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Q5E9Y0

- CDK2_BOVIN

UniProt

Q5E9Y0 - CDK2_BOVIN

Protein

Cyclin-dependent kinase 2

Gene

CDK2

Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 85 (01 Oct 2014)
      Sequence version 1 (15 Mar 2005)
      Previous versions | rss
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    Functioni

    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 By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei9 – 91CDK7 bindingBy similarity
    Binding sitei33 – 331ATPPROSITE-ProRule annotation
    Binding sitei86 – 861ATPPROSITE-ProRule annotation
    Sitei88 – 892CDK7 bindingBy similarity
    Active sitei127 – 1271Proton acceptorPROSITE-ProRule annotation
    Metal bindingi132 – 1321Magnesium; catalyticBy similarity
    Metal bindingi145 – 1451Magnesium; catalyticBy similarity
    Binding sitei145 – 1451ATPPROSITE-ProRule annotation
    Sitei166 – 1661CDK7 bindingBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi10 – 189ATPPROSITE-ProRule annotation
    Nucleotide bindingi81 – 833ATPPROSITE-ProRule annotation
    Nucleotide bindingi129 – 1324ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cyclin-dependent protein serine/threonine kinase activity Source: AgBase
    3. histone kinase activity Source: Ensembl
    4. kinase activity Source: AgBase
    5. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. cell cycle Source: AgBase
    2. DNA repair Source: UniProtKB-KW
    3. G1/S transition of mitotic cell cycle Source: Ensembl
    4. meiotic nuclear division Source: UniProtKB-KW
    5. mitotic nuclear division Source: UniProtKB-KW
    6. positive regulation of cell proliferation Source: Ensembl
    7. positive regulation of DNA-dependent DNA replication initiation Source: Ensembl
    8. positive regulation of transcription, DNA-templated Source: AgBase
    9. potassium ion transport Source: AgBase
    10. protein phosphorylation Source: AgBase
    11. Ras protein signal transduction Source: Ensembl
    12. regulation of cell cycle Source: GOC
    13. regulation of gene silencing Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_201949. G2 Phase.
    REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
    REACT_206864. Cyclin A:Cdk2-associated events at S phase entry.
    REACT_211635. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
    REACT_213030. Orc1 removal from chromatin.
    REACT_213075. Regulation of APC/C activators between G1/S and early anaphase.
    REACT_214732. DNA Damage/Telomere Stress Induced Senescence.
    REACT_215067. Factors involved in megakaryocyte development and platelet production.
    REACT_221628. Activation of the pre-replicative complex.
    REACT_222557. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_223494. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_224007. Cyclin A/B1 associated events during G2/M transition.
    REACT_226948. G0 and Early G1.
    REACT_227679. p53-Dependent G1 DNA Damage Response.
    REACT_227740. Activation of ATR in response to replication stress.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 2 (EC:2.7.11.22)
    Alternative name(s):
    Cell division protein kinase 2
    Gene namesi
    Name:CDK2
    Synonyms:CDKN2
    OrganismiBos taurus (Bovine)
    Taxonomic identifieri9913 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
    ProteomesiUP000009136: Chromosome 5

    Subcellular locationi

    Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. NucleusCajal body By similarity. Cytoplasm By similarity. Endosome By similarity
    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)2D3 By similarity.By similarity

    GO - Cellular componenti

    1. Cajal body Source: UniProtKB-SubCell
    2. chromosome, telomeric region Source: Ensembl
    3. condensed chromosome Source: Ensembl
    4. cyclin-dependent protein kinase holoenzyme complex Source: AgBase
    5. endosome Source: UniProtKB-SubCell
    6. microtubule organizing center Source: UniProtKB-SubCell
    7. nucleus Source: AgBase
    8. transcription factor complex Source: AgBase
    9. X chromosome Source: Ensembl
    10. Y chromosome Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Endosome, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 298298Cyclin-dependent kinase 2PRO_0000085767Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei6 – 61N6-acetyllysineBy similarity
    Modified residuei14 – 141PhosphothreonineBy similarity
    Modified residuei15 – 151Phosphotyrosine; by WEE1By similarity
    Modified residuei19 – 191PhosphotyrosineBy similarity
    Modified residuei160 – 1601Phosphothreonine; by CAK and CCRKBy similarity

    Post-translational modificationi

    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 By similarity.By similarity
    Nitrosylated after treatment with nitric oxide (DETA-NO).By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    PRIDEiQ5E9Y0.

    Interactioni

    Subunit structurei

    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 By similarity. Interacts with CACUL1 By similarity. May interact with CEP63 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi175836. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5E9Y0.
    SMRiQ5E9Y0. Positions 1-298.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 286283Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00720000108415.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiQ5E9Y0.
    KOiK02206.
    OMAiLVHRFFR.
    OrthoDBiEOG7966H8.
    TreeFamiTF101021.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5E9Y0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR    50
    EISLLKELNH PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP 100
    LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINADGS IKLADFGLAR 150
    AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMVTRR 200
    ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF PKWARQDFSK 250
    VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL 298
    Length:298
    Mass (Da):33,873
    Last modified:March 15, 2005 - v1
    Checksum:iEEC785D6A0E87A71
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BT020790 mRNA. Translation: AAX08807.1.
    BC150026 mRNA. Translation: AAI50027.1.
    RefSeqiNP_001014934.1. NM_001014934.1.
    UniGeneiBt.21444.

    Genome annotation databases

    EnsembliENSBTAT00000005252; ENSBTAP00000005252; ENSBTAG00000004021.
    GeneIDi519217.
    KEGGibta:519217.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BT020790 mRNA. Translation: AAX08807.1 .
    BC150026 mRNA. Translation: AAI50027.1 .
    RefSeqi NP_001014934.1. NM_001014934.1.
    UniGenei Bt.21444.

    3D structure databases

    ProteinModelPortali Q5E9Y0.
    SMRi Q5E9Y0. Positions 1-298.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 175836. 1 interaction.

    Proteomic databases

    PRIDEi Q5E9Y0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSBTAT00000005252 ; ENSBTAP00000005252 ; ENSBTAG00000004021 .
    GeneIDi 519217.
    KEGGi bta:519217.

    Organism-specific databases

    CTDi 1017.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00720000108415.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi Q5E9Y0.
    KOi K02206.
    OMAi LVHRFFR.
    OrthoDBi EOG7966H8.
    TreeFami TF101021.

    Enzyme and pathway databases

    Reactomei REACT_201949. G2 Phase.
    REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
    REACT_206864. Cyclin A:Cdk2-associated events at S phase entry.
    REACT_211635. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
    REACT_213030. Orc1 removal from chromatin.
    REACT_213075. Regulation of APC/C activators between G1/S and early anaphase.
    REACT_214732. DNA Damage/Telomere Stress Induced Senescence.
    REACT_215067. Factors involved in megakaryocyte development and platelet production.
    REACT_221628. Activation of the pre-replicative complex.
    REACT_222557. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_223494. SCF(Skp2)-mediated degradation of p27/p21.
    REACT_224007. Cyclin A/B1 associated events during G2/M transition.
    REACT_226948. G0 and Early G1.
    REACT_227679. p53-Dependent G1 DNA Damage Response.
    REACT_227740. Activation of ATR in response to replication stress.

    Miscellaneous databases

    NextBioi 20872832.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    2. NIH - Mammalian Gene Collection (MGC) project
      Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Hereford.
      Tissue: Thymus.

    Entry informationi

    Entry nameiCDK2_BOVIN
    AccessioniPrimary (citable) accession number: Q5E9Y0
    Secondary accession number(s): A6QQX1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 20, 2005
    Last sequence update: March 15, 2005
    Last modified: October 1, 2014
    This is version 85 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3