ID   SHUT_HHV11              Reviewed;         489 AA.
AC   P10225; Q09I92; Q82170;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   24-JUL-2013, entry version 58.
DE   RecName: Full=Virion host shutoff protein;
DE            Short=Vhs;
DE            EC=3.1.27.-;
GN   Name=UL41;
OS   Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus
OS   1).
OC   Viruses; dsDNA viruses, no RNA stage; Herpesvirales; Herpesviridae;
OC   Alphaherpesvirinae; Simplexvirus.
OX   NCBI_TaxID=10299;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2839594;
RA   McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C.,
RA   McNab D., Perry L.J., Scott J.E., Taylor P.;
RT   "The complete DNA sequence of the long unique region in the genome of
RT   herpes simplex virus type 1.";
RL   J. Gen. Virol. 69:1531-1574(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=HSZP;
RX   PubMed=9421879; DOI=10.1023/A:1007915025086;
RA   Vojvodova A., Matis J., Kudelova M., Rajcani J.;
RT   "Herpes simplex virus type 1 (HSV-1) strain HSZP host shutoff gene:
RT   nucleotide sequence and comparison with HSV-1 strains differing in
RT   early shutoff of host protein synthesis.";
RL   Virus Genes 15:155-159(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Nonneuroinvasive mutant HF10;
RA   Nishiyama Y., Ushijima Y.;
RT   "Sequence analysis of a nonneuroinvasive Herpes simplex virus type 1
RT   mutant HF10.";
RL   Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION.
RC   STRAIN=F;
RX   PubMed=12072498; DOI=10.1128/JVI.76.14.6974-6986.2002;
RA   Trgovcich J., Johnson D., Roizman B.;
RT   "Cell surface major histocompatibility complex class II proteins are
RT   regulated by the products of the gamma(1)34.5 and U(L)41 genes of
RT   herpes simplex virus 1.";
RL   J. Virol. 76:6974-6986(2002).
RN   [5]
RP   FUNCTION.
RX   PubMed=16940547; DOI=10.1128/JVI.01008-06;
RA   Taddeo B., Roizman B.;
RT   "The virion host shutoff protein (UL41) of herpes simplex virus 1 is
RT   an endoribonuclease with a substrate specificity similar to that of
RT   RNase A.";
RL   J. Virol. 80:9341-9345(2006).
RN   [6]
RP   FUNCTION.
RX   PubMed=17093196; DOI=10.1128/JVI.01812-06;
RA   Read G.S., Patterson M.;
RT   "Packaging of the virion host shutoff (Vhs) protein of herpes simplex
RT   virus: two forms of the Vhs polypeptide are associated with
RT   intranuclear B and C capsids, but only one is associated with
RT   enveloped virions.";
RL   J. Virol. 81:1148-1161(2007).
RN   [7]
RP   FUNCTION.
RX   PubMed=20357089; DOI=10.1128/JVI.01819-09;
RA   Saffran H.A., Read G.S., Smiley J.R.;
RT   "Evidence for translational regulation by the herpes simplex virus
RT   virion host shutoff protein.";
RL   J. Virol. 84:6041-6049(2010).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH EIF4H AND EIF4A1.
RX   PubMed=20427534; DOI=10.1128/JVI.00166-10;
RA   Page H.G., Read G.S.;
RT   "The virion host shutoff endonuclease (UL41) of herpes simplex virus
RT   interacts with the cellular cap-binding complex eIF4F.";
RL   J. Virol. 84:6886-6890(2010).
RN   [9]
RP   FUNCTION.
RX   PubMed=23077305; DOI=10.1128/JVI.01557-12;
RA   Shiflett L.A., Read G.S.;
RT   "mRNA decay during herpes simplex virus (HSV) infections: mutations
RT   that affect translation of an mRNA influence the sites at which it is
RT   cleaved by the HSV virion host shutoff (Vhs) protein.";
RL   J. Virol. 87:94-109(2013).
CC   -!- FUNCTION: Minor structural protein that acts as an
CC       endoribonuclease during lytic infection. Degrades host mRNAs in
CC       the cytoplasm by cutting them at preferred sites, including some
CC       in regions of translation initiation. Together with inhibition of
CC       host splicing by ICP27, contributes to an overall decrease in host
CC       protein synthesis. Also, after the onset of viral transcription,
CC       accelerates the turnover of viral mRNA, thereby facilitating the
CC       sequential expression of different classes of viral genes. Binds
CC       translation initiation factors eIF4H, eIF4AI, and eIF4AII, thereby
CC       may interact directly with the translation initiation complex and
CC       thus digest specifically mRNAs. Also impedes antigen presentation
CC       by major histocompatibility complex class I and class II
CC       molecules, inhibits secretion of cytokines that would otherwise
CC       recruit lymphocytes and neutrophils cells to the site of infection
CC       and blocks the activation of dendritic cells. Impedes the
CC       alpha/beta interferon-mediated response to infection.
CC   -!- SUBUNIT: Interacts with human EIF4H, EIF4A1 and EIF4A2;
CC       interaction with eIF4AI and EIF4A2 presumably allows Vhs protein
CC       to associate with the eIF4F cap-binding complex (Probable).
CC   -!- SUBCELLULAR LOCATION: Virion (Potential).
CC   -!- MISCELLANEOUS: Strain 17 is relatively weak regarding early
CC       shutoff compared to strain KOS. Strain HSZP protein is non-
CC       functional for host protein shutoff.
CC   -!- SIMILARITY: Belongs to the herpesviridae VHS protein family.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X14112; CAA32304.1; -; Genomic_DNA.
DR   EMBL; DQ889502; ABI63503.1; -; Genomic_DNA.
DR   EMBL; Z72337; CAA96524.1; -; Genomic_DNA.
DR   PIR; E30088; WMBEF1.
DR   RefSeq; NP_044643.1; NC_001806.1.
DR   ProteinModelPortal; P10225; -.
DR   IntAct; P10225; 6.
DR   MINT; MINT-6732794; -.
DR   GeneID; 2703365; -.
DR   ProtClustDB; CLSP2510162; -.
DR   GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0030683; P:evasion or tolerance by virus of host immune response; IEA:UniProtKB-KW.
DR   GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:GOC.
DR   InterPro; IPR006086; XPG-I_dom.
DR   Pfam; PF00867; XPG_I; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Decay of host mRNAs by virus; Endonuclease;
KW   Host gene expression shutoff by virus; Host mRNA suppression by virus;
KW   Host-virus interaction; Hydrolase;
KW   Interferon antiviral system evasion; Late protein; Nuclease;
KW   Reference proteome; RNA-binding; Viral immunoevasion; Virion.
FT   CHAIN         1    489       Virion host shutoff protein.
FT                                /FTId=PRO_0000116054.
FT   VARIANT      18     18       R -> H (in strain: HSZP).
FT   VARIANT     115    115       V -> A (in strain: HSZP).
FT   VARIANT     316    316       E -> K (in strain: Nonneuroinvasive
FT                                mutant HF10).
FT   VARIANT     364    364       P -> S (in strain: Nonneuroinvasive
FT                                mutant HF10).
FT   VARIANT     374    374       L -> R (in strain: HSZP).
FT   VARIANT     384    386       NPR -> SRQ (in strain: HSZP).
FT   VARIANT     385    385       P -> R (in strain: Nonneuroinvasive
FT                                mutant HF10).
FT   VARIANT     392    392       D -> N (in strain: HSZP).
FT   VARIANT     452    452       V -> M (in strain: HSZP).
SQ   SEQUENCE   489 AA;  54918 MW;  3DD706B26A1873BD CRC64;
     MGLFGMMKFA HTHHLVKRRG LGAPAGYFTP IAVDLWNVMY TLVVKYQRRY PSYDREAITL
     HCLCRLLKVF TQKSLFPIFV TDRGVNCMEP VVFGAKAILA RTTAQCRTDE EASDVDASPP
     PSPITDSRPS SAFSNMRRRG TSLASGTRGT AGSGAALPSA APSKPALRLA HLFCIRVLRA
     LGYAYINSGQ LEADDACANL YHTNTVAYVY TTDTDLLLMG CDIVLDISAC YIPTINCRDI
     LKYFKMSYPQ FLALFVRCHT DLHPNNTYAS VEDVLRECHW TPPSRSQTRR AIRREHTSSR
     STETRPPLPP AAGGTETRVS WTEILTQQIA GGYEDDEDLP LDPRDVTGGH PGPRSSSSEI
     LTPPELVQVP NAQLLEEHRS YVANPRRHVI HDAPESLDWL PDPMTITELV EHRYIKYVIS
     LIGPKERGPW TLLKRLPIYQ DIRDENLARS IVTRHITAPD IADRFLEQLR TQAPPPAFYK
     DVLAKFWDE
//