Search Results (2 kinases found)
Gene name
Organism
Protein name
CDK5
Human
Cyclin-dependent-like kinase 5
- Organism
- Human (Homo sapiens)
- Uniprot ID
- CDK5_HUMAN
- Accession #
- Q00535
- Protein names
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- Cyclin-dependent-like kinase 5
- EC 2.7.11.1
- Cell division protein kinase 5
- Serine/threonine-protein kinase PSSALRE
- Tau protein kinase II catalytic subunit
- TPKII catalytic subunit
- Gene names
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- CDK5
- CDKN5
- Description
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Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000269|PubMed:12393264, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15992363, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17121855, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17611284, ECO:0000269|PubMed:17671990, ECO:0000269|PubMed:18042622, ECO:0000269|PubMed:19081376, ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:20061803, ECO:0000269|PubMed:20213743, ECO:0000269|PubMed:20826806, ECO:0000269|PubMed:21209322, ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:21465480, ECO:0000269|PubMed:21499257, ECO:0000269|PubMed:24235147, ECO:0000269|PubMed:9822744}.
- Links
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Search Substrates of CDK5 (Human)
- ATP binding
- ErbB-2 class receptor binding
- ErbB-3 class receptor binding
- Hsp90 protein binding
- Schaffer collateral - CA1 synapse
- Schwann cell development
- acetylcholine receptor activator activity
- axon
- axon extension
- axonogenesis
- behavioral response to cocaine
- calcium ion import
- cell division
- cell junction
- cell-matrix adhesion
- cellular response to amyloid-beta
- central nervous system neuron development
- cerebellar cortex formation
- chemical synaptic transmission
- corpus callosum development
- cortical actin cytoskeleton organization
- cyclin-dependent protein serine/threonine kinase activity
- cytoplasm
- cytosol
- dendrite
- dendrite morphogenesis
- ephrin receptor binding
- excitatory postsynaptic potential
- filopodium
- glutamatergic synapse
- growth cone
- hippocampus development
- histone phosphorylation
- intracellular protein transport
- kinase activity
- lamellipodium
- layer formation in cerebral cortex
- membrane
- microtubule
- microtubule cytoskeleton organization
- mitochondrion organization
- motor neuron axon guidance
- negative regulation of axon extension
- negative regulation of cell cycle
- negative regulation of neuron death
- negative regulation of protein export from nucleus
- negative regulation of protein ubiquitination
- negative regulation of proteolysis
- negative regulation of synaptic plasticity
- negative regulation of transcription, DNA-templated
- neuromuscular junction
- neuron apoptotic process
- neuron differentiation
- neuron migration
- neuron projection
- neuron projection development
- neuronal cell body
- nucleocytoplasmic transport
- nucleoplasm
- nucleus
- oligodendrocyte differentiation
- p53 binding
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- perikaryon
- phosphorylation
- plasma membrane
- positive regulation of actin cytoskeleton reorganization
- positive regulation of calcium ion-dependent exocytosis
- positive regulation of glial cell apoptotic process
- positive regulation of neuron apoptotic process
- positive regulation of protein binding
- positive regulation of protein kinase activity
- positive regulation of protein targeting to membrane
- positive regulation of voltage-gated calcium channel activity
- postsynaptic density
- presynapse
- protein autophosphorylation
- protein kinase 5 complex
- protein kinase activity
- protein kinase binding
- protein localization to synapse
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- receptor catabolic process
- receptor clustering
- regulation of apoptotic process
- regulation of cell migration
- regulation of dendritic spine morphogenesis
- regulation of macroautophagy
- regulation of protein localization to plasma membrane
- regulation of signal transduction by p53 class mediator
- regulation of synaptic plasticity
- regulation of synaptic transmission, glutamatergic
- regulation of synaptic vesicle recycling
- regulation of transcription involved in G1/S transition of mitotic cell cycle
- response to wounding
- rhythmic process
- sensory perception of pain
- serine phosphorylation of STAT protein
- skeletal muscle tissue development
- synapse assembly
- synapse pruning
- synaptic transmission, dopaminergic
- synaptic transmission, glutamatergic
- synaptic vesicle endocytosis
- synaptic vesicle exocytosis
- synaptic vesicle transport
- tau protein binding
- tau-protein kinase activity
- visual learning
- voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels
GSK3B
Human
Glycogen synthase kinase-3 beta
- Organism
- Human (Homo sapiens)
- Uniprot ID
- GSK3B_HUMAN
- Accession #
- P49841
- Protein names
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- Glycogen synthase kinase-3 beta
- GSK-3 beta
- EC 2.7.11.26
- Serine/threonine-protein kinase GSK3B
- EC 2.7.11.1
- Gene names
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- GSK3B
- Description
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Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). {ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.
- Links
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Search Substrates of GSK3B (Human)
- Alzheimer disease
- Axon guidance
- B cell receptor signaling pathway
- Basal cell carcinoma
- Breast cancer
- Cell cycle
- Chemokine signaling pathway
- Colorectal cancer
- Cushing syndrome
- Diabetic cardiomyopathy
- Dopaminergic synapse
- EGFR tyrosine kinase inhibitor resistance
- Endometrial cancer
- ErbB signaling pathway
- Focal adhesion
- Gastric cancer
- Growth hormone synthesis, secretion and action
- Hedgehog signaling pathway
- Hepatitis C
- Hepatocellular carcinoma
- Hippo signaling pathway
- Human cytomegalovirus infection
- Human papillomavirus infection
- IL
- Insulin resistance
- Insulin signaling pathway
- Kaposi sarcoma
- Lipid and atherosclerosis
- Measles
- Melanogenesis
- Neurotrophin signaling pathway
- Non
- PI3K
- Pathways in cancer
- Pathways of neurodegeneration
- Prion disease
- Prolactin signaling pathway
- Prostate cancer
- Shigellosis
- Signaling pathways regulating pluripotency of stem cells
- T cell receptor signaling pathway
- Thyroid hormone signaling pathway
- Wnt signaling pathway
- Yersinia infection
- mTOR signaling pathway
- ATP binding
- ER overload response
- NF-kappaB binding
- Wnt signaling pathway
- Wnt signalosome
- axon
- beta-catenin binding
- beta-catenin destruction complex
- beta-catenin destruction complex assembly
- beta-catenin destruction complex disassembly
- cellular response to amyloid-beta
- cellular response to interleukin-3
- centrosome
- circadian rhythm
- cytoplasm
- cytosol
- dendrite
- dopamine receptor signaling pathway
- dynactin binding
- epithelial to mesenchymal transition
- establishment of cell polarity
- excitatory postsynaptic potential
- extrinsic apoptotic signaling pathway
- extrinsic apoptotic signaling pathway in absence of ligand
- glutamatergic synapse
- glycogen metabolic process
- hippocampus development
- insulin receptor signaling pathway
- intracellular signal transduction
- kinase activity
- maintenance of cell polarity
- mitochondrion
- negative regulation of apoptotic process
- negative regulation of calcineurin-NFAT signaling cascade
- negative regulation of canonical Wnt signaling pathway
- negative regulation of dopaminergic neuron differentiation
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of glycogen (starch) synthase activity
- negative regulation of glycogen biosynthetic process
- negative regulation of neuron death
- negative regulation of phosphoprotein phosphatase activity
- negative regulation of protein acetylation
- negative regulation of protein binding
- negative regulation of protein localization to nucleus
- negative regulation of protein-containing complex assembly
- negative regulation of type B pancreatic cell development
- neuron projection development
- neuron projection organization
- nucleoplasm
- nucleus
- p53 binding
- peptidyl-serine phosphorylation
- peptidyl-threonine phosphorylation
- plasma membrane
- positive regulation of GTPase activity
- positive regulation of autophagy
- positive regulation of cell-matrix adhesion
- positive regulation of gene expression
- positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
- positive regulation of mitochondrion organization
- positive regulation of neuron death
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- positive regulation of protein binding
- positive regulation of protein catabolic process
- positive regulation of protein export from nucleus
- positive regulation of protein localization to centrosome
- positive regulation of protein-containing complex assembly
- postsynapse
- protease binding
- protein autophosphorylation
- protein kinase A catalytic subunit binding
- protein kinase activity
- protein kinase binding
- protein phosphorylation
- protein serine kinase activity
- protein serine/threonine kinase activity
- regulation of axon extension
- regulation of axonogenesis
- regulation of cellular response to heat
- regulation of circadian rhythm
- regulation of dendrite morphogenesis
- regulation of long-term synaptic potentiation
- regulation of microtubule anchoring at centrosome
- regulation of microtubule cytoskeleton organization
- regulation of microtubule-based process
- regulation of neuron projection development
- regulation of synaptic vesicle exocytosis
- signal transduction
- superior temporal gyrus development
- tau protein binding
- tau-protein kinase activity
- ubiquitin protein ligase binding
- viral protein processing