Cyclin-dependent kinase 2

NameCyclin-dependent kinase 2
Synonyms
  • 2.7.11.22
  • CDKN2
  • Cell division protein kinase 2
  • p33 protein kinase
Gene NameCDK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002409|Cyclin-dependent kinase 2
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS
HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY
STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Number of residues298
Molecular Weight33929.215
Theoretical pI9.76
GO Classification
Functions
  • metal ion binding
  • cyclin binding
  • cyclin-dependent protein serine/threonine kinase activity
  • ATP binding
Processes
  • response to toxic substance
  • response to drug
  • G2/M transition of mitotic cell cycle
  • DNA repair
  • histone phosphorylation
  • mitotic cell cycle
  • G1/S transition of mitotic cell cycle
  • cell division
  • meiotic nuclear division
  • response to ethanol
  • response to cadmium ion
  • response to electrical stimulus
  • double-strand break repair
  • peptidyl-serine phosphorylation
  • double-strand break repair via homologous recombination
  • regulation of gene silencing
  • lens development in camera-type eye
  • mitotic nuclear division
  • mitotic G1 DNA damage checkpoint
  • organ regeneration
  • positive regulation of transcription, DNA-templated
  • response to cAMP
  • response to estradiol
  • anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
  • Ras protein signal transduction
  • centrosome duplication
  • blood coagulation
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
  • positive regulation of cell proliferation
  • positive regulation of DNA-dependent DNA replication initiation
  • regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
  • potassium ion transport
  • cellular response to nitric oxide
  • cellular response to insulin stimulus
  • DNA replication
Components
  • transcription factor complex
  • chromosome, telomeric region
  • cytosol
  • condensed chromosome
  • nucleoplasm
  • Cajal body
  • cyclin-dependent protein kinase holoenzyme complex
  • X chromosome
  • cytoplasm
  • Y chromosome
  • nucleus
  • endosome
  • centrosome
General FunctionMetal ion binding
Specific FunctionSerine/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).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID3551191
UniProtKB IDP24941
UniProtKB Entry NameCDK2_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019057|Cyclin-dependent kinase 2 (CDK2)
ATGGAGAACTTCCAAAAGGTGGAAAAGATCGGAGAGGGCACGTACGGAGTTGTGTACAAA
GCCAGAAACAAGTTGACGGGAGAGGTGGTGGCGCTTAAGAAAATCCGCCTGGACACGCTG
CTGGATGTCATTCACACAGAAAATAAACTCTACCTGGTTTTTGAATTTCTGCACCAAGAT
CTCAAGAAATTCATGGATGCCTCTGCTCTCACTGGCATTCCTCTTCCCCTCATCAAGAGC
TATCTGTTCCAGCTGCTCCAGGGCCTAGCTTTCTGCCATTCTCATCGGGTCCTCCACCGA
GACCTTAAACCTCAGAATCTGCTTATTAACACAGAGGGGGCCATCAAGCTAGCAGACTTT
GGACTAGCCAGAGCTTTTGGAGTCCCTGTTCGTACTTACACCCATGAGGTGACTCGCCGG
GCCCTATTCCCTGGAGATTCTGAGATTGACCAGCTCTTCCGGATCTTTCGGACTCTGGGG
ACCCCAGATGAGGTGGTGTGGCCAGGAGTTACTTCTATGCCTGATTACAAGCCAAGTTTC
CCCAAGTGGGCCCGGCAAGATTTTAGTAAAGTTGTACCTCCCCTGGATGAAGATGGACGG
AGCTTGTTATCGCAAATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGCAGCC
CTGGCTCACCCTTTCTTCCAGGATGTGACCAAGCCAGTACCCCATCTTCGACTCTGA
GenBank Gene IDAB012305
GeneCard IDNot Available
GenAtlas IDCDK2deltaT
HGNC IDHGNC:1771
Chromosome Location12
LocusNot Available
References
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