2jii › Citations

Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site.

Scheeff ED, Eswaran J, Bunkoczi G, Knapp S, Manning G
Structure 17 128-38 (2009)
Cited: 120 times
EuropePMC logo PMID: 19141289

Abstract

About 10% of all protein kinases are predicted to be enzymatically inactive pseudokinases, but the structural details of kinase inactivation have remained unclear. We present the first structure of a pseudokinase, VRK3, and that of its closest active relative, VRK2. Profound changes to the active site region underlie the loss of catalytic activity, and VRK3 cannot bind ATP because of residue substitutions in the binding pocket. However, VRK3 still shares striking structural similarity with VRK2, and appears to be locked in a pseudoactive conformation. VRK3 also conserves residue interactions that are surprising in the absence of enzymatic function; these appear to play important architectural roles required for the residual functions of VRK3. Remarkably, VRK3 has an "inverted" pattern of sequence conservation: although the active site is poorly conserved, portions of the molecular surface show very high conservation, suggesting that they form key interactions that explain the evolutionary retention of VRK3.

Reviews - 2jii mentioned but not cited (4)

  1. Pseudokinases-remnants of evolution or key allosteric regulators? Zeqiraj E, van Aalten DM. Curr. Opin. Struct. Biol. 20 772-781 (2010)
  2. Prospects for pharmacological targeting of pseudokinases. Kung JE, Jura N. Nat Rev Drug Discov 18 501-526 (2019)
  3. Nucleotide-binding mechanisms in pseudokinases. Hammarén HM, Virtanen AT, Silvennoinen O. Biosci. Rep. 36 e00282 (2015)
  4. Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease. Yeung W, Ruan Z, Kannan N. IUBMB Life 72 1189-1202 (2020)

Articles - 2jii mentioned but not cited (6)

  1. Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors. Talevich E, Kannan N. BMC Evol. Biol. 13 117 (2013)
  2. article-commentary Pseudokinases: functional insights gleaned from structure. Kornev AP, Taylor SS. Structure 17 5-7 (2009)
  3. Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allosteric Mechanism for Negative Regulation. Lange SM, Nelen MI, Cohen P, Kulathu Y. Structure 29 238-251.e4 (2021)
  4. STK40 Is a Pseudokinase that Binds the E3 Ubiquitin Ligase COP1. Durzynska I, Xu X, Adelmant G, Ficarro SB, Marto JA, Sliz P, Uljon S, Blacklow SC. Structure 25 287-294 (2017)
  5. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  6. Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations. Couñago RM, Allerston CK, Savitsky P, Azevedo H, Godoi PH, Wells CI, Mascarello A, de Souza Gama FH, Massirer KB, Zuercher WJ, Guimarães CRW, Gileadi O. Sci Rep 7 7501 (2017)


Reviews citing this publication (37)

  1. Protein kinases: evolution of dynamic regulatory proteins. Taylor SS, Kornev AP. Trends Biochem. Sci. 36 65-77 (2011)
  2. The structural basis for control of eukaryotic protein kinases. Endicott JA, Noble ME, Johnson LN. Annu. Rev. Biochem. 81 587-613 (2012)
  3. Plant innate immunity: perception of conserved microbial signatures. Schwessinger B, Ronald PC. Annu Rev Plant Biol 63 451-482 (2012)
  4. The evolution of protein kinase inhibitors from antagonists to agonists of cellular signaling. Dar AC, Shokat KM. Annu. Rev. Biochem. 80 769-795 (2011)
  5. Evolution of the eukaryotic protein kinases as dynamic molecular switches. Taylor SS, Keshwani MM, Steichen JM, Kornev AP. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 367 2517-2528 (2012)
  6. Day of the dead: pseudokinases and pseudophosphatases in physiology and disease. Reiterer V, Eyers PA, Farhan H. Trends Cell Biol. 24 489-505 (2014)
  7. Kinases and pseudokinases: lessons from RAF. Shaw AS, Kornev AP, Hu J, Ahuja LG, Taylor SS. Mol. Cell. Biol. 34 1538-1546 (2014)
  8. Dawn of the dead: protein pseudokinases signal new adventures in cell biology. Eyers PA, Murphy JM. Biochem. Soc. Trans. 41 969-974 (2013)
  9. Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases. Haan C, Behrmann I, Haan S. J. Cell. Mol. Med. 14 504-527 (2010)
  10. Proteus in the world of proteins: conformational changes in protein kinases. Rabiller M, Getlik M, Klüter S, Richters A, Tückmantel S, Simard JR, Rauh D. Arch. Pharm. (Weinheim) 343 193-206 (2010)
  11. Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease. Eyers PA, Keeshan K, Kannan N. Trends Cell Biol. 27 284-298 (2017)
  12. Structural Basis for the Non-catalytic Functions of Protein Kinases. Kung JE, Jura N. Structure 24 7-24 (2016)
  13. Insights into protein kinase regulation and inhibition by large scale structural comparison. Eswaran J, Knapp S. Biochim. Biophys. Acta 1804 429-432 (2010)
  14. Receptor tyrosine kinases with intracellular pseudokinase domains. Mendrola JM, Shi F, Park JH, Lemmon MA. Biochem. Soc. Trans. 41 1029-1036 (2013)
  15. The role of pseudokinases in cancer. Zhang H, Photiou A, Grothey A, Stebbing J, Giamas G. Cell. Signal. 24 1173-1184 (2012)
  16. Mechanisms of Receptor Tyrosine-Protein Kinase ErbB-3 (ERBB3) Action in Human Neoplasia. Black LE, Longo JF, Carroll SL. Am J Pathol 189 1898-1912 (2019)
  17. Pseudokinases from a structural perspective. Taylor SS, Shaw A, Hu J, Meharena HS, Kornev A. Biochem. Soc. Trans. 41 981-986 (2013)
  18. Bio-Zombie: the rise of pseudoenzymes in biology. Murphy JM, Farhan H, Eyers PA. Biochem. Soc. Trans. 45 537-544 (2017)
  19. Going for broke: targeting the human cancer pseudokinome. Bailey FP, Byrne DP, McSkimming D, Kannan N, Eyers PA. Biochem. J. 465 195-211 (2015)
  20. Mechanistic and functional diversity in the mechanosensory kinases of the titin-like family. Mayans O, Benian GM, Simkovic F, Rigden DJ. Biochem. Soc. Trans. 41 1066-1071 (2013)
  21. Techniques to examine nucleotide binding by pseudokinases. Lucet IS, Babon JJ, Murphy JM. Biochem. Soc. Trans. 41 975-980 (2013)
  22. Cataloguing the dead: breathing new life into pseudokinase research. Shrestha S, Byrne DP, Harris JA, Kannan N, Eyers PA. FEBS J 287 4150-4169 (2020)
  23. The molecular details of cytokine signaling via the JAK/STAT pathway. Morris R, Kershaw NJ, Babon JJ. Protein Sci. 27 1984-2009 (2018)
  24. ZRK atypical kinases: emerging signaling components of plant immunity. Roux F, Noël L, Rivas S, Roby D. New Phytol. 203 713-716 (2014)
  25. Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase. Kerr JS, Wilson CH. Biochem. Soc. Trans. 41 1055-1060 (2013)
  26. Pseudokinase drug intervention: a potentially poisoned chalice. Claus J, Cameron AJ, Parker PJ. Biochem. Soc. Trans. 41 1083-1088 (2013)
  27. Pseudokinases: update on their functions and evaluation as new drug targets. Byrne DP, Foulkes DM, Eyers PA. Future Med Chem 9 245-265 (2017)
  28. Diverse cellular functions of barrier-to-autointegration factor and its roles in disease. Sears RM, Roux KJ. J Cell Sci 133 jcs246546 (2020)
  29. Multiple functions of TBCK protein in neurodevelopment disorders and tumors. Wu J, Lu G. Oncol Lett 21 17 (2021)
  30. A pickup in pseudokinase activity. Dar AC. Biochem. Soc. Trans. 41 987-994 (2013)
  31. There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling. Mace PD, Murphy JM. J Biol Chem 296 100705 (2021)
  32. Phosphoproteomics Meets Chemical Genetics: Approaches for Global Mapping and Deciphering the Phosphoproteome. Jurcik J, Sivakova B, Cipakova I, Selicky T, Stupenova E, Jurcik M, Osadska M, Barath P, Cipak L. Int J Mol Sci 21 E7637 (2020)
  33. PseudoGTPase domains in p190RhoGAP proteins: a mini-review. Stiegler AL, Boggon TJ. Biochem. Soc. Trans. 46 1713-1720 (2018)
  34. Barrier-to-autointegration factor: a first responder for repair of nuclear ruptures. Halfmann CT, Roux KJ. Cell Cycle 20 647-660 (2021)
  35. Computational tools and resources for pseudokinase research. O'Boyle B, Shrestha S, Kochut K, Eyers PA, Kannan N. Methods Enzymol 667 403-426 (2022)
  36. Current Progress in Delineating the Roles of Pseudokinase TRIB1 in Controlling Human Diseases. Zhang X, Zhang B, Zhang C, Sun G, Sun X. J Cancer 12 6012-6020 (2021)
  37. Recent advances in targeting protein kinases and pseudokinases in cancer biology. Riegel K, Vijayarangakannan P, Kechagioglou P, Bogucka K, Rajalingam K. Front Cell Dev Biol 10 942500 (2022)

Articles citing this publication (73)

  1. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Jura N, Shan Y, Cao X, Shaw DE, Kuriyan J. Proc. Natl. Acad. Sci. U.S.A. 106 21608-21613 (2009)
  2. Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation. Zeqiraj E, Filippi BM, Deak M, Alessi DR, van Aalten DM. Science 326 1707-1711 (2009)
  3. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, Xu CF, Neubert TA, Skoda RC, Hubbard SR, Silvennoinen O. Nat. Struct. Mol. Biol. 18 971-976 (2011)
  4. The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions. Fukuda K, Gupta S, Chen K, Wu C, Qin J. Mol. Cell 36 819-830 (2009)
  5. A robust methodology to subclassify pseudokinases based on their nucleotide-binding properties. Murphy JM, Zhang Q, Young SN, Reese ML, Bailey FP, Eyers PA, Ungureanu D, Hammaren H, Silvennoinen O, Varghese LN, Chen K, Tripaydonis A, Jura N, Fukuda K, Qin J, Nimchuk Z, Mudgett MB, Elowe S, Gee CL, Liu L, Daly RJ, Manning G, Babon JJ, Lucet IS. Biochem. J. 457 323-334 (2014)
  6. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor. Zeqiraj E, Filippi BM, Goldie S, Navratilova I, Boudeau J, Deak M, Alessi DR, van Aalten DM. PLoS Biol. 7 e1000126 (2009)
  7. Structure and functional characterization of the atypical human kinase haspin. Eswaran J, Patnaik D, Filippakopoulos P, Wang F, Stein RL, Murray JW, Higgins JM, Knapp S. Proc. Natl. Acad. Sci. U.S.A. 106 20198-20203 (2009)
  8. The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Suijkerbuijk SJ, van Dam TJ, Karagöz GE, von Castelmur E, Hubner NC, Duarte AM, Vleugel M, Perrakis A, Rüdiger SG, Snel B, Kops GJ. Dev. Cell 22 1321-1329 (2012)
  9. The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology. Manning G, Reiner DS, Lauwaet T, Dacre M, Smith A, Zhai Y, Svard S, Gillin FD. Genome Biol. 12 R66 (2011)
  10. Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. de Cárcer G, Escobar B, Higuero AM, García L, Ansón A, Pérez G, Mollejo M, Manning G, Meléndez B, Abad-Rodríguez J, Malumbres M. Mol. Cell. Biol. 31 1225-1239 (2011)
  11. A conserved non-canonical motif in the pseudoactive site of the ROP5 pseudokinase domain mediates its effect on Toxoplasma virulence. Reese ML, Boothroyd JC. J. Biol. Chem. 286 29366-29375 (2011)
  12. An evolutionarily conserved pseudokinase mediates stem cell production in plants. Nimchuk ZL, Tarr PT, Meyerowitz EM. Plant Cell 23 851-854 (2011)
  13. Biochemical, proteomic, structural, and thermodynamic characterizations of integrin-linked kinase (ILK): cross-validation of the pseudokinase. Fukuda K, Knight JD, Piszczek G, Kothary R, Qin J. J. Biol. Chem. 286 21886-21895 (2011)
  14. Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL. Murphy JM, Lucet IS, Hildebrand JM, Tanzer MC, Young SN, Sharma P, Lessene G, Alexander WS, Babon JJ, Silke J, Czabotar PE. Biochem. J. 457 369-377 (2014)
  15. Kinase regulation by hydrophobic spine assembly in cancer. Hu J, Ahuja LG, Meharena HS, Kannan N, Kornev AP, Taylor SS, Shaw AS. Mol. Cell. Biol. 35 264-276 (2015)
  16. Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases. Cowan-Jacob SW, Jahnke W, Knapp S. Future Med Chem 6 541-561 (2014)
  17. Receptor guanylyl cyclase C (GC-C): regulation and signal transduction. Basu N, Arshad N, Visweswariah SS. Mol. Cell. Biochem. 334 67-80 (2010)
  18. Titin kinase is an inactive pseudokinase scaffold that supports MuRF1 recruitment to the sarcomeric M-line. Bogomolovas J, Gasch A, Simkovic F, Rigden DJ, Labeit S, Mayans O. Open Biol 4 140041 (2014)
  19. Vaccinia-related kinase 1 (VRK1) is an upstream nucleosomal kinase required for the assembly of 53BP1 foci in response to ionizing radiation-induced DNA damage. Sanz-García M, Monsalve DM, Sevilla A, Lazo PA. J. Biol. Chem. 287 23757-23768 (2012)
  20. Arginine transcriptional response does not require inositol phosphate synthesis. Bosch D, Saiardi A. J. Biol. Chem. 287 38347-38355 (2012)
  21. Human VRK2 modulates apoptosis by interaction with Bcl-xL and regulation of BAX gene expression. Monsalve DM, Merced T, Fernández IF, Blanco S, Vázquez-Cedeira M, Lazo PA. Cell Death Dis 4 e513 (2013)
  22. NMR solution structure of human vaccinia-related kinase 1 (VRK1) reveals the C-terminal tail essential for its structural stability and autocatalytic activity. Shin J, Chakraborty G, Bharatham N, Kang C, Tochio N, Koshiba S, Kigawa T, Kim W, Kim KT, Yoon HS. J. Biol. Chem. 286 22131-22138 (2011)
  23. Structure of the pseudokinase domain of BIR2, a regulator of BAK1-mediated immune signaling in Arabidopsis. Blaum BS, Mazzotta S, Nöldeke ER, Halter T, Madlung J, Kemmerling B, Stehle T. J. Struct. Biol. 186 112-121 (2014)
  24. A novel protein kinase-like domain in a selenoprotein, widespread in the tree of life. Dudkiewicz M, Szczepińska T, Grynberg M, Pawłowski K. PLoS ONE 7 e32138 (2012)
  25. ATP binding to the pseudokinase domain of JAK2 is critical for pathogenic activation. Hammarén HM, Ungureanu D, Grisouard J, Skoda RC, Hubbard SR, Silvennoinen O. Proc. Natl. Acad. Sci. U.S.A. 112 4642-4647 (2015)
  26. BAM 1 and RECEPTOR-LIKE PROTEIN KINASE 2 constitute a signaling pathway and modulate CLE peptide-triggered growth inhibition in Arabidopsis root. Shimizu N, Ishida T, Yamada M, Shigenobu S, Tabata R, Kinoshita A, Yamaguchi K, Hasebe M, Mitsumasu K, Sawa S. New Phytol. 208 1104-1113 (2015)
  27. Differential inhibitor sensitivity between human kinases VRK1 and VRK2. Vázquez-Cedeira M, Barcia-Sanjurjo I, Sanz-García M, Barcia R, Lazo PA. PLoS ONE 6 e23235 (2011)
  28. Vaccinia-related kinase 1 is required for the maintenance of undifferentiated spermatogonia in mouse male germ cells. Choi YH, Park CH, Kim W, Ling H, Kang A, Chang MW, Im SK, Jeong HW, Kong YY, Kim KT. PLoS ONE 5 e15254 (2010)
  29. TBCK influences cell proliferation, cell size and mTOR signaling pathway. Liu Y, Yan X, Zhou T. PLoS ONE 8 e71349 (2013)
  30. PINK1 rendered temperature sensitive by disease-associated and engineered mutations. Narendra DP, Wang C, Youle RJ, Walker JE. Hum. Mol. Genet. 22 2572-2589 (2013)
  31. Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response. Salzano M, Vázquez-Cedeira M, Sanz-García M, Valbuena A, Blanco S, Fernández IF, Lazo PA. Oncotarget 5 1770-1778 (2014)
  32. Human VRK2 (vaccinia-related kinase 2) modulates tumor cell invasion by hyperactivation of NFAT1 and expression of cyclooxygenase-2. Vázquez-Cedeira M, Lazo PA. J. Biol. Chem. 287 42739-42750 (2012)
  33. The Tribbles 2 (TRB2) pseudokinase binds to ATP and autophosphorylates in a metal-independent manner. Bailey FP, Byrne DP, Oruganty K, Eyers CE, Novotny CJ, Shokat KM, Kannan N, Eyers PA. Biochem. J. 467 47-62 (2015)
  34. Characterization of Staphylococcus aureus EssB, an integral membrane component of the Type VII secretion system: atomic resolution crystal structure of the cytoplasmic segment. Zoltner M, Fyfe PK, Palmer T, Hunter WN. Biochem. J. 449 469-477 (2013)
  35. Overexpression of the potential kinase serine/ threonine/tyrosine kinase 1 (STYK 1) in castration-resistant prostate cancer. Chung S, Tamura K, Furihata M, Uemura M, Daigo Y, Nasu Y, Miki T, Shuin T, Fujioka T, Nakamura Y, Nakagawa H. Cancer Sci. 100 2109-2114 (2009)
  36. Evolutionary divergence in the catalytic activity of the CAM-1, ROR1 and ROR2 kinase domains. Bainbridge TW, DeAlmeida VI, Izrael-Tomasevic A, Chalouni C, Pan B, Goldsmith J, Schoen AP, Quiñones GA, Kelly R, Lill JR, Sandoval W, Costa M, Polakis P, Arnott D, Rubinfeld B, Ernst JA. PLoS ONE 9 e102695 (2014)
  37. Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications. Sanz-García M, Vázquez-Cedeira M, Kellerman E, Renbaum P, Levy-Lahad E, Lazo PA. J Proteomics 75 548-560 (2011)
  38. Yet another "active" pseudokinase, Erb3. Taylor SS, Kornev AP. Proc. Natl. Acad. Sci. U.S.A. 107 8047-8048 (2010)
  39. CMASA: an accurate algorithm for detecting local protein structural similarity and its application to enzyme catalytic site annotation. Li GH, Huang JF. BMC Bioinformatics 11 439 (2010)
  40. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. Chong JX, Caputo V, Phelps IG, Stella L, Worgan L, Dempsey JC, Nguyen A, Leuzzi V, Webster R, Pizzuti A, Marvin CT, Ishak GE, Ardern-Holmes S, Richmond Z, University of Washington Center for Mendelian Genomics, Bamshad MJ, Ortiz-Gonzalez XR, Tartaglia M, Chopra M, Doherty D. Am. J. Hum. Genet. 98 772-781 (2016)
  41. Functional disruption of the moloney murine leukemia virus preintegration complex by vaccinia-related kinases. Suzuki Y, Ogawa K, Koyanagi Y, Suzuki Y. J. Biol. Chem. 285 24032-24043 (2010)
  42. Tracing the origin and evolution of pseudokinases across the tree of life. Kwon A, Scott S, Taujale R, Yeung W, Kochut KJ, Eyers PA, Kannan N. Sci Signal 12 (2019)
  43. Binding partners of the kinase domains in Drosophila obscurin and their effect on the structure of the flight muscle. Katzemich A, West RJ, Fukuzawa A, Sweeney ST, Gautel M, Sparrow J, Bullard B. J. Cell. Sci. 128 3386-3397 (2015)
  44. Sensitivity of the kinase activity of human vaccinia-related kinase proteins to toxic metals. Barcia-Sanjurjo I, Vázquez-Cedeira M, Barcia R, Lazo PA. J. Biol. Inorg. Chem. 18 473-482 (2013)
  45. Genome-wide analysis of the phosphoinositide kinome from two ciliates reveals novel evolutionary links for phosphoinositide kinases in eukaryotic cells. Leondaritis G, Siokos J, Skaripa I, Galanopoulou D. PLoS ONE 8 e78848 (2013)
  46. Altered conformational landscape and dimerization dependency underpins the activation of EGFR by αC-β4 loop insertion mutations. Ruan Z, Kannan N. Proc. Natl. Acad. Sci. U.S.A. 115 E8162-E8171 (2018)
  47. Genomics, evolution, and crystal structure of a new family of bacterial spore kinases. Scheeff ED, Axelrod HL, Miller MD, Chiu HJ, Deacon AM, Wilson IA, Manning G. Proteins 78 1470-1482 (2010)
  48. Landscape of drug-resistance mutations in kinase regulatory hotspots. Kim P, Li H, Wang J, Zhao Z. Brief Bioinform 22 bbaa108 (2021)
  49. The receptor-like pseudokinase MRH1 interacts with the voltage-gated potassium channel AKT2. Sklodowski K, Riedelsberger J, Raddatz N, Riadi G, Caballero J, Chérel I, Schulze W, Graf A, Dreyer I. Sci Rep 7 44611 (2017)
  50. The rise of the undead: pseudokinases as mediators of effector-triggered immunity. Lewis JD, Lo T, Bastedo P, Guttman DS, Desveaux D. Plant Signal Behav 9 e27563 (2014)
  51. p190RhoGAP proteins contain pseudoGTPase domains. Stiegler AL, Boggon TJ. Nat Commun 8 506 (2017)
  52. Classification of nonenzymatic homologues of protein kinases. Anamika K, Abhinandan KR, Deshmukh K, Srinivasan N. Comp. Funct. Genomics 365637 (2009)
  53. Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association. Patel O, Griffin MDW, Panjikar S, Dai W, Ma X, Chan H, Zheng C, Kropp A, Murphy JM, Daly RJ, Lucet IS. Nat Commun 8 1157 (2017)
  54. FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane. Ceccarelli DF, Ivantsiv S, Mullin AA, Coyaud E, Manczyk N, Maisonneuve P, Kurinov I, Zhao L, Go C, Gingras AC, Raught B, Cordes S, Sicheri F. Structure 27 1000-1012.e6 (2019)
  55. Glycogen synthase kinase 3β suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity. Lee E, Ryu HG, Kim S, Lee D, Jeong YH, Kim KT. Sci Rep 6 29097 (2016)
  56. Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface. Claus J, Patel G, Autore F, Colomba A, Weitsman G, Soliman TN, Roberts S, Zanetti-Domingues LC, Hirsch M, Collu F, George R, Ortiz-Zapater E, Barber PR, Vojnovic B, Yarden Y, Martin-Fernandez ML, Cameron A, Fraternali F, Ng T, Parker PJ. Elife 7 (2018)
  57. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. Sheetz JB, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttilä R, Preuss F, Suresh K, Stayrook SE, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon MA. Mol Cell 79 390-405.e7 (2020)
  58. Structural and functional studies of casein kinase I-like protein from rice. Park YI, Do KH, Kim IS, Park HH. Plant Cell Physiol. 53 304-311 (2012)
  59. Crystal structure of human vaccinia-related kinase 1 in complex with AMP-PNP, a non-hydrolyzable ATP analog. Ngow YS, Rajan S, Ye H, Yoon HS. Protein Sci 28 524-532 (2019)
  60. Decoding Diabetes Biomarkers and Related Molecular Mechanisms by Using Machine Learning, Text Mining, and Gene Expression Analysis. Elsherbini AM, Alsamman AM, Elsherbiny NM, El-Sherbiny M, Ahmed R, Ebrahim HA, Bakkach J. Int J Environ Res Public Health 19 13890 (2022)
  61. Dynamics of protein kinases and pseudokinases by HDX-MS. Sheetz JB, Lemmon MA, Tsutsui Y. Methods Enzymol 667 303-338 (2022)
  62. KinaseMD: kinase mutations and drug response database. Hu R, Xu H, Jia P, Zhao Z. Nucleic Acids Res 49 D552-D561 (2021)
  63. Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ. Sulpizio A, Minelli ME, Wan M, Burrowes PD, Wu X, Sanford EJ, Shin JH, Williams BC, Goldberg ML, Smolka MB, Mao Y. Elife 8 (2019)
  64. The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase. Stiegler AL, Boggon TJ. Structure 26 1451-1461.e4 (2018)
  65. Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2. Serafim RAM, de Souza Gama FH, Dutra LA, Dos Reis CV, Vasconcelos SNS, da Silva Santiago A, Takarada JE, Di Pillo F, Azevedo H, Mascarello A, Elkins JM, Massirer KB, Gileadi O, Guimarães CRW, Couñago RM. ACS Med Chem Lett 10 1266-1271 (2019)
  66. Dissecting the roles of Haspin and VRK1 in histone H3 phosphorylation during mitosis. Cartwright TN, Harris RJ, Meyer SK, Mon AM, Watson NA, Tan C, Marcelot A, Wang F, Zinn-Justin S, Traktman P, Higgins JMG. Sci Rep 12 11210 (2022)
  67. Dysregulation of Cellular VRK1, BAF, and Innate Immune Signaling by the Vaccinia Virus B12 Pseudokinase. Linville AC, Rico AB, Teague H, Binsted LE, Smith GL, Albarnaz JD, Wiebe MS. J Virol 96 e0039822 (2022)
  68. Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix. Oliver MR, Horne CR, Shrestha S, Keown JR, Liang LY, Young SN, Sandow JJ, Webb AI, Goldstone DC, Lucet IS, Kannan N, Metcalf P, Murphy JM. Nat Commun 12 1002 (2021)
  69. Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)? Beck-Wödl S, Harzer K, Sturm M, Buchert R, Rieß O, Mennel HD, Latta E, Pagenstecher A, Keber U. Acta Neuropathol Commun 6 145 (2018)
  70. How many kinases are druggable? A review of our current understanding. Anderson B, Rosston P, Ong HW, Hossain MA, Davis-Gilbert ZW, Drewry DH. Biochem J 480 1331-1363 (2023)
  71. Spatiotemporal expression of regulatory kinases directs the transition from mitosis to cellular morphogenesis in Drosophila. Yang S, McAdow J, Du Y, Trigg J, Taghert PH, Johnson AN. Nat Commun 13 772 (2022)
  72. VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes. Martín-Doncel E, Rojas AM, Cantarero L, Lazo PA. Sci Rep 9 13381 (2019)
  73. Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity. Gwak SH, Lee J, Oh E, Lee D, Han W, Kim J, Kim KT. Oncol Res 32 421-432 (2023)


Quick links