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Tnf | Tumor 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 (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces [...] (235 aa) | ||||
Rela | Transcription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kap [...] (549 aa) | ||||
Cdk2 | Cyclin-dependent kinase 2; Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK [...] (346 aa) | ||||
Pcna | Proliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'- phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA rep [...] (261 aa) | ||||
Lmna | Prelamin-A/C; Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation. Required for osteoblastogenesis and bone formation. A [...] (665 aa) | ||||
Ing3 | Inhibitor of growth protein 3; Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicat [...] (421 aa) | ||||
Ing4 | Inhibitor of growth protein 4; Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact [...] (248 aa) | ||||
Sap30 | Histone deacetylase complex subunit SAP30; Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones; Belongs to the SAP30 family. (220 aa) | ||||
Kat6a | Histone acetyltransferase KAT6A; Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2 (By similarity). Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML (By similarity). (2003 aa) | ||||
Gadd45a | Growth arrest and DNA damage-inducible protein GADD45 alpha; Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase. In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity. Belongs to the GADD45 family. (165 aa) | ||||
Polr2a | DNA-directed RNA polymerase II subunit RPB1; DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cl [...] (1970 aa) | ||||
Ccnb1 | G2/mitotic-specific cyclin-B1; Essential for the control of the cell cycle at the G2/M (mitosis) transition; Belongs to the cyclin family. Cyclin AB subfamily. (430 aa) | ||||
H3c7 | Histone 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) | ||||
Ing2 | Inhibitor of growth protein 2; Seems to be involved in p53/TP53 activation and p53/TP53- dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53. Component of a mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity seems to be modulated by binding to phosphoinositides (PtdInsPs) (By similarity); Belongs to the ING family. (281 aa) | ||||
H3c8 | Histone 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) | ||||
H4c11 | Histone H4; 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. (103 aa) | ||||
Map3k4 | Mitogen-activated protein kinase kinase kinase 4; Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. (1597 aa) | ||||
Ccnd1 | G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (295 aa) | ||||
Hdac1 | Histone deacetylase 1; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium st [...] (482 aa) | ||||
H3f3b | Histone 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) | ||||
Kat7 | Histone acetyltransferase KAT7; Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Involved in H3K14 (histone H3 lysine 14) acetylation and cell proliferation. Through chromatin acetylation it may regulate DNA replication and act as a coactivator of TP53-dependent transcription. Acts as a coactivator of the licensing factor CDT1. Specifically represses AR-mediated transcription; Belongs to the MYST (SAS/MOZ) family. (611 aa) | ||||
Ccne1 | G1/S-specific cyclin-E1; Essential for the control of the cell cycle at the G1/S (start) transition. (408 aa) | ||||
Trp53 | 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. Its pro-apoptotic activity is activated via its intera [...] (390 aa) | ||||
Kat5 | Histone acetyltransferase KAT5; Catalytic subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (By similarity). This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (By similarity). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor me [...] (513 aa) | ||||
Jade1 | Protein Jade-1; Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Transcriptional coactivator, it may also promote acetylation of nucleosomal histone H4 by KAT5. Promotes apoptosis. May act as a renal tumor suppressor. Negatively regulates canonical Wnt signaling; at least in part, cooperates with NPHP4 in this function (By similarity). Belongs to the JADE family. (834 aa) | ||||
Sin3a | Paired amphipathic helix protein Sin3a; Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates wi [...] (1277 aa) | ||||
Hspa1b | Heat shock 70 kDa protein 1B; Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and AD [...] (642 aa) | ||||
Casp8 | Caspase-8 subunit p10; Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CA [...] (500 aa) | ||||
Cdkn1a | Cyclin-dependent kinase inhibitor 1; May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin- dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D- CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 [...] (159 aa) | ||||
Mapk14 | Mitogen-activated protein kinase 14; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are a [...] (360 aa) | ||||
Myc | Myc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release. (454 aa) | ||||
Rad50 | DNA repair protein RAD50; Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease [...] (1312 aa) | ||||
Mdm2 | E3 ubiquitin-protein ligase Mdm2; E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73- mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity). Also acts as a ubiquitin ligase E3 toward itself, ARRB1 and ARBB2. Permits the nuclear export of p53/TP53 (By similarity). Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein (By similarity). Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and [...] (489 aa) | ||||
Ywhah | 14-3-3 protein eta; Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1 (By similarity). (246 aa) | ||||
Twsg1 | Twisted gastrulation protein homolog 1; May be involved in dorsoventral axis formation. Seems to antagonize BMP signaling by forming ternary complexes with CHRD and BMPs, thereby preventing BMPs from binding to their receptors. In addition to the anti-BMP function, also has pro-BMP activity, partly mediated by cleavage and degradation of CHRD, which releases BMPs from ternary complexes. May be an important modulator of BMP-regulated cartilage development and chondrocyte differentiation. May play a role in thymocyte development. (222 aa) | ||||
Mmp13 | Collagenase 3; Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bon [...] (472 aa) |