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Names & Taxonomy

Uniprot ID:: P24941
Entry Name:: CDK2_HUMAN
Status:: reviewed
Protein Names:: Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase)
Gene Names:: CDK2 CDKN2
Gene Names Primary:: CDK2
Organism:: Homo sapiens (Human)

Structure

Length:: 298
Sequence:: MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus, Cajal body. Cytoplasm. Endosome. Note=Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic trafficking is mediated during the inhibition by 1,25-(OH)(2)D(3).

Function

Function:: Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Cofactor:: COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:: ENZYME REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo-1,3,5-triazine, pyrazolopyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolopyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21).
Active Site:: ACT_SITE 127 127 Proton acceptor.
Cross Reference Drug Bank:: DB06616
Gene Ontology Go:: Cajal body
centrosome
chromosome, telomeric region
condensed chromosome
cyclin-dependent protein kinase holoenzyme complex
cytoplasm
cytosol
endosome
nucleoplasm
nucleus
transcription factor complex
X chromosome
Y chromosome
ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
metal ion binding
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
blood coagulation
cell division
cellular response to insulin stimulus
cellular response to nitric oxide
centriole replication
centrosome duplication
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
histone phosphorylation
lens development in camera-type eye
meiotic nuclear division
mitotic cell cycle
mitotic G1 DNA damage checkpoint
mitotic nuclear division
organ regeneration
peptidyl-serine phosphorylation
positive regulation of cell proliferation
positive regulation of DNA-dependent DNA replication initiation
positive regulation of transcription, DNA-templated
potassium ion transport
Ras protein signal transduction
regulation of gene silencing
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
response to cadmium ion
response to cAMP
response to drug
response to electrical stimulus
response to estradiol
response to ethanol
response to toxic substance
Gene Ontology Biological Process:: anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
blood coagulation
cell division
cellular response to insulin stimulus
cellular response to nitric oxide
centriole replication
centrosome duplication
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
histone phosphorylation
lens development in camera-type eye
meiotic nuclear division
mitotic cell cycle
mitotic G1 DNA damage checkpoint
mitotic nuclear division
organ regeneration
peptidyl-serine phosphorylation
positive regulation of cell proliferation
positive regulation of DNA-dependent DNA replication initiation
positive regulation of transcription, DNA-templated
potassium ion transport
Ras protein signal transduction
regulation of gene silencing
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
response to cadmium ion
response to cAMP
response to drug
response to electrical stimulus
response to estradiol
response to ethanol
response to toxic substance
Gene Ontology Molecular Function:: ATP binding
cyclin binding
cyclin-dependent protein serine/threonine kinase activity
metal ion binding
Gene Ontology Cellular Component:: Cajal body
centrosome
chromosome, telomeric region
condensed chromosome
cyclin-dependent protein kinase holoenzyme complex
cytoplasm
cytosol
endosome
nucleoplasm
nucleus
transcription factor complex
X chromosome
Y chromosome
Keywords:: 3D-structure
ATP-binding
Acetylation
Alternative splicing
Cell cycle
Cell division
Complete proteome
Cytoplasm
Cytoskeleton
DNA damage
DNA repair
Endosome
Kinase
Magnesium
Meiosis
Metal-binding
Mitosis
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
S-nitrosylation
Serine/threonine-protein kinase
Transferase
Interacts With:: P20248; O95067; P24385; P24864; O96020; P51946; P38936; P46527; Q16667; P61024; Q09472; Q969H0-4; Q08619; Q9Y6K9; Q8TD08; P06400; Q9UBI4; Q96PU4

Names & Taxonomy

Structure

Subcellular location

Function

Publication