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Protein

Cyclin-dependent kinase 2

Gene

CDK2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: 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. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability. Interacts with CEBPA (when phosphorylated) (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

GO - Biological processi

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_277841. Cyclin E associated events during G1/S transition.
REACT_288697. Activation of ATR in response to replication stress.
REACT_290505. SCF(Skp2)-mediated degradation of p27/p21.
REACT_296366. Activation of the pre-replicative complex.
REACT_301565. G2 Phase.
REACT_302171. Cyclin A/B1 associated events during G2/M transition.
REACT_302851. CDK-mediated phosphorylation and removal of Cdc6.
REACT_302866. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
REACT_307894. Regulation of APC/C activators between G1/S and early anaphase.
REACT_313471. G0 and Early G1.
REACT_320089. p53-Dependent G1 DNA Damage Response.
REACT_326216. DNA Damage/Telomere Stress Induced Senescence.
REACT_328795. Orc1 removal from chromatin.
REACT_335907. Factors involved in megakaryocyte development and platelet production.
REACT_345483. Cyclin A:Cdk2-associated events at S phase entry.
REACT_348678. Meiotic recombination.
REACT_351362. Senescence-Associated Secretory Phenotype (SASP).

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 Componenti: Chromosome 5

Subcellular locationi

GO - Cellular componenti

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_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). Interacts with ANKRD17.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.
GeneTreeiENSGT00790000122973.
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.
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

        10         20         30         40         50
MENFQKVEKI GEGTYGVVYK AKNKLTGEVV ALKKIRLDTE TEGVPSTAIR
60 70 80 90 100
EISLLKELNH PNIVKLLDVI HTENKLYLVF EFLHQDLKKF MDASALTGIP
110 120 130 140 150
LPLIKSYLFQ LLQGLAFCHS HRVLHRDLKP QNLLINADGS 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):33,873
Last modified:March 15, 2005 - v1
Checksum:iEEC785D6A0E87A71
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
BT020790 mRNA. Translation: AAX08807.1.
BC150026 mRNA. Translation: AAI50027.1.
RefSeqiNP_001014934.1. NM_001014934.1.
UniGeneiBt.21444.

3D structure databases

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

Protein-protein interaction databases

BioGridi175836. 1 interaction.

Proteomic databases

PRIDEiQ5E9Y0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1017.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00790000122973.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ5E9Y0.
KOiK02206.
OMAiLVHRFFR.
OrthoDBiEOG7966H8.
TreeFamiTF101021.

Enzyme and pathway databases

ReactomeiREACT_277841. Cyclin E associated events during G1/S transition.
REACT_288697. Activation of ATR in response to replication stress.
REACT_290505. SCF(Skp2)-mediated degradation of p27/p21.
REACT_296366. Activation of the pre-replicative complex.
REACT_301565. G2 Phase.
REACT_302171. Cyclin A/B1 associated events during G2/M transition.
REACT_302851. CDK-mediated phosphorylation and removal of Cdc6.
REACT_302866. Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
REACT_307894. Regulation of APC/C activators between G1/S and early anaphase.
REACT_313471. G0 and Early G1.
REACT_320089. p53-Dependent G1 DNA Damage Response.
REACT_326216. DNA Damage/Telomere Stress Induced Senescence.
REACT_328795. Orc1 removal from chromatin.
REACT_335907. Factors involved in megakaryocyte development and platelet production.
REACT_345483. Cyclin A:Cdk2-associated events at S phase entry.
REACT_348678. Meiotic recombination.
REACT_351362. Senescence-Associated Secretory Phenotype (SASP).

Miscellaneous databases

NextBioi20872832.

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]
ProtoNetiSearch...

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: May 27, 2015
This is version 92 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.