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Enc1 | Ectoderm-neural cortex protein 1; Actin-binding protein involved in the regulation of neuronal process formation and in differentiation of neural crest cells. Down- regulates transcription factor NF2L2/NRF2 by decreasing the rate of protein synthesis and not via a ubiquitin-mediated proteasomal degradation mechanism (By similarity). (589 aa) | ||||
Cops4 | COP9 signalosome complex subunit 4; Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 (By similarity). Also involved in the deneddylation of non-cullin subunits such as STON2 (By similarity). The complex is also involved in phosphorylation of p53 [...] (406 aa) | ||||
Btbd10 | BTB/POZ domain-containing protein 10; Plays a major role as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated. Plays a role in preventing motor neuronal death and in accelerating the growth of pancreatic beta cells. (475 aa) | ||||
Flnc | Filamin-C; Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers. (2726 aa) | ||||
Nudcd3 | NudC domain-containing protein 3. (363 aa) | ||||
Rhobtb1 | Rho-related BTB domain-containing protein 1. (695 aa) | ||||
Itgam | Integrin alpha-M; Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens (By similarity). It is identical with CR-3, the receptor for the iC3b fragment of the third complement component. It probably recognizes the R-G-D peptide in C3b. Integrin ITGAM/ITGB2 is also a receptor for fibrinogen, factor X and ICAM1. It recognizes P1 and P2 peptides of fibrinogen gamma chain. Regulates neutrophil migration. In association with beta subunit ITGB2/CD18, require [...] (1154 aa) | ||||
Wnk1 | Serine/threonine-protein kinase WNK1; Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thia [...] (2635 aa) | ||||
Akt1 | RAC-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) | ||||
Klhl21 | Kelch-like protein 21; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome (By similarity). (597 aa) | ||||
Kctd20 | BTB/POZ domain-containing protein KCTD20; Promotes the phosphorylation of AKT family members. (419 aa) | ||||
Klhl25 | Kelch-like protein 25; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for translational homeostasis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. The BCR(KLHL25) complex does not target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated with eIF4E. (589 aa) | ||||
Keap1 | Kelch-like ECH-associated protein 1; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine [...] (624 aa) | ||||
Gapdh | Glyceraldehyde-3-phosphate dehydrogenase; Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubu [...] (359 aa) | ||||
Pxdn | Peroxidasin homolog; Displays low peroxidase activity and is likely to participate in H(2)O(2) metabolism and peroxidative reactions in the cardiovascular system (By similarity). Plays a role in extracellular matrix formation. (1475 aa) | ||||
Cops7b | COP9 signalosome complex subunit 7b; Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF- type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-de [...] (264 aa) | ||||
Cops7a | COP9 signalosome complex subunit 7a; Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF- type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-de [...] (277 aa) | ||||
Tnfaip1 | BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 2; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(TNFAIP1) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Its interaction with RHOB may regulate apoptosis. May enhance the PCNA- dependent DNA polymerase delta activity (By similarity). (316 aa) | ||||
Stk39 | STE20/SPS1-related proline-alanine-rich protein kinase; May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation. Phosphorylates RELT. (556 aa) | ||||
Wnk4 | Serine/threonine-protein kinase WNK4; Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-in [...] (1222 aa) | ||||
Uba3 | NEDD8-activating enzyme E1 catalytic subunit; Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down- regulates steroid receptor activity. Necessary for cell cycle progression. (462 aa) | ||||
Hsp90aa1 | Heat shock protein HSP 90-alpha; Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a ra [...] (733 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) | ||||
Rhoa | Transforming protein RhoA; Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (By similarity). [...] (193 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) | ||||
Cops6 | COP9 signalosome complex subunit 6; Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 (By similarity). The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with [...] (324 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) | ||||
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) | ||||
Usp25 | Ubiquitin carboxyl-terminal hydrolase 25; Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains (By similarity). (1055 aa) | ||||
Hsp90ab1 | Heat shock protein HSP 90-beta; Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co- chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interact [...] (724 aa) | ||||
Cops5 | COP9 signalosome complex subunit 5; Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Promotes the proteasomal degradation of BRSK2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, [...] (334 aa) | ||||
Klhl7 | Kelch-like protein 7; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. The BCR(KLHL7) complex acts by mediating ubiquitination and subsequent degradation of substrate proteins. Probably mediates 'Lys-48'-linked ubiquitination (By similarity). (586 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) | ||||
Klhl2 | Kelch-like protein 2; Promotes growth of cell projections in oligodendrocyte precursors. Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4 (By similarity). Component of a cullin- RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation. Plays a role in the reorganization of the actin cytoskeleton. (593 aa) | ||||
Nae1 | NEDD8-activating enzyme E1 regulatory subunit; Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation (By similarity); Belongs to the ubiquitin-activating E1 family. ULA1 subfamily. (534 aa) | ||||
Cops8 | COP9 signalosome complex subunit 8; Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF- type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN- [...] (209 aa) | ||||
Zup1 | Zinc finger-containing ubiquitin peptidase 1; Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains. Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress. (566 aa) | ||||
Usp28 | Ubiquitin carboxyl-terminal hydrolase 28; Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically intera [...] (1051 aa) |