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RPTOR RPTOR TNFRSF10A TNFRSF10A AKT3 AKT3 PRKCZ PRKCZ MTOR MTOR TNFRSF10B TNFRSF10B FASLG FASLG RIPK3 RIPK3 TNFSF10 TNFSF10 PRKCQ PRKCQ FAS FAS IKBKG IKBKG CD14 CD14 IKBKB IKBKB MAP3K14 MAP3K14 CHUK CHUK CD40 CD40 RELA RELA UBE2V1 UBE2V1 UBE2M UBE2M NFKBIA NFKBIA LY96 LY96 USP4 USP4 IRAK4 IRAK4 IRAK2 IRAK2 IL1A IL1A
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
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empty nodes:
proteins of unknown 3D structure
filled nodes:
some 3D structure is known or predicted
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Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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RIPK3Receptor-interacting serine/threonine-protein kinase 3; Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes- GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (518 aa)
NFKBIANF-kappa-B inhibitor alpha; Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (317 aa)
TNFRSF10ATumor necrosis factor receptor superfamily member 10A; Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling 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-kappa-B; CD molecules (468 aa)
TNFSF10Tumor necrosis factor ligand superfamily member 10; Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis; CD molecules (281 aa)
UBE2MNEDD8-conjugating enzyme Ubc12; Accepts the ubiquitin-like protein NEDD8 from the UBA3- NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation (183 aa)
IRAK2Interleukin-1 receptor-associated kinase-like 2; Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization (625 aa)
PRKCQProtein kinase C theta type; Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non- redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transact [...] (706 aa)
IL1AInterleukin-1 alpha; Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells (271 aa)
AKT3RAC-gamma serine/threonine-protein kinase; AKT3 is one of 3 closely related serine/threonine- protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial f [...] (479 aa)
USP4Ubiquitin carboxyl-terminal hydrolase 4; Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May also play a role in the regulation of quality control in the ER; Ubiquitin specific peptidases (963 aa)
TNFRSF10BTumor necrosis factor receptor superfamily member 10B; Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling 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-kappa-B. Essential for ER stress-induced apoptosis; CD molecules (440 aa)
LY96Lymphocyte antigen 96; Binds bacterial lipopolysaccharide (LPS). Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram- positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both LY96 and TLR4, but not TLR4 alone, respond to LPS (160 aa)
CD14Monocyte differentiation antigen CD14; Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Acts as a coreceptor for TLR2-TLR6 heterodimer in response to diacylated lipopeptides and for TLR2-TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell su [...] (375 aa)
RPTORRegulatory-associated protein of mTOR; Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1- mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTO [...] (1335 aa)
UBE2V1Ubiquitin-conjugating enzyme E2 variant 1; Has no ubiquitin ligase activity on its own. The UBE2V1- UBE2N heterodimer catalyzes the synthesis of non-canonical poly- ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair [...] (170 aa)
FASTumor necrosis factor receptor superfamily member 6; Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death- inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS- mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro); CD molecules (335 aa)
MTORSerine/threonine-protein kinase mTOR; Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF [...] (2549 aa)
FASLGTumor necrosis factor ligand superfamily member 6; Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apopto [...] (281 aa)
CHUKInhibitor of nuclear factor kappa-B kinase subunit alpha; Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into [...] (745 aa)
CD40Tumor necrosis factor receptor superfamily member 5; Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (277 aa)
PRKCZProtein kinase C zeta type; Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Requ [...] (592 aa)
RELATranscription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kapp [...] (551 aa)
IRAK4Interleukin-1 receptor-associated kinase 4; Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino- mediated polyubiquit [...] (460 aa)
IKBKBInhibitor of nuclear factor kappa-B kinase subunit beta; Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is transloc [...] (756 aa)
MAP3K14Mitogen-activated protein kinase kinase kinase 14; Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non- canonical pathway. Could act in a receptor-selective manner; Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily (947 aa)
IKBKGNF-kappa-B essential modulator; Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either ’Lys-63’- linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activat [...] (487 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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