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MGP000505

UniProt Annotations

Entry Information
Gene Namecyclin-dependent kinase 2
Protein EntryCDK2_HUMAN
UniProt IDP24941
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P24941-1; Sequence=Displayed; Name=2; Synonyms=CDK2deltaT; IsoId=P24941-2; Sequence=VSP_041998;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
Enzyme RegulationPhosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG- 024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H- pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1- ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21). {ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:9030781, ECO:0000269|PubMed:9334743}.
FunctionSerine/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:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315}.
InductionInduced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis.
InteractionP20248:CCNA2; NbExp=19; IntAct=EBI-375096, EBI-457097; O95067:CCNB2; NbExp=2; IntAct=EBI-375096, EBI-375024; P24864:CCNE1; NbExp=10; IntAct=EBI-375096, EBI-519526; O96020:CCNE2; NbExp=7; IntAct=EBI-375096, EBI-375033; P51946:CCNH; NbExp=2; IntAct=EBI-375096, EBI-741406; P38936:CDKN1A; NbExp=14; IntAct=EBI-375096, EBI-375077; P46527:CDKN1B; NbExp=16; IntAct=EBI-375096, EBI-519280; Q16667:CDKN3; NbExp=3; IntAct=EBI-375096, EBI-1031527; P61024:CKS1B; NbExp=3; IntAct=EBI-375096, EBI-456371; Q09472:EP300; NbExp=5; IntAct=EBI-375096, EBI-447295; Q969H0-4:FBXW7; NbExp=2; IntAct=EBI-375096, EBI-6502391; Q08619:Ifi205b (xeno); NbExp=2; IntAct=EBI-375096, EBI-8064290; Q9Y6K9:IKBKG; NbExp=4; IntAct=EBI-375096, EBI-81279; P06400:RB1; NbExp=3; IntAct=EBI-375096, EBI-491274; Q9UBI4:STOML1; NbExp=2; IntAct=EBI-375096, EBI-2681162; Q96PU4:UHRF2; NbExp=5; IntAct=EBI-375096, EBI-625304;
PtmNitrosylated after treatment with nitric oxide (DETA-NO). {ECO:0000269|PubMed:20079829}.
PtmPhosphorylated 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. {ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:1396589, ECO:0000269|PubMed:14597612, ECO:0000269|PubMed:16325401, ECO:0000269|PubMed:17095507, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17570665, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:21565702}.
SimilarityBelongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationCytoplasm, 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).
SubunitFound 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. Interacts with CACUL1. May interact with CEP63. {ECO:0000250, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:11980914, ECO:0000269|PubMed:12185076, ECO:0000269|PubMed:12839962, ECO:0000269|PubMed:12972555, ECO:0000269|PubMed:15178429, ECO:0000269|PubMed:15611625, ECO:0000269|PubMed:16325401, ECO:0000269|PubMed:17095507, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:17570665, ECO:0000269|PubMed:17937404, ECO:0000269|PubMed:18656911, ECO:0000269|PubMed:19445729, ECO:0000269|PubMed:19829063, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21406398, ECO:0000269|PubMed:21565702, ECO:0000269|PubMed:7630397, ECO:0000269|PubMed:8610110, ECO:0000269|PubMed:8684460, ECO:0000269|PubMed:8756328, ECO:0000269|PubMed:9334743}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdk2/";
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