"PROSCI"

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IL-36RN is is a member of the interleukin 1 cytokine family whose gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. IL-36RN specifically inhibits the activation of NF-kappaB induced IL-36A. The opposing activities of these cytokines have been suggested to be involved in the regulation of skin inflammation. Like the IL-36 cytokines (IL-36A, IL-36B and IL-36G), IL-36RN requires post-translational processing for full agonist activity, but the cleavage mechanism is currently unknown.

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izTRAIL is a newly available, highly active recombinant form of soluble human TRAIL. Due to a trimerizing N-terminal isoleucine zipper (iz) motif the intrinsic trimerization of TRAIL, required for apoptosis-inducing activity of TRAIL, is enhanced when compared to non-tagged soluble human TRAIL (shTRAIL). Therefore, izTRAIL is a potent inducer of apoptosis in many human cancer cells, but not normal human hepatocytes. In addition, the half-life of izTRAIL is about eight-fold higher than the half-life of shTRAIL. These properties render izTRAIL highly suitable for both in vitro and in vivo use, particularly for studies in which investigators plan to transfer their in vitro results into an in vivo system with human cancer cells in xenotransplant settings examining susceptibility to TRAIL-induced apoptosis.

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AIMP1 (Endothelial monocyte-activating polypeptide II, EMAP2) is a proinflammatory cytokine for monocytes and granulocytes. It is specifically induced by apoptosis and is involved in the control of angiogenesis, inflammation, and wound healing (1,2). AIMP1 was identified as one of three auxiliary factors of the mammalian aminoacyl tRNA synthetase (ARS) complex. It binds and facilitates the catalytic reaction of arginyl-tRNA synthetase. Recent studies show that CD23 plays an essential role in the AIMP1-induced immune response and might be a target in the treatment of inflammatory diseases.

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TRAIL-R1 (DR4; CD261) is a receptor for the cytotoxic ligand TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signalling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappaB.

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AIMP2 was initially identified as a part of an aminoacyl-tRNA synthesase complex. It was later discovered to be a cofactor and substrate of Parkin, a Ring-type E3 ubiquitin ligase that is important for the survival of dopamine neurons in Parkinson’s disease; accumulation of AIMP2 in these cells lead to catecholaminergic cell death. AIMP2 can also bind to TRAF2, a key player in the TNF-alpha signaling pathway, causing the ubiquitination of TRAF2 by cIAP1, leading to TNF-alpha-dependent apoptosis. Finally, AIMP2 has been suggested to function as a tumor suppressor.

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TRAIL-R2 (DR5; CD262) is a receptor for the cytotoxic ligand TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signalling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappaB.

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ADROPIN is a recently identified protein that has been implicated in the maintenance of energy homeostasis and insulin resistance. ADROPIN expression is regulated by energy status and dietary nutrient content and is altered by obesity and regulates the expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor gamma (PPAR-gamma). ADROPIN levels increase with dietary fat content. ADROPIN has also been proposed to play a role in the regulation of endothelial function.

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TNF-R1 is a receptor for TNF-alpha and homotrimeric lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signalling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis.

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PCDHA12 is a potential calcium-dependent cell-adhesion protein. PCDHA12 may be involved in the establishment and maintenance of specific neuronal connections in the brain.This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.

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The gene encoding PCDHA5 is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. PCDHA5 is a single-pass type I membrane protein. It contains 6 cadherin domains. PCDHA5 is a potential calcium-dependent cell-adhesion protein. It may be involved in the establishment and maintenance of specific neuronal connections in the brain.This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.

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PCDHGA4 is a single-pass type I membrane protein. It contains 6 cadherin domains. PCDHGA4 is a potential calcium-dependent cell-adhesion protein. It may be involved in the establishment and maintenance of specific neuronal connections in the brain.This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes.

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PCDHGB1 is a single-pass type I membrane protein. It contains 6 cadherin domains. PCDHGB1 is a potential calcium-dependent cell-adhesion protein. It may be involved in the establishment and maintenance of specific neuronal connections in the brain.This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes.

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PCDHGC4 is a single-pass type I membrane protein. It contains 6 cadherin domains.PCDHGC4 is a potential calcium-dependent cell-adhesion protein. It may be involved in the establishment and maintenance of specific neuronal connections in the brain.This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes.

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CLN8 is a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with progressive epilepsy with mental retardation (EMPR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. Childhood-onset NCL are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescent material, mainly ATP synthase subunit C, in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular genetic background of the disorder, at least seven different forms are thought to exist. CLN8 is characterized by normal early development, onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation.This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with progressive epilepsy with mental retardation (EMPR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain.

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HLA-F belongs to the HLA class I heavy chain paralogues. It is a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene exhibits few polymorphisms. Multiple transcript variants encoding different isoforms have been found for this gene. These variants lack a coding exon found in transcripts from other HLA paralogues due to an altered splice acceptor site, resulting in a shorter cytoplasmic domain.

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YIPF1 is a multi-pass membrane protein. It belongs to the YIP1 family. The exact function of YIPF1 remains unknown.