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 183
Pathways Dopaminergic Synapse
Inhibitors alvocidib hydrochloride; seliciclib; 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; Dinaciclib; alvocidib
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

Viewer

Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation CDKN1B 0.646
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation VRK3 0.353
Publications: 1
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation CLIC4 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation GRIN2B 0.44
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ERBB3 0.343
Publications: 2 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation RAPGEF2 0.387
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NOS3 0.368
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation SYNJ1 0.505
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTT 0.443
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GRIN2A 0.524
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 0.354
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 0.365
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PLD2 0.365
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DBN1 0.539
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation LMTK2 0.497
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation TP53 0.728
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DNMT1 0.355
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.296
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.516
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.554
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation TPPP 0.4
Publications: 3 Organism: In Vitro
+ down-regulates quantity img/direct_inhibition.png phosphorylation PPP1R9B 0.393
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CTNNB1 0.368
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NDEL1 0.767
Publications: 3 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation NR3C1 0.476
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.758
Publications: 4 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DLG4 0.65
Publications: 3 Organism: Homo Sapiens
+ img/unknown.png phosphorylation AMPH 0.521
Publications: 3 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation PPARG 0.573
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png phosphorylation ALDH1A1 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AGAP2 0.262
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 0.743
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 0.382
Publications: 1 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation HTR6 0.374
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation SIRT2 0.394
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.374
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTRA2 0.457
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2A 0.506
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TLN1 0.459
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2D 0.411
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TPX2 0.271
Publications: 1 Organism: Homo Sapiens
Tissue: Hepatobiliary Carcinoma Cell
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation AMFR 0.247
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.758
Publications: 11 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DPYSL3 0.596
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.615
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation DPYSL2 0.647
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SYN1 0.562
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DLC1 0.2
Publications: 5 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation VIM 0.269
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1L 0.461
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIP5K1C 0.366
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R1A 0.369
Publications: 1 Organism: Rattus Norvegicus
+ img/unknown.png phosphorylation STMN3 0.321
Publications: 2 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation HIF1A 0.258
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.398
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Myotube, Brain
+ up-regulates img/direct-activation.png phosphorylation PTK2 0.303
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SRC 0.392
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation DLGAP1 0.406
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1 0.516
Publications: 2 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation PARP1 0.257
Publications: 3 Organism: In Vitro
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation CALD1 0.339
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ATM 0.411
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 0.338
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AR 0.368
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PXN 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 0.277
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NES 0.547
Publications: 2 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPK10 0.348
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 0.354
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PAK1 0.539
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation APEX1 0.374
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation EZR 0.465
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BACE1 0.436
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation HTR1A 0.27
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 0.51
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation PEBP1 0.335
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CORO1A 0.287
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CLOCK 0.326
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation KIF13B 0.362
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 0.354
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ADD1 0.254
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R2 0.358
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation MAPK7 0.2
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation APP 0.564
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R1B 0.772
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 0.583
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.607
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation CDH1 0.297
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 phosphorylation FOXC2 0.347
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png phosphorylation PRNP 0.33
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DYNLL1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation NEFM 0.418
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CREB1 0.371
Publications: 1 Organism: Homo Sapiens
Pathways:Dopaminergic Synapse
+ down-regulates activity img/direct_inhibition.png phosphorylation NR1I2 0.342
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation XDH 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NGEF 0.417
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png phosphorylation SOX6 0.364
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LMTK2 0.497
Publications: 2 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 0.943
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
+ up-regulates activity img/direct-activation.png phosphorylation KALRN 0.397
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NOTCH1 0.318
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 phosphorylation ERBB2 0.273
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SYNGAP1 0.381
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CTNND2 0.325
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRPV1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TRIO 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PRKAA2 0.216
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MIB1 0.326
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CASK 0.289
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation SPAAR 0.2
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 phosphorylation CDK16 0.338
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding CDK5 0.943
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TH 0.404
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PP1 0.472
Publications: 1 Organism: Homo Sapiens