Recombinant human CDK2 + CCNA1 protein

Specifications

Form

Liquid

Additional notes

Purity was determined to be >85% by densitometry. Affinity purified.

General info

Function

Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed : 10499802, PubMed : 10884347, PubMed : 10995386, PubMed : 10995387, PubMed : 11051553, PubMed : 11113184, PubMed : 12944431, PubMed : 15800615, PubMed : 17495531, PubMed : 19966300, PubMed : 20935635, PubMed : 21262353, PubMed : 21596315, PubMed : 28216226, PubMed : 28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2 (PubMed : 10499802, PubMed : 10995386, PubMed : 10995387, PubMed : 11051553, PubMed : 11113184, PubMed : 12944431, PubMed : 15800615, PubMed : 19966300, PubMed : 20935635, PubMed : 21262353, PubMed : 21596315, PubMed : 28216226). Triggers duplication of centrosomes and DNA (PubMed : 11051553). 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 (PubMed : 18372919, PubMed : 19238148, PubMed : 19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed : 18372919, PubMed : 19238148, PubMed : 19561645). 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 (PubMed : 18372919, PubMed : 19238148, PubMed : 19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed : 20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed : 19966300). 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 (PubMed : 15800615, PubMed : 20195506, PubMed : 21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed : 15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed : 28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed : 10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed : 11051553). 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 (PubMed : 10995386, PubMed : 10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed : 20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed : 20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed : 21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed : 21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed : 29203878).

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Post-translational modifications

Phosphorylated at Thr-160 by CDK7 in a CAK complex (PubMed:28666995). Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A.. Nitrosylated after treatment with nitric oxide (DETA-NO).

Subcellular localisation

Cytoskeleton