Hmdb loader
Identification
HMDB Protein ID HMDBP13407
Secondary Accession Numbers None
Name Serine/threonine-protein kinase US3 homolog
Synonyms
  1. Protein kinase ORF66
Gene Name 66
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 proteins 24 and 27, 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 (By similarity). Downregulates class I major histocompatibility complex (MHC-I) surface expression. Additionally, phosphorylates IE62 and targets it to the cytoplasm. The nuclear exclusion of IE62 enables the packaging of abundant levels of IE62 into virions.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
modulation by virus of host apoptotic process
modulation by virus of host chromatin organization
suppression by virus of host adaptive immune response
suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I
Cellular Component
host cell cytoplasm
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 393
Molecular Weight 43679.27
Theoretical pI 6.093
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P09251
UniProtKB/Swiss-Prot Entry Name US03_VZVD
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. Davison AJ, Scott JE: The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816. doi: 10.1099/0022-1317-67-9-1759. [PubMed:3018124 ]
  2. Davison AJ: DNA sequence of the US component of the varicella-zoster virus genome. EMBO J. 1983;2(12):2203-9. [PubMed:6321154 ]
  3. 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 ]
  4. Kinchington PR, Fite K, Seman A, Turse SE: Virion association of IE62, the varicella-zoster virus (VZV) major transcriptional regulatory protein, requires expression of the VZV open reading frame 66 protein kinase. J Virol. 2001 Oct;75(19):9106-13. doi: 10.1128/JVI.75.19.9106-9113.2001. [PubMed:11533174 ]
  5. Eisfeld AJ, Turse SE, Jackson SA, Lerner EC, Kinchington PR: Phosphorylation of the varicella-zoster virus (VZV) major transcriptional regulatory protein IE62 by the VZV open reading frame 66 protein kinase. J Virol. 2006 Feb;80(4):1710-23. doi: 10.1128/JVI.80.4.1710-1723.2006. [PubMed:16439528 ]
  6. Eisfeld AJ, Yee MB, Erazo A, Abendroth A, Kinchington PR: Downregulation of class I major histocompatibility complex surface expression by varicella-zoster virus involves open reading frame 66 protein kinase-dependent and -independent mechanisms. J Virol. 2007 Sep;81(17):9034-49. doi: 10.1128/JVI.00711-07. Epub 2007 Jun 13. [PubMed:17567702 ]
  7. 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 ]