protamine kinase


Summary: An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.

Top Publications

  1. Perez Cadahia B, Drobic B, Davie J. H3 phosphorylation: dual role in mitosis and interphase. Biochem Cell Biol. 2009;87:695-709 pubmed publisher
    ..The cellular contexts under which specific residues on H3 are phosphorylated in mitosis and interphase are known to some extent. However, the functional consequences of H3 phosphorylation are still unclear. ..
  2. Ivanovska I, Khandan T, Ito T, Orr Weaver T. A histone code in meiosis: the histone kinase, NHK-1, is required for proper chromosomal architecture in Drosophila oocytes. Genes Dev. 2005;19:2571-82 pubmed
    ..These studies reveal a critical role for histone modifications in chromosome dynamics in meiosis and mitosis. ..
  3. Dai J, Higgins J. Haspin: a mitotic histone kinase required for metaphase chromosome alignment. Cell Cycle. 2005;4:665-8 pubmed
    ..Here we discuss possible mechanisms of haspin action and the function of histone phosphorylation in mitosis. We also outline some of the questions raised by these new findings and consider what role haspin might play in cancer. ..
  4. Aihara H, Nakagawa T, Yasui K, Ohta T, Hirose S, Dhomae N, et al. Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. Genes Dev. 2004;18:877-88 pubmed
    ..These studies reveal that NHK-1-catalyzed phosphorylation of a conserved serine/threonine residue in H2A is a new component of the histone code that might be related to cell cycle progression. ..
  5. Lin S, Manchester J, Gordon J. Sip2, an N-myristoylated beta subunit of Snf1 kinase, regulates aging in Saccharomyces cerevisiae by affecting cellular histone kinase activity, recombination at rDNA loci, and silencing. J Biol Chem. 2003;278:13390-7 pubmed
  6. Knuesel M, Meyer K, Donner A, Espinosa J, Taatjes D. The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator. Mol Cell Biol. 2009;29:650-61 pubmed publisher
    ..In support of this, electron microscopy analysis suggests TRiC sequesters the CDK8 subcomplex and kinase assays reveal the endogenous CDK8 subcomplex--unlike the recombinant submodule--is unable to phosphorylate the Pol II CTD. ..
  7. Lancaster O, Cullen C, Ohkura H. NHK-1 phosphorylates BAF to allow karyosome formation in the Drosophila oocyte nucleus. J Cell Biol. 2007;179:817-24 pubmed
    ..We propose that BAF phosphorylation by NHK-1 disrupts anchorage of chromosomes to the nuclear envelope, allowing karyosome formation in oocytes. These data provide the first mechanistic insight into how the karyosome forms. ..
  8. Swain J, Ding J, Brautigan D, Villa Moruzzi E, Smith G. Proper chromatin condensation and maintenance of histone H3 phosphorylation during mouse oocyte meiosis requires protein phosphatase activity. Biol Reprod. 2007;76:628-38 pubmed
    ..Furthermore, GSK3 inhibition results in aberrant chromatin condensation and appears to regulate phosphorylation of PPP1R2. ..
  9. Cullen C, Brittle A, Ito T, Ohkura H. The conserved kinase NHK-1 is essential for mitotic progression and unifying acentrosomal meiotic spindles in Drosophila melanogaster. J Cell Biol. 2005;171:593-602 pubmed
    ..NHK-1 itself is phosphorylated in mitosis and female meiosis, suggesting that this kinase is part of the regulatory system coordinating progression of mitosis and meiosis. ..

More Information


  1. Peterson C, Laniel M. Histones and histone modifications. Curr Biol. 2004;14:R546-51 pubmed
  2. Ivanovska I, Orr Weaver T. Histone modifications and the chromatin scaffold for meiotic chromosome architecture. Cell Cycle. 2006;5:2064-71 pubmed
    ..A meiotic mutation in the Drosophila histone kinase, NHK-1, uncovered a critical requirement for histone modifications in chromosome architecture, underscoring the power of this approach. ..
  3. Azzi L, Meijer L, Reed S, Pidikiti R, Tung H. Interaction between the cell-cycle-control proteins p34cdc2 and p9CKShs2. Evidence for two cooperative binding domains in p9CKShs2. Eur J Biochem. 1992;203:353-60 pubmed
    ..The implications of the existence of two cooperative p34cdc2-binding domains in p9CKShs2 on the structure of the active M-phase-specific kinase is discussed. ..
  4. Swain J, Ding J, Wu J, Smith G. Regulation of spindle and chromatin dynamics during early and late stages of oocyte maturation by aurora kinases. Mol Hum Reprod. 2008;14:291-9 pubmed publisher
    ..These data suggest a ZM-sensitive AURK may be an oocyte histone-H3 kinase capable of regulating chromatin remodeling throughout oocyte meiosis, both pre- and post-MI. ..
  5. Chen D, Chen S, Gee M, Pan J, Kuo T. A variant of Saccharomyces cerevisiae pep4 strain with improved oligotrophic proliferation, cell survival and heterologous secretion of alpha-amylase. Appl Microbiol Biotechnol. 1999;51:185-92 pubmed
    ..The results imply that the NI-C variant is an improved pep4 strain that can be used for heterologous expression and for the development of new selective markers in the yeast transformation system. ..
  6. Ma F, Zhang C. Histone modifying enzymes: novel disease biomarkers and assay development. Expert Rev Mol Diagn. 2016;16:297-306 pubmed publisher
    ..In this review, we summarize the recent researches about the histone modifying enzymes as the disease biomarkers, and highlight the development of methods for histone modifying enzyme assays. ..
  7. Wang Y, Burke D. Cdc55p, the B-type regulatory subunit of protein phosphatase 2A, has multiple functions in mitosis and is required for the kinetochore/spindle checkpoint in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17:620-6 pubmed
    ..Finally, cdc55::LEU2 suppresses the temperature sensitivity of cdc20-1, suggesting additional roles for CDC55 in mitosis. ..
  8. Monroy A, Labbe E, Dhindsa R. Low temperature perception in plants: effects of cold on protein phosphorylation in cell-free extracts. FEBS Lett. 1997;410:206-9 pubmed
  9. Reiss K, Cheng W, Pierzchalski P, Kodali S, Li B, Wang S, et al. Insulin-like growth factor-1 receptor and its ligand regulate the reentry of adult ventricular myocytes into the cell cycle. Exp Cell Res. 1997;235:198-209 pubmed
    ..The failure of IGF-1 to enhance cyclin B kinase activity may be responsible for a block in the cell cycle and the inability of myocytes to progress through the M phase and subsequently divide. ..
  10. Nakaya N, Sugano N, Nishi A, Tsukada K. Protein kinase in cultured plant cells. Biochim Biophys Acta. 1975;410:273-8 pubmed
    ..It was thermolabile and completely dependent on the presence of Mg2+ or Mn2+ for activity. p-Chloromercuribenzoate inactivated this enzyme and this inactivation was overcome by mercaptoethanol. ..
  11. Moll T, Tebb G, Surana U, Robitsch H, Nasmyth K. The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. Cell. 1991;66:743-58 pubmed
    ..As all three serines are phosphorylated by purified CDC28-dependent H1 kinase activity in vitro, we propose a model in which the CDC28 kinase acts directly to control nuclear entry of SWI5. ..
  12. McLay D, Carroll J, Clarke H. The ability to develop an activity that transfers histones onto sperm chromatin is acquired with meiotic competence during oocyte growth. Dev Biol. 2002;241:195-206 pubmed
  13. Morice W, Wiederrecht G, Brunn G, Siekierka J, Abraham R. Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes. J Biol Chem. 1993;268:22737-45 pubmed
    ..The inhibitory effects of RAP on the activation of cyclin E- and cyclin A-associated cyclin-dependent kinases suggest that one or both events participate in the regulation of T cell entry into S-phase. ..
  14. Yamano H, Gannon J, Hunt T. The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe. EMBO J. 1996;15:5268-79 pubmed
  15. Cho H, Lee Y, Bae Y, Kim E, Kang B. Activation of ATP binding for the autophosphorylation of DosS, a Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif. J Biol Chem. 2013;288:12437-47 pubmed publisher
    ..ATP binding can, therefore, function as a control mechanism for histidine kinase activity...
  16. Kesari K, Kumar S, Behari J. Effects of radiofrequency electromagnetic wave exposure from cellular phones on the reproductive pattern in male Wistar rats. Appl Biochem Biotechnol. 2011;164:546-59 pubmed publisher
    ..It is concluded that radiofrequency electromagnetic wave from commercially available cell phones might affect the fertilizing potential of spermatozoa. ..
  17. Cho H, Cho H, Kim Y, Oh J, Kang B. Crystallization and preliminary crystallographic analysis of the second GAF domain of DevS from Mycobacterium smegmatis. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008;64:274-6 pubmed publisher
    ..The asymmetric unit contains one molecule, corresponding to a packing density of 2.5 A(3) Da(-1). The selenium substructure was determined by the single anomalous dispersion method and structure refinement is in progress. ..
  18. Swaminathan V, Reddy B, Ruthrotha Selvi B, Sukanya M, Kundu T. Small molecule modulators in epigenetics: implications in gene expression and therapeutics. Subcell Biochem. 2007;41:397-428 pubmed
    ..enzymes involved in gene regulation, their connection to disease manifestation and focuses on the role of small molecule modulators in understanding enzyme function and also the design and the evolution of chromatin therapeutics ..
  19. Clark K, Ohtsubo M, Nishimoto T, Goebl M, Sprague G. The yeast SRM1 protein and human RCC1 protein share analogous functions. Cell Regul. 1991;2:781-92 pubmed
    ..Finally, like RCC1, SRM1 is a nuclear protein. Together, these data imply that SRM1 and RCC1 have a common role in their respective organisms. ..
  20. Oda Y, Okada T, Yoshida H, Kaufman R, Nagata K, Mori K. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J Cell Biol. 2006;172:383-93 pubmed
    ..These findings indicate that Derlin-2 and -3 provide the missing link between EDEM and p97 in the process of degrading misfolded glycoproteins. ..
  21. Chen R, Waters J, Salmon E, Murray A. Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science. 1996;274:242-6 pubmed
    ..This study furthers understanding of the mechanism of cell cycle checkpoints in metazoa and provides a marker for studying the role of the spindle assembly checkpoint in the genetic instability of tumors...
  22. Lo W, Henry K, Schwartz M, Berger S. Histone modification patterns during gene activation. Methods Enzymol. 2004;377:130-53 pubmed
  23. Arima N, Kao C, Licht T, Sasaguri Y, Padmanabhan R. Modulation of cell growth by the hepatitis C virus nonstructural protein NS5A. J Biol Chem. 2001;276:12675-84 pubmed
    ..Our results suggest that the NS5A protein causes growth inhibition and cell cycle perturbations by targeting the Cdk1/2-cyclin complexes. ..
  24. Paula C, Techio V, Sobrinho F, Freitas A. Distribution pattern of histone H3 phosphorylation at serine 10 during mitosis and meiosis in Brachiaria species. J Genet. 2013;92:259-66 pubmed
    ..Regarding spatiotemporal coordination in the Brachiaria species evaluated, H3S10ph is related to maintenance of sister chromatid cohesion during cell divisions. ..
  25. Zhou P, Long Q, Zhou Y, Wang H, Xie J. Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs. Crit Rev Eukaryot Gene Expr. 2012;22:37-52 pubmed
    ..This review focuses on the physiological roles of TCSs and the network of M.tb TCSs from a systems biology perspective. The implications of TCSs for better vaccine and new drug targets against tuberculosis are also examined. ..
  26. Planchais S, Glab N, Trehin C, Perennes C, Bureau J, Meijer L, et al. Roscovitine, a novel cyclin-dependent kinase inhibitor, characterizes restriction point and G2/M transition in tobacco BY-2 cell suspension. Plant J. 1997;12:191-202 pubmed
    ..The implications of these experimental observations for the requirement for CDK activity during progression through the plant cell cycle are discussed. ..
  27. Fallow A, Domenech P, Reed M. Strains of the East Asian (W/Beijing) lineage of Mycobacterium tuberculosis are DosS/DosT-DosR two-component regulatory system natural mutants. J Bacteriol. 2010;192:2228-38 pubmed publisher
    ..Our data serve to highlight the evolutionary pressure that exists among distinct M. tuberculosis lineages to maintain tight control over DosR regulon expression...
  28. Yamauchi H, Katayama K, Ueno M, Kanemitsu H, Nam C, Mikami T, et al. Etoposide induces TRP53-dependent apoptosis and TRP53-independent cell cycle arrest in trophoblasts of the developing mouse placenta. Biol Reprod. 2009;80:813-22 pubmed publisher
    ..Our study demonstrated that etoposide injection induced TRP53-dependent apoptosis and TRP53-independent cell cycle arrest in labyrinthine trophoblasts, providing insights into the molecular pathway of placental disorders. ..
  29. Kumar A, Toledo J, Patel R, Lancaster J, Steyn A. Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor. Proc Natl Acad Sci U S A. 2007;104:11568-73 pubmed
    ..We conclude that Mtb has evolved finely tuned redox and hypoxia-mediated sensing strategies for detecting O2, NO, and CO. Data presented here establish a paradigm for understanding the mechanism of bacilli persistence. ..
  30. Gerber M, Farrell A, Deshaies R, Herskowitz I, Morgan D. Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins. Proc Natl Acad Sci U S A. 1995;92:4651-5 pubmed
    ..cdc37-1 mutants also exhibit a defect in the binding and activation of Cdc28 by the mitotic cyclin Clb2. Thus Cdc37 may be a regulator that is required for the association of Cdc28 with multiple cyclins. ..
  31. Baatout S, Derradji H. About histone H1 phosphorylation during mitosis. Cell Biochem Funct. 2006;24:93-4 pubmed
  32. Hollingsworth R, Sclafani R. DNA metabolism gene CDC7 from yeast encodes a serine (threonine) protein kinase. Proc Natl Acad Sci U S A. 1990;87:6272-6 pubmed
    ..Because Cdc7 kinase acts downstream of Cdc28/cdc2 kinase function at "start," the transition from G1 to S phase in the cell cycle may be the result of a cascade of protein phosphorylation. ..
  33. Kristeleit R, Stimson L, Workman P, Aherne W. Histone modification enzymes: novel targets for cancer drugs. Expert Opin Emerg Drugs. 2004;9:135-54 pubmed
    ..It is likely that many of the enzymes involved in the control of histone modification will provide therapeutic opportunities for the treatment of cancer, including histone methyltransferases and Aurora kinases. ..
  34. Nikalayevich E, Ohkura H. The NuRD nucleosome remodelling complex and NHK-1 kinase are required for chromosome condensation in oocytes. J Cell Sci. 2015;128:566-75 pubmed
    ..We further show that NHK-1 is important for chromosome condensation during mitosis as well as in oocytes. ..
  35. Noguchi E, Sekiguchi T, Yamashita K, Nishimoto T. Molecular cloning and identification of two types of hamster cyclin-dependent kinases: cdk2 and cdk2L. Biochem Biophys Res Commun. 1993;197:1524-9 pubmed
    ..Immunoblotting analysis suggested that these two types of cdk2 protein exist in mammalian cells. The cdk2hm has the activity of protein kinase, while the cdk2Lhm does not, however, both bind with cyclin E. ..
  36. Motlik J, Sutovsky P, Kalous J, Kubelka M, Moos J, Schultz R. Co-culture with pig membrana granulosa cells modulates the activity of cdc2 and MAP kinase in maturing cattle oocytes. Zygote. 1996;4:247-56 pubmed
    ..While these events are fully reversible in late diakinesis oocytes, metaphase I oocytes did not complete maturation after release from co-culture. ..
  37. He H, Bretl D, Penoske R, Anderson D, Zahrt T. Components of the Rv0081-Rv0088 locus, which encodes a predicted formate hydrogenlyase complex, are coregulated by Rv0081, MprA, and DosR in Mycobacterium tuberculosis. J Bacteriol. 2011;193:5105-18 pubmed publisher
    ..Based on this and other published information, a model is proposed detailing Rv0081-Rv0088 expression by these transcription factors within particular growth environments. ..
  38. Abraham S, Carter M, Moran E. Transforming growth factor beta 1 (TGF beta 1) reduces cellular levels of p34cdc2, and this effect is abrogated by adenovirus independently of the E1A-associated pRB binding activity. Mol Biol Cell. 1992;3:655-65 pubmed
    ..Overall our results suggest that TGF beta 1 acts by signaling changes at the level of control of G1 gene expression, not at the level of posttranslational modification of p34cdc2 or its substrates. ..
  39. Giordano A, Lee J, Scheppler J, Herrmann C, Harlow E, Deuschle U, et al. Cell cycle regulation of histone H1 kinase activity associated with the adenoviral protein E1A. Science. 1991;253:1271-5 pubmed
    ..This E1A complex displayed histone H1-specific kinase activity; the kinase activity was modulated during the cell division cycle, and association of pRb with E1A apparently was not required for this activity. ..
  40. Brittle A, Nanba Y, Ito T, Ohkura H. Concerted action of Aurora B, Polo and NHK-1 kinases in centromere-specific histone 2A phosphorylation. Exp Cell Res. 2007;313:2780-5 pubmed
    ..Epistasis analysis indicated that Polo functions upstream of the H2A kinase NHK-1 but parallel to Aurora B. Therefore, multiple mitotic kinases work together to specify the spatial and temporal pattern of H2A T119 phosphorylation. ..
  41. Chakravarthy M, Abraha T, Schwartz R, Fiorotto M, Booth F. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway. J Biol Chem. 2000;275:35942-52 pubmed
    ..These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known. ..
  42. Gupta R, Thakur T, Desiraju G, Tyagi J. Structure-based design of DevR inhibitor active against nonreplicating Mycobacterium tuberculosis. J Med Chem. 2009;52:6324-34 pubmed publisher
    ..These results provide proof-of-concept for DevR as a novel target to develop molecules with sterilizing activity against tubercle bacilli. ..
  43. Tommasino M, Adamczewski J, Carlotti F, Barth C, Manetti R, Contorni M, et al. HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. Oncogene. 1993;8:195-202 pubmed
    ..The interaction appears to be via cyclin A, since probing of similar immunoblots showed a 50 kDa band corresponding to cyclin A. The association of E7 with cyclin A appeared to be direct, not involving Rb 1 or other proteins. ..
  44. Honaker R, Dhiman R, Narayanasamy P, Crick D, Voskuil M. DosS responds to a reduced electron transport system to induce the Mycobacterium tuberculosis DosR regulon. J Bacteriol. 2010;192:6447-55 pubmed publisher
    ..Although this report demonstrates that DosS responds to a reduced ETS, it does not rule out a role for oxygen in silencing signaling. ..
  45. Lee C, Lin Y, Chang W, Lin P, Wu Y, Chang J. Squamocin modulates histone H3 phosphorylation levels and induces G1 phase arrest and apoptosis in cancer cells. BMC Cancer. 2011;11:58 pubmed publisher
    ..This study is the first to show that squamocin affects epigenetic alterations by modulating histone H3 phosphorylation at S10 and S28, providing a novel view of the antitumor mechanism of squamocin. ..
  46. Bagchi G, Chauhan S, Sharma D, Tyagi J. Transcription and autoregulation of the Rv3134c-devR-devS operon of Mycobacterium tuberculosis. Microbiology. 2005;151:4045-53 pubmed
    ..Furthermore, DevR modulated the activity of both devR and Rv3134c promoters. From these findings it is inferred that the Rv3134c-devR-devS operon is transcribed from multiple promoters and is autoregulated. ..
  47. Tyers M, Tokiwa G, Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993;12:1955-68 pubmed
    ..Given the large number of known cyclins, such cyclin cascades may be a common theme in cell cycle control. ..
  48. Li H, Xie B, Rahmeh A, Zhou Y, Lee M. Direct interaction of p21 with p50, the small subunit of human DNA polymerase delta. Cell Cycle. 2006;5:428-36 pubmed
    ..Our results suggested that p50 might target or anchor p21 to pol delta complex upon certain DNA damage such as adriamycin treatment. ..
  49. Morla A, Draetta G, Beach D, Wang J. Reversible tyrosine phosphorylation of cdc2: dephosphorylation accompanies activation during entry into mitosis. Cell. 1989;58:193-203 pubmed
    ..Tyrosine dephosphorylation of cdc2 may be one of a number of obligatory steps in the mitotic activation of the kinase. ..
  50. Yamamoto A, Guacci V, Koshland D. Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s). J Cell Biol. 1996;133:99-110 pubmed
    ..Therefore, in the DNA-damage checkpoint, Pds1p is required for the inhibition of cytokinesis and DNA replication as well as anaphase. The role of Pds1 protein in anaphase inhibition and general cell cycle regulation is discussed. ..
  51. Kim M, Park K, Ko I, Kim Y, Oh J. Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria. J Bacteriol. 2010;192:4868-75 pubmed publisher
  52. Loury R, Sassone Corsi P. Analysis of histone phosphorylation: coupling intracellular signaling to chromatin remodeling. Methods Enzymol. 2004;377:197-212 pubmed
  53. Crosio C, Fimia G, Loury R, Kimura M, Okano Y, Zhou H, et al. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol. 2002;22:874-85 pubmed
    ..Since Aurora-A and Aurora-B are known to be overexpressed in a variety of human cancers, our findings provide an attractive link between cell transformation, chromatin modifications and a specific kinase system. ..