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TNFRSF1A
Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα). Function The protein encoded by this gene is a member of the tumor necrosis factor receptor superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate the transcription factor NF-κB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the signal transduction mediated by the receptor. Clinical significance Germline mutations of the extracellular domains of this receptor were found to be associated with the human genetic disorder called tumor necrosis factor associated periodic syndrome ...
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TNF Receptor Associated Periodic Syndrome
TNF receptor associated periodic syndrome (TRAPSsubscription needed) is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor (TNF) that is inheritable in an autosomal dominant manner. Individuals with TRAPS have episodic symptoms such as recurrent high fevers, rash, abdominal pain, joint/muscle aches and puffy eyes. Symptoms and signs TNF receptor associated periodic syndrome presents with the following signs and symptoms: * Episodic fever * Elevated erythrocyte sedimentation rate * Pericarditis * Splenomegaly * Uveitis * Vertigo Cause TNF receptor associated periodic syndrome is autosomal dominant, and about 70 mutations of the TNFRSF1A gene have been linked to this condition. Its cytogenetic location is at 12p13.31. Mechanism The main source of TNF (tumor necrosis factor) are cells in the immune system called macrophages which produce it in response to infection and other stimuli. TNF helps activate other immune cells and ...
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TRADD
Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the ''TRADD'' gene. TRADD is an adaptor protein. Function The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/ TNFR1 and mediates programmed cell death signaling and NF-κB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/ FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway. Interactions TRADD has been shown to interact with: * FADD, * Keratin 18 * RIPK1, * STAT1, * TNFRSF1A, * TNFRSF25, and * TRAF2. See also * TRAF TNF receptor associated factors (TRAFs) are a family of proteins primarily involved in the regulation of inflammation, antiviral responses and apoptosis. Currently ...
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Tumor Necrosis Factor-alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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Janus Kinase 1
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, IL-7R, IL-9R and IL-15R), the IL-4 receptor family (e.g. IL-4R and IL-13R), the gp130 receptor family (e.g. IL-6R, IL-11R, LIF-R, OSM-R, cardiotrophin-1 receptor (CT-1R), ciliary neurotrophic factor receptor (CNTF-R), neurotrophin-1 receptor (NNT-1R) and Leptin-R). It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and me ...
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UBE2I
SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the ''UBE2I'' gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function. Expression Four alternatively spliced transcript variants encoding the same protein have been found for this gene. Function The UBC9 protein encoded by the UBE2I gene constitutes a core machinery in the cell's sumoylation pathway. Sumoylation is a process in which a Small Ubiquitin-like MOdifier (SUMO) is covalently attached to other proteins in order to modify their behaviour. For example, sumoylation may affect a protein's localization in the cell, its ability to interact with other proteins or DNA. UBC9 performs the third step in the sumoylation life cycle: the conjugation step. When SUMO protein precursors are first expressed, they first undergo a maturation step in which the four C-terminal amino acids are rem ...
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Tumor Necrosis Factor-alpha
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. As an adipokine, TNF promotes insulin resistance, and is associated with obesity-induced type 2 diabetes. As a cytokine, TNF is used by the immune system for cell signaling. If macrophages (certain white blood cells) detect an infection, they release TNF to alert other immune system cells as part of an inflammatory response. TNF signaling occurs through two receptors: TNFR1 and TNFR2. TNFR1 is constituitively expressed on most cell types, whereas TNFR2 is restricted primarily to endothelial, epithelial, and subsets of immune cells. TNFR1 signaling tends to be pro-inflammatory and apoptotic, whereas TNFR2 signaling is anti-inflammatory and promotes cell proliferation. Suppression of TNFR1 signaling has been important for ...
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TRPC4AP
Trpc4-associated protein is a protein that in humans is encoded by the ''TRPC4AP'' gene. Model organisms Model organisms have been used in the study of TRPC4AP function. A conditional knockout mouse line, called ''Trpc4aptm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation, and thus fewer than expected survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; females had an abnormal anagen phase of the hair cycle. Interactions TRPC4AP has been shown to interact with TNFRSF1A. See also * TRPC TRPC is a f ...
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TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively ...
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Small Ubiquitin-related Modifier 1
Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the ''SUMO1'' gene. Function This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein and functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin, which is primarily associated with targeting proteins for proteasomal degradation, SUMO1 is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last four amino acids of the carboxy-terminus have been cleaved off. Several pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized. Most cleft genes have a sumoylation component. Analysis of chromosomal anomalies in patients has led to the ...
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RIPK1
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. Some of the cell survival pathways RIPK1 participates in include NF-κB, Akt, and JNK. RIPK1 is an enzyme that in humans is encoded by the ''RIPK1'' gene, which is located on chromosome 6. This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family. Structure RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. It contains a serine/threonine kinase domain (KD) in the 300 aa N-Terminus, a death domain (DD) in the 112 aa C-Terminus, and a central region between the KD and DD called intermediate domain (ID). *The kinase domain plays different roles in cell survival and is important in necroptosis induction. RIP interacts with TRAF2 vi ...
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PSMD2
26S proteasome non-ATPase regulatory subunit 2, also as known as 26S Proteasome Regulatory Subunit Rpn1 (systematic nomenclature), is an enzyme that in humans is encoded by the ''PSMD2'' gene. Structure Gene expression The gene ''PSMD2'' encodes a non-ATPase subunit of the 19S regulator base, which is responsible for substrate recognition and binding. The gene ''PSMD2'' encodes one of the non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. The human ''PSMD2'' gene has 23 exons and locates at chromosome band 3q27.1. The human protein 26S proteasome non-ATPase regulatory subunit 2 is 100 kDa in size and composed of 909 amino acids. The calculated theoretical pI of this protein is 5.10. Two expression isoforms are generated by alternative splicing, in which e ...
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PIP4K2B
Phosphatidylinositol-5-phosphate 4-kinase type-2 beta is an enzyme that in humans is encoded by the ''PIP4K2B'' gene. The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol 4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol 4,5-bisphosphate. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor. Interactions PIP4K2B has been shown to interact with TNFRSF1A. In addition, PIP4K2B has been shown to interact with PIP4K2A and may modulate the cellular localisation of PIP4K2A. Structure The structure of PIP4K2B has been determined through X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structur ...
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