General Information of the Protein
Protein ID |
PT00874
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Protein Name |
Cyclin-dependent kinase 2
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Secondarily Protein Name |
Cell division protein kinase 2
p33 protein kinase
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Gene Name |
CDK2
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Secondarily Gene Name |
CDKN2
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Sequence |
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
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Organism |
Homo sapiens, Human
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Protein Classification |
Enzyme
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Kinase
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Protein Kinase
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CMGC protein kinase group
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CMGC protein kinase CDK family
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CMGC protein kinase CDC2 subfamily
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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. 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). Phosphorylates CDK2AP2 (PubMed:12944431). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878).
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Uniprot ID |
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Subcellular Location |
Cytoplasm
Cytoskeleton
Microtubule organizing center
Centrosome
Nucleus
Cajal body
Cytoplasm
Endosome
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Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity |
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Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL001040 , 293-NB2
Cell Line ID: CL000713 , COV318
Cell Line ID: CL000012 , Sf21
Cell Line ID: CL000013 , Sf9
Biochemical Assays
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 2 (CDK2) )
Target Type | Clinical trial Target | ||||
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Disease | 10 Target-related Diseases | 10 | |||
1 | Thymic cancer [ICD-11: 2C27] | ||||
2 | Non-small-cell lung cancer [ICD-11: 2C25.Y] | ||||
3 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | ||||
4 | Lymphoma [ICD-11: 2A80-2A86] | ||||
5 | Anaplastic astrocytoma [ICD-11: 2A00.0] | ||||
6 | Acute lymphoblastic leukaemia [ICD-11: 2A85] | ||||
7 | Small-cell lung cancer [ICD-11: 2C25.Y] | ||||
8 | Advanced solid tumour [ICD-11: 2A00-2F9Z] | ||||
9 | Obesity [ICD-11: 5B81] | ||||
10 | Retinoblastoma [ICD-11: 2D02.2] | ||||
Clinical Trial Drug(s) | 11 Clinical Trial Drugs | 11 | |||
1 | PHA848125 | Phase 2 | |||
2 | R-roscovitine | Phase 2 | |||
3 | Ro 31-7453 | Phase 2 | |||
4 | AG-024322 | Phase 1 | |||
5 | AT7519 | Phase 1 | |||
6 | AZD-5438 | Phase 1 | |||
7 | CYC065 | Phase 1 | |||
8 | FN-1501 | Phase 1 | |||
9 | PHA-793887 | Phase 1 | |||
10 | SNS-032 | Phase 1 | |||
11 | TG02 | Phase 1/2 | |||
Discontinued Drug(s) | 4 Discontinued Drugs | 4 | |||
1 | SCH 727965 | Discontinued in Phase 3 | |||
2 | BAY 10-00394 | Discontinued in Phase 2 | |||
3 | R547 | Discontinued in Phase 1 | |||
4 | PD-0183812 | Terminated | |||
Investigative Drug(s) | 1 Investigative Drug | 1 | |||
1 | SCH-546909 | Investigative | |||
Preclinical Drug(s) | 1 Preclinical Drug | 1 | |||
1 | L-751250 | Preclinical |