InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDK1

Summary

InnateDB Protein

IDBP-239863.6

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

ENSP00000378699

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:0004674	protein serine/threonine 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:0000082	G1/S transition of mitotic cell cycle
GO:0000083	regulation of transcription involved in G1/S transition of mitotic cell cycle
GO:0000086	G2/M transition of mitotic cell cycle
GO:0000165	MAPK cascade
GO:0000186	activation of MAPKK activity
GO:0000187	activation of MAPK activity
GO:0000226	microtubule cytoskeleton organization
GO:0000278	mitotic cell cycle
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006260	DNA replication
GO:0006281	DNA repair
GO:0006461	protein complex assembly
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007067	mitotic nuclear division
GO:0007077	mitotic nuclear envelope disassembly
GO:0007095	mitotic G2 DNA damage checkpoint
GO:0007098	centrosome cycle
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007264	small GTPase mediated signal transduction
GO:0007265	Ras protein signal transduction
GO:0007344	pronuclear fusion
GO:0007411	axon guidance
GO:0007569	cell aging
GO:0008286	insulin receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0009636	response to toxic substance
GO:0010243	response to organonitrogen compound
GO:0010628	positive regulation of gene expression
GO:0014038	regulation of Schwann cell differentiation
GO:0014070	response to organic cyclic compound
GO:0014075	response to amine
GO:0014823	response to activity
GO:0016477	cell migration
GO:0016572	histone phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0030261	chromosome condensation
GO:0030855	epithelial cell differentiation
GO:0031100	organ regeneration
GO:0031145	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0033160	positive regulation of protein import into nucleus, translocation
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0034501	protein localization to kinetochore
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0042493	response to drug
GO:0042542	response to hydrogen peroxide
GO:0043066	negative regulation of apoptotic process
GO:0045087	innate immune response
GO:0045471	response to ethanol
GO:0045740	positive regulation of DNA replication
GO:0045931	positive regulation of mitotic cell cycle
GO:0045995	regulation of embryonic development
GO:0046686	response to cadmium ion
GO:0046688	response to copper ion
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048678	response to axon injury
GO:0051403	stress-activated MAPK cascade
GO:0051437	positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0051439	regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
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:0005829	cytosol
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

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