| UniProt ID | CDK1_MOUSE | |
|---|---|---|
| UniProt AC | P11440 | |
| Protein Name | Cyclin-dependent kinase 1 | |
| Gene Name | Cdk1 | |
| Organism | Mus musculus (Mouse). | |
| Sequence Length | 297 | |
| Subcellular Localization | Nucleus . Cytoplasm . Mitochondrion . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic ce | |
| Protein Description | 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, CENPA, 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. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis.. | |
| Protein Sequence | MEDYIKIEKIGEGTYGVVYKGRHRVTGQIVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQFMDSSLVKSYLHQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLVYDPAKRISGKMALKHPYFDDLDNQIKKM | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 1 | Acetylation | -------MEDYIKIE -------CCCCEEEE | 8.80 | 23806337 | |
| 4 | Phosphorylation | ----MEDYIKIEKIG ----CCCCEEEEEEC | 7.27 | 25367039 | |
| 6 | Acetylation | --MEDYIKIEKIGEG --CCCCEEEEEECCC | 38.29 | 23806337 | |
| 9 | Acetylation | EDYIKIEKIGEGTYG CCCEEEEEECCCCCE | 60.53 | 23806337 | |
| 14 | Phosphorylation | IEKIGEGTYGVVYKG EEEECCCCCEEEEEC | 16.89 | 22322096 | |
| 15 | Phosphorylation | EKIGEGTYGVVYKGR EEECCCCCEEEEECC | 20.84 | 22322096 | |
| 19 | Phosphorylation | EGTYGVVYKGRHRVT CCCCEEEEECCCCEE | 12.81 | 25177544 | |
| 20 | Acetylation | GTYGVVYKGRHRVTG CCCEEEEECCCCEEE | 37.55 | 23236377 | |
| 33 | Acetylation | TGQIVAMKKIRLESE EEEEEEEEEEECCCC | 35.00 | 23806337 | |
| 39 | Phosphorylation | MKKIRLESEEEGVPS EEEEECCCCCCCCCH | 55.70 | 28066266 | |
| 46 | Phosphorylation | SEEEGVPSTAIREIS CCCCCCCHHHHHHHH | 28.23 | 25338131 | |
| 56 | Ubiquitination | IREISLLKELRHPNI HHHHHHHHHCCCCCC | 61.06 | - | |
| 77 | Phosphorylation | LMQDSRLYLIFEFLS HHCCCHHHHHHHHHH | 9.17 | - | |
| 139 | Ubiquitination | QNLLIDDKGTIKLAD CCEEECCCCCEEEHH | 54.96 | - | |
| 141 | Phosphorylation | LLIDDKGTIKLADFG EEECCCCCEEEHHHH | 22.22 | 22817900 | |
| 160 | Phosphorylation | FGIPIRVYTHEVVTL HCCCEEEEECEEEEE | 7.79 | 26239621 | |
| 161 | Phosphorylation | GIPIRVYTHEVVTLW CCCEEEEECEEEEEE | 14.54 | 26824392 | |
| 166 | Phosphorylation | VYTHEVVTLWYRSPE EEECEEEEEEECCHH | 19.42 | 26745281 | |
| 169 | Phosphorylation | HEVVTLWYRSPEVLL CEEEEEEECCHHHHH | 12.34 | 26745281 | |
| 178 | Phosphorylation | SPEVLLGSARYSTPV CHHHHHCCCCCCCCC | 15.00 | - | |
| 201 | Acetylation | FAELATKKPLFHGDS HHHHHHCCCCCCCCH | 42.47 | 23806337 | |
| 201 | Ubiquitination | FAELATKKPLFHGDS HHHHHHCCCCCCCCH | 42.47 | 22790023 | |
| 222 | Phosphorylation | RIFRALGTPNNEVWP HHHHHHCCCCCCCCC | 24.56 | - | |
| 245 | Acetylation | KNTFPKWKPGSLASH HHCCCCCCCCCHHHH | 45.70 | 23806337 | |
| 245 | Succinylation | KNTFPKWKPGSLASH HHCCCCCCCCCHHHH | 45.70 | - | |
| 245 | Succinylation | KNTFPKWKPGSLASH HHCCCCCCCCCHHHH | 45.70 | 23806337 | |
| 248 | Phosphorylation | FPKWKPGSLASHVKN CCCCCCCCHHHHHCC | 29.32 | - | |
| 270 | Phosphorylation | LLSKMLVYDPAKRIS HHHHHHHCCHHHHCC | 16.55 | 28059163 | |
| 283 | Acetylation | ISGKMALKHPYFDDL CCCCHHHCCCCHHHH | 32.75 | 23236377 | |
| 283 | Ubiquitination | ISGKMALKHPYFDDL CCCCHHHCCCCHHHH | 32.75 | - | |
| 295 | Ubiquitination | DDLDNQIKKM----- HHHHHHHHCC----- | 32.78 | - | |
| 296 | Ubiquitination | DLDNQIKKM------ HHHHHHHCC------ | 52.01 | - |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 4 | Y | Phosphorylation | Kinase | PKR | Q03963 | Uniprot |
| 15 | Y | Phosphorylation | Kinase | CDK1 | P11440 | PSP |
| 15 | Y | Phosphorylation | Kinase | WEE1 | P47810 | Uniprot |
| 15 | Y | Phosphorylation | Kinase | WEE1B | Q66JT0 | PSP |
| 161 | T | Phosphorylation | Kinase | CAK | Q03147 | Uniprot |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of CDK1_MOUSE !! | ||||||
| Kegg Drug | ||||||
|---|---|---|---|---|---|---|
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, AND MASSSPECTROMETRY. | |
| "The phagosomal proteome in interferon-gamma-activated macrophages."; Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.; Immunity 30:143-154(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14, AND MASSSPECTROMETRY. | |
| "Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15 AND THR-161,AND MASS SPECTROMETRY. | |
| "A differential phosphoproteomic analysis of retinoic acid-treated P19cells."; Smith J.C., Duchesne M.A., Tozzi P., Ethier M., Figeys D.; J. Proteome Res. 6:3174-3186(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, AND MASSSPECTROMETRY. | |
| "Quantitative time-resolved phosphoproteomic analysis of mast cellsignaling."; Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,Kawakami T., Salomon A.R.; J. Immunol. 179:5864-5876(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15 AND TYR-19,AND MASS SPECTROMETRY. | |
| "Protein tyrosine kinase Wee1B is essential for metaphase II exit inmouse oocytes."; Oh J.S., Susor A., Conti M.; Science 332:462-465(2011). Cited for: PHOSPHORYLATION AT TYR-15. | |
| "The protein kinase Cdelta catalytic fragment is critical formaintenance of the G2/M DNA damage checkpoint."; LaGory E.L., Sitailo L.A., Denning M.F.; J. Biol. Chem. 285:1879-1887(2010). Cited for: PHOSPHORYLATION AT TYR-15. | |
| "Wee1B is an oocyte-specific kinase involved in the control of meioticarrest in the mouse."; Han S.J., Chen R., Paronetto M.P., Conti M.; Curr. Biol. 15:1670-1676(2005). Cited for: PHOSPHORYLATION AT TYR-15. | |
