STRINGSTRING
TSC2 TSC2 AKT1 AKT1 BCAT1 BCAT1 RPS6KB1 RPS6KB1 SESN1 SESN1 IL6 IL6 PPARA PPARA GAPDH GAPDH BCKDK BCKDK PIK3CD PIK3CD ACADSB ACADSB MTOR MTOR PXDNL PXDNL BCAT2 BCAT2 CASP3 CASP3 RPTOR RPTOR ALB ALB BCKDHA BCKDHA TP53 TP53 PIK3CA PIK3CA RHEB RHEB KRAS KRAS SESN2 SESN2 PXDN PXDN ACADS ACADS TNF TNF PIK3CB PIK3CB CTNNB1 CTNNB1 COX4I1 COX4I1 SESN3 SESN3 H2AX H2AX PIK3CG PIK3CG LAMP2 LAMP2
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:
TSC2Tuberin; 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. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). (1807 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)
BCAT1Branched-chain-amino-acid aminotransferase, cytosolic; Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. (398 aa)
RPS6KB1Ribosomal 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)
SESN1Sestrin-1; Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitatin [...] (551 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 [...] (212 aa)
PPARAPeroxisome proliferator-activated receptor alpha; Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn- glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and [...] (468 aa)
GAPDHGlyceraldehyde-3-phosphate dehydrogenase; Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations throu [...] (335 aa)
BCKDK[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial; Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex. (412 aa)
PIK3CDPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform; Phosphoinositide-3-kinase (PI3K) 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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell recepto [...] (1044 aa)
ACADSBShort/branched chain specific acyl-CoA dehydrogenase, mitochondrial; Has greatest activity toward short branched chain acyl-CoA derivative such as (s)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2- methylhexanoyl-CoA as well as toward short straight chain acyl-CoAs such as butyryl-CoA and hexanoyl-CoA. Can use valproyl-CoA as substrate and may play a role in controlling the metabolic flux of valproic acid in the development of toxicity of this agent. (432 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)
PXDNLPeroxidasin-like protein; [Isoform PMR1]: Endonuclease selectively degrading some target mRNAs while they are engaged by translating ribosomes, among which albumin and beta-globin mRNAs. (1463 aa)
BCAT2Branched-chain-amino-acid aminotransferase, mitochondrial; Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids. (392 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)
RPTORRegulatory-associated protein of mTOR; Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1- TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTO [...] (1335 aa)
ALBSerum albumin; Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc. Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific man [...] (609 aa)
BCKDHA2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial; The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). (445 aa)
TP53Cellular tumor antigen p53; Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its intera [...] (393 aa)
PIK3CAPhosphatidylinositol 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). 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. Participates in cellular signaling in response to v [...] (1068 aa)
RHEBGTP-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. (184 aa)
KRASGTPase KRas, N-terminally processed; Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation. Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner. (189 aa)
SESN2Sestrin-2; Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway. This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via TORC1. May positively regulate the transcripti [...] (480 aa)
PXDNPeroxidasin homolog; Displays low peroxidase activity and is likely to participate in H(2)O(2) metabolism and peroxidative reactions in the cardiovascular system. Plays a role in extracellular matrix formation. (1479 aa)
ACADSShort-chain specific acyl-CoA dehydrogenase, mitochondrial; Short-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (By similarity). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl- CoA (By similarity). Among the different mitochondrial ac [...] (412 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)
PIK3CBPhosphatidylinositol 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)
CTNNB1Catenin beta-1; Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an [...] (781 aa)
COX4I1Cytochrome c oxidase subunit 4 isoform 1, mitochondrial; Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol- cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives tran [...] (169 aa)
SESN3Sestrin-3; May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway. May also regulate the insulin-receptor signaling pathway through activation of TORC2 (By similarity). This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). (492 aa)
H2AXHistone H2AX; Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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. Required for checkpoint-mediated arrest of cell cycle progression in response to low dos [...] (143 aa)
PIK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; Phosphoinositide-3-kinase (PI3K) 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. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates [...] (1102 aa)
LAMP2Lysosome-associated membrane glycoprotein 2; Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live. Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation. Plays a role in lysosomal protein degradation in response to starvation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy. Cells that lack LAMP2 express normal levels o [...] (411 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (16%) [HD]