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| CRY1 | Cryptochrome-1; Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time- keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots ’circa’ (about) and ’diem’ (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and rena [...] (586 aa) | |||
| KCNQ1 | Potassium voltage-gated channel subfamily KQT member 1; Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity). Associates with KCNE beta subunits that modulates current kinetics (By similarity). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta- adrenergic receptor stimulation participates in cardiac [...] (676 aa) | |||
| TAB1 | TGF-beta-activated kinase 1 and MAP3K7-binding protein 1; May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis (504 aa) | |||
| AURKA | Aurora kinase A; Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDE [...] (403 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) | |||
| 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) | |||
| CCNA1 | Cyclin-A1; May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells; Belongs to the cyclin family. Cyclin AB subfamily (465 aa) | |||
| RIPK1 | Receptor-interacting serine/threonine-protein kinase 1; Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at ’Ser-728’ in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via ’Lys-63’-link chains acts as a critical enhancer of communication with do [...] (671 aa) | |||
| USP2 | Ubiquitin carboxyl-terminal hydrolase 2; Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Regulates the circadian [...] (605 aa) | |||
| BIRC3 | Baculoviral IAP repeat-containing protein 3; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions- acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins [...] (604 aa) | |||
| ZAP70 | Tyrosine-protein kinase ZAP-70; Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated T [...] (619 aa) | |||
| RPS27A | Ubiquitin-40S ribosomal protein S27a; 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 inv [...] (156 aa) | |||
| FADD | FAS-associated death domain protein; Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling; Death effector domain containing (208 aa) | |||
| UBB | Polyubiquitin-B; 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; [...] (229 aa) | |||
| RNF31 | E3 ubiquitin-protein ligase RNF31; E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear (’Met-1’-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF- [...] (1072 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) | |||
| TAB2 | TGF-beta-activated kinase 1 and MAP3K7-binding protein 2; Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of ’Lys-63’- linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at ’Thr-187’. Involved in heart development; Zinc fingers RANBP2-type (693 aa) | |||
| XIAP | E3 ubiquitin-protein ligase XIAP; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligas [...] (497 aa) | |||
| TAB3 | TGF-beta-activated kinase 1 and MAP3K7-binding protein 3; Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator of MAP3K7 activation, respectively in the IL1 and TNF signaling pathways. Plays a role in activation of NF-kappa-B and AP1 transcription factor. Isoform 2 may be an oncogenic factor; Zinc fingers RANBP2-type (712 aa) | |||
| SHARPIN | Sharpin; Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC c [...] (387 aa) | |||
| UBA52 | Ubiquitin-60S ribosomal protein L40; 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 invo [...] (128 aa) | |||
| TNF | Tumor necrosis factor; 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 (PP1), which de [...] (233 aa) | |||
| TRAF6 | TNF receptor-associated factor 6; E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of ’Lys-63’-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation. Leads to the activation of NF-kappa-B and JUN. May be essential for the formation of functional osteoclasts. Seems to also play a role in dendritic cells (DCs) maturation and/or activation. Represses c- Myb-mediated transactivation, in B-lymphocytes. Adapter protein that see [...] (522 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) | |||
| UBBP4 | Ubiquitin B pseudogene 4 (229 aa) | |||
| BIRC2 | Baculoviral IAP repeat-containing protein 2; Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions- acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target protein [...] (618 aa) | |||
