Homo sapiens Protein: CDK2 | |||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Summary | |||||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-39549.7 | ||||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||
Gene Symbol | CDK2 | ||||||||||||||||||||||||||||||||||||||||
Protein Name | cyclin-dependent kinase 2 | ||||||||||||||||||||||||||||||||||||||||
Synonyms | CDKN2; p33(CDK2); | ||||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000243067 | ||||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-39545 (CDK2) | ||||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||||
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. {ECO:0000250, ECO:0000269PubMed:10499802, ECO:0000269PubMed:10884347, ECO:0000269PubMed:10995386, ECO:0000269PubMed:10995387, ECO:0000269PubMed:11051553, ECO:0000269PubMed:11113184, ECO:0000269PubMed:15800615, ECO:0000269PubMed:17495531, ECO:0000269PubMed:18372919, ECO:0000269PubMed:19966300, ECO:0000269PubMed:20079829, ECO:0000269PubMed:20147522, ECO:0000269PubMed:20195506, ECO:0000269PubMed:20935635, ECO:0000269PubMed:21262353, ECO:0000269PubMed:21319273, ECO:0000269PubMed:21596315}. | ||||||||||||||||||||||||||||||||||||||||
Subcellular Localization | Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus, Cajal body. Cytoplasm. Endosome. 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). | ||||||||||||||||||||||||||||||||||||||||
Disease Associations | |||||||||||||||||||||||||||||||||||||||||
Tissue Specificity | |||||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 655 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.
|
||||||||||||||||||||||||||||||||||||||||
Gene Ontology | |||||||||||||||||||||||||||||||||||||||||
Molecular Function |
|
||||||||||||||||||||||||||||||||||||||||
Biological Process |
|
||||||||||||||||||||||||||||||||||||||||
Cellular Component |
|
||||||||||||||||||||||||||||||||||||||||
Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000719
Protein kinase domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR011009 Protein kinase-like domain IPR020635 Tyrosine-protein kinase, catalytic domain |
||||||||||||||||||||||||||||||||||||||||
PFAM |
PF00069
PF07714 |
||||||||||||||||||||||||||||||||||||||||
PRINTS |
PR00109
|
||||||||||||||||||||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||||||||||||||||||||
SMART |
SM00220
SM00219 |
||||||||||||||||||||||||||||||||||||||||
TIGRFAMs | |||||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||||
SwissProt | P24941 | ||||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P24941 | ||||||||||||||||||||||||||||||||||||||||
TrEMBL | G3V317 | ||||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||
Entrez Gene | 1017 | ||||||||||||||||||||||||||||||||||||||||
UniGene | Hs.717547 | ||||||||||||||||||||||||||||||||||||||||
RefSeq | NP_439892 | ||||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:1771 | ||||||||||||||||||||||||||||||||||||||||
OMIM | 116953 | ||||||||||||||||||||||||||||||||||||||||
CCDS | CCDS8899 | ||||||||||||||||||||||||||||||||||||||||
HPRD | 00310 | ||||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||||
EMBL | AB012305 AC025162 AC034102 AF512553 AK291941 BC003065 BT006821 CH471054 M68520 X61622 X62071 | ||||||||||||||||||||||||||||||||||||||||
GenPept | AAA35667 AAH03065 AAM34794 AAP35467 BAA32794 BAF84630 CAA43807 CAA43985 EAW96856 EAW96857 EAW96858 | ||||||||||||||||||||||||||||||||||||||||