US03_HHV11
ID US03_HHV11 Reviewed; 481 AA.
AC P04413;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Serine/threonine-protein kinase US3;
DE EC=2.7.11.1;
GN Name=US3;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2984429; DOI=10.1016/0022-2836(85)90320-1;
RA McGeoch D.J., Dolan A., Donald S., Rixon F.J.;
RT "Sequence determination and genetic content of the short unique region in
RT the genome of herpes simplex virus type 1.";
RL J. Mol. Biol. 181:1-13(1985).
RN [2]
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 [3]
RP FUNCTION IN PHOSPHORYLATION OF UL34.
RC STRAIN=F;
RX PubMed=1656069; DOI=10.1128/jvi.65.11.5757-5764.1991;
RA Purves F.C., Spector D., Roizman B.;
RT "The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates
RT posttranslational modification of the phosphoprotein encoded by the UL34
RT gene.";
RL J. Virol. 65:5757-5764(1991).
RN [4]
RP FUNCTION.
RC STRAIN=F;
RX PubMed=9223283; DOI=10.1073/pnas.94.15.7891;
RA Leopardi R., Van Sant C., Roizman B.;
RT "The herpes simplex virus 1 protein kinase US3 is required for protection
RT from apoptosis induced by the virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7891-7896(1997).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF UL31; ICP22 AND US9.
RC STRAIN=F;
RX PubMed=15994828; DOI=10.1128/jvi.79.14.9325-9331.2005;
RA Kato A., Yamamoto M., Ohno T., Kodaira H., Nishiyama Y., Kawaguchi Y.;
RT "Identification of proteins phosphorylated directly by the Us3 protein
RT kinase encoded by herpes simplex virus 1.";
RL J. Virol. 79:9325-9331(2005).
RN [6]
RP PHOSPHORYLATION BY UL13.
RC STRAIN=F;
RX PubMed=16415024; DOI=10.1128/jvi.80.3.1476-1486.2006;
RA Kato A., Yamamoto M., Ohno T., Tanaka M., Sata T., Nishiyama Y.,
RA Kawaguchi Y.;
RT "Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral
RT Us3 protein kinase and regulates nuclear localization of viral envelopment
RT factors UL34 and UL31.";
RL J. Virol. 80:1476-1486(2006).
RN [7]
RP FUNCTION.
RX PubMed=17652388; DOI=10.1128/jvi.00196-07;
RA Leach N., Bjerke S.L., Christensen D.K., Bouchard J.M., Mou F., Park R.,
RA Baines J., Haraguchi T., Roller R.J.;
RT "Emerin is hyperphosphorylated and redistributed in herpes simplex virus
RT type 1-infected cells in a manner dependent on both UL34 and US3.";
RL J. Virol. 81:10792-10803(2007).
RN [8]
RP AUTOPHOSPHORYLATION.
RC STRAIN=F;
RX PubMed=18417577; DOI=10.1128/jvi.00044-08;
RA Kato A., Tanaka M., Yamamoto M., Asai R., Sata T., Nishiyama Y.,
RA Kawaguchi Y.;
RT "Identification of a physiological phosphorylation site of the herpes
RT simplex virus 1-encoded protein kinase Us3 which regulates its optimal
RT catalytic activity in vitro and influences its function in infected
RT cells.";
RL J. Virol. 82:6172-6189(2008).
RN [9]
RP FUNCTION.
RC STRAIN=F;
RX PubMed=19279109; DOI=10.1128/jvi.00090-09;
RA Mou F., Wills E., Baines J.D.;
RT "Phosphorylation of the UL31 protein of herpes simplex virus 1 by the US3-
RT encoded kinase regulates localization of the nuclear envelopment complex
RT and egress of nucleocapsids.";
RL J. Virol. 83:5181-5191(2009).
RN [10]
RP MUTAGENESIS OF SER-147.
RX PubMed=19297494; DOI=10.1128/jvi.00103-09;
RA Sagou K., Imai T., Sagara H., Uema M., Kawaguchi Y.;
RT "Regulation of the catalytic activity of herpes simplex virus 1 protein
RT kinase Us3 by autophosphorylation and its role in pathogenesis.";
RL J. Virol. 83:5773-5783(2009).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF GLYCOPROTEIN B.
RX PubMed=19846518; DOI=10.1128/jvi.01447-09;
RA Imai T., Sagou K., Arii J., Kawaguchi Y.;
RT "Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein
RT B by Us3 kinase in vivo and in vitro.";
RL J. Virol. 84:153-162(2010).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF HOST HDAC2.
RX PubMed=20660201; DOI=10.1128/jvi.00981-10;
RA Walters M.S., Kinchington P.R., Banfield B.W., Silverstein S.;
RT "Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3
RT kinases.";
RL J. Virol. 84:9666-9676(2010).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF HOST MATR3.
RC STRAIN=RC;
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 UL31 and UL34, two critical regulators of capsid budding
CC from nucleus to endoplasmic reticulum, thereby facilitating virion
CC egress. Modulates and redistributes host components of the nuclear
CC envelope, including LMNA, emerin/EMD and the nuclear matrix protein
CC MATR3. Phosphorylates envelope glycoprotein B (gB), probably to direct
CC 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. {ECO:0000269|PubMed:15994828, ECO:0000269|PubMed:1656069,
CC ECO:0000269|PubMed:17652388, ECO:0000269|PubMed:19279109,
CC ECO:0000269|PubMed:19846518, ECO:0000269|PubMed:20660201,
CC ECO:0000269|PubMed:20962082, ECO:0000269|PubMed:9223283}.
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 UL13; this phosphorylation regulates subsequent
CC phosphorylation of UL31 and UL34 by US3. Autophosphorylated.
CC {ECO:0000269|PubMed:16415024}.
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; L00036; AAA96685.1; -; Genomic_DNA.
DR EMBL; X14112; CAA32280.1; -; Genomic_DNA.
DR EMBL; X02138; CAA26057.1; -; Genomic_DNA.
DR PIR; A00656; TVBE17.
DR RefSeq; YP_009137138.1; NC_001806.2.
DR SMR; P04413; -.
DR BioGRID; 971434; 32.
DR IntAct; P04413; 29.
DR iPTMnet; P04413; -.
DR PRIDE; P04413; -.
DR DNASU; 2703401; -.
DR GeneID; 2703401; -.
DR KEGG; vg:2703401; -.
DR Proteomes; UP000009294; 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:0019033; C:viral tegument; IDA:CACAO.
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 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; Kinase;
KW Modulation of host cell apoptosis by virus;
KW Modulation of host chromatin by virus; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..481
FT /note="Serine/threonine-protein kinase US3"
FT /id="PRO_0000086180"
FT DOMAIN 191..478
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 12..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 305
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 147
FT /note="S->A: Complete loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19297494"
SQ SEQUENCE 481 AA; 52835 MW; 71838AB0483BE055 CRC64;
MACRKFCRVY GGQGRRKEEA VPPETKPSRV FPHGPFYTPA EDACLDSPPP ETPKPSHTTP
PSEAERLCHL QEILAQMYGN QDYPIEDDPS ADAADDVDED APDDVAYPEE YAEELFLPGD
ATGPLIGAND HIPPPCGASP PGIRRRSRDE IGATGFTAEE LDAMDREAAR AISRGGKPPS
TMAKLVTGMG FTIHGALTPG SEGCVFDSSH PDYPQRVIVK AGWYTSTSHE ARLLRRLDHP
AILPLLDLHV VSGVTCLVLP KYQADLYTYL SRRLNPLGRP QIAAVSRQLL SAVDYIHRQG
IIHRDIKTEN IFINTPEDIC LGDFGAACFV QGSRSSPFPY GIAGTIDTNA PEVLAGDPYT
TTVDIWSAGL VIFETAVHNA SLFSAPRGPK RGPCDSQITR IIRQAQVHVD EFSPHPESRL
TSRYRSRAAG NNRPPYTRPA WTRYYKMDID VEYLVCKALT FDGALRPSAA ELLCLPLFQQ
K
