InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDK1

Summary

InnateDB Protein

IDBP-377289.5

Last Modified

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

Gene Symbol

CDK1

Protein Name

cyclin-dependent kinase 1

Synonyms

CDC2; CDC28A; P34CDC2;

Species

Homo sapiens

Ensembl Protein

ENSP00000397973

InnateDB Gene

IDBG-75344 (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:16371510, ECO:0000269PubMed:16407259, ECO:0000269PubMed:16933150, ECO:0000269PubMed:17459720, ECO:0000269PubMed:18356527, ECO:0000269PubMed:18480403, ECO:0000269PubMed:19509060, ECO:0000269PubMed:19917720, ECO:0000269PubMed:20171170, ECO:0000269PubMed:20360007, ECO:0000269PubMed:20395957, ECO:0000269PubMed:20935635, ECO:0000269PubMed:20937773, ECO:0000269PubMed:21063390}.

Subcellular Localization

Nucleus. Cytoplasm. Mitochondrion. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Note=Cytoplasmic during the interphase. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle. 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.

Disease Associations

Tissue Specificity

Isoform 2 is found in breast cancer tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 242 experimentally validated interaction(s) in this database.
They are also associated with 23 interaction(s) predicted by orthology.

Experimentally validated
Total	242 [view]
Protein-Protein	236 [view]
Protein-DNA	6 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	23 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468

protein phosphorylation

Cellular Component

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