Summary

Name CDK5
Full Name Cyclin-dependent-like kinase 5
Synonyms Cell division protein kinase 5, Serine/threonine-protein kinase PSSALRE, Tau protein kinase II catalytic subunit, TPKII catalytic subunit | CDKN5
Primary ID Q00535
Links - -
Type protein
Relations 130
Pathways Dopaminergic Synapse
Inhibitors seliciclib; Dinaciclib; 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide; alvocidib hydrochloride; alvocidib; N-[6,6-dimethyl-5-[(1-methyl-4-piperidinyl)-oxomethyl]-1,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide
Function 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

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation VRK3 0.365
Publications: 1
+ up-regulates activity img/direct-activation.png phosphorylation ERBB3 0.346
Publications: 2 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation NOS3 0.38
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTT 0.46
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GRIN2A 0.541
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation CAMKK2 0.2
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PMAIP1 0.365
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PRKN 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ down-regulates activity img/direct_inhibition.png phosphorylation PLD2 0.377
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LMTK2 0.512
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation TP53 0.722
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DNMT1 0.367
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.303
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.535
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation TPPP 0.414
Publications: 3 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation NDEL1 0.764
Publications: 3 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation NR3C1 0.459
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.754
Publications: 4 Organism: Homo Sapiens
+ img/unknown.png phosphorylation AMPH 0.537
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation AGAP2 0.265
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation BAG3 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRIM59 0.2
Publications: 1
+ img/unknown.png phosphorylation CABLES1 0.73
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates quantity img/direct_inhibition.png phosphorylation PHACTR3 0.2
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png phosphorylation DRD2 0.393
Publications: 1 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation HTR6 0.382
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.386
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTRA2 0.468
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2A 0.521
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TLN1 0.471
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TPX2 0.277
Publications: 1 Organism: Homo Sapiens
Tissue: Hepatobiliary Carcinoma Cell
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation AMFR 0.25
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.754
Publications: 11 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DPYSL3 0.588
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL2 0.642
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.608
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SYN1 0.581
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DLC1 0.2
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIP5K1C 0.371
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R1A 0.381
Publications: 1 Organism: Rattus Norvegicus
+ img/unknown.png phosphorylation STMN3 0.329
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.413
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Myotube, Brain
+ up-regulates img/direct-activation.png phosphorylation PTK2 0.311
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SRC 0.398
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1 0.531
Publications: 2 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation PARP1 0.261
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation ATM 0.427
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDK5R1 0.942
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RB1 0.342
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AR 0.381
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EPRS1 0.2
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NES 0.564
Publications: 2 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPK10 0.351
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NFAT5 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIK3C3 0.365
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PAK1 0.519
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation APEX1 0.387
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation EZR 0.477
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation HTR1A 0.274
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates activity img/direct_inhibition.png phosphorylation PPP1CA 0.403
Publications: 2 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ up-regulates img/direct-activation.png phosphorylation PSEN1 0.526
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation PEBP1 0.344
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CORO1A 0.293
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CLOCK 0.335
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation KIF13B 0.374
Publications: 1 Organism: Cricetulus Griseus
+ down-regulates img/direct_inhibition.png phosphorylation STXBP2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PIK3C3 0.365
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ADD1 0.258
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R2 0.363
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation APP 0.584
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R1B 0.769
Publications: 1 Organism: Rattus Norvegicus
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation CDK5 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.567
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.59
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LMTK2 0.512
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CDK5 0.942
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding CDK5/CDK5R1 0.942
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding CDK5 0.942
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PP1 0.484
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens