US03_VZVD
ID US03_VZVD Reviewed; 393 AA.
AC P09251;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Serine/threonine-protein kinase US3 homolog;
DE AltName: Full=Protein kinase ORF66;
DE EC=2.7.11.1;
GN Name=66;
OS Varicella-zoster virus (strain Dumas) (HHV-3) (Human herpesvirus 3).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Varicellovirus.
OX NCBI_TaxID=10338;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=3018124; DOI=10.1099/0022-1317-67-9-1759;
RA Davison A.J., Scott J.E.;
RT "The complete DNA sequence of varicella-zoster virus.";
RL J. Gen. Virol. 67:1759-1816(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6321154; DOI=10.1002/j.1460-2075.1983.tb01724.x;
RA Davison A.J.;
RT "DNA sequence of the US component of the varicella-zoster virus genome.";
RL EMBO J. 2:2203-2209(1983).
RN [3]
RP REVIEW.
RX PubMed=2855680; DOI=10.1016/0968-0004(88)90157-0;
RA Leader D.P., Purves F.C.;
RT "The herpesvirus protein kinase: a new departure in protein
RT phosphorylation?";
RL Trends Biochem. Sci. 13:244-246(1988).
RN [4]
RP PHOSPHORYLATION OF IE62.
RX PubMed=10666257; DOI=10.1128/jvi.74.5.2265-2277.2000;
RA Kinchington P.R., Fite K., Turse S.E.;
RT "Nuclear accumulation of IE62, the varicella-zoster virus (VZV) major
RT transcriptional regulatory protein, is inhibited by phosphorylation
RT mediated by the VZV open reading frame 66 protein kinase.";
RL J. Virol. 74:2265-2277(2000).
RN [5]
RP FUNCTION.
RX PubMed=11533174; DOI=10.1128/jvi.75.19.9106-9113.2001;
RA Kinchington P.R., Fite K., Seman A., Turse S.E.;
RT "Virion association of IE62, the varicella-zoster virus (VZV) major
RT transcriptional regulatory protein, requires expression of the VZV open
RT reading frame 66 protein kinase.";
RL J. Virol. 75:9106-9113(2001).
RN [6]
RP FUNCTION.
RX PubMed=16439528; DOI=10.1128/jvi.80.4.1710-1723.2006;
RA Eisfeld A.J., Turse S.E., Jackson S.A., Lerner E.C., Kinchington P.R.;
RT "Phosphorylation of the varicella-zoster virus (VZV) major transcriptional
RT regulatory protein IE62 by the VZV open reading frame 66 protein kinase.";
RL J. Virol. 80:1710-1723(2006).
RN [7]
RP FUNCTION.
RX PubMed=17567702; DOI=10.1128/jvi.00711-07;
RA Eisfeld A.J., Yee M.B., Erazo A., Abendroth A., Kinchington P.R.;
RT "Downregulation of class I major histocompatibility complex surface
RT expression by varicella-zoster virus involves open reading frame 66 protein
RT kinase-dependent and -independent mechanisms.";
RL J. Virol. 81:9034-9049(2007).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF MATR3.
RX PubMed=20962082; DOI=10.1128/jvi.01611-10;
RA Erazo A., Yee M.B., Banfield B.W., Kinchington P.R.;
RT "The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of
RT the nuclear matrix protein matrin 3.";
RL J. Virol. 85:568-581(2011).
CC -!- FUNCTION: Multifunctional serine/threonine kinase that plays a role in
CC several processes including egress of virus particles from the nucleus,
CC modulation of the actin cytoskeleton and inhibition of apoptosis.
CC Phosphorylates proteins 24 and 27, two critical regulators of capsid
CC budding from nucleus to endoplasmic reticulum, thereby facilitating
CC virion egress. Modulates and redistributes host components of the
CC nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix
CC protein MATR3. Phosphorylates envelope glycoprotein B (gB), probably to
CC direct it to the cell surface. Promotes virus intracellular spread by
CC restructuring host cell cytoskeleton. Blocks host apoptosis to extend
CC cell survival and allow efficient viral replication. Promotes viral
CC gene expression by phosphorylating host HDAC2 to reduce viral genome
CC silencing (By similarity). Down-regulates class I major
CC histocompatibility complex (MHC-I) surface expression. Additionally,
CC phosphorylates IE62 and targets it to the cytoplasm. The nuclear
CC exclusion of IE62 enables the packaging of abundant levels of IE62 into
CC virions. {ECO:0000250, ECO:0000269|PubMed:11533174,
CC ECO:0000269|PubMed:16439528, ECO:0000269|PubMed:17567702,
CC ECO:0000269|PubMed:20962082}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250}. Host nucleus
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by ORF47; this phosphorylation regulates subsequent
CC phosphorylation of proteins 24 and 27 by ORF66. Autophosphorylated (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; X04370; CAA27949.1; -; Genomic_DNA.
DR EMBL; X00208; CAA25031.1; -; Genomic_DNA.
DR PIR; E27345; TVBE66.
DR RefSeq; NP_040188.1; NC_001348.1.
DR SMR; P09251; -.
DR PRIDE; P09251; -.
DR GeneID; 1487703; -.
DR KEGG; vg:1487703; -.
DR Proteomes; UP000002602; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host MHC class I molecule presentation by virus; Kinase;
KW Modulation of host cell apoptosis by virus;
KW Modulation of host chromatin by virus; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Viral immunoevasion.
FT CHAIN 1..393
FT /note="Serine/threonine-protein kinase US3 homolog"
FT /id="PRO_0000086183"
FT DOMAIN 93..378
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 206
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 99..107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 122
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 393 AA; 43680 MW; 2396280DC40AFBF7 CRC64;
MNDVDATDTF VGQGKFRGAI STSPSHIMQT CGFIQQMFPV EMSPGIESED DPNYDVNMDI
QSFNIFDGVH ETEAEASVAL CAEARVGINK AGFVILKTFT PGAEGFAFAC MDSKTCEHVV
IKAGQRQGTA TEATVLRALT HPSVVQLKGT FTYNKMTCLI LPRYRTDLYC YLAAKRNLPI
CDILAIQRSV LRALQYLHNN SIIHRDIKSE NIFINHPGDV CVGDFGAACF PVDINANRYY
GWAGTIATNS PELLARDPYG PAVDIWSAGI VLFEMATGQN SLFERDGLDG NCDSERQIKL
IIRRSGTHPN EFPINPTSNL RRQYIGLAKR SSRKPGSRPL WTNLYELPID LEYLICKMLS
FDARHRPSAE VLLNHSVFQT LPDPYPNPME VGD
