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| NLRP12 | NACHT, LRR and PYD domains-containing protein 12; Plays an essential role as an potent mitigator of inflammation. Primarily expressed in dendritic cells and macrophages, inhibits both canonical and non-canonical NF-kappa-B and ERK activation pathways. Functions as a negative regulator of NOD2 by targeting it to degradation via the proteasome pathway. In turn, promotes bacterial tolerance. Inhibits also the DDX58-mediated immune signaling against RNA viruses by reducing the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked DDX58 activation but enhancing the E3 ubiquitin ligase RNF125- [...] (1062 aa) | ||||
| BTK | Tyrosine-protein kinase BTK; Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker prote [...] (693 aa) | ||||
| TNFAIP3 | Tumor necrosis factor alpha-induced protein 3; Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in [...] (790 aa) | ||||
| NLRP1 | NACHT, LRR and PYD domains-containing protein 1; As the sensor component of the NLRP1 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP1, CASP1, and possibly PYCARD. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP1 inflammasome is also required for HMGB1 secretion. The active cytokines and HMGB1 stimulat [...] (1473 aa) | ||||
| NLRP2 | NACHT, LRR and PYD domains-containing protein 2; Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature proinflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of proinflammatory caspases; Belongs to the NLRP family. (1062 aa) | ||||
| CASP1 | Caspase-1 subunit p10; 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. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracell [...] (404 aa) | ||||
| GPBAR1 | G-protein coupled bile acid receptor 1; Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids. (330 aa) | ||||
| NAIP | Baculoviral IAP repeat-containing protein 1; Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor- neuron ap [...] (1403 aa) | ||||
| CD200 | OX-2 membrane glycoprotein; Costimulates T-cell proliferation. May regulate myeloid cell activity in a variety of tissues. (294 aa) | ||||
| NLRX1 | NLR family member X1; Participates in antiviral signaling. Acts as a negative regulator of MAVS-mediated antiviral responses, through the inhibition of the virus-induced RLH (RIG-like helicase)-MAVS interaction. Instead, promotes autophagy by interacting with TUFM and subsequently recruiting the autophagy-related proteins ATG5 and ATG12. Regulates also MAVS-dependent NLRP3 inflammasome activation to attenuate apoptosis. Has no inhibitory function on NF-kappa-B signaling pathway, but enhances NF-kappa-B and JUN N-terminal kinase dependent signaling through the production of reactive oxy [...] (975 aa) | ||||
| MARCHF7 | E3 ubiquitin-protein ligase MARCHF7; E3 ubiquitin-protein ligase which may specifically enhance the E2 activity of HIP2. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May be involved in T-cell proliferation by regulating LIF secretion (By similarity). May play a role in lysosome homeostasis. (704 aa) | ||||
| IL1R1 | Interleukin-1 receptor type 1, membrane form; Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1- dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling comp [...] (569 aa) | ||||
| DRD1 | D(1A) dopamine receptor; Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase; Belongs to the G-protein coupled receptor 1 family. (446 aa) | ||||
| VDAC1 | Voltage-dependent anion-selective channel protein 1; Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. May participate in the formation of the permeability transition p [...] (283 aa) | ||||
| NLRC4 | NLR family CARD domain-containing protein 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. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity). (1024 aa) | ||||
| NOD1 | Nucleotide-binding oligomerization domain-containing protein 1; Enhances caspase-9-mediated apoptosis. Induces NF-kappa-B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shi [...] (953 aa) | ||||
| DHX33 | ATP-dependent RNA helicase DHX33; Implicated in nucleolar organization, ribosome biogenesis, protein synthesis and cytoplasmic dsRNA sensing (By similarity). Stimulates RNA polymerase I transcription of the 47S precursor rRNA. Associates with ribosomal DNA (rDNA) loci where it is involved in POLR1A recruitment. In the cytoplasm, promotes elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation. Senses cytosolic dsRNA mediating NLRP3 inflammasome formation in macrophages and type I interferon production in myeloid dendritic cells. Required for NLRP3 ac [...] (707 aa) | ||||
| CCND1 | G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (295 aa) | ||||
| PANX1 | Pannexin-1; Structural component of the gap junctions and the hemichannels. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis. (426 aa) | ||||
| IFNG | Interferon gamma; Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons; Belongs to the type II (or gamma) interferon family. (166 aa) | ||||
| EIF2AK2 | Interferon-induced, double-stranded RNA-activated protein kinase; IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation fac [...] (551 aa) | ||||
| AHR | Aryl hydrocarbon receptor; Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing [...] (848 aa) | ||||
| PYCARD | Apoptosis-associated speck-like protein containing a CARD; Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8- dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase- 9, -2 and -3. Involved in macrophage pyroptosis, a cas [...] (195 aa) | ||||
| NR0B2 | Nuclear receptor subfamily 0 group B member 2; Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways (By similarity). Specifically inhibits transactivation of the nuclear receptor with which it interacts (By similarity). Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1. Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism [...] (257 aa) | ||||
| IL1B | Interleukin-1 beta; Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B- cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T- helper 1 (Th1) cells. (269 aa) | ||||
| IL18 | Interleukin-18; A proinflammatory cytokine primarily involved in polarized T- helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable). Belongs to the IL-1 family. (193 aa) | ||||
| NOD2 | Nucleotide-binding oligomerization domain-containing protein 2; Involved in gastrointestinal immunity. Upon stimulation by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, binds the proximal adapter receptor-interacting RIPK2, which recruits ubiquitin ligases as XIAP, BIRC2, BIRC3, INAVA and the LUBAC complex, triggering activation of MAP kinases and activation of NF-kappa-B signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response. Required for MDP-induced NLRP1-dependent CASP1 activation and IL1B release in macroph [...] (1040 aa) | ||||
| NLRP4 | NACHT, LRR and PYD domains-containing protein 4; May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. 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. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways. (994 aa) | ||||
| NLRP6 | NACHT, LRR and PYD domains-containing protein 6; As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity). Essent [...] (892 aa) | ||||
| CASP2 | Caspase-2 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival. Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress. (452 aa) | ||||
| NLRP9 | NACHT, LRR and PYD domains-containing protein 9; As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell [...] (991 aa) | ||||
| CTSB | Cathepsin B heavy chain; Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Cleaves matrix extracellular phosphoglycoprotein MEPE. Involved in the solubilization of cross-linked TG/thyroglobulin in the thyroid follicle lumen (By similarity). Has also been implicated in tumor invasion and metastasis. Belongs to the peptidase C1 family. (339 aa) | ||||
| TRIM33 | E3 ubiquitin-protein ligase TRIM33; Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor o [...] (1127 aa) | ||||
| STAT1 | Signal transducer and activator of transcription 1-alpha/beta; Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF [...] (750 aa) | ||||
| CXCL9 | C-X-C motif chemokine 9; Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3; Belongs to the intercrine alpha (chemokine CxC) family. (125 aa) | ||||
| AIM2 | Interferon-inducible protein AIM2; Involved in innate immune response by recognizing cytosolic double-stranded DNA and inducing caspase-1-activating inflammasome formation in macrophages. Upon binding to DNA is thought to undergo oligomerization and to associate with PYCARD initiating the recruitment of caspase-1 precusrsor and processing of interleukin-1 beta and interleukin-18. Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner. Can also trigger PYCARD-dependent, caspase-1-independent cell death that involves caspase-8 (By similarity). Tumor suppr [...] (343 aa) | ||||
| CGAS | Cyclic GMP-AMP synthase; Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity. Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p]. Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second m [...] (522 aa) | ||||
| MCU | Calcium uniporter protein, mitochondrial; Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex). Activity is regulated by MICU1 and MICU2. At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. Involved in buffe [...] (351 aa) | ||||
| TLR4 | Toll-like receptor 4; Cooperates with LY96 and CD14 to mediate 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. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non- conserved histidines and are, therefore, species-specific. Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression. In complex with [...] (839 aa) | ||||
| DDX58 | Antiviral innate immune response receptor RIG-I; Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and proinflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Up [...] (925 aa) | ||||
| IL6 | Interleukin-6; Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasm [...] (212 aa) | ||||
| JAK1 | Tyrosine-protein kinase JAK1; Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor. (1154 aa) | ||||
| CARD8 | Caspase recruitment domain-containing protein 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) | ||||