Your Input: | |
| | Pik3r3 | Phosphatidylinositol 3-kinase regulatory subunit gamma; Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1. (461 aa) |
| | Phkg1 | Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform; Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity); Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. (388 aa) |
| | Prkab1 | 5'-AMP-activated protein kinase subunit beta-1; Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a reg [...] (270 aa) |
| | Irs3 | Insulin receptor substrate 3, isoform CRA_a. (494 aa) |
| | Sh2b2 | SH2B adapter protein 2; Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis (By similarity). Involved in stimulation of glucose uptake by insulin. Involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Induces cytoskeletal reorganization and neurite outgrowth in cultured neurons. (621 aa) |
| | Mapk1 | Mitogen-activated protein kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (358 aa) |
| | Crkl | Crk-like protein; May mediate the transduction of intracellular signals. Belongs to the CRK family. (303 aa) |
| | Socs1 | Suppressor of cytokine signaling 1; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity (By similarity). Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival. Probable substrate recognition component of an [...] (212 aa) |
| | Socs3 | Suppressor 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) |
| | Mapk9 | Mitogen-activated protein kinase 9; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress- activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as J [...] (423 aa) |
| | Rps6kb1 | Ribosomal protein S6 kinase beta-1; Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTO [...] (525 aa) |
| | Rptor | Regulatory-associated protein of MTOR, complex 1. (1335 aa) |
| | Grb2 | Growth factor receptor-bound protein 2; Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. (217 aa) |
| | Ppargc1a | Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in [...] (796 aa) |
| | Ppp1cb | Serine/threonine-protein phosphatase PP1-beta catalytic subunit; Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progressi [...] (327 aa) |
| | Crk | Adapter molecule crk; [Isoform Crk-II]: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. (304 aa) |
| | Sos2 | SOS Ras/Rho guanine nucleotide exchange factor 2. (1333 aa) |
| | Hk2 | Hexokinase-2; Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D- fructose 6-phosphate, respectively). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate. Plays a key role in maintaining the integrity of the outer mitochondrial membrane by preventing the release of apoptogenic molecules from the intermembrane space and subsequent apoptosis (By similarity). (917 aa) |
| | Pygl | Glycogen phosphorylase, liver form; Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. (850 aa) |
| | Sos1 | SOS Ras/Rac guanine nucleotide exchange factor 1. (1319 aa) |
| | Calml4 | RCG58306, isoform CRA_b. (153 aa) |
| | Pygb | Glycogen phosphorylase, brain form; Glycogen phosphorylase that regulates glycogen mobilization (By similarity). Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. (846 aa) |
| | LOC100911372 | 40S ribosomal protein S6; May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA. (247 aa) |
| | Prkaa2 | 5'-AMP-activated protein kinase catalytic subunit alpha-2; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (552 aa) |
| | Shc2 | SHC-transforming protein 2; Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons (By similarity). (573 aa) |
| | Shc4 | SHC adaptor protein 4. (622 aa) |
| | Socs2 | Suppressor of cytokine signaling 2; SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). (241 aa) |
| | Prkar2b | cAMP-dependent protein kinase type II-beta regulatory subunit; Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. (416 aa) |
| | Prkci | Protein kinase C iota type; Calcium- and diacylglycerol-independent serine/ threonine- protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process [...] (596 aa) |
| | Exoc7 | Exocyst complex component 7; Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. In adipocytes, plays a crucial role in targeting SLC2A4 vesicle to the plasma membrane in response to insulin, perhaps directing the vesicle to the precise site of fusion (By similarity); Belongs to the EXO70 family. (653 aa) |
| | Elk1 | ETS domain-containing protein Elk-1; Transcription factor that binds to purine-rich DNA sequences. Forms a ternary complex with SRF and the ETS and SRF motifs of the serum response element (SRE) on the promoter region of immediate early genes such as FOS and IER2 (By similarity). Induces target gene transcription upon JNK-signaling pathway stimulation. (427 aa) |
| | Raf1 | RAF proto-oncogene serine/threonine-protein kinase; Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal- regulated kin [...] (648 aa) |
| | Map2k1 | Dual specificity mitogen-activated protein kinase kinase 1; Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine resid [...] (368 aa) |
| | Flot2 | Flotillin-2; May play a role in axon growth and regeneration. May be involved in epidermal cell adhesion and epidermal structure and function; Belongs to the band 7/mec-2 family. Flotillin subfamily. (428 aa) |
| | Mtor | Serine/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 (By similarity). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (By similarity). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (By similarity). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome [...] (2549 aa) |
| | Ptpn1 | Tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c- src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET (By similarity). (432 aa) |
| | Socs4 | Suppressor of cytokine signaling 4 (Predicted). (436 aa) |
| | Pde3b | cGMP-inhibited 3',5'-cyclic phosphodiesterase B; Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis (By similarity). (1111 aa) |
| | Ins1 | Insulin-1 A chain; Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. (110 aa) |
| | Tsc2 | Tuberin; In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (By similarity). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (By similarity). May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5. (1809 aa) |
| | Eif4ebp1 | Eukaryotic translation initiation factor 4E-binding protein 1; Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase a [...] (117 aa) |
| | Tsc1 | Hamartin; In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (By similarity). Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling. Acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (By similarity). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (By similarity). Competes wit [...] (1163 aa) |
| | Prkaa1 | 5'-AMP-activated protein kinase catalytic subunit alpha-1; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (559 aa) |
| | Foxo1 | Forkhead box protein O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalc [...] (649 aa) |
| | Shc3 | SHC-transforming protein 3; Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons (By similarity). (594 aa) |
| | Irs1 | Insulin receptor substrate 1; May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit. (1235 aa) |
| | Ppp1r3e | Protein phosphatase 1 regulatory subunit 3E; Acts as a glycogen-targeting subunit for PP1. PP1 is involved in glycogen metabolism and contributes to the activation of glycogen synthase leading to an increase in glycogen synthesis. (279 aa) |
| | Rhoq | Rho-related GTP-binding protein RhoQ; Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. May play a role in CFTR trafficking to the plasma membrane. Causes the formation of thin, actin-rich surface projections called filopodia. (205 aa) |
| | Prkcz | Protein kinase C zeta type; Calcium- and diacylglycerol-independent serine/threonine- protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Req [...] (592 aa) |
| | Pik3cb | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation [...] (1070 aa) |
| | Hras | GTPase HRas, N-terminally processed; Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. (189 aa) |
| | Calm3 | Calmodulin-1; Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium- dependent inactivation of CACNA1C. Positively regulates calcium- activated potassium channel activity of KCNN2. (149 aa) |
| | Slc2a4 | Solute carrier family 2, facilitated glucose transporter member 4; Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells. Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell ; Belongs to the major facilitator superfamily. Sugar transporte [...] (509 aa) |
| | Prkag3 | Protein kinase, AMP-activated, gamma 3 non-catatlytic subunit (Predicted). (493 aa) |
| | Fbp1 | Fructose-1,6-bisphosphatase 1; Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism [...] (363 aa) |
| | Fbp2 | Fructose-1,6-bisphosphatase isozyme 2; Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate. (339 aa) |
| | Ppp1r3c | Protein phosphatase 1 regulatory subunit 3C; Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown. Dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression in a variety of cell types (By similarity). (317 aa) |
| | Ppp1ca | Serine/threonine-protein phosphatase PP1-alpha catalytic subunit; Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin de [...] (330 aa) |
| | Akt2 | RAC-beta serine/threonine-protein kinase; AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinases, 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 [...] (481 aa) |
| | Phkg2 | Phosphorylase b kinase gamma catalytic chain, liver/testis isoform; Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM. (406 aa) |
| | Pik3r1 | Phosphatidylinositol 3-kinase regulatory subunit alpha; Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling. Modulates the cellular response to ER stress by promoting nuclear translocation [...] (724 aa) |
| | Ikbkb | Inhibitor of nuclear factor kappa-B kinase subunit beta; 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 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is transloca [...] (757 aa) |
| | Pik3r2 | Phosphatidylinositol 3-kinase regulatory subunit beta; Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein- tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating t [...] (722 aa) |
| | Map2k2 | Dual specificity mitogen-activated protein kinase kinase 2; Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (By similarity). (400 aa) |
| | Ins2 | Insulin-2 A chain; Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. (110 aa) |
| | Pklr | Pyruvate kinase PKLR; Plays a key role in glycolysis. (574 aa) |
| | Lipe | Hormone-sensitive lipase; In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production; Belongs to the 'GDXG' lipolytic enzyme family. (1068 aa) |
| | G6pc | Glucose-6-phosphatase; Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production through glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels (By similarity). Belongs to the glucose-6-phosphatase family. (357 aa) |
| | Shc1 | SHC-transforming protein 1; Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis (By similarity). (579 aa) |
| | Gys1 | Glycogen [starch] synthase, muscle; Transfers the glycosyl residue from UDP-Glc to the non- reducing end of alpha-1,4-glucan; Belongs to the glycosyltransferase 3 family. (738 aa) |
| | G6pc3 | Glucose-6-phosphatase 3; Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function (By similarity). (346 aa) |
| | Pygm | Glycogen phosphorylase, muscle form; Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. (842 aa) |
| | Bad | Bcl2-associated agonist of cell death; Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways. (205 aa) |
| | Rps6kb2 | Ribosomal protein S6 kinase; Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily. (485 aa) |
| | Pck1 | Phosphoenolpyruvate carboxykinase, cytosolic [GTP]; Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle. At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate. (622 aa) |
| | Prkar1b | cAMP-dependent protein kinase type I-beta regulatory subunit. (358 aa) |
| | Nras | GTPase NRas; Ras proteins bind GDP/GTP and possess intrinsic GTPase activity; Belongs to the small GTPase superfamily. Ras family. (189 aa) |
| | Irs2 | Insulin receptor substrate 2. (1327 aa) |
| | Akt1 | RAC-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) |
| | Mknk2 | MAP kinase-interacting serine/threonine-protein kinase 2; Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A- inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during sp [...] (459 aa) |
| | Phkb | Phosphorylase b kinase regulatory subunit; Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. Belongs to the phosphorylase b kinase regulatory chain family. (1100 aa) |
| | Ppp1r3b | Protein phosphatase 1 regulatory subunit 3B; Acts as a glycogen-targeting subunit for phosphatase PP1. Facilitates interaction of the PP1 with enzymes of the glycogen metabolism and regulates its activity. Suppresses the rate at which PP1 dephosphorylates (inactivates) glycogen phosphorylase and enhances the rate at which it activates glycogen synthase and therefore limits glycogen breakdown. Its activity is inhibited by PYGL, resulting in inhibition of the glycogen synthase and glycogen phosphorylase phosphatase activities of PP1. Dramatically increases basal and insulin-stimulated gl [...] (284 aa) |
| | Calml3 | Calmodulin-like protein 3; May function as a specific light chain of unconventional myosin-10 (MYO10), also enhances MYO10 translation, possibly by acting as a chaperone for the emerging MYO10 heavy chain protein. May compete with calmodulin by binding, with different affinities, to cellular substrates (By similarity). (149 aa) |
| | Prkaca | cAMP-dependent protein kinase catalytic subunit alpha; Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA and VASP. RORA is activated by phosphorylation. Required for glucose- mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the [...] (351 aa) |
| | Ppp1cc | Serine/threonine-protein phosphatase PP1-gamma catalytic subunit; Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density- asso [...] (337 aa) |
| | Araf | Serine/threonine-protein kinase A-Raf; Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade (By similarity). (604 aa) |
| | Insr | Insulin receptor subunit alpha; Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lea [...] (1384 aa) |
| | Srebf1 | Processed sterol regulatory element-binding protein 1; Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'- ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC- 3'). (1134 aa) |
| | Inpp5a | Inositol polyphosphate-5-phosphatase A (Predicted), isoform CRA_a. (412 aa) |
| | Inppl1 | Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2; Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways. Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear. While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling [...] (1022 aa) |
| | Pik3cd | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit. (944 aa) |
| | Pdpk1 | 3-phosphoinositide-dependent protein kinase 1; Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central rol [...] (559 aa) |
| | Mapk8 | Mitogen-activated protein kinase 8; Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress- activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as J [...] (427 aa) |
| | Prkacb | cAMP-dependent protein kinase catalytic subunit beta; Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subu [...] (351 aa) |
| | Prkag2 | Protein kinase AMP-activated non-catalytic subunit gamma 2. (566 aa) |
| | Cbl | Cbl proto-oncogene. (914 aa) |
| | Phka2 | Phosphorylase b kinase regulatory subunit; Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. Belongs to the phosphorylase b kinase regulatory chain family. (511 aa) |
| | Rheb | GTP-binding protein Rheb; Activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Has low intrinsic GTPase activity. Belongs to the small GTPase superfamily. Rheb family. (183 aa) |
| | Fasn | 3-hydroxyacyl-[acyl-carrier-protein] dehydratase; Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein. (2505 aa) |
| | Prkar1a | cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed; Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. (381 aa) |
| | Phka1 | Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform; Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin. (1241 aa) |
| | Ptprf | Receptor-type tyrosine-protein phosphatase F; Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity. (1904 aa) |
| | Ppp1r3d | Protein phosphatase 1 regulatory subunit. (279 aa) |
| | Hk3 | Hexokinase-3; Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D- fructose 6-phosphate, respectively). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate. (963 aa) |
| | Prkab2 | 5'-AMP-activated protein kinase subunit beta-2; Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a reg [...] (271 aa) |
| | Akt3 | RAC-gamma serine/threonine-protein kinase; AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial fo [...] (474 aa) |
| | Mapk3 | Mitogen-activated protein kinase 3; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays a [...] (380 aa) |
| | Flot1 | Flotillin-1; May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. (428 aa) |
| | Ppp1r3a | Similar to type 1 protein phosphatase targeting subunit RGL/GM (Predicted). (1096 aa) |
| | G6pc2 | Uncharacterized protein. (170 aa) |
| | Pik3ca | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology (By similarity). Participates in cel [...] (1068 aa) |
| | Mknk1 | MAP kinase-interacting serine/threonine-protein kinase 1; May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine- containing mRNA cap (By similarity). (419 aa) |
| | Acaca | Acetyl-CoA carboxylase 1; Cytosolic enzyme that catalyzes the carboxylation of acetyl- CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. This is a 2 steps reaction starting with the ATP- dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. (2227 aa) |
| | LOC685590 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit. (1063 aa) |
| | Eif4e | Eukaryotic translation initiation factor 4E; Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E- FMR1 complex this subunit mediates the binding to the mRNA cap (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell [...] (217 aa) |
| | Cblb | E3 ubiquitin-protein ligase CBL-B; E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs [...] (982 aa) |
| | Gys2 | Glycogen [starch] synthase, liver; Transfers the glycosyl residue from UDP-Glc to the non- reducing end of alpha-1,4-glucan; Belongs to the glycosyltransferase 3 family. (704 aa) |
| | Eif4e2 | Eukaryotic translation initiation factor 4E family member 2; Belongs to the eukaryotic initiation factor 4E family. (256 aa) |
| | Gsk3b | Glycogen synthase kinase-3 beta; Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glyc [...] (430 aa) |
| | Mapk10 | Mitogen-activated protein kinase 10; Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF [...] (426 aa) |
