STRINGSTRING
Il11 Il11 Il4 Il4 Tbx21 Tbx21 Akt1 Akt1 Il27ra Il27ra Il12rb2 Il12rb2 Il10 Il10 Irf4 Irf4 Il10rb Il10rb Il6 Il6 Il1b Il1b Il2 Il2 Rorc Rorc Il2rg Il2rg Il10ra Il10ra Ctf1 Ctf1 Il27 Il27 Socs3 Socs3 Jak3 Jak3 Ifng Ifng Jak2 Jak2 Lif Lif Osm Osm H3c7 H3c7 H3c8 H3c8 Stat6 Stat6 Mtor Mtor Jak1 Jak1 Gata3 Gata3 Csf3r Csf3r H3f3b H3f3b Jun Jun Stat5a Stat5a Cntf Cntf Foxp3 Foxp3 Il23r Il23r Stat3 Stat3 Stat1 Stat1 Il7 Il7 Tyk2 Tyk2 Il12rb1 Il12rb1
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:
Il11Interleukin-11; Cytokine that stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. Also promotes the proliferation of hepatocytes in response to liver damage. Binding to its receptor formed by IL6ST and either IL11RA1 or IL11RA2 activates a signaling cascade that promotes cell proliferation, also in the context of various cancers. Signaling leads to the activation of intracellular protein kinases and the phosphorylation of STAT3. Belongs to the IL-6 superfamily. (199 aa)
Il4Interleukin-4; Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4. Belongs to the IL- [...] (140 aa)
Tbx21T-box transcription factor TBX21; Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs. Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. Activates IFNG and CXCR3 genes in part by recruiting chromatin remodeling complexes including KDM6B, a SMARCA4- containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to their promoters and [...] (530 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)
Il27raInterleukin-27 receptor subunit alpha; Receptor for IL27. Requires IL6ST/gp130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Involved in the regulation of Th1-type immune responses. Also appears to be involved in innate defense mechanisms. (623 aa)
Il12rb2Interleukin-12 receptor subunit beta-2; Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production. Can also activate STAT3. (874 aa)
Il10Interleukin-10; Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines in [...] (178 aa)
Irf4Interferon regulatory factor 4; Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA- 3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and [...] (450 aa)
Il10rbInterleukin-10 receptor subunit beta; Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state (By similarity). (351 aa)
Il6Interleukin-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 [...] (211 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; Belongs to the IL-1 family. (269 aa)
Il2Interleukin-2; Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. (169 aa)
RorcNuclear receptor ROR-gamma; Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respective [...] (516 aa)
Il2rgCytokine receptor common subunit gamma; Common subunit for the receptors for a variety of interleukins. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (By similarity). (369 aa)
Il10raInterleukin-10 receptor subunit alpha; Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well. In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively. These kinases then phosphorylate specific tyrosine residues in the intracellul [...] (575 aa)
Ctf1Cardiotrophin-1; Induces cardiac myocyte hypertrophy in vitro. Binds to and activates the ILST/gp130 receptor. (203 aa)
Il27Interleukin-27 subunit alpha; Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal ex [...] (234 aa)
Socs3Suppressor of cytokine signaling 3; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL [...] (225 aa)
Jak3Tyrosine-protein kinase JAK3; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails o [...] (1100 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. (155 aa)
Jak2Tyrosine-protein kinase JAK2; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors [...] (1132 aa)
LifLeukemia inhibitory factor; LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes; Belongs to the LIF/OSM family. (203 aa)
OsmOncostatin-M; Growth regulator. Inhibits the proliferation of a number of tumor cell lines. It regulates cytokine production, including IL-6, G- CSF and GM-CSF from endothelial cells (By similarity). Uses only type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity). (263 aa)
H3c7Histone H3.2; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (136 aa)
H3c8Histone H3.1; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (136 aa)
Stat6Signal transducer and transcription activator 6; Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling; Belongs to the transcription factor STAT family. (837 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 (By similarity). This includes phosph [...] (2549 aa)
Jak1Tyrosine-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. (1153 aa)
Gata3Trans-acting T-cell-specific transcription factor GATA-3; Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses. (443 aa)
Csf3rGranulocyte colony-stimulating factor receptor; Receptor for granulocyte colony-stimulating factor (CSF3). In addition it may function in some adhesion or recognition events at the cell surface. (837 aa)
H3f3bHistone H3.3; Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in [...] (136 aa)
JunTranscription factor AP-1; Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 (By similarity). Binds to the USP28 promoter (By similarity). (334 aa)
Stat5aSignal transducer and activator of transcription. (797 aa)
CntfCiliary neurotrophic factor; CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy. (198 aa)
Foxp3Forkhead box protein P3, C-terminally processed; Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The s [...] (429 aa)
Il23rInterleukin-23 receptor; Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis (By similarity). (659 aa)
Stat3Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (By similarity). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Binds to the interleukin-6 (IL-6)- responsive elements identified in the promoters of various acute-phase protein genes (By similarity). Activated by IL31 through IL31RA (By s [...] (770 aa)
Stat1Signal transducer and activator of transcription 1; 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. ISGF3 binds to [...] (755 aa)
Il7Interleukin-7; Hematopoietic growth factor capable of stimulating the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation. (154 aa)
Tyk2Non-receptor tyrosine-protein kinase TYK2; Involved in intracellular signal transduction by amplifying type I and type II IFN signaling. Phosphorylates the interferon- alpha/beta receptor alpha chain. Plays an essential role in promoting selective immune responses, including innate host defense mechanisms and specific antiviral activities. (1207 aa)
Il12rb1Interleukin-12 receptor subunit beta-1; Functions as an interleukin receptor which binds interleukin- 12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade; Belongs to the type I cytokine receptor family. Type 2 subfamily. (738 aa)
Your Current Organism:
Mus musculus
NCBI taxonomy Id: 10090
Other names: LK3 transgenic mice, M. musculus, Mus sp. 129SV, house mouse, mouse, nude mice, transgenic mice
Server load: low (38%) [HD]