

Supplier: Prosci

RTN4RL2 Antibody: Reticulon 4 receptor-like 2 (RTN4RL2), also known as NgR2and NgRH1, is a 60 kDa glycosylphosphatidylinositol-anchored protein that is expressed primarily in the brain. It contains eight leucine-rich repeats that are flanked by cysteine-rich sequences at both the N- and C-termini. The membrane anchored RTN4RL2 can be solubilized through the action of phospholipase or an unidentified MTMMP to generate a 46 kDa soluble receptor. It has been suggested that RTN4RL2 may play a role in regulating axonal regeneration and plasticity in the adult central nervous system.

Supplier: Prosci

RC3H1 Antibody: The ring finger protein RC3H1, also known as Roquin, is a highly conserved member of the RING type ubiquitin ligase protein family whose M199R mutation leads to the excessive production of follicular helper T cells and germinal centers in the sanroque strain of mice, a strain with excessive IL-21 production and high titers of autoantibodies. The complete loss of RC3H1 induces early death and immune deregulation but not autoimmunity in RC3H1-null mice, suggesting that the mutant RC3H1 is more disruptive to the immune system than its complete loss.

Supplier: Biosensis

SOD1 binds copper and zinc ions ans is one of two isozymes responsible for destroying free superoxide radicals which are normally produced within the cells and which are toxic to biological systems. SOD1 is a soluble cytoplasmic protein, acting as a homodimer to convert superoxide radicals to molecular oxygen and hydrogen peroxide. Defects in SOD1 are the cause of amyotrophic lateral sclerosis type 1 (ALS1) which is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis.

Supplier: Prosci

Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels. Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are designated by their molecular mass. Another system of nomenclature divides gap junction proteins into 2 categories, alpha and beta, according to sequence similarities at the nucleotide and amino acid levels. For example, CX43 (MIM 121014) is designated alpha-1 gap junction protein, whereas CX32 (GJB1; MIM 304040) and CX26 are called beta-1 and beta-2 gap junction proteins, respectively. This nomenclature emphasizes that CX32 and CX26 are more homologous to each other than either of them is to CX43.

Supplier: Prosci

RHOBTB1 belongs to the Rho family of the small GTPase superfamily. It contains a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The protein plays a role in small GTPase-mediated signal transduction and the organization of the actin filament system.The protein encoded by this gene belongs to the Rho family of the small GTPase superfamily. It contains a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The protein plays a role in small GTPase-mediated signal transduction and the organization of the actin filament system. Alternate transcriptional splice variants have been characterized.

Supplier: Prosci

PAX6 is one of many human homologues of the Drosophila melanogaster gene prd. In addition to the hallmark feature of this gene family, a conserved paired box domain, the encoded protein also contains a homeo box domain. Both domains are known to bind DNA,This gene encodes paired box gene 6, one of many human homologues of the Drosophila melanogaster gene prd. In addition to the hallmark feature of this gene family, a conserved paired box domain, the encoded protein also contains a homeo box domain. Both domains are known to bind DNA, and function as regulators of gene transcription. This gene is expressed in the developing nervous system, and in developing eyes. Mutations in this gene are known to cause aniridia as well as Peter's anomaly, both ocular diseases.

Supplier: Enzo Life Sciences

The 70 kDa heat shock protein Hsp70 belongs to the Hsp70 family of highly-related protein isoforms ranging in size from 66 kDa to 78 kDa. Hsc70 shares close biochemical and biological ties to Hsp70, and also belongs to the Hsp70 family. These proteins include cognate members found within major intracellular compartments and highly inducible isoforms predominantly cytoplasmic or nuclear in distribution. Members of the Hsp70 family function as molecular chaperones involved in such cellular functions as protein folding, transport, maturation and degradation, operating in an ATP-dependent manner. The molecular chaperones of the Hsp70 family recognize and bind to nascent polypeptide chains or partially folded intermediates of proteins, preventing their aggregation and misfolding, and the binding of ATP triggers a critical conformational change leading to the release of the bound substrate protein. Data demonstrates that with a ubiquitin-like domain at its amino terminus and its association with the 26S proteosome in HeLa cells, Bag-1 modulates the chaperone activity of Hsc70 and Hsp70. These findings reveal Bag-1's role as a physical link between the Hsc70/Hsp70 chaperone system and the proteasome. Experimental data also shows that the ATPase domain and the substrate-binding domain of Hsp70 (or Hsc70) cooperate to form a co-chaperone-chaperone complex with the synaptic vesicle cysteine string protein (csp), essential for normal neurotransmitter release.

Supplier: Bioss

Glutamic Acid Decarboxylase (GAD) catalyzes the conversion of L glutamate to g-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, and a putative paracrine signal molecule in pancreatic islets. GAD has a restricted tissue distribution. It is highly expressed in the cytoplasm of GABAergic neurons in the central nervous system (CNS) and pancreatic beta cells. It is also present in other non-neuronal tissues such as testis, oviduct and ovary. GAD is also transiently expressed in non-GABAergic cells of the embryonic and adult nervous system, suggesting its involvement in development and plasticity. GAD exists as two isoforms, GAD65 and GAD67 (molecular masses of 65 and 67 kD, respectively) that are encoded by two different genes. GAD65 is an ampiphilic, membraneanchored protein, (585 amino acid residues) and is encoded on human chromosome 10. GAD67 is a cytoplasmic protein (594 amino acid residues) and is encoded on chromosome 2. There is 64% amino acid identity between the two isoforms, with the highest diversity located at the N terminus, which in GAD65 is required for targeting the enzyme to GABA-containing secretory vesicles. The two isoforms appear to have distinct intraneuronal distribution in the brain. GAD65 has been identified as an autoantigen in insulindependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS), IDDM is an autoimmune disease that results from T cell mediated destruction of pancreatic insulin-secreting beta cells. Islet-reactive T cells and primarily to GAD65 (also named beta cell autoantigen) can be detected in peripheral blood of 80% of recent-onset IDD patients and in pre-diabetic high-risk subjects before onset of clinical symptoms. This suggests that GAD may be an important marker in the early stages of the disease.

Supplier: Bioss

Glutamic Acid Decarboxylase (GAD) catalyzes the conversion of L glutamate to g-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, and a putative paracrine signal molecule in pancreatic islets. GAD has a restricted tissue distribution. It is highly expressed in the cytoplasm of GABAergic neurons in the central nervous system (CNS) and pancreatic beta cells. It is also present in other non-neuronal tissues such as testis, oviduct and ovary. GAD is also transiently expressed in non-GABAergic cells of the embryonic and adult nervous system, suggesting its involvement in development and plasticity. GAD exists as two isoforms, GAD65 and GAD67 (molecular masses of 65 and 67 kD, respectively) that are encoded by two different genes. GAD65 is an ampiphilic, membraneanchored protein, (585 amino acid residues) and is encoded on human chromosome 10. GAD67 is a cytoplasmic protein (594 amino acid residues) and is encoded on chromosome 2. There is 64% amino acid identity between the two isoforms, with the highest diversity located at the N terminus, which in GAD65 is required for targeting the enzyme to GABA-containing secretory vesicles. The two isoforms appear to have distinct intraneuronal distribution in the brain. GAD65 has been identified as an autoantigen in insulindependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS), IDDM is an autoimmune disease that results from T cell mediated destruction of pancreatic insulin-secreting beta cells. Islet-reactive T cells and primarily to GAD65 (also named beta cell autoantigen) can be detected in peripheral blood of 80% of recent-onset IDD patients and in pre-diabetic high-risk subjects before onset of clinical symptoms. This suggests that GAD may be an important marker in the early stages of the disease.

Supplier: Prosci

The transient receptor potential (TRP) protein family consists of a diverse group of cation channels functioning in a variety of homeostatic and regulatory pathways. Four subfamilies exist, based on channel domain homology: C type (canonical), V type (vanilloid receptor related), M type (melastatin related) and P type (PKD). TRPV4, belongs to the V type subfamily and plays a role in systemic osmoregulation. TRPV4 is a calcium channel multi-pass membrane protein activated by various stimuli, including thermal stress, fatty acid metabolites and hypotonicity. TRPV4 is highly expressed in lung and kidney and widely expressed in brain. It plays an important role in regulating neural excitability.

Supplier: Prosci

GABARAP Antibody: Gamma-aminobutyric acid (GABA) is the main inhibitory transmitter by increasing a Cl-conductance that inhibits neuronal firing in the central nervous system. It has been shown to activate both ionotropic (GABAA) and metabotropic (GABAB) receptors as well as a third class of receptors called GABAC. GABARAP (GABAA receptor-associated protein) links GABAA receptors to the cytoskeleton and may play a role in intracellular transport of GABAA receptors and its interaction with the cytoskeleton. GABARAP belongs to the MAP1 or ATG8 like family and recent studies show that MAPK15/ERK8 is acting through interaction with ATG8 family proteins to regulate autophagy.

Supplier: Prosci

TLX3 Antibody: The Hox proteins play a role in patterns of embryonic development and cellular differentiation by regulating downstream target genes. TLX3, also known as homeobox11-like1 (HOX11L2), is a DNA-binding nuclear transcription factor that is expressed in a subset of the primary sensory nervous system. TLX3, along with the related TLX1, is a selector transcription factor that promotes an excitatory glutamatergic neuronal phenotype over an inhibitory GABAergic phenotype opposing LBX1 signals during dorsal spinal cord development. Chromosomal translocations of the TLX3 gene have been shown to result in some forms of T-cell acute lymphoblastic leukemia (T-ALL).

Supplier: Prosci

The G protein–coupled receptor kinases (GRKs) are a versatile family of kinases that play a critical role in cancer metastasis through their regulation of G-protein coupled receptors (GPCRs) involved in growth factor mediated cell migration (1,2). Phosphorylation of receptors by GRKs appears to be strictly dependent on the receptor being in its agonist-activated state. GRK6 is one of 7 members of the GRK serine/threonine kinase subfamily, which has been shown to modulate the Wnt signaling pathway via phosphorylation of LRP6 (3,4), and the insulin-like growth factor signaling pathway. GRK6 may also play a role in immune system function.

Supplier: Bioss

Vasopressin (AVP), the antidiuretic hormone, is a cyclic nonpeptide that is involved in the regulation of body fluid osmolality (1-3). AVP mediates its effects through a family of G-protein coupled receptors, the vasopressin receptors type V1a, V2 and V3 (also designated V1b) (1,2). The AVP receptor V1a is responsible for several functions, including blood vessel constriction, liver glycogenolysis and platelet adhesion (3). It is detected as a full length protein and a shorter protein, which results from proteolytic cleavage of its amino terminus (4). The V1a receptor is coupled to Gq/11 protein, which increases the intracellular calcium concentration (3). The human AVP receptor V2 gene maps to chromosome Xq28 and is expressed in lung and kidney (5,6). Mutations in the V2 receptor result in nephrogenic diabetes insipidus (NDI), a rare X-linked disorder characterized by the inability of the kidney to concentrate urine in response to AVP (5,7). The AVP Receptor V2 activates the Gs protein and the cyclic AMP second messenger system (7). The AVP receptor V3 is preferentially expressed in the pituitary and stimulates the release of adrenocorticotropic hormone (ACTH) in response to AVP by mobilizing intracellular calcium stores (8). AVP receptor antagonists may have potential therapeutic effects in hypertension, congestive heart failure, nephrotic syndrome and ACTH-secreting tumors (2).

Supplier: Biosensis

Alpha synuclein is an abundant 140 amino acid neuronal protein, expressed primarily at presynaptic terminals in the central nervous system. Alpha synuclein has been associated with several neurodegenerative diseases. A point mutation in the gene coding for the alpha-synuclein protein was the first discovery linking this protein to a rare familial form of Parkinson's disease (PD). Subsequently, other mutations in the alpha-synuclein gene have been identified in familial PD. The aggregated proteinaceous inclusions called Lewy bodies found in PD and cortical Lewy body dementia (LBD) were discovered to be predominantly alpha-synuclein. Aberrant aggregation of alpha-synuclein has been detected in an increasing number of neurodegenerative diseases, collectively known as synucleopathies. Alpha-synuclein exists physiologically in both soluble and membrane-bound states, in unstructured and alpha-helical conformations, respectively. The physiological function of alpha-synuclein appears to require its translocation between these subcellular compartments and interconversion between the 2 conformations. Abnormal processing of alpha-synuclein is predicted to lead to pathological changes in its binding properties and function.

Supplier: Prosci

NELF Antibody: NELF (nasal embryonic luteinizing hormone-releasing hormone factor) is a 530 amino acid transcription factor involved in the migration of LHRH neurons, outgrowth of olfactory axons and suppression of transcription elongation. NELF is found in the peripheral and central nervous system during embryonic development, and is highly expressed in adult testis, kidney and brain. Known to couple NMDA receptor signaling to the nucleus, NELF knockdown impaired GnRH neuronal migration of NLT cells in vitro and the gene encoding NELF has been linked to the development of Idiopathic hypogonadotropic hypogonadism (IHH), a disorder resulting in impaired pubertal maturation and reproductive function.

Supplier: Prosci

MECR Antibody: The mitochondrial trans-2-enoyl-CoA reductase (MECR), was initially identified as nuclear receptor-binding factor 1 (NRBF1), which can interact with a multitude of nuclear hormone receptors in the presence of the respective ligands. MECR has been shown to be part of the mitochondrial fatty acid synthesis (FAS II) system and to catalyze the NAPDH-dependent reduction of 2-enoyl thioesters, generating saturated acyl-groups. Overexpression of this gene in transgenic mice can lead to cardiac abnormalities, suggesting that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy.

Supplier: Rockland Immunochemical

PI3K (p55 gamma) control protein-HIS Epitope

Supplier: Enzo Life Sciences

The 70 kDa heat shock protein Hsp70 belongs to the Hsp70 family of highly-related protein isoforms ranging in size from 66 kDa to 78 kDa. Hsc70 shares close biochemical and biological ties to Hsp70, and also belongs to the Hsp70 family. These proteins include cognate members found within major intracellular compartments and highly inducible isoforms predominantly cytoplasmic or nuclear in distribution. Members of the Hsp70 family function as molecular chaperones involved in such cellular functions as protein folding, transport, maturation and degradation, operating in an ATP-dependent manner. The molecular chaperones of the Hsp70 family recognize and bind to nascent polypeptide chains or partially folded intermediates of proteins, preventing their aggregation and misfolding, and the binding of ATP triggers a critical conformational change leading to the release of the bound substrate protein. Data demonstrates that with a ubiquitin-like domain at its amino terminus and its association with the 26S proteosome in HeLa cells, Bag-1 modulates the chaperone activity of Hsc70 and Hsp70. These findings reveal Bag-1's role as a physical link between the Hsc70/Hsp70 chaperone system and the proteasome. Experimental data also shows that the ATPase domain and the substrate-binding domain of Hsp70 (or Hsc70) cooperate to form a co-chaperone-chaperone complex with the synaptic vesicle cysteine string protein (csp), essential for normal neurotransmitter release.

Supplier: Enzo Life Sciences

The 70 kDa heat shock protein Hsp70 belongs to the Hsp70 family of highly-related protein isoforms ranging in size from 66 kDa to 78 kDa. Hsc70 shares close biochemical and biological ties to Hsp70, and also belongs to the Hsp70 family. These proteins include cognate members found within major intracellular compartments and highly inducible isoforms predominantly cytoplasmic or nuclear in distribution. Members of the Hsp70 family function as molecular chaperones involved in such cellular functions as protein folding, transport, maturation and degradation, operating in an ATP-dependent manner. The molecular chaperones of the Hsp70 family recognize and bind to nascent polypeptide chains or partially folded intermediates of proteins, preventing their aggregation and misfolding, and the binding of ATP triggers a critical conformational change leading to the release of the bound substrate protein. Data demonstrates that with a ubiquitin-like domain at its amino terminus and its association with the 26S proteosome in HeLa cells, Bag-1 modulates the chaperone activity of Hsc70 and Hsp70. These findings reveal Bag-1's role as a physical link between the Hsc70/Hsp70 chaperone system and the proteasome. Experimental data also shows that the ATPase domain and the substrate-binding domain of Hsp70 (or Hsc70) cooperate to form a co-chaperone-chaperone complex with the synaptic vesicle cysteine string protein (csp), essential for normal neurotransmitter release.

Supplier: Enzo Life Sciences

P62, also known as Sequestosome I, is a 62kDa, 440 amino acid protein, initially identified as a ligand of the SH2 domain of p56lck, now known to be expressed in many tissues. In addition to TRAF6, PEST and zinc finger motifs, p62 has a C-terminal ubiquitin binding association (UBA) domain with an affinity for multi-ubiquitin chains, and it is considered to serve as a scaffold protein, capable of binding to multiple signalling molecules and uniting receptor-mediated signalling events with ubiquitinylation. Elevated levels of p62 have been reported in breast tumours and in alcoholic liver disease where p62 has been shown to be involved in the formation of Mallory bodies. Several mutations in the p62 UBA domain have been identified and the etiology of Paget’s disease of bone has been linked to one such mutation. Kuusisto and colleagues have demonstrated that p62 is also present in elevated levels in the hallmark inclusions found in various neurodegenerative conditions, including tauopathies (Alzheimer’s disease, Picks disease, and frontotemporal dementia) and synucleinopathies (Parkinson’s disease, dementia with Lewy body disease and multiple system atrophy). In recent years ubiquitin immunostaining has been used to provide adjunct information for neuropathological diagnosis, but it is becoming evident that p62 may be an even more reliable marker of neurodegenerative disease inclusion detection than tau, alpha-synuclein or ubiquitin immunostaining.