| Predicate | Object |
|---|---|
| rdf:type | |
| biopax3:comment |
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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) (By similarity). SUBUNIT: Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1 (By similarity). Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Found in a complex with both SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta- catenin/CTNNB1. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, centrosome (By similarity). Nucleus, Cajal body (By similarity). Cytoplasm (By similarity). Endosome (By similarity). 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) (By similarity). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=CDK2-beta; IsoId=P97377-1; Sequence=Displayed; Name=CDK2-alpha; IsoId=P97377-2; Sequence=VSP_004800; PTM: Phosphorylated at Thr-160 by CDK7 in a CAK complex. 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 (By similarity). PTM: Nitrosylated after treatment with nitric oxide (DETA-NO) (By similarity). DISRUPTION PHENOTYPE: Reduced body size and impaired neural progenitor cell proliferation. Sterility due to defective meiosis; no effect on mitotic cells. Premature translocation of CDK1 from the cytoplasm to the nucleus compensating CDK2 loss. Prolonged and impaired DNA repair activity upon DNA damage by gamma-irradiation. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain. GENE SYNONYMS:Cdk2 Cdkn2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.,
SEQUENCE 346 AA; 38978 MW; D806BC2F150AEDFC CRC64;
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| biopax3:xref | |
| biopax3:displayName |
CDK2_MOUSE
|
| biopax3:name |
2.7.11.22,
Cdk2,
Cell division protein kinase 2
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| biopax3:entityFeature |
urn:biopax:ModificationFeature:CDK2_MOUSE_1,
urn:biopax:ModificationFeature:CDK2_MOUSE_2,
urn:biopax:ModificationFeature:CDK2_MOUSE_3,
urn:biopax:ModificationFeature:CDK2_MOUSE_4,
urn:biopax:ModificationFeature:CDK2_MOUSE_5,
urn:biopax:ModificationFeature:CDK2_MOUSE_6,
urn:biopax:ModificationFeature:CDK2_MOUSE_7,
urn:biopax:ModificationFeature:CDK2_MOUSE_8
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| biopax3:organism | |
| biopax3:sequence |
MENFQKVEKIGEGTYGVVYKAKNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINAEGSIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMHLVCTQHHAKCCGEHRRNGRHSLCPLCSYLEVAASQGGGMTAVSAPHPVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
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| biopax3:standardName |
Cyclin-dependent kinase 2
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