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 97
Inhibitors Flavopiridol; roscovitine; Dinaciclib; Flavopiridol hydrochloride; AT7519; PHA-793887
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 ERBB3 0.18
Publications: 2 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation NOS3 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTT 0.24
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GRIN2A 0.15
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation CAMKK2 0.39
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PMAIP1 0.28
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PRKN 0.20
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation LMTK2 0.31
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation TP53 0.06
Publications: 4 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DNMT1 0.23
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.51
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation NDEL1 0.41
Publications: 3 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation NR3C1 0.11
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MAPT 0.57
Publications: 4 Organism: Homo Sapiens
+ img/unknown.png phosphorylation AMPH 0.43
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation AGAP2 0.21
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.34
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation HTRA2 0.38
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ down-regulates activity img/direct_inhibition.png phosphorylation MEF2A 0.37
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TLN1 0.41
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPT 0.57
Publications: 11 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DPYSL3 0.30
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CRMP1 0.30
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SYN1 0.30
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIP5K1C 0.26
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R1A 0.32
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png phosphorylation STAT3
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Myotube, Brain
+ up-regulates img/direct-activation.png phosphorylation PTK2 0.20
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SRC 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation DNM1 0.29
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation ATM 0.30
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDK5R1 1.00
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation RB1 0.23
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation AR
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation EPRS 0.48
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NES 0.26
Publications: 2 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation MAPK10 0.22
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation NFAT5 0.24
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PIK3C3 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PAK1 0.36
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation EZR 0.50
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PPP1CA 0.45
Publications: 3 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation PSEN1 0.20
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CORO1A 0.34
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CLOCK 0.21
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STXBP2 0.34
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation PPP1R2 0.38
Publications: 1 Organism: In Vitro
+ img/unknown.png phosphorylation APP 0.17
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation PPP1R1B 0.34
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.28
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates activity img/direct-activation.png phosphorylation CDK5 0.36
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LMTK2 0.31
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Brain
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition CDK5
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding CDK5/CDK5R1
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding CDK5 1.00
Publications: 1 Organism: Homo Sapiens
Tissue: Brain