Cyclin-dependent kinase 2

NameCyclin-dependent kinase 2
Synonyms
  • 2.7.11.22
  • CDKN2
  • Cell division protein kinase 2
  • p33 protein kinase
Gene NameCDK2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002409|Cyclin-dependent kinase 2
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS
HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY
STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
Number of residues298
Molecular Weight33929.215
Theoretical pI9.76
GO Classification
Functions
  • metal ion binding
  • cyclin binding
  • cyclin-dependent protein serine/threonine kinase activity
  • ATP binding
Processes
  • potassium ion transport
  • cellular response to nitric oxide
  • cellular response to insulin stimulus
  • DNA replication
  • response to toxic substance
  • response to drug
  • G2/M transition of mitotic cell cycle
  • DNA repair
  • histone phosphorylation
  • mitotic cell cycle
  • meiotic nuclear division
  • G1/S transition of mitotic cell cycle
  • cell division
  • response to ethanol
  • response to cadmium ion
  • double-strand break repair
  • response to electrical stimulus
  • double-strand break repair via homologous recombination
  • peptidyl-serine phosphorylation
  • mitotic nuclear division
  • regulation of gene silencing
  • lens development in camera-type eye
  • positive regulation of transcription, DNA-templated
  • mitotic G1 DNA damage checkpoint
  • organ regeneration
  • response to cAMP
  • response to estradiol
  • anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
  • Ras protein signal transduction
  • centrosome duplication
  • blood coagulation
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
  • positive regulation of cell proliferation
  • positive regulation of DNA-dependent DNA replication initiation
  • regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Components
  • endosome
  • centrosome
  • transcription factor complex
  • chromosome, telomeric region
  • condensed chromosome
  • cytosol
  • nucleoplasm
  • Cajal body
  • cyclin-dependent protein kinase holoenzyme complex
  • X chromosome
  • cytoplasm
  • Y chromosome
  • nucleus
General FunctionMetal ion binding
Specific FunctionSerine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID3551191
UniProtKB IDP24941
UniProtKB Entry NameCDK2_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019057|Cyclin-dependent kinase 2 (CDK2)
ATGGAGAACTTCCAAAAGGTGGAAAAGATCGGAGAGGGCACGTACGGAGTTGTGTACAAA
GCCAGAAACAAGTTGACGGGAGAGGTGGTGGCGCTTAAGAAAATCCGCCTGGACACGCTG
CTGGATGTCATTCACACAGAAAATAAACTCTACCTGGTTTTTGAATTTCTGCACCAAGAT
CTCAAGAAATTCATGGATGCCTCTGCTCTCACTGGCATTCCTCTTCCCCTCATCAAGAGC
TATCTGTTCCAGCTGCTCCAGGGCCTAGCTTTCTGCCATTCTCATCGGGTCCTCCACCGA
GACCTTAAACCTCAGAATCTGCTTATTAACACAGAGGGGGCCATCAAGCTAGCAGACTTT
GGACTAGCCAGAGCTTTTGGAGTCCCTGTTCGTACTTACACCCATGAGGTGACTCGCCGG
GCCCTATTCCCTGGAGATTCTGAGATTGACCAGCTCTTCCGGATCTTTCGGACTCTGGGG
ACCCCAGATGAGGTGGTGTGGCCAGGAGTTACTTCTATGCCTGATTACAAGCCAAGTTTC
CCCAAGTGGGCCCGGCAAGATTTTAGTAAAGTTGTACCTCCCCTGGATGAAGATGGACGG
AGCTTGTTATCGCAAATGCTGCACTACGACCCTAACAAGCGGATTTCGGCCAAGGCAGCC
CTGGCTCACCCTTTCTTCCAGGATGTGACCAAGCCAGTACCCCATCTTCGACTCTGA
GenBank Gene IDAB012305
GeneCard IDNot Available
GenAtlas IDCDK2deltaT
HGNC IDHGNC:1771
Chromosome Location12
LocusNot Available
References
  1. Elledge SJ, Spottswood MR: A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1. EMBO J. 1991 Sep;10(9):2653-9. 1714386
  2. Tsai LH, Harlow E, Meyerson M: Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature. 1991 Sep 12;353(6340):174-7. 1653904
  3. Ninomiya-Tsuji J, Nomoto S, Yasuda H, Reed SI, Matsumoto K: Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9006-10. 1717994
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. 16541075
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Gu Y, Rosenblatt J, Morgan DO: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. EMBO J. 1992 Nov;11(11):3995-4005. 1396589
  8. Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP: Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem. 1997 Jan 15;243(1-2):527-36. 9030781
  9. Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC: Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell. 1999 Sep 17;98(6):859-69. 10499802
  10. Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K: Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell. 2000 Sep 29;103(1):127-40. 11051553
  11. Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E: NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. Genes Dev. 2000 Sep 15;14(18):2283-97. 10995386
  12. Ma T, Van Tine BA, Wei Y, Garrett MD, Nelson D, Adams PD, Wang J, Qin J, Chow LT, Harper JW: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription. Genes Dev. 2000 Sep 15;14(18):2298-313. 10995387
  13. Luciani MG, Hutchins JR, Zheleva D, Hupp TR: The C-terminal regulatory domain of p53 contains a functional docking site for cyclin A. J Mol Biol. 2000 Jul 14;300(3):503-18. 10884347
  14. Garrett S, Barton WA, Knights R, Jin P, Morgan DO, Fisher RP: Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. Mol Cell Biol. 2001 Jan;21(1):88-99. 11113184
  15. Nguyen TB, Manova K, Capodieci P, Lindon C, Bottega S, Wang XY, Refik-Rogers J, Pines J, Wolgemuth DJ, Koff A: Characterization and expression of mammalian cyclin b3, a prepachytene meiotic cyclin. J Biol Chem. 2002 Nov 1;277(44):41960-9. Epub 2002 Aug 15. 12185076
  16. Porter LA, Dellinger RW, Tynan JA, Barnes EA, Kong M, Lenormand JL, Donoghue DJ: Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2. J Cell Biol. 2002 Apr 29;157(3):357-66. Epub 2002 Apr 29. 11980914
  17. Barnes EA, Porter LA, Lenormand JL, Dellinger RW, Donoghue DJ: Human Spy1 promotes survival of mammalian cells following DNA damage. Cancer Res. 2003 Jul 1;63(13):3701-7. 12839962
  18. Porter LA, Kong-Beltran M, Donoghue DJ: Spy1 interacts with p27Kip1 to allow G1/S progression. Mol Biol Cell. 2003 Sep;14(9):3664-74. Epub 2003 Jul 11. 12972555
  19. Li Y, Mori T, Hata H, Homma Y, Kochi H: NIRF induces G1 arrest and associates with Cdk2. Biochem Biophys Res Commun. 2004 Jun 25;319(2):464-8. 15178429
  20. Wang GL, Iakova P, Wilde M, Awad S, Timchenko NA: Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity. Genes Dev. 2004 Apr 15;18(8):912-25. 15107404
  21. Liu Y, Wu C, Galaktionov K: p42, a novel cyclin-dependent kinase-activating kinase in mammalian cells. J Biol Chem. 2004 Feb 6;279(6):4507-14. Epub 2003 Nov 3. 14597612
  22. Cheng A, Xiong W, Ferrell JE Jr, Solomon MJ: Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins. Cell Cycle. 2005 Jan;4(1):155-65. Epub 2005 Jan 5. 15611625
  23. Esashi F, Christ N, Gannon J, Liu Y, Hunt T, Jasin M, West SC: CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature. 2005 Mar 31;434(7033):598-604. 15800615
  24. Lolli G, Johnson LN: Recognition of Cdk2 by Cdk7. Proteins. 2007 Jun 1;67(4):1048-59. 17373709
  25. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  26. De Boer L, Oakes V, Beamish H, Giles N, Stevens F, Somodevilla-Torres M, Desouza C, Gabrielli B: Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events. Oncogene. 2008 Jul 17;27(31):4261-8. doi: 10.1038/onc.2008.74. Epub 2008 Mar 31. 18372919
  27. Kong Y, Nan K, Yin Y: Identification and characterization of CAC1 as a novel CDK2-associated cullin. Cell Cycle. 2009 Nov 1;8(21):3552-61. Epub 2009 Dec 1. 19829063
  28. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  29. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  30. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  31. Flores O, Wang Z, Knudsen KE, Burnstein KL: Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Endocrinology. 2010 Mar;151(3):896-908. doi: 10.1210/en.2009-1116. Epub 2010 Feb 10. 20147522
  32. Kumar S, Barthwal MK, Dikshit M: Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-dependent biphasic effect on HL-60 cell cycle. Free Radic Biol Med. 2010 Mar 15;48(6):851-61. doi: 10.1016/j.freeradbiomed.2010.01.004. Epub 2010 Jan 15. 20079829
  33. Timofeev O, Cizmecioglu O, Settele F, Kempf T, Hoffmann I: Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition. J Biol Chem. 2010 May 28;285(22):16978-90. doi: 10.1074/jbc.M109.096552. Epub 2010 Apr 1. 20360007
  34. Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, Bagchi A, Simon JA, Huang H: Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol. 2010 Nov;12(11):1108-14. doi: 10.1038/ncb2116. Epub 2010 Oct 10. 20935635
  35. Chung JH, Bunz F: Cdk2 is required for p53-independent G2/M checkpoint control. PLoS Genet. 2010 Feb 26;6(2):e1000863. doi: 10.1371/journal.pgen.1000863. 20195506
  36. Hydbring P, Bahram F, Su Y, Tronnersjo S, Hogstrand K, von der Lehr N, Sharifi HR, Lilischkis R, Hein N, Wu S, Vervoorts J, Henriksson M, Grandien A, Luscher B, Larsson LG: Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation. Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):58-63. doi: 10.1073/pnas.0900121106. Epub 2009 Dec 4. 19966300
  37. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  38. Loffler H, Fechter A, Matuszewska M, Saffrich R, Mistrik M, Marhold J, Hornung C, Westermann F, Bartek J, Kramer A: Cep63 recruits Cdk1 to the centrosome: implications for regulation of mitotic entry, centrosome amplification, and genome maintenance. Cancer Res. 2011 Mar 15;71(6):2129-39. doi: 10.1158/0008-5472.CAN-10-2684. 21406398
  39. Fiset A, Xu E, Bergeron S, Marette A, Pelletier G, Siminovitch KA, Olivier M, Beauchemin N, Faure RL: Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization. Cell Signal. 2011 May;23(5):911-9. doi: 10.1016/j.cellsig.2011.01.019. Epub 2011 Jan 22. 21262353
  40. Lee J, Kim KH, Jeong S: Discovery of a novel class of 2-aminopyrimidines as CDK1 and CDK2 inhibitors. Bioorg Med Chem Lett. 2011 Jul 15;21(14):4203-5. doi: 10.1016/j.bmcl.2011.05.081. Epub 2011 May 27. 21684737
  41. Huang X, Summers MK, Pham V, Lill JR, Liu J, Lee G, Kirkpatrick DS, Jackson PK, Fang G, Dixit VM: Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry. Mol Cell. 2011 May 20;42(4):511-23. doi: 10.1016/j.molcel.2011.03.027. 21596315
  42. Neganova I, Vilella F, Atkinson SP, Lloret M, Passos JF, von Zglinicki T, O'Connor JE, Burks D, Jones R, Armstrong L, Lako M: An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells. Stem Cells. 2011 Apr;29(4):651-9. doi: 10.1002/stem.620. 21319273
  43. Satyanarayana A, Kaldis P: A dual role of Cdk2 in DNA damage response. Cell Div. 2009 May 18;4:9. doi: 10.1186/1747-1028-4-9. 19445729
  44. Malumbres M, Barbacid M: Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602. 19238148
  45. Satyanarayana A, Kaldis P: Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene. 2009 Aug 20;28(33):2925-39. doi: 10.1038/onc.2009.170. Epub 2009 Jun 29. 19561645
  46. Hydbring P, Larsson LG: Tipping the balance: Cdk2 enables Myc to suppress senescence. Cancer Res. 2010 Sep 1;70(17):6687-91. doi: 10.1158/0008-5472.CAN-10-1383. Epub 2010 Aug 16. 20713526
  47. Wang Q, Su L, Liu N, Zhang L, Xu W, Fang H: Cyclin dependent kinase 1 inhibitors: a review of recent progress. Curr Med Chem. 2011;18(13):2025-43. 21517772
  48. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  49. De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH: Crystal structure of cyclin-dependent kinase 2. Nature. 1993 Jun 17;363(6430):595-602. 8510751
  50. Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massague J, Pavletich NP: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature. 1995 Jul 27;376(6538):313-20. 7630397
  51. Bourne Y, Watson MH, Hickey MJ, Holmes W, Rocque W, Reed SI, Tainer JA: Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1. Cell. 1996 Mar 22;84(6):863-74. 8601310
  52. Schulze-Gahmen U, De Bondt HL, Kim SH: High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design. J Med Chem. 1996 Nov 8;39(23):4540-6. 8917641
  53. Russo AA, Jeffrey PD, Patten AK, Massague J, Pavletich NP: Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex. Nature. 1996 Jul 25;382(6589):325-31. 8684460
  54. Russo AA, Jeffrey PD, Pavletich NP: Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat Struct Biol. 1996 Aug;3(8):696-700. 8756328
  55. De Azevedo WF Jr, Mueller-Dieckmann HJ, Schulze-Gahmen U, Worland PJ, Sausville E, Kim SH: Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2735-40. 8610110
  56. Lawrie AM, Noble ME, Tunnah P, Brown NR, Johnson LN, Endicott JA: Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nat Struct Biol. 1997 Oct;4(10):796-801. 9334743
  57. Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L, Kim SH, Lockhart DJ, Schultz PG: Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24;281(5376):533-8. 9677190
  58. Richardson CM, Williamson DS, Parratt MJ, Borgognoni J, Cansfield AD, Dokurno P, Francis GL, Howes R, Moore JD, Murray JB, Robertson A, Surgenor AE, Torrance CJ: Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7. Epub 2005 Dec 1. 16325401
  59. Richardson CM, Nunns CL, Williamson DS, Parratt MJ, Dokurno P, Howes R, Borgognoni J, Drysdale MJ, Finch H, Hubbard RE, Jackson PS, Kierstan P, Lentzen G, Moore JD, Murray JB, Simmonite H, Surgenor AE, Torrance CJ: Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3880-5. Epub 2007 May 6. 17570665
  60. Brown NR, Lowe ED, Petri E, Skamnaki V, Antrobus R, Johnson LN: Cyclin B and cyclin A confer different substrate recognition properties on CDK2. Cell Cycle. 2007 Jun 1;6(11):1350-9. Epub 2007 Jun 11. 17495531
  61. Welburn JP, Tucker JA, Johnson T, Lindert L, Morgan M, Willis A, Noble ME, Endicott JA: How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A. J Biol Chem. 2007 Feb 2;282(5):3173-81. Epub 2006 Nov 9. 17095507
  62. Fischmann TO, Hruza A, Duca JS, Ramanathan L, Mayhood T, Windsor WT, Le HV, Guzi TJ, Dwyer MP, Paruch K, Doll RJ, Lees E, Parry D, Seghezzi W, Madison V: Structure-guided discovery of cyclin-dependent kinase inhibitors. Biopolymers. 2008 May;89(5):372-9. 17937404
  63. Wyatt PG, Woodhead AJ, Berdini V, Boulstridge JA, Carr MG, Cross DM, Davis DJ, Devine LA, Early TR, Feltell RE, Lewis EJ, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Reule M, Saxty G, Seavers LC, Smith DM, Squires MS, Trewartha G, Walker MT, Woolford AJ: Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J Med Chem. 2008 Aug 28;51(16):4986-99. doi: 10.1021/jm800382h. Epub 2008 Jul 26. 18656911
  64. Bao ZQ, Jacobsen DM, Young MA: Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis. Structure. 2011 May 11;19(5):675-90. doi: 10.1016/j.str.2011.02.016. 21565702
  65. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846
  66. Menning M, Kufer TA: A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses. FEBS Lett. 2013 Jul 11;587(14):2137-42. doi: 10.1016/j.febslet.2013.05.037. Epub 2013 May 24. 23711367