InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Cdk1

Summary

InnateDB Protein

IDBP-160474.6

Last Modified

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

Gene Symbol

Cdk1

Protein Name

cyclin-dependent kinase 1

Synonyms

Cdc2; Cdc2a; p34;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000020099

InnateDB Gene

IDBG-160472 (Cdk1)

Protein Structure

UniProt Annotation

Function

Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl- xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C- mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl- xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. {ECO:0000269PubMed:16007079, ECO:0000269PubMed:17700700, ECO:0000269PubMed:17942597, ECO:0000269PubMed:22405274}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:17942597}. Cytoplasm {ECO:0000269PubMed:17942597}. Mitochondrion {ECO:0000269PubMed:17942597}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm, cytoskeleton, spindle {ECO:0000250}. Note=Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle (By similarity). Cytoplasmic during the interphase. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin-B1. Accumulates in mitochondria in G2- arrested cells upon DNA-damage. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 125 experimentally validated interaction(s) in this database.
They are also associated with 146 interaction(s) predicted by orthology.

Experimentally validated
Total	125 [view]
Protein-Protein	125 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	146 [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:0008353	RNA polymerase II carboxy-terminal domain kinase activity
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030332	cyclin binding
GO:0030544	Hsp70 protein binding
GO:0035173	histone kinase activity

Biological Process

GO:0000278	mitotic cell cycle
GO:0006461	protein complex assembly
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007067	mitotic nuclear division
GO:0007095	mitotic G2 DNA damage checkpoint
GO:0007569	cell aging
GO:0009636	response to toxic substance
GO:0010243	response to organonitrogen compound
GO:0010628	positive regulation of gene expression
GO:0014070	response to organic cyclic compound
GO:0014075	response to amine
GO:0014823	response to activity
GO:0016572	histone phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0030261	chromosome condensation
GO:0030855	epithelial cell differentiation
GO:0031100	organ regeneration
GO:0033160	positive regulation of protein import into nucleus, translocation
GO:0034501	protein localization to kinetochore
GO:0042493	response to drug
GO:0042542	response to hydrogen peroxide
GO:0043066	negative regulation of apoptotic process
GO:0045471	response to ethanol
GO:0045740	positive regulation of DNA replication
GO:0045931	positive regulation of mitotic cell cycle
GO:0046686	response to cadmium ion
GO:0046688	response to copper ion
GO:0048678	response to axon injury
GO:0055015	ventricular cardiac muscle cell development
GO:0060045	positive regulation of cardiac muscle cell proliferation
GO:0070301	cellular response to hydrogen peroxide

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005813	centrosome
GO:0005876	spindle microtubule
GO:0016020	membrane
GO:0030496	midbody
GO:0070062	extracellular vesicular exosome
GO:0072686	mitotic spindle

Protein Structure and Domains

PDB ID

MGI:88351

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