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Q5E9Y0

- CDK2_BOVIN

UniProt

Q5E9Y0 - CDK2_BOVIN

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Protein
Cyclin-dependent kinase 2
Gene
CDK2, CDKN2
Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei9 – 91CDK7 binding By similarity
Binding sitei33 – 331ATP By similarity
Binding sitei86 – 861ATP By similarity
Sitei88 – 892CDK7 binding By similarity
Active sitei127 – 1271Proton acceptor By similarity
Metal bindingi132 – 1321Magnesium; catalytic By similarity
Metal bindingi145 – 1451Magnesium; catalytic By similarity
Binding sitei145 – 1451ATP By similarity
Sitei166 – 1661CDK7 binding By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi10 – 189ATP By similarity
Nucleotide bindingi81 – 833ATP By similarity
Nucleotide bindingi129 – 1324ATP By similarity

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

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.

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Endosome, Nucleus

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity
Modified residuei6 – 61N6-acetyllysine By similarity
Modified residuei14 – 141Phosphothreonine By similarity
Modified residuei15 – 151Phosphotyrosine; by WEE1 By similarity
Modified residuei19 – 191Phosphotyrosine By similarity
Modified residuei160 – 1601Phosphothreonine; by CAK and CCRK By 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.
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.

Protein-protein interaction databases

BioGridi175836. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ5E9Y0.
SMRiQ5E9Y0. Positions 1-298.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 286283Protein kinase
Add
BLAST

Sequence similaritiesi

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

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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: September 3, 2014
This is version 84 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

Similar proteinsi