Cyclin-dependent kinase 1 (Protein name
), CDK1_HUMAN from NCBI database.
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General Annotation
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Antigen Annotation
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Predicted Eptitope
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Vaild Sequence
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Gene name:
CDK1(CDC2;CDC28A;CDKN1;P34CDC2);
Protein name:
Cyclin-dependent kinase 1(CDK1);
Alternative:
Cell division protein kinase 1;Cell division control protein 2 homolog;p34 protein kinase;
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1 and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M transition when in complex with a cyclin-B. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC.
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, 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, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1 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.
Subcellular Location:
Nucleus
Cytoplasm
Mitochondrion
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.
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
5.
NIEHS SNPs program
Submitted (2002-05) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Cited for: ENZYME REGULATION BY ROSCOVITINE AND OLOMOUCINE
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Cited for: FUNCTION AS RB1 KINASE;ENZYME REGULATION BY TGFB1;REPRESSION BY TGFB1
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: FUNCTION DURING THE M PHASE;MUTAGENESIS OF 14-THR-TYR-15
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-19; SER-39; TYR-77 AND THR-222;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-89
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Cited for: FUNCTION AS FOXO1 KINASE;INTERACTION WITH FOXO1
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Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1;PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-19; SER-39; SER-178; THR-222 AND SER-248;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15 AND THR-161;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND LYS-6;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: FUNCTION IN G2 ARREST UPON DNA DAMAGE;PHOSPHORYLATION AT TYR-4 BY PKR/EIF2AK2;POLYUBIQUITINATION;MUTAGENESIS OF TYR-4
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Cited for: FUNCTION IN G2-M TRANSITION;DEPHOSPHORYLATION AT THR-14 AND TYR-15 BY CDC25;PHOSPHORYLATION AT THR-161 BY CDK7/CAK;INTERACTION WITH B-CYCLIN
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Cited for: FUNCTION AS BCL-XL/BCL2L1 KINASE;SUBCELLULAR LOCATION
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: REVIEW ON CELL CYCLE CONTROL AND INHIBITORS;GENE FAMILY
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]