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 138
Pathways Dopaminergic Synapse
Inhibitors 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide; N-[6,6-dimethyl-5-[(1-methyl-4-piperidinyl)-oxomethyl]-1,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide; alvocidib; Dinaciclib; alvocidib hydrochloride; seliciclib
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 0.359
Publications: 1
+ down-regulates quantity img/direct_inhibition.png phosphorylation GRIN2B 0.448
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ERBB3 0.341
Publications: 2 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation RAPGEF2 0.394
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NOS3 0.374
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTT 0.451
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GRIN2A 0.529
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 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PRKN 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates activity img/direct-activation.png phosphorylation PLD2 0.371
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PLD2 0.371
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LMTK2 0.501
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation TP53 0.732
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DNMT1 0.361
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.299
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.551
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation TPPP 0.407
Publications: 3 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation NDEL1 0.772
Publications: 3 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation NR3C1 0.478
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.763
Publications: 4 Organism: Homo Sapiens
+ img/unknown.png phosphorylation AMPH 0.525
Publications: 3 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation PPARG 0.579
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AGAP2 0.263
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 0.739
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 0.387
Publications: 1 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation HTR6 0.376
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.38
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTRA2 0.459
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2A 0.509
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TLN1 0.461
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TPX2 0.274
Publications: 1 Organism: Homo Sapiens
Tissue: Hepatobiliary Carcinoma Cell
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation AMFR 0.248
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.763
Publications: 11 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DPYSL3 0.602
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL2 0.655
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.621
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SYN1 0.568
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DLC1 0.2
Publications: 4 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1L 0.468
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIP5K1C 0.365
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R1A 0.375
Publications: 1 Organism: Rattus Norvegicus
+ img/unknown.png phosphorylation STMN3 0.325
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.405
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Myotube, Brain
+ up-regulates img/direct-activation.png phosphorylation PTK2 0.307
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SRC 0.391
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1 0.52
Publications: 2 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation PARP1 0.259
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation ATM 0.419
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDK5R1 0.943
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RB1 0.337
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AR 0.374
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EPRS1 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ERBB4 0.279
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NES 0.551
Publications: 2 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPK10 0.346
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 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PAK1 0.535
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation APEX1 0.38
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation EZR 0.467
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BACE1 0.445
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation HTR1A 0.271
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates activity img/direct_inhibition.png phosphorylation PPP1CA 0.396
Publications: 2 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ up-regulates img/direct-activation.png phosphorylation PSEN1 0.514
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation PEBP1 0.339
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CORO1A 0.29
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CLOCK 0.33
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation KIF13B 0.368
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 0.36
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ADD1 0.256
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R2 0.357
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation APP 0.57
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R1B 0.777
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 0.582
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.604
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 0.943
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PP1 0.474
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding CDK5/CDK5R1 0.943
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CDK5 0.943
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
+ down-regulates img/direct_inhibition.png phosphorylation LMTK2 0.501
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRPV1 0.2
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