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| Usp7 | Ubiquitin carboxyl-terminal hydrolase 7; Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presen [...] (1103 aa) | ||||
| Hltf | Helicase-like transcription factor; Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity. This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'- linked polyubiquitination of chromatin-bound PCNA (By similarity). (1003 aa) | ||||
| Ube2m | NEDD8-conjugating enzyme Ubc12; Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation (By similarity). (183 aa) | ||||
| Nedd8 | NEDD8; Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. (81 aa) | ||||
| Cul4a | Cullin-4A; Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin- protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends [...] (759 aa) | ||||
| Ube2d1 | Ubiquitin-conjugating enzyme E2 D1; Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'- linked polyubiquitination. Mediates the selective degradation of short- lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto- ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. Ubiquitinates STUB1- associated HSP90AB1 in vitro. Lacks inherent specificity for any particular lysine residue of ubiquitin. Essential for viral activation of IRF3. Mediates pol [...] (147 aa) | ||||
| Cand1 | Cullin-associated NEDD8-dissociated protein 1; Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate- recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar [...] (1230 aa) | ||||
| Cdc34 | Ubiquitin-conjugating enzyme E2 R1; Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'- linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooper [...] (235 aa) | ||||
| Nfkbia | NF-kappa-B inhibitor alpha; Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription. (314 aa) | ||||
| Rbx1 | E3 ubiquitin-protein ligase RBX1, N-terminally processed; E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair. CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). The functional spec [...] (108 aa) | ||||
| Ifnar1 | Interferon alpha/beta receptor 1; Component of the receptor for type I interferons, including interferons alpha, IFNB1 and IFNW1. Functions in general as heterodimer with IFNAR2 (By similarity). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta- subunits themselves. Can form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway. Contributes to modulate the innate immune res [...] (590 aa) | ||||
| Psmb8 | Proteasome subunit beta type-8; The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. May participate in the inflammatory response pathway. Required for adipocyte differentiation. May be involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleava [...] (276 aa) | ||||
| Ddb1 | DNA damage-binding protein 1; Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6- 4 photoproducts (6-4 PP), apurinic sites and short mismatches (By similarity). Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which m [...] (1140 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) | ||||
| Cul1 | Cullin-1; Core component of multiple cullin-RING-based SCF (SKP1-CUL1- F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the [...] (776 aa) | ||||
| Ctrl | Chymotrypsin A CTRA-1; Belongs to the peptidase S1 family. (264 aa) | ||||
| Psmb10 | Proteasome subunit beta type-10; The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Plays a role in determining the T-cell repertoire for an antiviral T-cell response; Belongs to the peptidase T1B family. (273 aa) | ||||
| Bclaf1 | Bcl-2-associated transcription factor 1; Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA (By similarity). (919 aa) | ||||
| Adrm1 | Proteasomal ubiquitin receptor ADRM1; Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Within the complex, functions as a proteasomal ubiquitin receptor. Engag [...] (407 aa) | ||||
| Ifnb1 | Interferon beta; Has antiviral, antibacterial and anticancer activities; Belongs to the alpha/beta interferon family. (182 aa) | ||||
| Ifng | Interferon gamma; Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons. (155 aa) | ||||
| Jak2 | Tyrosine-protein kinase JAK2; Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors [...] (1132 aa) | ||||
| Sp100 | Nuclear autoantigen Sp-100; Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regul [...] (591 aa) | ||||
| Jak1 | Tyrosine-protein kinase JAK1; Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor. (1153 aa) | ||||
| Stat5a | Signal transducer and activator of transcription. (797 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) | ||||
| Skp1a | S-phase kinase-associated protein 1; Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC [...] (163 aa) | ||||
| Snx5 | Sorting nexin-5; Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-me [...] (404 aa) | ||||
| Cul4b | Cullin-4B; Core component of multiple cullin-RING-based E3 ubiquitin- protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and [...] (970 aa) | ||||
| Irf9 | Interferon regulatory factor 9; Transcription factor that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. (465 aa) | ||||
| Dda1 | DET1- and DDB1-associated protein 1; May be involved in ubiquitination and subsequent proteasomal degradation of target proteins. Component of the DDD-E2 complexes which may provide a platform for interaction with CUL4A and WD repeat proteins (By similarity); Belongs to the DDA1 family. (102 aa) | ||||
| Dcaf1 | DDB1- and CUL4-associated factor 1; Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine- protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin- protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds me [...] (1419 aa) | ||||
| Daxx | Death domain-associated protein 6; Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 throu [...] (740 aa) | ||||
| Cul3 | Cullin-3; Core component of multiple cullin-RING-based BCR (BTB-CUL3- RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (By similarity). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (By similarity). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhi [...] (768 aa) | ||||
| Psmb9 | Proteasome subunit beta type-9; The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Contributes to NFKBIA degradation and subsequently NFKB1 generation; Belongs to the peptidase T1B family. (219 aa) | ||||
| Tyk2 | Non-receptor tyrosine-protein kinase TYK2; Involved in intracellular signal transduction by amplifying type I and type II IFN signaling. Phosphorylates the interferon- alpha/beta receptor alpha chain. Plays an essential role in promoting selective immune responses, including innate host defense mechanisms and specific antiviral activities. (1207 aa) | ||||
| 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) | ||||
| Dnah8 | Dynein heavy chain 8, axonemal; Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly. (4731 aa) | ||||