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RALB RALB SRF SRF NLRC3 NLRC3 RIPK1 RIPK1 DDX58 DDX58 BECN1 BECN1 IFI16 IFI16 NLRP12 NLRP12 BAX BAX CASP8 CASP8 AIM2 AIM2 PYCARD PYCARD MEFV MEFV CASP1 CASP1 PYDC2 PYDC2 USP50 USP50 NLRC4 NLRC4 NLRP3 NLRP3 SYK SYK CASP5 CASP5 CASP4 CASP4 PAK1 PAK1 IGBP1 IGBP1 CARD17 CARD17 CARD16 CARD16 ARIH2 ARIH2
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
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
some 3D structure is known or predicted
Edges:
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
Others
textmining
co-expression
protein homology
Your Input:
MEFVPyrin; Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18- mediated inflammation. However, i [...] (781 aa)
PYCARDApoptosis-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 caspa [...] (195 aa)
RIPK1Receptor-interacting serine/threonine-protein kinase 1; Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at ’Ser-728’ in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via ’Lys-63’-link chains acts as a critical enhancer of communication with do [...] (671 aa)
SRFSerum response factor; SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5’ of the site of transcription initiation of some genes (such as FOS). Required for cardiac differentiation and maturation; MADS box family (508 aa)
RALBRas-related protein Ral-B; Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles (By similarity). Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells (By similarity). Required for suppression of apoptosis. In l [...] (206 aa)
PAK1Serine/threonine-protein kinase PAK 1; Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby media [...] (553 aa)
BAXApoptosis regulator BAX; Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis; Belongs to the Bcl-2 family (218 aa)
NLRP3NACHT, LRR and PYD domains-containing protein 3; As the sensor component of the NLRP3 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 NLRP3, 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. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. The active cytoki [...] (1036 aa)
ARIH2E3 ubiquitin-protein ligase ARIH2; E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin- conjugating enzyme E2 UBE2L3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates- associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (By similarity). The initial ubiquitin is then elongated (By similarity). E3 ubiquitin-protein ligase activity is activate [...] (493 aa)
CASP8Caspase-8; Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death- inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, [...] (538 aa)
NLRC3NLR family CARD domain-containing protein 3; Negative regulator of the innate immune response. Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA-dT), but not poly(I-C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (By similarity). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating ’Lys-63’- linked ubiquitination and leaving unchanged the degradative ’Lys- 48’-l [...] (1065 aa)
BECN1Beclin-1; Plays a central role in autophagy. Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways- PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Invo [...] (450 aa)
AIM2Interferon-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)
IFI16Gamma-interferon-inducible protein 16; Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA bi [...] (729 aa)
IGBP1Immunoglobulin-binding protein 1; Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of the phosphatases PP2A, PP4 and PP6 by protecting their partially folded catalytic subunits from degradative polyubiquitination until they associate with regulatory subunits (339 aa)
CARD16Caspase recruitment domain-containing protein 16; Caspase inhibitor. Acts as a regulator of procaspase- 1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-interleukin-1 beta (IL1B) and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. Also induces NF-kappa-B activation during the pro- inflammatory cytokine response. Also able to inhibit CASP1- mediated neuronal cell death, TNF-alpha, hypoxia-, UV-, and staurosporine-mediated cell death but not ER stress-mediated cell death. Acts by preventing activation of c [...] (197 aa)
CARD17Caspase recruitment domain-containing protein 17; Regulator of procaspase-1/CASP1 activation implicated in the regulation of the proteolytic maturation of pro-IL-1beta/IL1B and its release during inflammation. Inhibits the release of IL1B in response to LPS in monocytes. However, unlike CASP1, do not induce NF-kappa-B activation; Caspase recruitment domain containing (110 aa)
SYKTyrosine-protein kinase SYK; Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine- phosphorylated ITAM domains. The association with the receptor can [...] (635 aa)
DDX58Probable ATP-dependent RNA helicase DDX58; Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include- 5’- triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5’-triphosphate moiety, blunt-end base pairing at the 5’-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impac [...] (925 aa)
NLRP12NACHT, LRR and PYD domains-containing protein 12; May mediate activation of CASP1 via ASC and promote activation of NF-kappa-B via IKK; NLR family (1062 aa)
CASP5Caspase-5; Mediator of programmed cell death (apoptosis). During non-canonical inflammasome activation, cuts MB21D1 and may play a role in the regulation of antiviral innate immune activation; Caspase recruitment domain containing (447 aa)
NLRC4NLR 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; Caspase recruitment domain containing (1024 aa)
CASP4Caspase-4; Inflammatory caspase. Essential effector of NLRP3 inflammasome- dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS. Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators. Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection. In later stages of the infectio [...] (377 aa)
PYDC2Pyrin domain-containing protein 2; May play a role in innate immunity by disrupting the interaction between PYCARD and NLRP3, thereby regulating the NLRP3 inflammasome. May also inhibit NF-kappa-B signaling distally by affecting the nuclear accumulation of RELA; Pyrin domain containing (97 aa)
CASP1Caspase-1; 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 MB21D1/cGAS, rendering it inactive; Belongs to the peptidase C14A family (404 aa)
USP50Inactive ubiquitin carboxyl-terminal hydrolase 50; Has no peptidase activity; Ubiquitin specific peptidases (334 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo sapiens, human, man
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