SHUT_HHV1K
ID SHUT_HHV1K Reviewed; 489 AA.
AC Q82171; Q77ZF2;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Virion host shutoff protein;
DE Short=Vhs;
DE EC=3.1.27.-;
GN Name=UL41;
OS Human herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10306;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1312822; DOI=10.1007/bf01317150;
RA Matis J., Krivjanska M., Rajcani J.;
RT "Herpes simplex virus type 1 (HSV-1) HSZP interferes also after antibody
RT neutralization with early shutoff of host protein synthesis induced by HSV-
RT 1 KOS.";
RL Arch. Virol. 123:209-214(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9311788; DOI=10.1128/jvi.71.10.7157-7166.1997;
RA Everly D.N. Jr., Read G.S.;
RT "Mutational analysis of the virion host shutoff gene (UL41) of herpes
RT simplex virus (HSV): characterization of HSV type 1 (HSV-1)/HSV-2
RT chimeras.";
RL J. Virol. 71:7157-7166(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 early
RT shutoff of host protein synthesis.";
RL Virus Genes 15:155-159(1997).
RN [4]
RP INTERACTION WITH HUMAN EIF4H.
RX PubMed=11581395; DOI=10.1128/jvi.75.21.10272-10280.2001;
RA Feng P., Everly D.N. Jr., Read G.S.;
RT "mRNA decay during herpesvirus infections: interaction between a putative
RT viral nuclease and a cellular translation factor.";
RL J. Virol. 75:10272-10280(2001).
RN [5]
RP INTERACTION WITH HUMAN EIF4A2 AND EIF4H, AND MUTAGENESIS OF ASP-34; ASP-82;
RP GLU-192; ASP-194; ASP-195; THR-211; ASP-213; THR-214; ASP-215; ASP-261 AND
RP ARG-435.
RX PubMed=16014927; DOI=10.1128/jvi.79.15.9651-9664.2005;
RA Feng P., Everly D.N. Jr., Read G.S.;
RT "mRNA decay during herpes simplex virus (HSV) infections: protein-protein
RT interactions involving the HSV virion host shutoff protein and translation
RT factors eIF4H and eIF4A.";
RL J. Virol. 79:9651-9664(2005).
RN [6]
RP FUNCTION.
RX PubMed=28077645; DOI=10.1128/jvi.02414-16;
RA Su C., Zheng C.;
RT "Herpes simplex virus 1 abrogates the cGAS/STING-mediated Cytosolic DNA-
RT Sensing Pathway via its virion host shutoff protein, UL41.";
RL J. Virol. 91:0-0(2017).
CC -!- FUNCTION: Minor structural protein that acts as an endoribonuclease
CC during lytic infection. Degrades host mRNAs in the cytoplasm by cutting
CC them at preferred sites, including some in regions of translation
CC initiation. Together with inhibition of host splicing by ICP27,
CC contributes to an overall decrease in host protein synthesis. Also,
CC after the onset of viral transcription, accelerates the turnover of
CC viral mRNA, thereby facilitating the sequential expression of different
CC classes of viral genes. Binds translation initiation factors eIF4H,
CC eIF4AI, and eIF4AII, thereby may interact directly with the translation
CC initiation complex and thus digest specifically mRNAs. Also impedes
CC antigen presentation by major histocompatibility complex class I and
CC class II molecules, inhibits secretion of cytokines that would
CC otherwise recruit lymphocytes and neutrophils cells to the site of
CC infection and blocks the activation of dendritic cells. Impedes the
CC alpha/beta interferon-mediated response to infection by evading the
CC cGAS/ STING-mediated DNA-sensing pathway and degrading CGAS via its
CC RNase activity. {ECO:0000269|PubMed:28077645}.
CC -!- SUBUNIT: Interacts with human EIF4H, EIF4A1 and EIF4A2; interaction
CC with eIF4AI and EIF4A2 presumably allows Vhs protein to associate with
CC the eIF4F cap-binding complex. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the herpesviridae VHS protein family.
CC {ECO:0000305}.
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DR EMBL; Z72338; CAA96525.1; -; Genomic_DNA.
DR EMBL; AF007815; AAC58446.1; -; Genomic_DNA.
DR PRIDE; Q82171; -.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004540; F:ribonuclease activity; TAS:AgBase.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW.
DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0046774; P:suppression by virus of host intracellular interferon activity; IMP:AgBase.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR Pfam; PF00867; XPG_I; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW Decay of host mRNAs by virus; Endonuclease;
KW Eukaryotic host gene expression shutoff by virus;
KW Host gene expression shutoff by virus; Host mRNA suppression by virus;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Interferon antiviral system evasion; Late protein; Nuclease; RNA-binding;
KW Viral immunoevasion; Virion.
FT CHAIN 1..489
FT /note="Virion host shutoff protein"
FT /id="PRO_0000283698"
FT REGION 110..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 34
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 82
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 192
FT /note="E->Q: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 194
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 195
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 211
FT /note="T->A: Complete loss of human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 211
FT /note="T->S: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 213
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 214
FT /note="T->I: Complete loss of human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 215
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 261
FT /note="D->N: No effect on human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
FT MUTAGEN 435
FT /note="R->H: Complete loss of human eIF4H binding."
FT /evidence="ECO:0000269|PubMed:16014927"
SQ SEQUENCE 489 AA; 54952 MW; 57C38A6186545B5E CRC64;
MGLFGMMKFA HTHHLVKRQG 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 AAGGTEMRVS WTEILTQQIA GGYEDDEDLP LDPRDVTGGH PGPRSSSSEI
LTPPELVQVP NAQLLEEHRS YVASRRRHVI HDAPESLDWL PDPMTITELV EHRYIKYVIS
LIGPKERGPW TLLKRLPIYQ DIRDENLARS IVTRHITAPD IADRFLEQLR TQAPPPAFYK
DVLAKFWDE
