Hmdb loader
Identification
HMDB Protein ID HMDBP13408
Secondary Accession Numbers None
Name Serine/threonine-protein kinase US3
Synonyms Not Available
Gene Name US3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of apoptosis. Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress. Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3. Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface. Promotes virus intracellular spread by restructuring host cell cytoskeleton. Blocks host apoptosis to extend cell survival and allow efficient viral replication. Promotes viral gene expression by phosphorylating host HDAC2 to reduce viral genome silencing.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
modulation by virus of host apoptotic process
modulation by virus of host chromatin organization
Cellular Component
host cell cytoplasm
viral tegument
host cell nucleus
Molecular Function
ATP binding
protein serine kinase activity
protein threonine kinase activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 481
Molecular Weight 52833.95
Theoretical pI 5.905
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P04413
UniProtKB/Swiss-Prot Entry Name US03_HHV11
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Leader DP, Purves FC: The herpesvirus protein kinase: a new departure in protein phosphorylation? Trends Biochem Sci. 1988 Jul;13(7):244-6. doi: 10.1016/0968-0004(88)90157-0. [PubMed:2855680 ]
  2. Erazo A, Yee MB, Banfield BW, Kinchington PR: The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of the nuclear matrix protein matrin 3. J Virol. 2011 Jan;85(1):568-81. doi: 10.1128/JVI.01611-10. Epub 2010 Oct 20. [PubMed:20962082 ]
  3. McGeoch DJ, Dolan A, Donald S, Rixon FJ: Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J Mol Biol. 1985 Jan 5;181(1):1-13. doi: 10.1016/0022-2836(85)90320-1. [PubMed:2984429 ]
  4. Purves FC, Spector D, Roizman B: The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene. J Virol. 1991 Nov;65(11):5757-64. doi: 10.1128/JVI.65.11.5757-5764.1991. [PubMed:1656069 ]
  5. Leopardi R, Van Sant C, Roizman B: The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7891-6. doi: 10.1073/pnas.94.15.7891. [PubMed:9223283 ]
  6. Kato A, Yamamoto M, Ohno T, Tanaka M, Sata T, Nishiyama Y, Kawaguchi Y: Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. J Virol. 2006 Feb;80(3):1476-86. doi: 10.1128/JVI.80.3.1476-1486.2006. [PubMed:16415024 ]
  7. Leach N, Bjerke SL, Christensen DK, Bouchard JM, Mou F, Park R, Baines J, Haraguchi T, Roller RJ: Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. J Virol. 2007 Oct;81(19):10792-803. doi: 10.1128/JVI.00196-07. Epub 2007 Jul 25. [PubMed:17652388 ]
  8. Kato A, Tanaka M, Yamamoto M, Asai R, Sata T, Nishiyama Y, Kawaguchi Y: Identification of a physiological phosphorylation site of the herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells. J Virol. 2008 Jul;82(13):6172-89. doi: 10.1128/JVI.00044-08. Epub 2008 Apr 16. [PubMed:18417577 ]
  9. Mou F, Wills E, Baines JD: Phosphorylation of the U(L)31 protein of herpes simplex virus 1 by the U(S)3-encoded kinase regulates localization of the nuclear envelopment complex and egress of nucleocapsids. J Virol. 2009 May;83(10):5181-91. doi: 10.1128/JVI.00090-09. Epub 2009 Mar 11. [PubMed:19279109 ]
  10. Sagou K, Imai T, Sagara H, Uema M, Kawaguchi Y: Regulation of the catalytic activity of herpes simplex virus 1 protein kinase Us3 by autophosphorylation and its role in pathogenesis. J Virol. 2009 Jun;83(11):5773-83. doi: 10.1128/JVI.00103-09. Epub 2009 Mar 18. [PubMed:19297494 ]
  11. Imai T, Sagou K, Arii J, Kawaguchi Y: Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by Us3 kinase in vivo and in vitro. J Virol. 2010 Jan;84(1):153-62. doi: 10.1128/JVI.01447-09. [PubMed:19846518 ]
  12. Walters MS, Kinchington PR, Banfield BW, Silverstein S: Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases. J Virol. 2010 Oct;84(19):9666-76. doi: 10.1128/JVI.00981-10. Epub 2010 Jul 21. [PubMed:20660201 ]