Cyclin-dependent kinase 2

Cyclin-dependent kinase 2

Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis10499802,10884347,10995386,10995387,11051553,11113184,12944431,15800615,17495531,19966300,20935635,21262353,21596315,28216226,28666995. Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH210499802,10995386,10995387,11051553,11113184,12944431,15800615,19966300,20935635,21262353,21596315,24728993,28216226. Triggers duplication of centrosomes and DNA11051553. 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 nucleus18372919,19238148,19561645. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs)18372919,19238148,19561645. Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity41100585. 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 phase18372919,19238148,19561645. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing20935635. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC19966300. 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 mitosis15800615,20195506,21319273. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation15800615. Involved in regulation of telomere repair by mediating phosphorylation of NBN28216226. Phosphorylation of RB1 disturbs its interaction with E2F110499802. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication11051553. 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 phase10995386,10995387. Required for vitamin D-mediated growth inhibition by being itself inactivated20147522. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner20079829. USP37 is activated by phosphorylation and thus triggers G1-S transition21596315. CTNNB1 phosphorylation regulates insulin internalization21262353. 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 breaks29203878. Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation24670654

Quoted from UniProt’s FUNCTION annotation for P24941 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Plasma membraneadditional
• Centrosomeadditional
• Basal bodyadditional
• Calyxadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm, cytoskeleton, microtubule organizing center, centrosome · Nucleus, Cajal body · Cytoplasm · Endosome

Expression by cell type

Single cell type RNA, the 5 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Syncytiotrophoblasts245.2 nCPM
• Migrating cytotrophoblasts145.1 nCPM
• Melanocytes141.9 nCPM
• Cytotrophoblasts120.3 nCPM
• Extravillous trophoblasts99.4 nCPM