ID:CDK2_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase 2; EC=2.7.11.22; AltName: Full=Cell division protein kinase 2; AltName: Full=p33 protein kinase; 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. 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). 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. Interacts with CACUL1. May interact with CEP63. INTERACTION: P20248:CCNA2; NbExp=16; IntAct=EBI-375096, EBI-457097; P24864:CCNE1; NbExp=9; IntAct=EBI-375096, EBI-519526; O96020:CCNE2; NbExp=5; IntAct=EBI-375096, EBI-375033; P51946:CCNH; NbExp=2; IntAct=EBI-375096, EBI-741406; P38936:CDKN1A; NbExp=9; IntAct=EBI-375096, EBI-375077; P46527:CDKN1B; NbExp=12; IntAct=EBI-375096, EBI-519280; Q16667:CDKN3; NbExp=2; IntAct=EBI-375096, EBI-1031527; Q9Y6K9:IKBKG; NbExp=4; IntAct=EBI-375096, EBI-81279; P06400:RB1; NbExp=3; IntAct=EBI-375096, EBI-491274; Q96PU4:UHRF2; NbExp=5; IntAct=EBI-375096, EBI-625304; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, 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). INDUCTION: Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis. 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. PTM: Nitrosylated after treatment with nitric oxide (DETA-NO). SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdk2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P24941
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0000086 G2/M transition of mitotic cell cycle GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006260 DNA replication GO:0006281 DNA repair GO:0006468 protein phosphorylation GO:0006813 potassium ion transport GO:0006974 cellular response to DNA damage stimulus GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0007049 cell cycle GO:0007099 centriole replication GO:0007265 Ras protein signal transduction GO:0007275 multicellular organism development GO:0008284 positive regulation of cell proliferation GO:0010033 response to organic substance GO:0010389 regulation of G2/M transition of mitotic cell cycle GO:0016310 phosphorylation GO:0016572 histone phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0031571 mitotic G1 DNA damage checkpoint GO:0032298 positive regulation of DNA-dependent DNA replication initiation GO:0045893 positive regulation of transcription, DNA-templated GO:0051298 centrosome duplication GO:0051301 cell division GO:0051321 meiotic cell cycle GO:0060968 regulation of gene silencing GO:0071732 cellular response to nitric oxide GO:1901796 regulation of signal transduction by p53 class mediator
M68520 - Human cdc2-related protein kinase mRNA, complete cds. AK293246 - Homo sapiens cDNA FLJ54979 complete cds, highly similar to Homo sapiens cyclin-dependent kinase 2 (CDK2), transcript variant 2, mRNA. AK291941 - Homo sapiens cDNA FLJ76907 complete cds, highly similar to Homo sapiens cyclin-dependent kinase 2 (CDK2), transcript variant 1, mRNA. X62071 - H.sapiens cdk2 mRNA. BC003065 - Homo sapiens cyclin-dependent kinase 2, mRNA (cDNA clone MGC:1784 IMAGE:3504348), complete cds. DQ890598 - Synthetic construct clone IMAGE:100003228; FLH164346.01X; RZPDo839F04162D cyclin-dependent kinase 2 (CDK2) gene, encodes complete protein. AB012305 - Homo sapiens mRNA for d-HSCDK2, complete cds. AB463549 - Synthetic construct DNA, clone: pF1KB8304, Homo sapiens CDK2 gene for cyclin-dependent kinase 2, without stop codon, in Flexi system. AM393136 - Synthetic construct Homo sapiens clone IMAGE:100001830 for hypothetical protein (CDK2 gene). DQ893767 - Synthetic construct Homo sapiens clone IMAGE:100008227; FLH164342.01L; RZPDo839F04161D cyclin-dependent kinase 2 (CDK2) gene, encodes complete protein. KJ890882 - Synthetic construct Homo sapiens clone ccsbBroadEn_00276 CDK2 gene, encodes complete protein. KJ905163 - Synthetic construct Homo sapiens clone ccsbBroadEn_14572 CDK2 gene, encodes complete protein. BT006821 - Homo sapiens cyclin-dependent kinase 2 mRNA, complete cds. X61622 - H.sapiens CDK2 mRNA. JD481517 - Sequence 462541 from Patent EP1572962. JD425686 - Sequence 406710 from Patent EP1572962. JD077871 - Sequence 58895 from Patent EP1572962. JD054987 - Sequence 36011 from Patent EP1572962. JD462140 - Sequence 443164 from Patent EP1572962. JD410936 - Sequence 391960 from Patent EP1572962. JD557945 - Sequence 538969 from Patent EP1572962. JD042082 - Sequence 23106 from Patent EP1572962. JD334142 - Sequence 315166 from Patent EP1572962. JD494862 - Sequence 475886 from Patent EP1572962. JD288153 - Sequence 269177 from Patent EP1572962. JD516331 - Sequence 497355 from Patent EP1572962. JD319852 - Sequence 300876 from Patent EP1572962. JD550840 - Sequence 531864 from Patent EP1572962. JD237842 - Sequence 218866 from Patent EP1572962. JD349296 - Sequence 330320 from Patent EP1572962. JD342023 - Sequence 323047 from Patent EP1572962. JD199926 - Sequence 180950 from Patent EP1572962. JD469505 - Sequence 450529 from Patent EP1572962. JD526947 - Sequence 507971 from Patent EP1572962. JD252871 - Sequence 233895 from Patent EP1572962. JD507018 - Sequence 488042 from Patent EP1572962. JD228840 - Sequence 209864 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_p27Pathway - Regulation of p27 Phosphorylation during Cell Cycle Progression h_fbw7Pathway - Cyclin E Destruction Pathway h_RacCycDPathway - Influence of Ras and Rho proteins on G1 to S Transition h_cellcyclePathway - Cyclins and Cell Cycle Regulation h_EfpPathway - Estrogen-responsive protein Efp controls cell cycle and breast tumors growth h_g1Pathway - Cell Cycle: G1/S Check Point h_mcmPathway - CDK Regulation of DNA Replication h_rbPathway - RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage h_skp2e2fPathway - E2F1 Destruction Pathway h_p53Pathway - p53 Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P24941 (Reactome details) participates in the following event(s):
R-HSA-1013881 Cables1 links CDK2 and WEE1 R-HSA-69191 Formation of Cyclin E:Cdk2 complexes R-HSA-174054 Formation of Cyclin A:Cdk2 complexes R-HSA-69195 Phosphorylation of Cyclin E:Cdk2 complexes by Wee-1 R-HSA-69562 Inactivation of Cyclin E:Cdk2 complexes by p27/p21 R-HSA-188350 CAK-mediated phosphorylation of Cyclin E:Cdk2 R-HSA-69199 Dephosphorylation of Cyclin E:Cdk2 complexes by Cdc25A R-HSA-157906 Translocation of Cyclin E:Cdk2 complex to the nucleus R-HSA-68918 CDK and DDK associate with the Mcm10:pre-replicative complex R-HSA-174164 Phosphorylation of Cyclin A:Cdk2 at Tyr 15 R-HSA-187934 Inactivation of Cyclin A:Cdk2 complexes by p27/p21 R-HSA-187949 CAK-mediated phosphorylation of Cyclin A:Cdk2 R-HSA-174110 Cdc25A mediated dephosphorylation of Cyclin A:phospho-Cdk2 R-HSA-174273 Translocation of Cyclin A:Cdk2 complexes to the nucleus R-HSA-1363303 p130 (RBL2) in complex with E2F4/5:DP1/2 binds to cyclin E/A:CDK2 R-HSA-1363306 p130 (RBL2) binds Cyclin E/A:CDK2 R-HSA-1363311 p107 (RBL1) in complex with E2F4:DP1/2 binds to cyclin E/A:CDK2 R-HSA-1363314 p107 (RBL1) binds CyclinE/A:CDK2 R-HSA-187937 Association of Cyclin A:phospho-Cdk2(Thr 160) with E2F1/E2F3 R-HSA-188371 Association of Cyclin A:Cdk2 with Cdh1 R-HSA-3788708 CDKN1A (p21) prevents association of Cyclin A:Cdk2 with Cdh1 R-HSA-5684081 MRN complex binds CDK2 and RBBP8 R-HSA-5684096 CDK2 phosphorylates RBBP8 R-HSA-188386 Association of Rb with Cyclin E:Cdk2 complexes R-HSA-68917 Cdc45 associates with the pre-replicative complex at the origin R-HSA-187916 Cyclin A:Cdk2 mediated phosphorylation of p27/p21 R-HSA-187959 Phosphorylation of E2F1/E2F3 by Cyclin A:phosph-Cdk2(Thr 160) R-HSA-174079 Phosphorylation of Cdh1 by Cyclin A:Cdk2 R-HSA-3788705 CDKN1A (p21) prevents phosphorylation of Cdh1 by Cyclin A:Cdk2 R-HSA-68944 Orc1 is phosphorylated by cyclin A/CDK2 R-HSA-187948 Phosphorylation of proteins involved in the G1/S transition by Cyclin A:Cdk2 R-HSA-6805109 CDK2 phosphorylates TP53 R-HSA-188390 Cyclin E:Cdk2-mediated phosphorylation of Rb R-HSA-68916 DNA Replication Factor A (RPA) associates with the pre-replicative complex at the origin R-HSA-176318 Loading of claspin onto DNA during replication origin firing R-HSA-8848414 Activated PTK6 binds CDKN1B R-HSA-8848436 PTK6 phosphorylates CDKN1B R-HSA-6793661 (CDK1,CDK2):CCNA phosphorylates MDM2 at T218 R-HSA-187520 Cyclin E/A:Cdk2-mediated phosphorylation of p27/p21 R-HSA-187552 Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex R-HSA-69005 Cdc6 protein is phosphorylated by CDK R-HSA-176298 Activation of claspin R-HSA-4088024 CCNA:CDK1/2 complexes and CCNB1:CDK1 complexes phosphorylate FOXM1 R-HSA-187575 Ubiquitination of phospho-p27/p21 R-HSA-912446 Meiotic recombination R-HSA-983231 Factors involved in megakaryocyte development and platelet production R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-69563 p53-Dependent G1 DNA Damage Response R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest R-HSA-68962 Activation of the pre-replicative complex R-HSA-1538133 G0 and Early G1 R-HSA-1500620 Meiosis R-HSA-109582 Hemostasis R-HSA-69206 G1/S Transition R-HSA-69242 S Phase R-HSA-68911 G2 Phase R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint R-HSA-2559583 Cellular Senescence R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-69002 DNA Replication Pre-Initiation R-HSA-453279 Mitotic G1-G1/S phases R-HSA-1474165 Reproduction R-HSA-1640170 Cell Cycle R-HSA-69278 Cell Cycle (Mitotic) R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 R-HSA-453274 Mitotic G2-G2/M phases R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-68949 Orc1 removal from chromatin R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes R-HSA-69615 G1/S DNA Damage Checkpoints R-HSA-2262752 Cellular responses to stress R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-176187 Activation of ATR in response to replication stress R-HSA-68874 M/G1 Transition R-HSA-8849470 PTK6 Regulates Cell Cycle R-HSA-6804757 Regulation of TP53 Degradation R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 R-HSA-453276 Regulation of mitotic cell cycle R-HSA-5693538 Homology Directed Repair R-HSA-69052 Switching of origins to a post-replicative state R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-8953897 Cellular responses to external stimuli R-HSA-212436 Generic Transcription Pathway R-HSA-69481 G2/M Checkpoints R-HSA-69306 DNA Replication R-HSA-8848021 Signaling by PTK6 R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-6806003 Regulation of TP53 Expression and Degradation R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-69239 Synthesis of DNA R-HSA-73857 RNA Polymerase II Transcription R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases R-HSA-69275 G2/M Transition R-HSA-73894 DNA Repair R-HSA-74160 Gene expression (Transcription) R-HSA-162582 Signal Transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
