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 114
Pathways Dopaminergic Synapse
Inhibitors alvocidib; Dinaciclib; alvocidib hydrochloride; N-[6,6-dimethyl-5-[(1-methyl-4-piperidinyl)-oxomethyl]-1,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide; seliciclib; 4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide
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 0.368
Publications: 1
+ up-regulates activity img/direct-activation.png phosphorylation ERBB3 0.347
Publications: 2 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation NOS3 0.384
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTT 0.467
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GRIN2A 0.546
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 0.369
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PRKN 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation LMTK2 0.516
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 0.37
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.53
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation TPPP 0.419
Publications: 3 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation NDEL1 0.765
Publications: 3 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation NR3C1 0.456
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.755
Publications: 4 Organism: Homo Sapiens
+ img/unknown.png phosphorylation AMPH 0.541
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation AGAP2 0.266
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRIM59 0.2
Publications: 1
+ 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 0.397
Publications: 1 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation HTR6 0.384
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.391
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTRA2 0.471
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2A 0.525
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TLN1 0.474
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TPX2 0.278
Publications: 1 Organism: Homo Sapiens
Tissue: Hepatobiliary Carcinoma Cell
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.755
Publications: 11 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DPYSL3 0.588
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.608
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL2 0.644
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SYN1 0.587
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIP5K1C 0.372
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R1A 0.385
Publications: 1 Organism: Rattus Norvegicus
+ img/unknown.png phosphorylation STMN3 0.332
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.418
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Myotube, Brain
+ up-regulates img/direct-activation.png phosphorylation PTK2 0.314
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SRC 0.399
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1 0.535
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation ATM 0.432
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDK5R1 0.941
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RB1 0.343
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AR 0.385
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 0.569
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 0.369
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PAK1 0.514
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation EZR 0.48
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation HTR1A 0.275
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates activity img/direct_inhibition.png phosphorylation PPP1CA 0.405
Publications: 2 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ up-regulates img/direct-activation.png phosphorylation PSEN1 0.53
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CORO1A 0.295
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CLOCK 0.338
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation KIF13B 0.378
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 0.369
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R2 0.363
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation APP 0.589
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R1B 0.77
Publications: 1 Organism: Rattus Norvegicus
Pathways:Dopaminergic Synapse
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.586
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.563
Publications: 1 Organism: Chlorocebus Aethiops
+ 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
+ up-regulates img/direct-activation.png binding CDK5 0.941
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LMTK2 0.516
Publications: 2 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 activity img/direct_inhibition.png phosphorylation PP1 0.487
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding CDK5 0.941
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 0.941
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens