P10225 (VHS_HHV11) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Virion host shutoff protein
Short name=Vhs
EC=3.1.27.-

Gene names

Name:

UL41

Organism

Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) [Reference proteome]

Taxonomic identifier

10299 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 1

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	489 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Endoribonuclease that is a minor structural component of the virion. Following release from infecting virions, accelerates the degradation of most cellular mRNAs in the cytoplasm. Together with inhibition of host splicing by ICP27, contributes to an overall decrease in host protein synthesis. Also, after the onset of viral transcription, accelerates the turnover of viral mRNA, thereby facilitating the sequential expression of different classes of viral genes. Binds human eIF4H, thereby may interact directly with the translation initiation complex and thus digest specifically mRNAs. Also impedes antigen presentation by major histocompatibility complex class I and class II molecules, inhibits secretion of cytokines that would otherwise recruit lymphocytes and neutrophils cells to the site of infection and blocks the activation of dendritic cells. Impedes the alpha/beta interferon-mediated response to infection. Ref.4 Ref.5 Ref.6
Subunit structure	Interacts with human EIF4A2 and EIF4H By similarity.
Subcellular location	Virion Potential.
Miscellaneous	Strain 17 is relatively weak regarding early shutoff compared to strain KOS. Strain HSZP protein is non-functional for host protein shutoff.
Sequence similarities	Belongs to the herpesviridae VHS protein family.

Ontologies

Keywords
Biological process	Host-virus interaction Interferon antiviral system evasion Viral immunoevasion
Cellular component	Virion
Developmental stage	Late protein
Molecular function	Endonuclease Hydrolase Nuclease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	evasion or tolerance by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC
Cellular_component	virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 489	489	Virion host shutoff protein		PRO_0000116054
Natural variations
	Natural variant	18	1	R → H in strain: HSZP.
	Natural variant	115	1	V → A in strain: HSZP.
	Natural variant	316	1	E → K in strain: Nonneuroinvasive mutant HF10.
	Natural variant	364	1	P → S in strain: Nonneuroinvasive mutant HF10.
	Natural variant	374	1	L → R in strain: HSZP.
	Natural variant	384 – 386	3	NPR → SRQ in strain: HSZP.
	Natural variant	385	1	P → R in strain: Nonneuroinvasive mutant HF10.
	Natural variant	392	1	D → N in strain: HSZP.
	Natural variant	452	1	V → M in strain: HSZP.

Sequences

	Sequence		Length	Mass (Da)
	P10225 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 3DD706B26A1873BD	FASTA	489	54,918
	10 20 30 40 50 60 MGLFGMMKFA HTHHLVKRRG LGAPAGYFTP IAVDLWNVMY TLVVKYQRRY PSYDREAITL 70 80 90 100 110 120 HCLCRLLKVF TQKSLFPIFV TDRGVNCMEP VVFGAKAILA RTTAQCRTDE EASDVDASPP 130 140 150 160 170 180 PSPITDSRPS SAFSNMRRRG TSLASGTRGT AGSGAALPSA APSKPALRLA HLFCIRVLRA 190 200 210 220 230 240 LGYAYINSGQ LEADDACANL YHTNTVAYVY TTDTDLLLMG CDIVLDISAC YIPTINCRDI 250 260 270 280 290 300 LKYFKMSYPQ FLALFVRCHT DLHPNNTYAS VEDVLRECHW TPPSRSQTRR AIRREHTSSR 310 320 330 340 350 360 STETRPPLPP AAGGTETRVS WTEILTQQIA GGYEDDEDLP LDPRDVTGGH PGPRSSSSEI 370 380 390 400 410 420 LTPPELVQVP NAQLLEEHRS YVANPRRHVI HDAPESLDWL PDPMTITELV EHRYIKYVIS 430 440 450 460 470 480 LIGPKERGPW TLLKRLPIYQ DIRDENLARS IVTRHITAPD IADRFLEQLR TQAPPPAFYK DVLAKFWDE

References

[1]	"The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1." McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D., Perry L.J., Scott J.E., Taylor P. J. Gen. Virol. 69:1531-1574(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Herpes simplex virus type 1 (HSV-1) strain HSZP host shutoff gene: nucleotide sequence and comparison with HSV-1 strains differing in early shutoff of host protein synthesis." Vojvodova A., Matis J., Kudelova M., Rajcani J. Virus Genes 15:155-159(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: HSZP.
[3]	"Sequence analysis of a nonneuroinvasive Herpes simplex virus type 1 mutant HF10." Nishiyama Y., Ushijima Y. Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Nonneuroinvasive mutant HF10.
[4]	"Cell surface major histocompatibility complex class II proteins are regulated by the products of the gamma(1)34.5 and U(L)41 genes of herpes simplex virus 1." Trgovcich J., Johnson D., Roizman B. J. Virol. 76:6974-6986(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. Strain: F.
[5]	"The virion host shutoff protein (UL41) of herpes simplex virus 1 is an endoribonuclease with a substrate specificity similar to that of RNase A." Taddeo B., Roizman B. J. Virol. 80:9341-9345(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Packaging of the virion host shutoff (Vhs) protein of herpes simplex virus: two forms of the Vhs polypeptide are associated with intranuclear B and C capsids, but only one is associated with enveloped virions." Read G.S., Patterson M. J. Virol. 81:1148-1161(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X14112 Genomic DNA. Translation: CAA32304.1. DQ889502 Genomic DNA. Translation: ABI63503.1. Z72337 Genomic DNA. Translation: CAA96524.1.
PIR	WMBEF1. E30088.
RefSeq	NP_044643.1. NC_001806.1.
3D structure databases
ProteinModelPortal	P10225.
ModBase	Search...
Protein-protein interaction databases
IntAct	P10225. 6 interactions.
MINT	MINT-6732794.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	2703365.
Phylogenomic databases
ProtClustDB	CLSP2510162.
Family and domain databases
InterPro	IPR006086. XPG-I_dom. [Graphical view]
Pfam	PF00867. XPG_I. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

VHS_HHV11

Accession

Primary (citable) accession number: P10225
Secondary accession number(s): Q09I92, Q82170

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 57 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program