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Q63699

- CDK2_RAT

UniProt

Q63699 - CDK2_RAT

Protein

Cyclin-dependent kinase 2

Gene

Cdk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      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 binding Source: RGD
    3. cyclin-dependent protein serine/threonine kinase activity Source: RGD
    4. metal ion binding Source: UniProtKB-KW
    5. protein complex binding Source: RGD

    GO - Biological processi

    1. cellular response to insulin stimulus Source: RGD
    2. DNA repair Source: UniProtKB-KW
    3. lens development in camera-type eye Source: RGD
    4. meiotic nuclear division Source: UniProtKB-KW
    5. mitotic nuclear division Source: UniProtKB-KW
    6. organ regeneration Source: RGD
    7. regulation of cell cycle Source: GOC
    8. response to cadmium ion Source: RGD
    9. response to cAMP Source: RGD
    10. response to drug Source: RGD
    11. response to electrical stimulus Source: RGD
    12. response to estradiol Source: RGD
    13. response to ethanol Source: RGD
    14. response to toxic substance Source: RGD

    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

    BRENDAi2.7.11.22. 5301.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi70486. Cdk2.

    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. cytosol Source: RGD
    3. endosome Source: UniProtKB-SubCell
    4. intracellular membrane-bounded organelle Source: RGD
    5. microtubule organizing center Source: UniProtKB-SubCell
    6. nucleus Source: RGD

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Endosome, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 298298Cyclin-dependent kinase 2PRO_0000085772Add
    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

    PaxDbiQ63699.
    PRIDEiQ63699.

    PTM databases

    PhosphoSiteiQ63699.

    Expressioni

    Inductioni

    Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis.1 Publication

    Gene expression databases

    GenevestigatoriQ63699.

    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 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. Binds to RB1. Interacts with CACUL1 By similarity. May interact with CEP63 By similarity.By similarity

    Protein-protein interaction databases

    DIPiDIP-36536N.
    IntActiQ63699. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ63699.
    SMRiQ63699. 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.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    PhylomeDBiQ63699.

    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform CDK2-alpha (identifier: Q63699-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR    50
    EISLLKELNH PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGLP 100
    LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINAEGS IKLADFGLAR 150
    AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMVTRR 200
    ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF PKWARQDFSK 250
    VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL 298
    Length:298
    Mass (Da):33,887
    Last modified:November 1, 1996 - v1
    Checksum:iC8CB3ADCE9B97F88
    GO
    Isoform CDK2-beta (identifier: Q63699-2)

    Sequence is not available
    Length:
    Mass (Da):

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti79 – 791V → C in BAA09638. (PubMed:8673024)Curated
    Sequence conflicti99 – 991L → I in BAA09638. (PubMed:8673024)Curated
    Sequence conflicti124 – 1241L → C in BAA09638. (PubMed:8673024)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28753 mRNA. Translation: BAA05947.1.
    D63162 mRNA. Translation: BAA09638.1.
    UniGeneiRn.104460.

    Genome annotation databases

    UCSCiRGD:70486. rat. [Q63699-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28753 mRNA. Translation: BAA05947.1 .
    D63162 mRNA. Translation: BAA09638.1 .
    UniGenei Rn.104460.

    3D structure databases

    ProteinModelPortali Q63699.
    SMRi Q63699. Positions 1-298.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-36536N.
    IntActi Q63699. 1 interaction.

    PTM databases

    PhosphoSitei Q63699.

    Proteomic databases

    PaxDbi Q63699.
    PRIDEi Q63699.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:70486. rat. [Q63699-1 ]

    Organism-specific databases

    RGDi 70486. Cdk2.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    PhylomeDBi Q63699.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 5301.

    Miscellaneous databases

    PROi Q63699.

    Gene expression databases

    Genevestigatori Q63699.

    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. "A variant form of cyclin-dependent kinase 2 (Cdk2) in a malignantly transformed rat thyroid (FRTL-Tc) cell line."
      Kotani S., Endo T., Kitagawa M., Higashi H., Onaya T.
      Oncogene 10:663-669(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thyroid.
    2. "Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells."
      Hosokawa Y., Yang M., Kaneko S., Tanaka M., Nakashima K.
      Biochem. Mol. Biol. Int. 37:393-399(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-124.
    3. "Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells."
      Choi K.S., Eom Y.W., Kang Y., Ha M.J., Rhee H., Yoon J.-W., Kim S.-J.
      J. Biol. Chem. 274:31775-31783(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS RB1 KINASE, INDUCTION BY TGFB1, INTERACTION WITH RB1.

    Entry informationi

    Entry nameiCDK2_RAT
    AccessioniPrimary (citable) accession number: Q63699
    Secondary accession number(s): O09136
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 120 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