ID CDK2_BOVIN Reviewed; 298 AA. AC Q5E9Y0; A6QQX1; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2005, sequence version 1. DT 27-MAR-2024, entry version 149. 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 Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Thymus; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Serine/threonine-protein kinase involved in the control of CC the cell cycle; essential for meiosis, but dispensable for mitosis. CC Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, CC NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the CC G1-S transition to promote the E2F transcriptional program and the CC initiation of DNA synthesis, and modulates G2 progression; controls the CC timing of entry into mitosis/meiosis by controlling the subsequent CC activation of cyclin B/CDK1 by phosphorylation, and coordinates the CC activation of cyclin B/CDK1 at the centrosome and in the nucleus. CC Crucial role in orchestrating a fine balance between cellular CC proliferation, cell death, and DNA repair in human embryonic stem cells CC (hESCs). Activity of CDK2 is maximal during S phase and G2; activated CC by interaction with cyclin E during the early stages of DNA synthesis CC to permit G1-S transition, and subsequently activated by cyclin A2 CC (cyclin A1 in germ cells) during the late stages of DNA replication to CC drive the transition from S phase to mitosis, the G2 phase. EZH2 CC phosphorylation promotes H3K27me3 maintenance and epigenetic gene CC silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 CC prevents oxidative stress-mediated Ras-induced senescence by CC phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that CC prevents cells with damaged DNA from initiating mitosis; regulates CC homologous recombination-dependent repair by phosphorylating BRCA2, CC this phosphorylation is low in S phase when recombination is active, CC but increases as cells progress towards mitosis. In response to DNA CC damage, double-strand break repair by homologous recombination a CC reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of CC RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin CC E/CDK2 promotes its dissociates from unduplicated centrosomes, thus CC initiating centrosome duplication. Cyclin E/CDK2-mediated CC phosphorylation of NPAT at G1-S transition and until prophase CC stimulates the NPAT-mediated activation of histone gene transcription CC during S phase. Required for vitamin D-mediated growth inhibition by CC being itself inactivated. Involved in the nitric oxide- (NO) mediated CC signaling in a nitrosylation/activation-dependent manner. USP37 is CC activated by phosphorylation and thus triggers G1-S transition. CTNNB1 CC phosphorylation regulates insulin internalization. Phosphorylates FOXP3 CC and negatively regulates its transcriptional activity and protein CC stability (By similarity). Phosphorylates CDK2AP2 (By similarity). CC Phosphorylates ERCC6 which is essential for its chromatin remodeling CC activity at DNA double-strand breaks (By similarity). CC {ECO:0000250|UniProtKB:P24941, ECO:0000250|UniProtKB:P97377, CC ECO:0000250|UniProtKB:Q63699}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; 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=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.22; 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. Stimulated CC by MYC. Inactivated by CDKN1A (p21) (By similarity). CC {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}. 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; BT020790; AAX08807.1; -; mRNA. DR EMBL; BC150026; AAI50027.1; -; mRNA. DR RefSeq; NP_001014934.1; NM_001014934.1. DR AlphaFoldDB; Q5E9Y0; -. DR SMR; Q5E9Y0; -. DR BioGRID; 175836; 1. DR STRING; 9913.ENSBTAP00000005252; -. DR PaxDb; 9913-ENSBTAP00000005252; -. DR Ensembl; ENSBTAT00000005252.3; ENSBTAP00000005252.2; ENSBTAG00000004021.3. DR GeneID; 519217; -. DR KEGG; bta:519217; -. DR CTD; 1017; -. DR VEuPathDB; HostDB:ENSBTAG00000004021; -. DR VGNC; VGNC:27123; CDK2. DR eggNOG; KOG0594; Eukaryota. DR GeneTree; ENSGT00940000159517; -. DR HOGENOM; CLU_000288_181_1_1; -. DR InParanoid; Q5E9Y0; -. DR OMA; HKEKCIY; -. DR TreeFam; TF101021; -. DR Reactome; R-BTA-1538133; G0 and Early G1. DR Reactome; R-BTA-171319; Telomere Extension By Telomerase. DR Reactome; R-BTA-176187; Activation of ATR in response to replication stress. DR Reactome; R-BTA-176408; Regulation of APC/C activators between G1/S and early anaphase. DR Reactome; R-BTA-187577; SCF(Skp2)-mediated degradation of p27/p21. DR Reactome; R-BTA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-BTA-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-BTA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-BTA-6804116; TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest. DR Reactome; R-BTA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-BTA-6804757; Regulation of TP53 Degradation. DR Reactome; R-BTA-68911; G2 Phase. DR Reactome; R-BTA-68949; Orc1 removal from chromatin. DR Reactome; R-BTA-68962; Activation of the pre-replicative complex. DR Reactome; R-BTA-69017; CDK-mediated phosphorylation and removal of Cdc6. DR Reactome; R-BTA-69200; Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes. DR Reactome; R-BTA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-BTA-69231; Cyclin D associated events in G1. DR Reactome; R-BTA-69273; Cyclin A/B1/B2 associated events during G2/M transition. DR Reactome; R-BTA-69563; p53-Dependent G1 DNA Damage Response. DR Reactome; R-BTA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-BTA-8849470; PTK6 Regulates Cell Cycle. DR Proteomes; UP000009136; Chromosome 5. DR Bgee; ENSBTAG00000004021; Expressed in spermatocyte and 103 other cell types or tissues. 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; ISS:AgBase. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:AgBase. DR GO; GO:0005667; C:transcription regulator complex; ISS:AgBase. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0030332; F:cyclin binding; IBA:GO_Central. 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:AgBase. DR GO; GO:0016301; F:kinase activity; ISS:AgBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:AgBase. DR GO; GO:0006813; P:potassium ion transport; ISS:AgBase. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd07860; STKc_CDK2_3; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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_0000085767" 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..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 81..83 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 86 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 129..132 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" 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:0000255|PROSITE-ProRule:PRU00159" 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" FT SITE 88..89 FT /note="CDK7 binding" FT /evidence="ECO:0000250" FT SITE 166 FT /note="CDK7 binding" FT /evidence="ECO:0000250" 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; 33873 MW; EEC785D6A0E87A71 CRC64; MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINADGS IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL //