InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDK2

Summary

InnateDB Protein

IDBP-39547.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CDK2

Protein Name

cyclin-dependent kinase 2

Synonyms

CDKN2; p33(CDK2);

Species

Homo sapiens

Ensembl Protein

ENSP00000266970

InnateDB Gene

IDBG-39545 (CDK2)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:10499802, ECO:0000269PubMed:10884347, ECO:0000269PubMed:10995386, ECO:0000269PubMed:10995387, ECO:0000269PubMed:11051553, ECO:0000269PubMed:11113184, ECO:0000269PubMed:15800615, ECO:0000269PubMed:17495531, ECO:0000269PubMed:18372919, ECO:0000269PubMed:19966300, ECO:0000269PubMed:20079829, ECO:0000269PubMed:20147522, ECO:0000269PubMed:20195506, ECO:0000269PubMed:20935635, ECO:0000269PubMed:21262353, ECO:0000269PubMed:21319273, ECO:0000269PubMed:21596315}.

Subcellular Localization

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus, Cajal body. Cytoplasm. Endosome. 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)(2)D(3).

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 655 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	655 [view]
Protein-Protein	646 [view]
Protein-DNA	6 [view]
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004693	cyclin-dependent protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030332	cyclin binding
GO:0035173	histone kinase activity
GO:0046872	metal ion binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000085	mitotic G2 phase
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006468	protein phosphorylation
GO:0006813	potassium ion transport
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007067	mitotic nuclear division
GO:0007126	meiotic nuclear division
GO:0007265	Ras protein signal transduction
GO:0007596	blood coagulation
GO:0008284	positive regulation of cell proliferation
GO:0016572	histone phosphorylation
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031571	mitotic G1 DNA damage checkpoint
GO:0032298	positive regulation of DNA-dependent DNA replication initiation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0051298	centrosome duplication
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0060968	regulation of gene silencing
GO:0071732	cellular response to nitric oxide

Cellular Component

GO:0000307	cyclin-dependent protein kinase holoenzyme complex
GO:0000781	chromosome, telomeric region
GO:0000793	condensed chromosome
GO:0000805	X chromosome
GO:0000806	Y chromosome
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005737	cytoplasm
GO:0005768	endosome
GO:0005813	centrosome
GO:0005829	cytosol
GO:0015030	Cajal body

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt