Information on EC 2.7.11.22 - cyclin-dependent kinase and Organism(s) Mus musculus and UniProt Accession Q04859

for references in articles please use BRENDA:EC2.7.11.22
Word Map on EC 2.7.11.22
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Mus musculus
UNIPROT: Q04859


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.11.22
-
RECOMMENDED NAME
GeneOntology No.
cyclin-dependent kinase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
150428-23-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
cyclin-dependent kinase 5, Cdk5, is a member of the family of Cdks. Cdks are proline-directed Ser/Thr protein kinases that are activated by binding a regulatory subunit called cyclin, comparison of neuronal and cycling Cdks, overview. Cdk5 may have evolved from cycling Cdks to function in post-mitotic neurons
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + amphiphysin I
ADP + phosphorylated amphiphysin
show the reaction diagram
-
-
-
-
?
ATP + B-cell lymphoma protein 2
ADP + phosphorylated B-cell lymphoma protein 2
show the reaction diagram
-
B-cell lymphoma protein 2 is phosphorylated at Ser70, Cdk5-mediated B-cell lymphoma protein 2 phosphorylation is pivotal for the antiapoptotic effect of Bcl-2 and contributes to the maintenance of neuronal survival by Cdk5
-
-
?
ATP + c-Jun N-terminal kinase 3
ADP + phosphorylated c-Jun N-terminal kinase 3
show the reaction diagram
ATP + collapsing response mediator protein
ADP + phosphorylated collapsing response mediator protein
show the reaction diagram
-
-
-
-
?
ATP + dynamin I
ADP + phosphorylated dynamin
show the reaction diagram
-
-
-
-
?
ATP + ephexin 1
ADP + phosphorylated ephexin 1
show the reaction diagram
-
-
-
-
?
ATP + ErbB2
ADP + phosphorylated ErbB2
show the reaction diagram
ATP + ErbB3
ADP + phosphorylated ErbB3
show the reaction diagram
ATP + high-molecular-weight neurofilament
ADP + phosphorylated high-molecular-weight neurofilament
show the reaction diagram
-
-
-
-
-
ATP + histone 1
ADP + phosphorylated histone 1
show the reaction diagram
-
-
-
-
?
ATP + histone H1
ADP + phosphorylated histone H1
show the reaction diagram
ATP + huntingtin
ADP + phosphorylated huntingtin
show the reaction diagram
ATP + MAP1B
ADP + phosphorylated MAP1B
show the reaction diagram
-
-
-
-
?
ATP + MAP2
ADP + phosphorylated MAP2
show the reaction diagram
-
-
-
-
?
ATP + MEF2
ADP + phosphorylated MEF2
show the reaction diagram
-
-
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
ATP + MEP50 protein
ADP + MEP50 phosphoprotein
show the reaction diagram
-
a PRMT5 co-regulatory factor
-
-
?
ATP + microtubule-associated tau
ADP + phosphorylated microtubule-associated tau
show the reaction diagram
-
-
-
-
-
ATP + neuregulin receptor ErbB2
ADP + phosphorylated neuregulin receptor ErbB2
show the reaction diagram
ATP + neuregulin receptor ErbB3
ADP + phosphorylated neuregulin receptor ErbB3
show the reaction diagram
ATP + neurofilament heavy chain
ADP + phosphorylated neurofilament heavy chain
show the reaction diagram
-
-
-
-
?
ATP + NF-H
ADP + phosphorylated NF-H
show the reaction diagram
ATP + NF-M
ADP + phosphorylated NF-M
show the reaction diagram
ATP + Pak1
ADP + phosphorylated Pak1
show the reaction diagram
-
-
-
-
?
ATP + pocket protein p107
ADP + phosphorylated pocket protein 107
show the reaction diagram
ATP + pocket protein p130
ADP + phosphorylated pocket protein 130
show the reaction diagram
ATP + pre-synaptic P/Q-type voltage-dependent calcium channel
ADP + phosphorylated pre-synaptic P/Q-type voltage-dependent calcium channel
show the reaction diagram
-
-
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + PSD-95
ADP + phosphorylated PSD-95
show the reaction diagram
-
-
-
-
?
ATP + RasGRF1
ADP + phosphorylated RasGRF1
show the reaction diagram
-
-
-
-
?
ATP + RasGRF2
ADP + phosphorylated RasGRF2
show the reaction diagram
-
-
-
-
?
ATP + retinoblastoma protein
ADP + phosphorylated retinoblastoma protein
show the reaction diagram
ATP + RNA polymerase II
ADP + phosphorylated RNA polymerase II
show the reaction diagram
-
-
-
-
-
ATP + Sept5 protein
ADP + phosphorylated Sept5 protein
show the reaction diagram
-
Sept5 protein is phosphorylated at Ser17
-
-
?
ATP + septine 5
ADP + phosphorylated septine 5
show the reaction diagram
-
Ser327 is the major phosphorylation site for Cdk5 in presence of activator p35
-
-
?
ATP + STAT3
ADP + phosphorylated STAT3
show the reaction diagram
ATP + steroidogenic factor 1
ADP + phosphorylated steroidogenic factor 1
show the reaction diagram
-
also known as Ad4BP, systematic name NR5A1, the phosphorylation site is at Ser203
-
-
?
ATP + synaptojanin I
ADP + phosphorylated synaptojanin I
show the reaction diagram
-
-
-
-
?
ATP + syntaxin-1
ADP + phosphorylated syntaxin-1
show the reaction diagram
-
-
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
show the reaction diagram
ATP + WAVE1
ADP + phosphorylated WAVE1
show the reaction diagram
-
-
-
-
?
ATP + [tau protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
-
Cdk5-p25 or Cdk5-p35, see also EC 2.7.11.26
-
-
?
ATP + [tau protein]
ADP + [O-phospho-tau protein]
show the reaction diagram
ATP + [tau-protein]
ADP + O-phospho -[tau-protein]
show the reaction diagram
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun N-terminal kinase 3
ADP + phosphorylated c-Jun N-terminal kinase 3
show the reaction diagram
-
i.e. JNK3, phosphorylation inhibits JNK3 and leads to reduced phosphorylation of c-jun and to reduced apoptosis
-
-
?
ATP + ErbB2
ADP + phosphorylated ErbB2
show the reaction diagram
-
phosphorylation of the neuregulin receptor by Cdk5 is involved in regulation of neuregulin
-
-
?
ATP + ErbB3
ADP + phosphorylated ErbB3
show the reaction diagram
-
phosphorylation of the neuregulin receptor by Cdk5 is involved in regulation of neuregulin
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
-
Cdk5 regulates the ERK1/2 pathway through phosphorylation of MEK1, overview
-
-
?
ATP + MEP50 protein
ADP + MEP50 phosphoprotein
show the reaction diagram
-
a PRMT5 co-regulatory factor
-
-
?
ATP + neuregulin receptor ErbB2
ADP + phosphorylated neuregulin receptor ErbB2
show the reaction diagram
-
phosphorylation at Ser1176 by Cdk5
-
-
?
ATP + neuregulin receptor ErbB3
ADP + phosphorylated neuregulin receptor ErbB3
show the reaction diagram
-
phosphorylation at Thr871 and Ser1120 in the consensus sequence RSRSPR by Cdk5, Cdk5 associates with Erb3 in vivo
-
-
?
ATP + NF-H
ADP + phosphorylated NF-H
show the reaction diagram
-
neurofilament protein that correlates neurit outgrowth, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + NF-M
ADP + phosphorylated NF-M
show the reaction diagram
-
neurofilament protein, phosphorylation at the KSP repeats, regulated by the myelin-associate glycoprotein
-
-
?
ATP + pocket protein p107
ADP + phosphorylated pocket protein 107
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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 + STAT3
ADP + phosphorylated STAT3
show the reaction diagram
-
specific phosphorylation at Ser727 by CDK5-p35, CDK5 is involved in regulation of the signal transducer and transcription activator STAT3 in brain and muscle
-
-
?
ATP + tau protein
ADP + phosphorylated tau protein
show the reaction diagram
ATP + [tau protein]
ADP + [O-phospho-tau protein]
show the reaction diagram
-
substrate of CDK5 in the central nervous system, see also EC 2.7.11.26, tau hyperphosphorylation is involved in neurodegeneration and Alzheimer's disease, tau protein phosphorylation by CDK5 is involved in apoptosis in cortical cells
-
-
?
ATP + [tau-protein]
ADP + O-phospho -[tau-protein]
show the reaction diagram
-
cdk5 substrate in brain, cdk5 associated with p39, tau is a microtubule-associated and developmentally regulated protein involved in axonal development in neurons, tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules, reaction of EC 2.7.11.26
-
-
?
ATP + [tau-protein]
ADP + O-phospho-[tau-protein]
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cyclin
-
cyclin B
-
interacts with and activates Cdc2/Cdk1
-
cyclin E
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
-
cyclin-dependent kinase inhibitor 1B
-
protein CDKN1B, also called p27kip1
-
INK4 proteins
-
inhibit CDK4
-
NMDA
-
inactivates Cdk5 by modulation of Ser67 on the protein phosphatase inhibitor-I, overview
Olomoucine
-
-
p15Ink4b
-
INK4 protein
-
p16(INK4a)
-
-
-
p16Ink4a
-
INK4 protein
-
p18Ink4c
-
INK4 protein
-
p19Ink4d
-
INK4 protein
-
p21WAF1/CIP1
-
potent CDK inhibitor
-
p27Kip1
-
-
-
RNAi
depletion of PNQALRE by more than 80%, impairs cell proliferation, but fails to arrest the cell cycle at a discrete point
-
roscovitine
simvastatin
-
inhibition of CDK2
tranilast
-
inhibition of CDK2 and CDK4
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
-
Ca2+/calmodulin induce the phosphorylation of p35 by Cdk5 after stimulation of the Ca2+-permeable cation channels NMDA receptor and kainate receptor, leading to cleavage of p35 to p25
CDC25 phosphatase
-
major activator of CDK2
-
cyclin D1
-
CDK4 is dependent on
-
neuregulin
-
activates phosphorylation of STAT3 in vivo
-
additional information
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
myotube cells
Manually annotated by BRENDA team
-
; primary localization of CDK5
Manually annotated by BRENDA team
-
immortalized embryonic brain cortical cells; immortilized embryonic brain cortex cell line
Manually annotated by BRENDA team
-
dorsal root ganglia and trigeminal ganglia, Cdk5 is colocalized with p35
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
-
immortalized embryonic brain cortical cells, CN1.4 cells stably overexpressing human tau protein with four microtubule-binding repeats and no N-terminal inserts; immortilized embryonic brain cortex cell line overexpressing the human tau protein
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
-
primary tumors of a mouse lymphoma model
Manually annotated by BRENDA team
-
in MII oocytes only the dephosphorylated active form of cdk1 present, just after fertilization, the amount of the dephosphorylated form decreases, whereas that of the phosphorylated form increases
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
low expression
Manually annotated by BRENDA team
p58 expression is elevated between day 14 and day 16 post coitus
Manually annotated by BRENDA team
high expression
Manually annotated by BRENDA team
-
motor trigeminal nucleus
Manually annotated by BRENDA team
additional information
-
expression pattern during brain development
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
low activity
Manually annotated by BRENDA team
-
Cdk5-p25
-
Manually annotated by BRENDA team
additional information
-
Ca2+ induces cleavage of p35 to p25 by calpains, which changes the localization of Cdk5 from the particulate to the soluble fraction
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31000
-
SDS-PAGE
34000
-
x * 34000
40000
immunoblot analysis from testis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 34000
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
lipoprotein
-
membrane association of Cdk5 via myristoylation of p35
phosphoprotein
proteolytic modification
-
p35 is degraded by the proteasome after stimulation of NMDA or kainate receptors and subsequent Ca2+/calmodulin-dependent phosphorylation of p35 by Cdk5, p35 is cleaved to p25, reduced p35 leads to inhibition of Cdk5, overview
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
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by metal-ion affinity and subsequent gel filtration
recombinant GST-tagged CDK5 and p25 from Escherichia coli strain BL21 by glutathione affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculoviral vector, expression in Sf9 insect cells
-
Cdk5, DNA sequence determination and analysis
-
expression of GST-tagged CDK5 and p25 in Escherichia coli strain BL21
-
full-length PNQALRE cDNA (splice variant 1) expressed in HEK 293, U2OS and HCT116 cells, PNQALRE and components of the CAK trimer coexpressed in insect Sf9 cells
isolation of cDNA
regulation of p35 expression, overview
-
transient expression of CDK5 and p25 in HTAU cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K41R
-
catalytically inactive
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information