Serine/threonine protein kinase UL97

Details

Name
Serine/threonine protein kinase UL97
Synonyms
  • 2.7.1.-
  • Ganciclovir kinase
  • HSRF3 protein
Gene Name
UL97
Organism
HHV-5
Amino acid sequence
>lcl|BSEQ0017115|Serine/threonine protein kinase UL97
MSSALRSRARSASLGTTTQGWDPPPLRRPSRARRRQWMREAAQAAAQAAVQAAQAAAAQV
AQAHVDENEVVDLMADEAGGGVTTLTTLSSVSTTTVLGHATFSACVRSDVMRDGEKEDAA
SDKENLRRPVVPSTSSRGSAASGDGYHGLRCRETSAMWSFEYDRDGDVTSVRRALFTGGS
DPSDSVSGVRGGRKRPLRPPLVSLARTPLCRRRVGGVDAVLEENDVELRAESQDSAVASG
PGRIPQPLSGSSGEESATAVEADSTSHDDVHCTCSNDQIITTSIRGLTCDPRMFLRLTHP
ELCELSISYLLVYVPKEDDFCHKICYAVDMSDESYRLGQGSFGEVWPLDRYRVVKVARKH
SETVLTVWMSGLIRTRAAGEQQQPPSLVGTGVHRGLLTATGCCLLHNVTVHRRFHTDMFH
HDQWKLACIDSYRRAFCTLADAIKFLNHQCRVCHFDITPMNVLIDVNPHNPSEIVRAALC
DYSLSEPYPDYNERCVAVFQETGTARRIPNCSHRLRECYHPAFRPMPLQKLLICDPHARF
PVAGLRRYCMSELSALGNVLGFCLMRLLDRRGLDEVRMGTEALLFKHAGAACRALENGKL
THCSDACLLILAAQMSYGACLLGEHGAALVSHTLRFVEAKMSSCRVRAFRRFYHECSQTM
LHEYVRKNVERLLATSDGLYLYNAFRRTTSIICEEDLDGDCRQLFPE
Number of residues
707
Molecular Weight
78231.9
Theoretical pI
7.55
GO Classification
Functions
ATP binding / protein kinase activity
Processes
modulation by virus of host cell cycle
Components
virion
General Function
Protein kinase activity
Specific Function
Serine/threonine protein kinase that plays important roles in several processes including nuclear viral egress, viral replication or regulation of host cell cycle progression. Participates in the acquisition of tegument during virion morphogenesis in the nucleus. Redistributes the host nuclear lamina by phosphorylating cellular Lamins-A/C. Plays a role in viral DNA synthesis by phosphorylating the DNA polymerase processivity factor UL44. Stimulates host cell cycle to support viral DNA synthesis by phosphorylating host retinoblastoma/RB1 protein. Additional substrates have been identified including host EF1D or H2B.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Virion
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP16788
UniProtKB Entry NameUL97_HCMVA
GenBank Gene IDBK000394
General References
  1. Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, Horsnell T, Hutchison CA 3rd, Kouzarides T, Martignetti JA, et al.: Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125-69. [Article]
  2. Lurain NS, Weinberg A, Crumpacker CS, Chou S: Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing. Antimicrob Agents Chemother. 2001 Oct;45(10):2775-80. [Article]
  3. Davison AJ, Dolan A, Akter P, Addison C, Dargan DJ, Alcendor DJ, McGeoch DJ, Hayward GS: The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol. 2003 Jan;84(Pt 1):17-28. [Article]
  4. Littler E, Stuart AD, Chee MS: Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature. 1992 Jul 9;358(6382):160-2. [Article]
  5. Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK: A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature. 1992 Jul 9;358(6382):162-4. [Article]
  6. Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK: A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature. 1992 Sep 3;359(6390):85. [Article]
  7. He Z, He YS, Kim Y, Chu L, Ohmstede C, Biron KK, Coen DM: The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines. J Virol. 1997 Jan;71(1):405-11. [Article]
  8. Kawaguchi Y, Matsumura T, Roizman B, Hirai K: Cellular elongation factor 1delta is modified in cells infected with representative alpha-, beta-, or gammaherpesviruses. J Virol. 1999 May;73(5):4456-60. [Article]
  9. Baek MC, Krosky PM, He Z, Coen DM: Specific phosphorylation of exogenous protein and peptide substrates by the human cytomegalovirus UL97 protein kinase. Importance of the P+5 position. J Biol Chem. 2002 Aug 16;277(33):29593-9. Epub 2002 Jun 4. [Article]
  10. Krosky PM, Baek MC, Coen DM: The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J Virol. 2003 Jan;77(2):905-14. [Article]
  11. Krosky PM, Baek MC, Jahng WJ, Barrera I, Harvey RJ, Biron KK, Coen DM, Sethna PB: The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J Virol. 2003 Jul;77(14):7720-7. [Article]
  12. Varnum SM, Streblow DN, Monroe ME, Smith P, Auberry KJ, Pasa-Tolic L, Wang D, Camp DG 2nd, Rodland K, Wiley S, Britt W, Shenk T, Smith RD, Nelson JA: Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol. 2004 Oct;78(20):10960-6. [Article]
  13. Baek MC, Krosky PM, Pearson A, Coen DM: Phosphorylation of the RNA polymerase II carboxyl-terminal domain in human cytomegalovirus-infected cells and in vitro by the viral UL97 protein kinase. Virology. 2004 Jun 20;324(1):184-93. [Article]
  14. Prichard MN, Britt WJ, Daily SL, Hartline CB, Kern ER: Human cytomegalovirus UL97 Kinase is required for the normal intranuclear distribution of pp65 and virion morphogenesis. J Virol. 2005 Dec;79(24):15494-502. [Article]
  15. Kamil JP, Coen DM: Human cytomegalovirus protein kinase UL97 forms a complex with the tegument phosphoprotein pp65. J Virol. 2007 Oct;81(19):10659-68. Epub 2007 Jul 18. [Article]
  16. Hume AJ, Finkel JS, Kamil JP, Coen DM, Culbertson MR, Kalejta RF: Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science. 2008 May 9;320(5877):797-9. doi: 10.1126/science.1152095. [Article]
  17. Goldberg MD, Honigman A, Weinstein J, Chou S, Taraboulos A, Rouvinski A, Shinder V, Wolf DG: Human cytomegalovirus UL97 kinase and nonkinase functions mediate viral cytoplasmic secondary envelopment. J Virol. 2011 Apr;85(7):3375-84. doi: 10.1128/JVI.01952-10. Epub 2011 Jan 19. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06234Maribavirapproved, investigationalyesinhibitorDetails