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Q63699 (CDK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 2

EC=2.7.11.22
Alternative name(s):
Cell division protein kinase 2
Gene names
Name:Cdk2
Synonyms:Cdkn2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length298 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

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.

Subunit structure

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. Ref.3

Subcellular location

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.

Induction

Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis. Ref.3

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processCell cycle
Cell division
DNA damage
DNA repair
Meiosis
Mitosis
   Cellular componentCytoplasm
Cytoskeleton
Endosome
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to insulin stimulus

Inferred from direct assay PubMed 15994754. Source: RGD

lens development in camera-type eye

Inferred from expression pattern PubMed 10620399. Source: RGD

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

organ regeneration

Inferred from expression pattern PubMed 16534847. Source: RGD

response to cAMP

Inferred from direct assay PubMed 15994754. Source: RGD

response to cadmium ion

Inferred from expression pattern PubMed 16730872. Source: RGD

response to drug

Inferred from expression pattern PubMed 17706465. Source: RGD

response to electrical stimulus

Inferred from direct assay PubMed 15607308. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 16019103. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 16689928. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 17343987. Source: RGD

   Cellular_componentCajal body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 15994754. Source: RGD

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 8024548. Source: RGD

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 15994754. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cyclin binding

Inferred from physical interaction PubMed 15809057. Source: RGD

cyclin-dependent protein serine/threonine kinase activity

Inferred from direct assay PubMed 11823715. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein complex binding

Inferred from physical interaction PubMed 10952244. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Select]
Isoform CDK2-alpha (identifier: Q63699-1)

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.
Isoform CDK2-beta (identifier: Q63699-2)

The sequence of this isoform is not available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 298298Cyclin-dependent kinase 2
PRO_0000085772

Regions

Domain4 – 286283Protein kinase
Nucleotide binding10 – 189ATP By similarity
Nucleotide binding81 – 833ATP By similarity
Nucleotide binding129 – 1324ATP By similarity

Sites

Active site1271Proton acceptor By similarity
Metal binding1321Magnesium; catalytic By similarity
Metal binding1451Magnesium; catalytic By similarity
Binding site331ATP By similarity
Binding site861ATP By similarity
Binding site1451ATP By similarity
Site91CDK7 binding By similarity
Site88 – 892CDK7 binding By similarity
Site1661CDK7 binding By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue61N6-acetyllysine By similarity
Modified residue141Phosphothreonine By similarity
Modified residue151Phosphotyrosine; by WEE1 By similarity
Modified residue191Phosphotyrosine By similarity
Modified residue1601Phosphothreonine; by CAK and CCRK By similarity

Experimental info

Sequence conflict791V → C in BAA09638. Ref.2
Sequence conflict991L → I in BAA09638. Ref.2
Sequence conflict1241L → C in BAA09638. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform CDK2-alpha [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: C8CB3ADCE9B97F88

FASTA29833,887
        10         20         30         40         50         60 
MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR EISLLKELNH 

        70         80         90        100        110        120 
PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGLP LPLIKSYLFQ LLQGLAFCHS 

       130        140        150        160        170        180 
HRVLHRDLKP QNLLINAEGS IKLADFGLAR AFGVPVRTYT HEVVTLWYRA PEILLGCKYY 

       190        200        210        220        230        240 
STAVDIWSLG CIFAEMVTRR ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF 

       250        260        270        280        290 
PKWARQDFSK VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL 

« Hide

Isoform CDK2-beta (Sequence not available).

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D28753 mRNA. Translation: BAA05947.1.
D63162 mRNA. Translation: BAA09638.1.
UniGeneRn.104460.

3D structure databases

ProteinModelPortalQ63699.
SMRQ63699. Positions 1-298.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ63699. 1 interaction.

PTM databases

PhosphoSiteQ63699.

Proteomic databases

PaxDbQ63699.
PRIDEQ63699.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:70486. rat. [Q63699-1]

Organism-specific databases

RGD70486. Cdk2.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
PhylomeDBQ63699.

Enzyme and pathway databases

BRENDA2.7.11.22. 5301.

Gene expression databases

GenevestigatorQ63699.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROQ63699.

Entry information

Entry nameCDK2_RAT
AccessionPrimary (citable) accession number: Q63699
Secondary accession number(s): O09136
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: May 14, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families