CPLM-010633

Genbank Nucleotide ID

Cyclin-dependent kinase 2

Protein Synonyms/Alias

Cell division protein kinase 2

Mus musculus (Mouse)

Position	Peptide	Type	References
9	ENFQKVEKIGEGTYG	acetylation	[1]

[1] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]

Functional Description

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.

DOMAIN 4 334 Protein kinase.
NP_BIND 10 18 ATP (By similarity).
NP_BIND 81 83 ATP (By similarity).
NP_BIND 129 132 ATP (By similarity).
ACT_SITE 127 127 Proton acceptor (By similarity).
METAL 132 132 Magnesium; catalytic (By similarity).
METAL 145 145 Magnesium; catalytic (By similarity).
BINDING 33 33 ATP (By similarity).
BINDING 86 86 ATP (By similarity).
BINDING 145 145 ATP (By similarity).
MOD_RES 1 1 N-acetylmethionine (By similarity).
MOD_RES 6 6 N6-acetyllysine (By similarity).
MOD_RES 14 14 Phosphothreonine (By similarity).
MOD_RES 15 15 Phosphotyrosine; by WEE1.
MOD_RES 19 19 Phosphotyrosine (By similarity).
MOD_RES 160 160 Phosphothreonine; by CAK and CCRK (By

Acetylation; Alternative splicing; ATP-binding; Cell cycle; Cell division; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; Endosome; Kinase; Magnesium; Meiosis; Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0015030; C:Cajal body; IEA:UniProtKB-SubCell.
GO:0000781; C:chromosome, telomeric region; IDA:MGI.
GO:0000793; C:condensed chromosome; IDA:MGI.
GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:MGI.
GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
GO:0005667; C:transcription factor complex; IDA:MGI.
GO:0000805; C:X chromosome; IDA:MGI.
GO:0000806; C:Y chromosome; IDA:MGI.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
GO:0035173; F:histone kinase activity; IEA:Compara.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:MGI.
GO:0007126; P:meiosis; IEA:UniProtKB-KW.
GO:0007067; P:mitosis; IEA:UniProtKB-KW.
GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
GO:0032298; P:positive regulation of DNA-dependent DNA replication initiation; IGI:MGI.
GO:0045893; P:positive regulation of transcription, DNA-dependent; IGI:MGI.
GO:0006813; P:potassium ion transport; IGI:MGI.
GO:0007265; P:Ras protein signal transduction; IEA:Compara.
GO:0060968; P:regulation of gene silencing; IEA:Compara.

IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR002290; Ser/Thr_dual-sp_kinase_dom.
IPR008271; Ser/Thr_kinase_AS.

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST