STRINGSTRING
NOX3 NOX3 IFNG IFNG RAC2 RAC2 CD68 CD68 TLR2 TLR2 CYBA CYBA NOX4 NOX4 IL1B IL1B NCF1 NCF1 MAP1B MAP1B VPS35 VPS35 MAP1A MAP1A CASP3 CASP3 DUOX1 DUOX1 TAC1 TAC1 MAP1S MAP1S ATP13A2 ATP13A2 DNAH8 DNAH8 PARK7 PARK7 NOXA1 NOXA1 MTOR MTOR GPX6 GPX6 GPX7 GPX7 AGT AGT PRKN PRKN NCF2 NCF2 NOX1 NOX1 TLR4 TLR4 PINK1 PINK1 AIF1 AIF1 CYBB CYBB TH TH GPX3 GPX3 NOX5 NOX5 GPX2 GPX2 IGF1 IGF1 NCF4 NCF4 NOXO1 NOXO1 ITGB2 ITGB2 GPX5 GPX5 TNF TNF GPX8 GPX8 AKT1 AKT1
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.
Node Color
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:
a 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 to 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:
NOX3NADPH oxidase 3; NADPH oxidase which constitutively produces superoxide upon formation of a complex with CYBA/p22phox. Plays a role in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. (568 aa)
IFNGInterferon 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)
RAC2Ras-related C3 botulinum toxin substrate 2; Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase. (192 aa)
CD68Macrosialin; Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells. (354 aa)
TLR2Toll-like receptor 2; Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble [...] (784 aa)
CYBACytochrome b-245 light chain; Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide. Belongs to the p22phox family. (195 aa)
NOX4NADPH oxidase 4; Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and is [...] (578 aa)
IL1BInterleukin-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)
NCF1Neutrophil cytosol factor 1; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (390 aa)
MAP1BMicrotubule-associated protein 1B; Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B may play a role in the cytoskeletal changes that accompany neurite extension. Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. (2468 aa)
VPS35Vacuolar protein sorting-associated protein 35; Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may [...] (796 aa)
MAP1AMicrotubule-associated protein 1A; Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. (2803 aa)
CASP3Caspase-3 subunit p12; Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. (277 aa)
DUOX1Dual oxidase 1; Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. (1551 aa)
TAC1C-terminal-flanking peptide; Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. (129 aa)
MAP1SMicrotubule-associated protein 1S; Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity); Belongs to the MAP1 family. (1059 aa)
ATP13A2Cation-transporting ATPase 13A2; ATPase that plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity. Required for a proper lysosomal and mitochondrial maintenance. Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post- translational levels. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily. (1180 aa)
DNAH8Dynein heavy chain 8, axonemal; Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly (By similarity). (4707 aa)
PARK7Protein/nucleic acid deglycase DJ-1; Protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. Thus, functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminoca [...] (189 aa)
NOXA1NADPH oxidase activator 1; Functions as an activator of NOX1, a superoxide-producing NADPH oxidase. Functions in the production of reactive oxygen species (ROS) which participate in a variety of biological processes including host defense, hormone biosynthesis, oxygen sensing and signal transduction. May also activate CYBB/gp91phox and NOX3. Belongs to the NCF2/NOXA1 family. (483 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)
GPX6Glutathione peroxidase 6. (221 aa)
GPX7Glutathione peroxidase 7; It protects esophageal epithelia from hydrogen peroxide- induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks; Belongs to the glutathione peroxidase family. (187 aa)
AGTAngiotensin 1-4; Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis. [Angiotensin-3]: stimulates aldosterone release. (485 aa)
PRKNE3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'- linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of m [...] (465 aa)
NCF2Neutrophil cytosol factor 2; NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production). (526 aa)
NOX1NADPH oxidase 1; NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain. (564 aa)
TLR4Toll-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)
PINK1Serine/threonine-protein kinase PINK1, mitochondrial; Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PRKN. Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form. Required for ubiquinone reduct [...] (581 aa)
AIF1Allograft inflammatory factor 1; Actin-binding protein that enhances membrane ruffling and RAC activation. Enhances the actin-bundling activity of LCP1. Binds calcium. Plays a role in RAC signaling and in phagocytosis. May play a role in macrophage activation and function. Promotes the proliferation of vascular smooth muscle cells and of T-lymphocytes. Enhances lymphocyte migration. Plays a role in vascular inflammation. (147 aa)
CYBBCytochrome b-245 heavy chain; Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc. (570 aa)
THTyrosine 3-monooxygenase; Plays an important role in the physiology of adrenergic neurons. (528 aa)
GPX3Glutathione peroxidase 3; Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. (226 aa)
NOX5NADPH oxidase 5; Calcium-dependent NADPH oxidase that generates superoxide. Also functions as a calcium-dependent proton channel and may regulate redox-dependent processes in lymphocytes and spermatozoa. May play a role in cell growth and apoptosis. Isoform v2 and isoform v5 are involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin. (765 aa)
GPX2Glutathione peroxidase 2; Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors. (190 aa)
IGF1Insulin-like growth factor I; The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]- 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exo [...] (158 aa)
NCF4Neutrophil cytosol factor 4; Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex. (348 aa)
NOXO1NADPH oxidase organizer 1; Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. Isoform 3 is more potent than isoform 1 in activating NOX3. Together with NOXA1, may also substitute to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte NOX2/gp91phox superoxide-generating activity. (376 aa)
ITGB2Integrin beta-2; Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor [...] (769 aa)
GPX5Epididymal secretory glutathione peroxidase; Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids. (221 aa)
TNFTumor necrosis factor, membrane form; Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T- cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Upregulates the expression of protein phosphatase 1 [...] (233 aa)
GPX8Glutathione peroxidase 8; Belongs to the glutathione peroxidase family. (209 aa)
AKT1RAC-alpha serine/threonine-protein kinase; AKT1 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. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the [...] (480 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (20%) [HD]