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Q63699

- CDK2_RAT

UniProt

Q63699 - CDK2_RAT

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Protein

Cyclin-dependent kinase 2

Gene

Cdk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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).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
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

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. cytoskeleton Source: UniProtKB-KW
  2. cytosol Source: RGD
  3. endosome Source: UniProtKB-KW
  4. intracellular membrane-bounded organelle Source: RGD
  5. nucleus Source: RGD
Complete GO annotation...

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.
InParanoidiQ63699.
PhylomeDBiQ63699.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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) [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

        10         20         30         40         50
MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR
60 70 80 90 100
EISLLKELNH PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGLP
110 120 130 140 150
LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINAEGS IKLADFGLAR
160 170 180 190 200
AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMVTRR
210 220 230 240 250
ALFPGDSEID QLFRIFRTLG TPDEVVWPGV TSMPDYKPSF PKWARQDFSK
260 270 280 290
VVPPLDEDGR SLLSQMLHYD PNKRISAKAA LAHPFFQDVT KPVPHLRL
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.
InParanoidi Q63699.
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.
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 29, 2014
This is version 121 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