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| RB1CC1 | RB1-inducible coiled-coil protein 1; Involved in autophagy. Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1. Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their [...] (1594 aa) | |||
| TRAF2 | TNF receptor-associated factor 2; Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes ’Lys-63’- linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin- protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein level [...] (501 aa) | |||
| SESN2 | Sestrin-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) | |||
| VHL | Von Hippel-Lindau disease tumor suppressor; Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia- inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2; Belongs to the VHL family (213 aa) | |||
| SMARCB1 | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1; Core component of the BAF (hSWI/SNF) complex. This ATP- dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric struct [...] (385 aa) | |||
| TP53 | Cellular 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. In cooperation with mitochondrial PPIF is involved in [...] (393 aa) | |||
| LONP2 | Lon protease homolog 2, peroxisomal; ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import (By similarity). May indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1; AAA ATPases (852 aa) | |||
| ULK1 | Serine/threonine-protein kinase ULK1; Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3- kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy- acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, lead [...] (1050 aa) | |||
| TBK1 | Serine/threonine-protein kinase TBK1; Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form s [...] (729 aa) | |||
| ATG101 | Autophagy-related protein 101; Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation; Belongs to the ATG101 family (218 aa) | |||
| PTK2 | Focal adhesion kinase 1; Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required f [...] (1065 aa) | |||
| DYRK2 | Dual specificity tyrosine-phosphorylation-regulated kinase 2; Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at ’Ser-46’, and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosp [...] (601 aa) | |||
| CTNNB1 | Catenin 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) | |||
| MAP3K5 | Mitogen-activated protein kinase kinase kinase 5; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Me [...] (1374 aa) | |||
| RFWD2 | E3 ubiquitin-protein ligase RFWD2; E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activit [...] (731 aa) | |||
| ATG5 | Autophagy protein 5; Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is esse [...] (275 aa) | |||
| PINK1 | Serine/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) | |||
| SKI | Ski oncogene; May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Functions as a repressor of TGF-beta signaling; Belongs to the SKI family (728 aa) | |||
| ATG16L1 | Autophagy-related protein 16-1; Plays an essential role in autophagy- interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane. Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production. Negatively regulates NOD1- and NOD2- driven inflammatory cytokine response. Plays a role in regulating morphology and function of Paneth cell; Belongs to the W [...] (607 aa) | |||
| ULK2 | Serine/threonine-protein kinase ULK2; Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3- kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy- acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG [...] (1036 aa) | |||
| PTK2B | Protein-tyrosine kinase 2-beta; Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T- cells, and contributes to the regulation of T-cell responses. Promo [...] (1009 aa) | |||
| SKIL | Ski-like protein; May have regulatory role in cell division or differentiation in response to extracellular signals; Belongs to the SKI family (684 aa) | |||
| ATG13 | Autophagy-related protein 13; Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1- RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation (550 aa) | |||
| UBC | Polyubiquitin-C; Ubiquitin- Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked- Lys-6-linked may be involved in DNA repair; [...] (685 aa) | |||
| RNF111 | E3 ubiquitin-protein ligase Arkadia; E3 ubiquitin-protein ligase. Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP. In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and [...] (995 aa) | |||
| C9orf72 | Guanine nucleotide exchange C9orf72; Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation. The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and modulating its protein kinase activity. Positively [...] (481 aa) | |||
