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RIPK2 | receptor-interacting serine-threonine kinase 2; Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes ’Lys-63’-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces ’Lys-63’-linked polyubiquitination of IKBKG/NEMO and subsequent acti [...] (540 aa) | |||
DTX4 | deltex homolog 4 (Drosophila); Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations (By similarity). Functions as an ubiquitin ligase protein in vivo, mediating ’Lys48’-linked polyubiquitination and promoting degradation of TBK1, targeting to TBK1 requires interaction with NLRP4 (619 aa) | |||
RPS27A | ribosomal protein S27a (156 aa) | |||
ZNF526 | zinc finger protein 526; May be involved in transcriptional regulation (By similarity) (670 aa) | |||
NLRP4 | NLR family, pyrin domain containing 4; May be involved in inflammation. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation (994 aa) | |||
UBB | ubiquitin B (229 aa) | |||
IRF3 | interferon regulatory factor 3; Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive fo [...] (427 aa) | |||
TBK1 | TANK-binding kinase 1; Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN- alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form severa [...] (729 aa) | |||
TMEM173 | transmembrane protein 173; Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double- stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol- upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated [...] (379 aa) | |||
HSP90AA1 | heat shock protein 90kDa alpha (cytosolic), class A member 1; Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (854 aa) | |||
TRAF6 | TNF receptor-associated factor 6, E3 ubiquitin protein ligase; E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ’Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF- kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c-Myb-mediated transactivation, in B-lymphocytes. Ad [...] (522 aa) | |||
UBC | ubiquitin C (685 aa) | |||
SH3BP1 | SH3-domain binding protein 1; Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. This protein binds preferentially to the ABL1 proto-oncogene, SRC and GRB2. Shows GAP activity for Rac-related proteins but not for Rho- or Ras-related proteins. It inhibits PDGF-induced membrane ruffling mediated by Rac (By similarity) (701 aa) | |||
NLRC4 | NLR family, CARD domain containing 4; Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis (1024 aa) | |||
FASLG | Fas ligand (TNF superfamily, member 6); Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. May be involved in cytotoxic T-cell mediated apoptosis and in T-cell development. TNFRSF6/FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. Binding to the decoy receptor TNFRSF6B/DcR3 modulates its effects (281 aa) | |||
IKBKG | inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma; 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. Als [...] (487 aa) | |||
CHUK | conserved helix-loop-helix ubiquitous kinase; 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 the nucleus [...] (745 aa) | |||
ZBP1 | Z-DNA binding protein 1; Participates in the detection by the host’s innate immune system of DNA from viral, bacterial or even host origin. Plays a role in host defense against tumors and pathogens. Acts as a cytoplasmic DNA sensor which, when activated, induces the recruitment of TBK1 and IRF3 to its C-terminal region and activates the downstream interferon regulatory factor (IRF) and NF-kappa B transcription factors, leading to type-I interferon production. ZBP1-induced NF-kappaB activation probably involves the recruitment of the RHIM containing kinases RIPK1 and RIPK3 (By similarity) (429 aa) | |||
ITCH | itchy E3 ubiquitin protein ligase (862 aa) | |||
CARD8 | caspase recruitment domain family, member 8; Inhibits NF-kappa-B activation. May participate in a regulatory mechanism that coordinates cellular responses controlled by NF-kappa-B transcription factor. May be a component of the inflammasome, a protein complex which also includes PYCARD, NALP2 and CASP1 and whose function would be the activation of proinflammatory caspases (537 aa) | |||
CASP5 | caspase 5, apoptosis-related cysteine peptidase (447 aa) | |||
UBA52 | ubiquitin A-52 residue ribosomal protein fusion product 1 (128 aa) | |||
CASP1 | caspase 1, apoptosis-related cysteine peptidase; Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis (404 aa) | |||
PYDC2 | pyrin domain containing 2; Inhibits NF-kappa-B signaling distally by affecting the nuclear accumulation of RELA. Disrupts the interaction between PYCARD and NLRP3 (97 aa) | |||
CARD18 | caspase recruitment domain family, member 18; Inhibits generation of IL-1-beta by interacting with caspase-1 and preventing its association with RIP2. Down-regulates the release of IL1B (90 aa) |