UniProtKB - P97377 (CDK2_MOUSE)
Cyclin-dependent kinase 2
Cdk2
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. 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 (PubMed:23853094).
Phosphorylates CDK2AP2 (By similarity).
Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (By similarity).
By similarity5 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 9 | CDK7 bindingBy similarity | 1 | |
Binding sitei | 33 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 86 | ATPPROSITE-ProRule annotation | 1 | |
Sitei | 88 – 89 | CDK7 bindingBy similarity | 2 | |
Active sitei | 127 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Metal bindingi | 132 | MagnesiumBy similarity | 1 | |
Metal bindingi | 145 | MagnesiumBy similarity | 1 | |
Binding sitei | 145 | ATPPROSITE-ProRule annotation | 1 | |
Sitei | 166 | CDK7 bindingBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 10 – 18 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 81 – 83 | ATPPROSITE-ProRule annotation | 3 | |
Nucleotide bindingi | 129 – 132 | ATPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- cyclin binding Source: BHF-UCL
- cyclin-dependent protein kinase activity Source: MGI
- cyclin-dependent protein serine/threonine kinase activity Source: MGI
- histone kinase activity Source: Ensembl
- kinase activity Source: MGI
- magnesium ion binding Source: UniProtKB
- protein-containing complex binding Source: MGI
- protein domain specific binding Source: MGI
- protein kinase activity Source: MGI
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- cell division Source: UniProtKB-KW
- cellular response to insulin stimulus Source: MGI
- centriole replication Source: MGI
- DNA repair Source: UniProtKB-KW
- G1/S transition of mitotic cell cycle Source: MGI
- histone phosphorylation Source: MGI
- meiotic cell cycle Source: UniProtKB-KW
- negative regulation of transcription by RNA polymerase II Source: MGI
- peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of DNA-dependent DNA replication initiation Source: MGI
- positive regulation of heterochromatin assembly Source: MGI
- positive regulation of transcription, DNA-templated Source: MGI
- potassium ion transport Source: MGI
- protein phosphorylation Source: MGI
- Ras protein signal transduction Source: Ensembl
- regulation of G2/M transition of mitotic cell cycle Source: GO_Central
- regulation of gene expression Source: GO_Central
- response to cAMP Source: MGI
- response to electrical stimulus Source: MGI
- signal transduction Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Cell division, DNA damage, DNA repair, Meiosis, Mitosis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.22, 3474 |
Reactomei | R-MMU-1538133, G0 and Early G1 R-MMU-171319, Telomere Extension By Telomerase R-MMU-176187, Activation of ATR in response to replication stress R-MMU-176408, Regulation of APC/C activators between G1/S and early anaphase R-MMU-187577, SCF(Skp2)-mediated degradation of p27/p21 R-MMU-2559582, Senescence-Associated Secretory Phenotype (SASP) R-MMU-2559586, DNA Damage/Telomere Stress Induced Senescence R-MMU-5693607, Processing of DNA double-strand break ends R-MMU-6804116, TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation R-MMU-6804757, Regulation of TP53 Degradation R-MMU-68911, G2 Phase R-MMU-68949, Orc1 removal from chromatin R-MMU-68962, Activation of the pre-replicative complex R-MMU-69017, CDK-mediated phosphorylation and removal of Cdc6 R-MMU-69200, Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes R-MMU-69202, Cyclin E associated events during G1/S transition R-MMU-69231, Cyclin D associated events in G1 R-MMU-69273, Cyclin A/B1/B2 associated events during G2/M transition R-MMU-69563, p53-Dependent G1 DNA Damage Response R-MMU-69656, Cyclin A:Cdk2-associated events at S phase entry R-MMU-8849470, PTK6 Regulates Cell Cycle R-MMU-9616222, Transcriptional regulation of granulopoiesis |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclin-dependent kinase 2 (EC:2.7.11.221 Publication)Alternative name(s): Cell division protein kinase 2 |
Gene namesi | Name:Cdk2 Synonyms:Cdkn2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104772, Cdk2 |
VEuPathDBi | HostDB:ENSMUSG00000025358 |
Subcellular locationi
Nucleus
- Cajal body By similarity
Cytoskeleton
- centrosome By similarity
Endosome
- Endosome By similarity
Cytoplasm and Cytosol
- Cytoplasm 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
Cytoskeleton
- centrosome Source: MGI
Cytosol
- cytosol Source: MGI
Endosome
- endosome Source: MGI
Nucleus
- Cajal body Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Other locations
- chromosome, telomeric region Source: MGI
- condensed chromosome Source: MGI
- cyclin A1-CDK2 complex Source: MGI
- cyclin A2-CDK2 complex Source: MGI
- cyclin E1-CDK2 complex Source: MGI
- cyclin E2-CDK2 complex Source: MGI
- cyclin-dependent protein kinase holoenzyme complex Source: MGI
- cytoplasm Source: MGI
- intracellular membrane-bounded organelle Source: MGI
- transcription regulator complex Source: MGI
- X chromosome Source: MGI
- Y chromosome Source: MGI
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Endosome, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 15 | Y → F: Loss of tyrosine phosphorylation by WEE1 and CABLES1. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL4106185 CHEMBL4106186 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085771 | 1 – 346 | Cyclin-dependent kinase 2Add BLAST | 346 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 6 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 14 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 15 | Phosphotyrosine; by WEE11 Publication | 1 | |
Modified residuei | 19 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 160 | Phosphothreonine; by CAK and CCRKBy similarity | 1 | |
Modified residuei | 218 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P97377 |
jPOSTi | P97377 |
PaxDbi | P97377 |
PeptideAtlasi | P97377 |
PRIDEi | P97377 |
ProteomicsDBi | 281437 [P97377-1] 281438 [P97377-2] |
PTM databases
iPTMneti | P97377 |
PhosphoSitePlusi | P97377 |
SwissPalmi | P97377 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000025358, Expressed in limb and 273 other tissues |
Genevisiblei | P97377, MM |
Interactioni
Subunit structurei
Found in a complex with CABLES1, CCNA1 and CCNE1.
Interacts with CABLES1 (PubMed:11585773).
Interacts with UHRF2.
Part of a complex consisting of UHRF2, CDK2 and CCNE1.
Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Interaction with SPDYA promotes kinase activation via a conformation change that alleviates obstruction of the substrate-binding cleft by the T-loop.
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.
Interacts with CACUL1. May interact with CEP63.
Interacts with ANKRD17 (By similarity).
Interacts with CEBPA (when phosphorylated) (PubMed:15107404).
Forms a ternary complex with CCNA2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements.
Interacts with cyclins A, B1, B3, D, or E.
Interacts with CDK2AP2 (By similarity).
By similarity2 PublicationsBinary interactionsi
GO - Molecular functioni
- cyclin binding Source: BHF-UCL
- protein domain specific binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198644, 33 interactors |
ComplexPortali | CPX-2065, Cyclin A1-CDK2 complex CPX-2066, Cyclin A2-CDK2 complex CPX-2071, Cyclin B3-CDK2 complex CPX-2081, Cyclin E1-CDK2 complex CPX-2082, Cyclin E2-CDK2 complex |
CORUMi | P97377 |
DIPi | DIP-24176N |
ELMi | P97377 |
IntActi | P97377, 7 interactors |
MINTi | P97377 |
STRINGi | 10090.ENSMUSP00000026416 |
Miscellaneous databases
RNActi | P97377, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 334 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 331 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0594, Eukaryota |
GeneTreei | ENSGT00940000159517 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | P97377 |
OMAi | HKEKCIY |
PhylomeDBi | P97377 |
TreeFami | TF101021 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 2 hits |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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 QNLLINAEGS IKLADFGLAR
160 170 180 190 200
AFGVPVRTYT HEVVTLWYRA PEILLGCKYY STAVDIWSLG CIFAEMHLVC
210 220 230 240 250
TQHHAKCCGE HRRNGRHSLC PLCSYLEVAA SQGGGMTAVS APHPVTRRAL
260 270 280 290 300
FPGDSEIDQL FRIFRTLGTP DEVVWPGVTS MPDYKPSFPK WARQDFSKVV
310 320 330 340
PPLDEDGRSL LSQMLHYDPN KRISAKAALA HPFFQDVTKP VPHLRL
The sequence of this isoform differs from the canonical sequence as follows:
197-244: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004800 | 197 – 244 | Missing in isoform CDK2-alpha. 1 PublicationAdd BLAST | 48 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U63337 mRNA Translation: AAB37128.1 AJ223732 mRNA Translation: CAA11533.1 AJ223733 Genomic DNA Translation: CAA11534.1 AJ223733 Genomic DNA Translation: CAA11535.1 BC005654 mRNA Translation: AAH05654.1 |
CCDSi | CCDS24288.1 [P97377-2] CCDS24289.1 [P97377-1] |
RefSeqi | NP_058036.1, NM_016756.4 [P97377-2] NP_904326.1, NM_183417.3 [P97377-1] |
Genome annotation databases
Ensembli | ENSMUST00000026415; ENSMUSP00000026415; ENSMUSG00000025358 [P97377-2] ENSMUST00000026416; ENSMUSP00000026416; ENSMUSG00000025358 [P97377-1] |
GeneIDi | 12566 |
KEGGi | mmu:12566 |
UCSCi | uc007hny.2, mouse [P97377-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U63337 mRNA Translation: AAB37128.1 AJ223732 mRNA Translation: CAA11533.1 AJ223733 Genomic DNA Translation: CAA11534.1 AJ223733 Genomic DNA Translation: CAA11535.1 BC005654 mRNA Translation: AAH05654.1 |
CCDSi | CCDS24288.1 [P97377-2] CCDS24289.1 [P97377-1] |
RefSeqi | NP_058036.1, NM_016756.4 [P97377-2] NP_904326.1, NM_183417.3 [P97377-1] |
3D structure databases
AlphaFoldDBi | P97377 |
SMRi | P97377 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198644, 33 interactors |
ComplexPortali | CPX-2065, Cyclin A1-CDK2 complex CPX-2066, Cyclin A2-CDK2 complex CPX-2071, Cyclin B3-CDK2 complex CPX-2081, Cyclin E1-CDK2 complex CPX-2082, Cyclin E2-CDK2 complex |
CORUMi | P97377 |
DIPi | DIP-24176N |
ELMi | P97377 |
IntActi | P97377, 7 interactors |
MINTi | P97377 |
STRINGi | 10090.ENSMUSP00000026416 |
Chemistry databases
ChEMBLi | CHEMBL4106185 CHEMBL4106186 |
PTM databases
iPTMneti | P97377 |
PhosphoSitePlusi | P97377 |
SwissPalmi | P97377 |
Proteomic databases
EPDi | P97377 |
jPOSTi | P97377 |
PaxDbi | P97377 |
PeptideAtlasi | P97377 |
PRIDEi | P97377 |
ProteomicsDBi | 281437 [P97377-1] 281438 [P97377-2] |
Protocols and materials databases
Antibodypediai | 3404, 1711 antibodies from 50 providers |
DNASUi | 12566 |
Genome annotation databases
Ensembli | ENSMUST00000026415; ENSMUSP00000026415; ENSMUSG00000025358 [P97377-2] ENSMUST00000026416; ENSMUSP00000026416; ENSMUSG00000025358 [P97377-1] |
GeneIDi | 12566 |
KEGGi | mmu:12566 |
UCSCi | uc007hny.2, mouse [P97377-1] |
Organism-specific databases
CTDi | 1017 |
MGIi | MGI:104772, Cdk2 |
VEuPathDBi | HostDB:ENSMUSG00000025358 |
Phylogenomic databases
eggNOGi | KOG0594, Eukaryota |
GeneTreei | ENSGT00940000159517 |
HOGENOMi | CLU_000288_181_1_1 |
InParanoidi | P97377 |
OMAi | HKEKCIY |
PhylomeDBi | P97377 |
TreeFami | TF101021 |
Enzyme and pathway databases
BRENDAi | 2.7.11.22, 3474 |
Reactomei | R-MMU-1538133, G0 and Early G1 R-MMU-171319, Telomere Extension By Telomerase R-MMU-176187, Activation of ATR in response to replication stress R-MMU-176408, Regulation of APC/C activators between G1/S and early anaphase R-MMU-187577, SCF(Skp2)-mediated degradation of p27/p21 R-MMU-2559582, Senescence-Associated Secretory Phenotype (SASP) R-MMU-2559586, DNA Damage/Telomere Stress Induced Senescence R-MMU-5693607, Processing of DNA double-strand break ends R-MMU-6804116, TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation R-MMU-6804757, Regulation of TP53 Degradation R-MMU-68911, G2 Phase R-MMU-68949, Orc1 removal from chromatin R-MMU-68962, Activation of the pre-replicative complex R-MMU-69017, CDK-mediated phosphorylation and removal of Cdc6 R-MMU-69200, Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes R-MMU-69202, Cyclin E associated events during G1/S transition R-MMU-69231, Cyclin D associated events in G1 R-MMU-69273, Cyclin A/B1/B2 associated events during G2/M transition R-MMU-69563, p53-Dependent G1 DNA Damage Response R-MMU-69656, Cyclin A:Cdk2-associated events at S phase entry R-MMU-8849470, PTK6 Regulates Cell Cycle R-MMU-9616222, Transcriptional regulation of granulopoiesis |
Miscellaneous databases
BioGRID-ORCSi | 12566, 5 hits in 115 CRISPR screens |
ChiTaRSi | Cdk2, mouse |
PROi | PR:P97377 |
RNActi | P97377, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000025358, Expressed in limb and 273 other tissues |
Genevisiblei | P97377, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 2 hits |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CDK2_MOUSE | |
Accessioni | P97377Primary (citable) accession number: P97377 Secondary accession number(s): O55105 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | May 30, 2000 | |
Last modified: | May 25, 2022 | |
This is version 199 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families