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ORF6

From Wikipedia, the free encyclopedia
Coronavirus gene encoding an accessory protein
Protein family
Betacoronavirus NS6 protein
Identifiers
SymbolbCoV_NS6
PfamPF12133
InterProIPR022736
Available protein structures:
Pfam  structures /ECOD  
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary

ORF6 is agene that encodes aviral accessory protein incoronaviruses of thesubgenusSarbecovirus, includingSARS-CoV andSARS-CoV-2. It is not present inMERS-CoV. It is thought to reduce theimmune system response to viral infection throughinterferon antagonism.[1][2][3]

Structure

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The ORF6 protein is fairly small at 63amino acid residues long inSARS-CoV[2] and 61 inSARS-CoV-2.[3] The ORF6 sequence is not wellconserved and it has a relatively lowsequence identity between the two viruses at about 66%.[4] It has anamphipathicN-terminalalpha helix that associates with themembrane, but is not atransmembrane protein. Its approximately 20-residueC-terminal tail ispolar and extends into thecytosol, and containssignal sequences forprotein trafficking.[1][2]

Expression and localization

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Like the genes for other accessory proteins, the ORF6 gene is located near those encoding thestructural proteins, at the5' end of the coronavirus RNA genome. Along withORF7a,ORF7b, andORF8, ORF6 is located between themembrane (M) andnucleocapsid (N) genes.[1][2][3] It islocalized to theendoplasmic reticulum andGolgi apparatus,[1][2][3] with studies in SARS-CoV-2 also indicating association withvesicles such asautophagosomes andlysosomes.[3]

Function

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The primary function of the ORF6 protein is thought to beimmunomodulation andinterferon antagonism. It is notessential forviral replication, though its absence appears to reduce replication efficiency.[1][2]

Viral protein interactions

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Studies inSARS-CoV suggest that the ORF6 protein exhibitsprotein-protein interactions with another viral accessory protein,ORF9b protein.[1][5] In SARS-CoV, but not inrecombinantmurine hepatitis virus, ORF6 protein has been detected invirus-like particles and maturevirions, suggesting it can be a minorviral structural protein.[1][2]

Immune effects

[edit]

The ORF6 protein from both SARS-CoV and SARS-CoV-2 is aninterferon antagonist and thought to be involved inimmune evasion. Severalprotein-protein interactions withhost cell proteins have been described to mediate this effect. It has been reported to inhibitnuclear import of theSTATtranscription factor, inhibiting interferon activation.[1][3] Studies of SARS-CoV report this may be mediated by binding of ORF6 protein tokaryopherins.[1][4] In SARS-CoV-2, the ORF6 protein reportedly interacts withRAE1 andNUP98, blocking karyopherin interactions.[3][6]

References

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  1. ^abcdefghiLiu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R (September 2014)."Accessory proteins of SARS-CoV and other coronaviruses".Antiviral Research.109:97–109.doi:10.1016/j.antiviral.2014.06.013.PMC 7113789.PMID 24995382.
  2. ^abcdefgMcBride R, Fielding BC (November 2012)."The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis".Viruses.4 (11):2902–2923.doi:10.3390/v4112902.PMC 3509677.PMID 23202509.
  3. ^abcdefgRedondo N, Zaldívar-López S, Garrido JJ, Montoya M (7 July 2021)."SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns".Frontiers in Immunology.12: 708264.doi:10.3389/fimmu.2021.708264.PMC 8293742.PMID 34305949.
  4. ^abSuryawanshi RK, Koganti R, Agelidis A, Patil CD, Shukla D (March 2021)."Dysregulation of Cell Signaling by SARS-CoV-2".Trends in Microbiology.29 (3):224–237.doi:10.1016/j.tim.2020.12.007.PMC 7836829.PMID 33451855.
  5. ^Calvo E, DeDiego ML, García P, López JA, Pérez-Breña P, Falcón A (October 2012)."Severe acute respiratory syndrome coronavirus accessory proteins 6 and 9b interact in vivo".Virus Research.169 (1):282–288.doi:10.1016/j.virusres.2012.07.012.PMC 7114373.PMID 22820404.
  6. ^Miorin L, Kehrer T, Sanchez-Aparicio MT, Zhang K, Cohen P, Patel RS, et al. (November 2020)."SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling".Proceedings of the National Academy of Sciences of the United States of America.117 (45):28344–28354.Bibcode:2020PNAS..11728344M.doi:10.1073/pnas.2016650117.PMC 7668094.PMID 33097660.
Coronavirus genomes
Viral structural protein
Viral nonstructural protein
(expressed fromORF1ab)
Viral accessory protein
RNA
DNA
linear ds-DNA
(Duplodnaviria,
Varidnaviria)
Herpes simplex
VSPs:
capsid:
VNPs:
Vaccinia
VNPs:
Adenoviridae
VNPs:
circular ds-DNA
(Duplodnaviria,
Varidnaviria?)
Epstein–Barr
VSPs:
VNPs:
ncRNA:
Baculoviridae
VNPs:
other
(Riboviria,
Monodnaviria)
Polyomaviridae
(SV40,MPyV,MCPyV,HaPyV)
(non-enveloped circular ds-DNA)
VSPs:
capsid:
VNPs:
oncoprotein:
Hepatitis B
(circular partially ds-DNA)
VSPs:
VNPs:
RNA
ds-RNA
(Riboviria)
Rotavirus
(Duplornaviricota)
VNPs:
Rhinov.,Polio,Hep A,
etc. (Pisuviricota)
VNPs:
ss-RNA
positive-sense
(Riboviria)
Hepatitis C
(Kitrinoviricota)
VSPs:
VNPs:
SARS-CoV-2
(Pisuviricota)
VSPs:
VNPs:
ss-RNA
negative-sense
(Negarnaviricota)
Influenza virus
VSPs:
capsid:
glycoprotein:
VNPs:
Parainfluenza
VSPs:
glycoprotein:
Mumps
VSPs:
glycoprotein:
Measles
VSPs:
glycoprotein:
RSV
VSPs:
glycoprotein:
Zaire ebolavirus
VSPs:
capsid:
Indiana vesiculovirus
VSPs:
capsid:
RT
Structure and genome of HIV
VSPs:
VRAPs:
Multiple
Fusion protein
oncoprotein:
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