ID CDK2_MESAU Reviewed; 298 AA. AC P48963; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 02-SEP-2026, entry version 133. DE RecName: Full=Cyclin-dependent kinase 2; DE EC=2.7.11.22 {ECO:0000250|UniProtKB:P24941}; DE AltName: Full=Cell division protein kinase 2; GN Name=CDK2; Synonyms=CDKN2; OS Mesocricetus auratus (Golden hamster). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; OC Cricetidae; Cricetinae; Mesocricetus. OX NCBI_TaxID=10036; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8280171; DOI=10.1006/bbrc.1993.2650; RA Noguchi E., Sekiguchi T., Yamashita K., Nishimoto T.; RT "Molecular cloning and identification of two types of hamster cyclin- RT dependent kinases: cdk2 and cdk2L."; RL Biochem. Biophys. Res. Commun. 197:1524-1529(1993). CC -!- FUNCTION: Serine/threonine-protein kinase involved in the control of CC the cell cycle; essential for meiosis, but dispensable for mitosis (By CC similarity). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, CC USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 (By CC similarity). Triggers duplication of centrosomes and DNA (By CC similarity). Acts at the G1-S transition to promote the E2F CC transcriptional program and the initiation of DNA synthesis, and CC modulates G2 progression; controls the timing of entry into CC mitosis/meiosis by controlling the subsequent activation of cyclin CC B/CDK1 by phosphorylation, and coordinates the activation of cyclin CC B/CDK1 at the centrosome and in the nucleus (By similarity). Crucial CC role in orchestrating a fine balance between cellular proliferation, CC cell death, and DNA repair in embryonic stem cells (ESCs) (By CC similarity). Activated by the CDK-activating kinase (CAK) complex CC consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator CC of CDK activity (By similarity). Activity of CDK2 is maximal during S CC phase and G2; activated by interaction with cyclin E during the early CC stages of DNA synthesis to permit G1-S transition, and subsequently CC activated by cyclin A2 (cyclin A1 in germ cells) during the late stages CC of DNA replication to drive the transition from S phase to mitosis, the CC G2 phase (By similarity). EZH2 phosphorylation promotes H3K27me3 CC maintenance and epigenetic gene silencing (By similarity). Cyclin CC E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by CC phosphorylating MYC (By similarity). Involved in G1-S phase DNA damage CC checkpoint that prevents cells with damaged DNA from initiating CC mitosis; regulates homologous recombination-dependent repair by CC phosphorylating BRCA2, this phosphorylation is low in S phase when CC recombination is active, but increases as cells progress towards CC mitosis (By similarity). In response to DNA damage, double-strand break CC repair by homologous recombination a reduction of CDK2-mediated BRCA2 CC phosphorylation (By similarity). Involved in regulation of telomere CC repair by mediating phosphorylation of NBN (By similarity). CC Phosphorylation of RB1 disturbs its interaction with E2F1 (By CC similarity). NPM1 phosphorylation by cyclin E/CDK2 promotes its CC dissociation from unduplicated centrosomes, thus initiating centrosome CC duplication (By similarity). Cyclin E/CDK2-mediated phosphorylation of CC NPAT at G1-S transition and until prophase stimulates the NPAT-mediated CC activation of histone gene transcription during S phase (By CC similarity). Required for vitamin D-mediated growth inhibition by being CC itself inactivated (By similarity). Involved in the nitric oxide- (NO) CC mediated signaling in a nitrosylation/activation-dependent manner (By CC similarity). USP37 is activated by phosphorylation and thus triggers CC G1-S transition (By similarity). CTNNB1 phosphorylation regulates CC insulin internalization (By similarity). Phosphorylates FOXP3 and CC negatively regulates its transcriptional activity and protein stability CC (By similarity). Phosphorylates ERCC6 which is essential for its CC chromatin remodeling activity at DNA double-strand breaks (By CC similarity). Acts as a regulator of the phosphatidylinositol 3- CC kinase/protein kinase B signal transduction by mediating CC phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and CC PKB/AKT2), promoting its activation (By similarity). CC {ECO:0000250|UniProtKB:P24941, ECO:0000250|UniProtKB:P97377}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000250|UniProtKB:P24941}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000250|UniProtKB:P24941}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P24941}; CC Note=Binds 2 Mg(2+) ions. {ECO:0000250|UniProtKB:P24941}; CC -!- ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates CC the enzyme, while phosphorylation at Thr-160 activates it (By CC similarity). Phosphorylated and activated by CDK7 in the CDK-activating CC kinase (CAK) complex, and reciprocally phosphorylating its activating CC kinase CDK7 (By similarity). Stimulated by MYC. Inactivated by CDKN1A CC (p21). {ECO:0000250|UniProtKB:P24941}. CC -!- SUBUNIT: Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts CC with CABLES1 (By similarity). Interacts with UHRF2. Part of a complex CC consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo CC proteins SPDYA and SPDYC. Interaction with SPDYA promotes kinase CC activation via a conformation change that alleviates obstruction of the CC substrate-binding cleft by the T-loop. Found in a complex with both CC SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to CDKN1A (p21) CC leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage CC checkpoint, thereby arresting cells at the G1-S transition during DNA CC repair. Associated with PTPN6 and beta-catenin/CTNNB1. Interacts with CC CACUL1. May interact with CEP63. Interacts with ANKRD17. Interacts with CC CEBPA (when phosphorylated). Forms a ternary complex with CCNA2 and CC CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through CC conformational rearrangements. Interacts with cyclins A, B1, B3, D, or CC E. Interacts with CDK2AP2 (By similarity). CC {ECO:0000250|UniProtKB:P24941, ECO:0000250|UniProtKB:P97377, CC ECO:0000250|UniProtKB:Q63699}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome {ECO:0000250}. Nucleus, Cajal body {ECO:0000250}. CC Cytoplasm {ECO:0000250}. Endosome {ECO:0000250}. Note=Localized at the CC centrosomes in late G2 phase after separation of the centrosomes but CC before the start of prophase. Nuclear-cytoplasmic trafficking is CC mediated during the inhibition by 1,25-(OH)(2)D(3) (By similarity). CC {ECO:0000250}. CC -!- PTM: Phosphorylated at Thr-160 by CDK7 in a CAK complex. CC Phosphorylation at Thr-160 promotes kinase activity, whereas CC phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. CC Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being CC dephosphorylated by CDC25A. {ECO:0000250|UniProtKB:P24941}. CC -!- PTM: Nitrosylated after treatment with nitric oxide (DETA-NO). CC {ECO:0000250|UniProtKB:P24941}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D17350; BAA04165.1; -; mRNA. DR AlphaFoldDB; P48963; -. DR SMR; P48963; -. DR STRING; 10036.ENSMAUP00000021672; -. DR BRENDA; 2.7.11.22; 3239. DR Proteomes; UP000886700; Unplaced. DR GO; GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IEA:TreeGrafter. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0030332; F:cyclin binding; IEA:TreeGrafter. DR GO; GO:0097472; F:cyclin-dependent protein kinase activity; ISS:UniProtKB. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:TreeGrafter. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IEA:TreeGrafter. DR GO; GO:0010468; P:regulation of gene expression; IEA:TreeGrafter. DR GO; GO:0007165; P:signal transduction; IEA:TreeGrafter. DR CDD; cd07860; STKc_CDK2_3; 1. DR FunFam; 1.10.510.10:FF:000144; Cyclin-dependent kinase 2; 1. DR FunFam; 3.30.200.20:FF:000599; Cyclin-dependent kinase 2; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR050108; CDK. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF521; CYCLIN-DEPENDENT KINASE 2; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 2: Evidence at transcript level; KW Acetylation; ATP-binding; Cell cycle; Cell division; Cytoplasm; KW Cytoskeleton; DNA damage; DNA repair; Endosome; Kinase; Magnesium; Meiosis; KW Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT CHAIN 1..298 FT /note="Cyclin-dependent kinase 2" FT /id="PRO_0000085770" FT DOMAIN 4..286 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 127 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 10 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 11 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 12 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 13 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 14 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 14 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 15 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 16 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 17 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 33 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 81..83 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 81 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 83 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 86 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 127 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 129..132 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 132 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 145 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P24941" FT BINDING 145 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P24941" FT SITE 9 FT /note="CDK7 binding" FT /evidence="ECO:0000250|UniProtKB:P24941" FT SITE 88..89 FT /note="CDK7 binding" FT /evidence="ECO:0000250|UniProtKB:P24941" FT SITE 166 FT /note="CDK7 binding" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 6 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 14 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 15 FT /note="Phosphotyrosine; by WEE1" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 19 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P24941" FT MOD_RES 160 FT /note="Phosphothreonine; by CAK and CCRK" FT /evidence="ECO:0000250|UniProtKB:P24941" SQ SEQUENCE 298 AA; 33839 MW; D11C036664C4C7CE CRC64; MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH PNIVKLLDVI HTENKLYLVF ELLHQDLKKF MDASAVTGIP LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINAEGS IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL //