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Information on EC 2.7.11.22 - cyclin-dependent kinase and Organism(s) Rattus norvegicus and UniProt Accession Q63699
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2.7.11.22 cyclin-dependent kinaseIUBMB Comments
Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation.
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Word Map
- 2.7.11.22
- cyclins
- p27kip1
- retinoblastoma
-
mitosis
-
cell-cycle
-
checkpoint
- histone
- tumorigenesis
- tumour
- bcl-2
- p16ink4a
-
s-phase
-
hyperphosphorylation
- leukemia
- prostate
- chromatin
- epidermal
-
exit
-
antiproliferative
- mapks
- caspase-3
-
mitogen
- tau
- xenopus
- spindle
- c-myc
-
interphase
-
quiescent
- oocyte
- pcna
-
fission
- alzheimer
- proteasome
- microtubule
- analysis
- medicine
- cdc25c
- pharmacology
- letrozole
-
cycle-dependent
-
polo-like
- chk1
-
p53-independent
- drug development
-
cytokinesis
- centrosome
-
prophase
-
postmitotic
-
receptor-positive
-
cycle-related
-
anaphase
-
aurora
-
metaphase
-
her2-negative
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
cyclin-dependent kinase, cdk, p34cdc2, cdkl5, cdc2 kinase, cyclin-dependent kinase 5, cyclin-dependent kinase 2, cdc28, cyclin-dependent kinase 4, cyclin-dependent kinase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Cdk5
cyclin-dependent kinase 5
Cyclin-dependent kinase pef1
-
-
-
-
PHO85 homolog
-
-
-
-
Cdk5
-
-
cyclin-dependent kinase 5
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:cyclin phosphotransferase
Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation.
CAS REGISTRY NUMBER
COMMENTARY
150428-23-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + dopamine
ADP + phosphorylated dopamine
-
phosphorylation by cdk5
-
-
?
ATP + dopamine and cAMP-regulated phosphoprotein
ADP + phosphorylated dopamine and cAMP-regulated phosphoprotein
-
i.e. DARPP-32, phosphorylation by cdk5 at Thr75 and Thr34
-
-
?
ATP + glucocorticoid receptor
ADP + dephosphorylated glucocorticoid receptor
-
CDK5 phosphorylates glucocorticoid receptor at multiple serines, including Ser203 and Ser211 of its N-terminal domain, and suppresses the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to DNA
-
-
?
ATP + glucocorticoid receptor
ADP + phosphorylated glucocorticoid receptor
-
-
-
-
?
ATP + histone H1
ADP + phosphorylated histone H1
-
-
-
-
?
ATP + huntingtin
ADP + phosphorylated huntingtin
-
huntingtin is phosphorylated by Cdk5 at Ser1181 and Ser1201
-
-
?
ATP + neuregulin receptor ErbB3
ADP + phosphorylated neuregulin receptor ErbB3
-
phosphorylation at Thr871 and Ser1120 by Cdk5
-
-
?
ATP + septine 5
ADP + phosphorylated septine 5
-
Ser327 is the major phosphorylation site for Cdk5 in presence of activator p35
-
-
?
ATP + [tau protein]
ADP + O-phospho-[tau-protein]
-
Cdk5-p25 or Cdk5-p35, see also EC 2.7.11.26, phosphorylation at Ser202 and Thr205
-
-
?
ATP + c-Jun N-terminal kinase 3
ADP + phosphorylated c-Jun N-terminal kinase 3
-
i.e. JNK3, phosphorylation inhibits JNK3 and leads to reduced phosphorylation of c-jun and to reduced apoptosis
-
-
?
ATP + c-Jun N-terminal kinase 3
ADP + phosphorylated c-Jun N-terminal kinase 3
-
i.e. JNK3, phosphorylation at Thr131
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
Cdk5 regulates the ERK1/2 pathway through phosphorylation of MEK1, overview
-
-
?
ATP + NF-H
ADP + phosphorylated NF-H
-
neurofilament protein, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + NF-H
ADP + phosphorylated NF-H
-
neurofilament protein, phosphorylation at the KSP repeats
-
-
?
ATP + NF-H peptide
ADP + phosphorylated NF-H peptide
-
i.e. RREAKSPAKAKSPAKE
-
-
?
ATP + NF-M
ADP + phosphorylated NF-M
-
neurofilament protein, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + NF-M
ADP + phosphorylated NF-M
-
neurofilament protein, phosphorylation at the KSP repeats
-
-
?
ATP + parkin
ADP + phosphorylated parkin
parkin has four putative Cdk5 phosphorylation sites according to the motif (S/T)PX(K/R)
-
-
?
ATP + pocket protein p107
ADP + phosphorylated pocket protein 107
-
hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
ATP + pocket protein p107
ADP + phosphorylated pocket protein 107
-
hyperphosphorylation by CDK/cyclin
-
-
?
ATP + pocket protein p130
ADP + phosphorylated pocket protein 130
-
hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
ATP + pocket protein p130
ADP + phosphorylated pocket protein 130
-
hyperphosphorylation by CDK/cyclin
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
-
i.e. Rb protein
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
-
i.e. Rb protein, hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
-
i.e. Rb protein, hyperphosphorylation by CDK/cyclin
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
cdk5 substrate in brain, Cdk5-p25 or Cdk5-p35
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is microtubule-associated, phopshorylation at T231 by CDK5 causes its release into the cytoplasm
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
phosphorylation at T231, no activity with tau mutant T231A
-
-
?
additional information
?
-
Cdk2 protein might be required for entry into the S phase of the cell cycle in FRTL-Tc cells
-
-
?
additional information
?
-
enzyme plays an important role in spermatogenesis
-
-
?
additional information
?
-
-
CDK5-dependent clustering of endoplasmic reticulum ER and mitochondria during ceramide-mediated neuronal death: neurotoxic calcium transfer from ER to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau, inhibition of the process leads to cell death
-
-
?
additional information
?
-
-
CDK-cyclins and CDK inhibitory proteins are involved in the cell cycle regulation and of vascular cell proliferation and migration, as well as in the control of neointimal thickening, modeling, overview
-
-
?
additional information
?
-
-
Cdk5 regulates Akt activation and cell survival through the neuregulin-mediated PI 3-kinase signaling pathway, null mutants show lower phosphatidylinositol 3-kinase activity, Cdk5-p35 mediates neuroprotection
-
-
?
additional information
?
-
-
Cdk5 regulation, overview, Cdk5 is involved in neuronal migration and phosphorylation of neurofilaments and cytoskeletal proteins, deregulation of Cdk5 occurs in neurodegeneration
-
-
?
additional information
?
-
-
Cdk5-p35 is negatively regulated by interaction with membranes in brain and liver, mechanism
-
-
?
additional information
?
-
-
cyclin-dependent kinase activity is required for apoptotic death involving the retinoblastoma protein but not inclusion formation in cortical neurons after proteasomal inhibition, Cdk2, Cdk4, and Cdk6 promote the apoptosis induced by lactacystin and other proteasome inhibitors, expression of a defective retinoblastoma protein is neuroprotective
-
-
?
additional information
?
-
-
the CDKs are involved in regulation of cell cycle and neuronal differentiation, cleavage of p35 to p25 occurs in neurons undergoing induced cell death and in brains exposed to ischaemia
-
-
?
additional information
?
-
-
the phosphatidylinositol-linked dopamine receptor is involved in regulation of cdk5 enzyme activity in the brain
-
-
?
additional information
?
-
-
CDK5 induces caspase-independent mitochondrial fission
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun N-terminal kinase 3
ADP + phosphorylated c-Jun N-terminal kinase 3
-
i.e. JNK3, phosphorylation inhibits JNK3 and leads to reduced phosphorylation of c-jun and to reduced apoptosis
-
-
?
ATP + dopamine
ADP + phosphorylated dopamine
-
phosphorylation by cdk5
-
-
?
ATP + dopamine and cAMP-regulated phosphoprotein
ADP + phosphorylated dopamine and cAMP-regulated phosphoprotein
-
i.e. DARPP-32, phosphorylation by cdk5 at Thr75 and Thr34
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
-
Cdk5 regulates the ERK1/2 pathway through phosphorylation of MEK1, overview
-
-
?
ATP + neuregulin receptor ErbB3
ADP + phosphorylated neuregulin receptor ErbB3
-
phosphorylation at Thr871 and Ser1120 by Cdk5
-
-
?
ATP + NF-H
ADP + phosphorylated NF-H
-
neurofilament protein, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + NF-M
ADP + phosphorylated NF-M
-
neurofilament protein, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + pocket protein p107
ADP + phosphorylated pocket protein 107
-
hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
ATP + pocket protein p130
ADP + phosphorylated pocket protein 130
-
hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
-
cdk5 substrate in brain, Cdk5-p25 or Cdk5-p35
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
-
tau is microtubule-associated, phopshorylation at T231 by CDK5 causes its release into the cytoplasm
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
-
i.e. Rb protein
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
-
i.e. Rb protein, hyperphosphorylation by CDK/cyclin contributes to the transactivation of genes with functional E2F-binding sites, including growth and cell-cycle regulators, i.e. c-myc, Rb protein, cdc2, cyclin E, and cyclin A, and genes encoding proteins required for nucleotide and DNA biosynthesis
-
-
?
additional information
?
-
Cdk2 protein might be required for entry into the S phase of the cell cycle in FRTL-Tc cells
-
-
?
additional information
?
-
enzyme plays an important role in spermatogenesis
-
-
?
additional information
?
-
-
CDK5-dependent clustering of endoplasmic reticulum ER and mitochondria during ceramide-mediated neuronal death: neurotoxic calcium transfer from ER to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau, inhibition of the process leads to cell death
-
-
?
additional information
?
-
-
CDK-cyclins and CDK inhibitory proteins are involved in the cell cycle regulation and of vascular cell proliferation and migration, as well as in the control of neointimal thickening, modeling, overview
-
-
?
additional information
?
-
-
Cdk5 regulates Akt activation and cell survival through the neuregulin-mediated PI 3-kinase signaling pathway, null mutants show lower phosphatidylinositol 3-kinase activity, Cdk5-p35 mediates neuroprotection
-
-
?
additional information
?
-
-
Cdk5 regulation, overview, Cdk5 is involved in neuronal migration and phosphorylation of neurofilaments and cytoskeletal proteins, deregulation of Cdk5 occurs in neurodegeneration
-
-
?
additional information
?
-
-
Cdk5-p35 is negatively regulated by interaction with membranes in brain and liver, mechanism
-
-
?
additional information
?
-
-
cyclin-dependent kinase activity is required for apoptotic death involving the retinoblastoma protein but not inclusion formation in cortical neurons after proteasomal inhibition, Cdk2, Cdk4, and Cdk6 promote the apoptosis induced by lactacystin and other proteasome inhibitors, expression of a defective retinoblastoma protein is neuroprotective
-
-
?
additional information
?
-
-
the CDKs are involved in regulation of cell cycle and neuronal differentiation, cleavage of p35 to p25 occurs in neurons undergoing induced cell death and in brains exposed to ischaemia
-
-
?
additional information
?
-
-
the phosphatidylinositol-linked dopamine receptor is involved in regulation of cdk5 enzyme activity in the brain
-
-
?
additional information
?
-
-
CDK5 induces caspase-independent mitochondrial fission
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
induces cleavage of p35 to p25 by calpains, which changes the localization of Cdk5 from the particulate to the soluble fraction
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,5-hexanedione
-
activities of CDK5 in cerebral cortex of 200 or 400 mg/kg 2,5-hexanedione-treated rats are significantly decreased in both the cytosolic and membrane fractions, CDK5 activities are significantly decreased in the cytosolic fraction of spinal cord cord in 200 and 400 mg/kg 2,5-hexanedione-treated rats
CDK inhibitory proteins
-
members of the family of CDK inhibitory proteins, e.g. INK4 proteins, overview, CKIs may play a role as regulators in neointimal hyperplasia
-
CVT-313
-
inhibitor used in treatment of neointimal hyperplasia, IC50 for CDK1 is 0.004 mM, for CDK2 0.0005 mM, and for CDK4 0.215 mM
membranes
-
of brain and liver, Cdk5-p35 is negatively regulated by interaction with membranes, mechanism
-
flavopiridol
-
inhibitor used in treatment of neointimal hyperplasia, IC50 for CDK1 is 0.0005 mM, for CDK2 0.0001 mM, for CDK4 0.000065 mM, for CDK6 0.00006 mM, and for CDK7 0.00011-0.0003 mM
additional information
-
glutamate triggers the ubiquitination and subsequent degradation of p35 in neurons after autophosphorylation of Cdk5-p35 at p35
-
additional information
-
physiological effects of CDK inhibition, overview, CDKs are deactivated by dephosphorylation, protein p27Kip1 mediates CDK2 inhibition
-
additional information
-
R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, i.e. SCH23390, or the PLCbeta antagonist 1-[6-([17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione, i.e. U-73122, inhibit cdk5 transactivation by SKF83959 via the brain phosphatidylinositol-linked dopamin receptor, the transactivation is attenuated by calphostin C or by intracellular calcium chelator BAPTA
-
additional information
-
dysregulation of Cdk5 occurs with aging and concomitantly with an increase in DNA damage
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,5-hexanedione
-
CDK5 contents and activities in sciatic nerve of rats treated with 200 or 400 mg/kg 2,5-hexanedione are significantly increased in both the cytosolic and membrane fractions, increase of CDK5 content in both the cytosolic and membrane fractions of spinal cord in 200 and 400 mg/kg 2,5-hexanedione-treated rats are observed
CHAPS
-
the detergent increases Cdk5-p35 activity with histone H1 and the autophosphorylation at p35
ginsenoside Rb1
-
attenuates beta-amyloid peptide25-35-induced CDK5 activation
N-acetylcysteine
-
10 mM, increases cyclin-dependent kinase 5 phosphorylation, phosphorylation of Cdk5 on tyrosine 15 by c-Abl increases kinase activity of the p35/Cdk5 complex
NP-40
-
the detergent increases Cdk5-p35 activity with histone H1 and the autophosphorylation at p35
Triton X-100
-
the detergent increases Cdk5-p35 activity with histone H1 and the autophosphorylation at p35
Tween 20
-
the detergent increases Cdk5-p35 activity with histone H1 and the autophosphorylation at p35
p25
-
activator required for CDK5 activity, activation of CDK5 by p25 which is activated by cleavage of p35 to p25
-
p25
-
increased calpain activity in sensory neurons after inflammation results in the cleavage of p35 to p25, which forms a more stable complex with Cdk5 and, consequently, leads to elevation of Cdk5 activity
-
p25
-
physically interacts with ligand-bound glucocorticoid receptor in vitro through the C-terminal portion enclosed by amino acids 190 and 262, p25 with a much stronger effect than p35 on suppression of glucocorticoid receptor transcriptional activity
-
p35
-
activation subunit, required, interacts with and activates Cdk5, laminin induces upregulation of p35, regulation of p35 expression, overview
-
p35
-
physically interacts with ligand-bound glucocorticoid receptor in vitro through the C-terminal portion enclosed by amino acids 190 and 262
-
p35
-
Cdk5 activity is dysregulated by cleavage of activator p35 to p25 by calpain
-
p35
-
monomeric Cdk5 has no enzymatic activity and requires association with a regulatory binding partner p35 for its activation
-
p39
-
activation subunit, can substitute for p35, interacts with and activates Cdk5
-
additional information
-
6-chloro-7,8-dihydroxy-3-methyl-1-(3-methyl-phenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine, i.e. SKF83959, induces transctivation of cdk5 via the brain phosphatidylinositol-linked dopamine receptor, which is inhibited by SCH23390 or U-73122
-
additional information
-
the proteasomal inhibitor lactacystin induces the Cdk-dependent phosphorylation of the retinoblastoma protein
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004
CVT-313
Rattus norvegicus
-
inhibitor used in treatment of neointimal hyperplasia, IC50 for CDK1 is 0.004 mM
0.0005
flavopiridol
Rattus norvegicus
-
inhibitor used in treatment of neointimal hyperplasia, IC50 for CDK1 is 0.0005 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
pre-T, expressed during the prolactin (PRL)-induced G1/S transition in rat Nb2 pre-T lymphoma cell
beta-adrenergic receptor agonist isoproternol treated mouse parotid gland acinar cells
PCTAIRE 2 is concentrated in the neuronal layers of the hippocampus and olfactory bulb, which mostly consist of post-mitotic neurons. PCTAIRE 2 is detected in the cell bodies and extended neurites of neurons, but not in astrocytes
predominantly expressed in terminally differentiated neurons
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
associated to membrane in YC-8 and proliferating salivary cells
additional information
-
CDK5-dependent clustering of endoplasmic reticulum ER and mitochondria and translocation to the centrosome during ceramide-mediated neuronal death
-
additional information
-
Ca2+ induces cleavage of p35 to p25 by calpains, which changes the localization of Cdk5 from the particulate to the soluble fraction
-
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CDK2_RAT
298
0
33887
Swiss-Prot
other Location (Reliability: 1)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
additional information
-
p35 and cyclin B are ubiquitinated prior to degradation, proteasomal degradation of p35 is induced by phosphatase inhibitor okadaic acid, proteolytic patterns of p35 amd p39, overview
phosphoprotein
-
Cdk5 autophosphorylates at its cofactor p35 which activates the complex
phosphoprotein
-
in S/G2 phase of the cell cycle, Cdk1/Cdc2, upon binding of cyclin B, is phosphorylated and inactivated at T14, Y15, and T161 by protein kinases Wee1 and CAK, to activate the enzyme T14 and Y15 are dephosphorylated by phosphatase Cde25, the active enzyme is only phosphorylated at T161, release of cyclin B results in complete dephosphorylation of Cdk1/Cdc2, overview, Cdk5 binds p35 and is then activated by phosphorylation at T14, Y15, and S519, the bound p35 is also autophosphorylated by Cdk5-p35 at a single site, which induces ubiquitination and subsequent degradation of p35 in neurons, release of p35 leads to dephosphorylation of Cdk5, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D144N
-
defective in its kinase activity, weakly increases glucocorticoid receptor-induced transcriptional activity
additional information
-
expression of dominant negative mutants of Cdks or of Cdk inhibitors p16 and p27 can protect cells against lactcystin-induced cell death
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partial purification of Cdk5-p35 from brain homogenates, solubilization by NP-40 0.5% in presence of 0.6 M NaCl
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
CDK5, p35, p25 and glucocorticoid receptor expressed in HCT116 cells and COS-7 cells
-
co-expression of Cdk5-p35 and HA-tagged Erb3, wild-type and mutants T871A and S1120A, or HA-tagged Erb2, wild-type and mutant S1176A, in COS-7 cells, in contrast to the wild-type substrates, the mutant substrates are not phosphorylated by Cdk5
-
co-expression of dominant negative EGFP-tagged CDK5 and p25 in PC12 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the protein levels of cyclin A, cyclin E, and CDK2 are decreased significantly (up to 0.53, 0.49, and 0.36fold as compared to the control group, respectively) in a dose-dependent manner after treatment with mulberry leaf extract (0.5-2.0 mg/ml) for 24 h, and in a time-dependent manner (up to 0.9, 0.5, and 0.74fold as compared to the control group, respectively) after treatment with mulberry leaf extract (1.5 mg/ml)
-
the protein levels of cyclin D1 and CDK4 but not cyclin D3 are increased significantly (up to 1.8 and 1.3fold as compared to the control group, respectively) in a dose-dependent manner after treatment with mulberry leaf extract (0.5-2.0 mg/ml for 24 h) and increase significantly (up to 1.35 and 1.75fold as compared to the control group, respectively) in a time-dependent manner after treatment with mulberry leaf extract (1.5 mg/ml)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
-
CDK5 exerts some of its biologic activities in neuronal cells through the glucocorticoid receptor, dynamically modulating glucocorticoid receptor transcriptional activity in a target promoter dependent fashion
medicine
-
role for Cdk5/p35 activity in primary afferent nociceptive signaling, Cdk5/p35 may be a target for the development of analgesic drugs
medicine
-
Cdk5 in combination with p25 is a proapoptotic factor that promotes endoplasmic reticulum stress-induced neuronal cell death in nuclei
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hirose, T.; Tamaru, T.; Okumura, N.; Nagai, K.; Okada, M.
PCTAIRE 2, a Cdc2-related serine/threonine kinase, is predominantly expressed in terminally differentiated neurons
Eur. J. Biochem.
249
481-488
1997
Rattus norvegicus (O35831), Rattus norvegicus (O35832)
Matsushime, H.; Jinno, A.; Takagi, N.; Shibuya, M.
A novel mammalian protein kinase gene (mak) is highly expressed in testicular germ cells at and after meiosis
Mol. Cell. Biol.
10
2261-2268
1990
Rattus norvegicus (P20793), Homo sapiens (P20794)
Cho, F.S.; Phillips, K.S.; Khan, S.A.; Weaver, T.E.
Cloning of the rat cyclin-dependent kinase 4 cDNA: implication in proliferation-dependent expression in rat tissues
Biochem. Biophys. Res. Commun.
191
860-865
1993
Rattus norvegicus (P35426)
Riabowol, K.; Draetta, G.; Brizuela, L.; Vandre, D.; Beach, D.
The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells
Cell
57
393-401
1989
Rattus norvegicus (P39951)
Kerr, M.; Fischer, J.E.; Purushotham, K.R.; Gao, D.; Nakagawa, Y.; Maeda, N.; Ghanta, V.; Hiramoto, R.; Chegini, N.; Humphreys-Beher, M.G.
Characterization of the synthesis and expression of the GTA-kinase from transformed and normal rodent cells
Biochim. Biophys. Acta
1218
375-387
1994
Rattus norvegicus (P46892)
Xiong, Y.; Zhang, H.; Beach, D.
D Type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA
Cell
71
505-514
1992
Rattus norvegicus (Q03114)
Hellmich, M.R.; Pant, H.C.; Wada, E.; Battey, J.F.
Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression
Proc. Natl. Acad. Sci. USA
89
10867-10871
1992
Rattus norvegicus (Q03114)
Kotani, S.; Endo, T.; Kitagawa, M.; Higashi, H.; Onaya, T.
A variant form of cyclin-dependent kinase 2 (Cdk2) in a malignantly transformed rat thyroid (FRTL-Tc) cell line
Oncogene
10
663-669
1995
Rattus norvegicus (Q63699)
Hosokawa, Y.; Yang, M.; Kaneko, S.; Tanaka, M.; Nakashima, K.
Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells
Biochem. Mol. Biol. Int.
37
393-399
1995
Rattus norvegicus (Q63699)
Darios, F.; Muriel, M.P.; Khondiker, M.E.; Brice, A.; Ruberg, M.
Neurotoxic calcium transfer from endoplasmic reticulum to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau
J. Neurosci.
25
4159-4168
2005
Rattus norvegicus
Kesavapany, S.; Li, B.S.; Amin, N.; Zheng, Y.L.; Grant, P.; Pant, H.C.
Neuronal cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the Cdk5 inhibitory peptide
Biochim. Biophys. Acta
1697
143-153
2004
Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, Canis lupus familiaris, Drosophila melanogaster, Homo sapiens, Doryteuthis pealeii, Mus musculus, Rattus norvegicus, Sus scrofa
Andres, V.
Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential
Cardiovasc. Res.
63
11-21
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Li, B.S.; Ma, W.; Jaffe, H.; Zheng, Y.; Takahashi, S.; Zhang, L.; Kulkarni, A.B.; Pant, H.C.
Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival
J. Biol. Chem.
278
35702-35709
2003
Mus musculus, Rattus norvegicus
Zhu, Y.S.; Saito, T.; Asada, A.; Maekawa, S.; Hisanaga, S.
Activation of latent cyclin-dependent kinase 5 (Cdk5)-p35 complexes by membrane dissociation
J. Neurochem.
94
1535-1545
2005
Rattus norvegicus
Rideout, H.J.; Wang, Q.; Park, D.S.; Stefanis, L.
Cyclin-dependent kinase activity is required for apoptotic death but not inclusion formation in cortical neurons after proteasomal inhibition
J. Neurosci.
23
1237-1245
2003
Rattus norvegicus
Zhen, X.; Goswami, S.; Abdali, S.A.; Gil, M.; Bakshi, K.; Friedman, E.
Regulation of cyclin-dependent kinase 5 and calcium/calmodulin-dependent protein kinase II by phosphatidylinositol-linked dopamine receptor in rat brain
Mol. Pharmacol.
66
1500-1507
2004
Rattus norvegicus
Hisanaga, S.; Saito, T.
The regulation of cyclin-dependent kinase 5 activity through the metabolism of p35 or p39 Cdk5 activator
Neurosignals
12
221-229
2003
Homo sapiens, Mus musculus, Rattus norvegicus
Li, T.; Hawkes, C.; Qureshi, H.Y.; Kar, S.; Paudel, H.K.
Cyclin-dependent protein kinase 5 primes microtubule-associated protein tau site-specifically for glycogen synthase kinase 3beta
Biochemistry
45
3134-3145
2006
Bos taurus, Homo sapiens, Rattus norvegicus
Avraham, E.; Rott, R.; Liani, E.; Szargel, R.; Engelender, S.
Phosphorylation of Parkin by the cyclin-dependent kinase 5 at the linker region modulates its ubiquitin-ligase activity and aggregation
J. Biol. Chem.
282
12842-12850
2007
Homo sapiens, Rattus norvegicus, Rattus norvegicus (Q03114)
Kino, T.; Ichijo, T.; Amin, N.D.; Kesavapany, S.; Wang, Y.; Kim, N.; Rao, S.; Player, A.; Zheng, Y.L.; Garabedian, M.J.; Kawasaki, E.; Pant, H.C.; Chrousos, G.P.
Cyclin-dependent kinase 5 differentially regulates the transcriptional activity of the glucocorticoid receptor through phosphorylation: clinical implications for the nervous system response to glucocorticoids and stress
Mol. Endocrinol.
21
1552-1568
2007
Rattus norvegicus
Pareek, T.K.; Keller, J.; Kesavapany, S.; Pant, H.C.; Iadarola, M.J.; Brady, R.O.; Kulkarni, A.B.
Cyclin-dependent kinase 5 activity regulates pain signaling
Proc. Natl. Acad. Sci. USA
103
791-796
2006
Mus musculus, Rattus norvegicus
Moore, N.L.; Narayanan, R.; Weigel, N.L.
Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity
Steroids
72
202-209
2007
Homo sapiens, Rattus norvegicus
Chen, X.; Huang, T.; Zhang, J.; Song, J.; Chen, L.; Zhu, Y.
Involvement of calpain and p25 of CDK5 pathway in ginsenoside Rb1s attenuation of beta-amyloid peptide25-35-induced tau hyperphosphorylation in cortical neurons
Brain Res.
1200
99-106
2008
Rattus norvegicus
Meuer, K.; Suppanz, I.E.; Lingor, P.; Planchamp, V.; Goericke, B.; Fichtner, L.; Braus, G.H.; Dietz, G.P.; Jakobs, S.; Baehr, M.; Weishaupt, J.H.
Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis
Cell Death Differ.
14
651-661
2007
Rattus norvegicus
Saito, T.; Konno, T.; Hosokawa, T.; Asada, A.; Ishiguro, K.; Hisanaga, S.
p25/cyclin-dependent kinase 5 promotes the progression of cell death in nucleus of endoplasmic reticulum-stressed neurons
J. Neurochem.
102
133-140
2007
Rattus norvegicus
Anne, S.L.; Saudou, F.; Humbert, S.
Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons
J. Neurosci.
27
7318-7328
2007
Mus musculus, Rattus norvegicus
Amin, N.D.; Zheng, Y.L.; Kesavapany, S.; Kanungo, J.; Guszczynski, T.; Sihag, R.K.; Rudrabhatla, P.; Albers, W.; Grant, P.; Pant, H.C.
Cyclin-dependent kinase 5 phosphorylation of human septin SEPT5 (hCDCrel-1) modulates exocytosis
J. Neurosci.
28
3631-3643
2008
Mus musculus, Rattus norvegicus
Hsiao, Y.H.; Chen, P.S.; Yeh, S.H.; Lin, C.H.; Gean, P.W.
N-acetylcysteine prevents beta-amyloid toxicity by a stimulatory effect on p35/cyclin-dependent kinase 5 activity in cultured cortical neurons
J. Neurosci. Res.
86
2685-2695
2008
Rattus norvegicus
Wang, Q.S.; Zhang, C.L.; Hou, L.Y.; Zhao, X.L.; Yang, X.W.; Xie, K.Q.
Involvement of cyclin-dependent kinase 5 in 2,5-hexanedione-induced neuropathy
Toxicology
248
1-7
2008
Rattus norvegicus
Chan, K.C.; Ho, H.H.; Peng, C.H.; Lan, K.P.; Lin, M.C.; Chen, H.M.; Wang, C.J.
Polyphenol-rich extract from mulberry leaf inhibits vascular smooth muscle cell proliferation involving upregulation of p53 and inhibition of cyclin-dependent kinase
J. Agric. Food Chem.
58
2536-2542
2010
Rattus norvegicus
Mairet-Coello, G.; Tury, A.; DiCicco-Bloom, E.
Insulin-like growth factor-1 promotes G1/S cell cycle progression through bidirectional regulation of cyclins and cyclin-dependent kinase inhibitors via the phosphatidylinositol 3-kinase/Akt pathway in developing rat cerebral cortex
J. Neurosci.
29
775-788
2009
Rattus norvegicus
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