ID   NS6_CVHSA               Reviewed;          63 AA.
AC   P59634; Q7T6R9; Q7TA25; Q7TFA7; Q80BV3;
DT   23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-APR-2003, sequence version 1.
DT   12-AUG-2020, entry version 72.
DE   RecName: Full=ORF6 protein;
DE   AltName: Full=Accessory protein 6;
DE   AltName: Full=Non-structural protein 6;
DE            Short=ns6;
DE   AltName: Full=Protein X3;
GN   ORFNames=6;
OS   Human SARS coronavirus (SARS-CoV) (Severe acute respiratory syndrome
OS   coronavirus).
OC   Viruses; Riboviria; Nidovirales; Cornidovirineae; Coronaviridae;
OC   Orthocoronavirinae; Betacoronavirus; Sarbecovirus.
OX   NCBI_TaxID=694009;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9675; Paguma larvata (Masked palm civet).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Urbani;
RX   PubMed=12730500; DOI=10.1126/science.1085952;
RA   Rota P.A., Oberste M.S., Monroe S.S., Nix W.A., Campagnoli R.,
RA   Icenogle J.P., Penaranda S., Bankamp B., Maher K., Chen M.-H., Tong S.,
RA   Tamin A., Lowe L., Frace M., DeRisi J.L., Chen Q., Wang D., Erdman D.D.,
RA   Peret T.C.T., Burns C., Ksiazek T.G., Rollin P.E., Sanchez A., Liffick S.,
RA   Holloway B., Limor J., McCaustland K., Olsen-Rasmussen M., Fouchier R.,
RA   Guenther S., Osterhaus A.D.M.E., Drosten C., Pallansch M.A., Anderson L.J.,
RA   Bellini W.J.;
RT   "Characterization of a novel coronavirus associated with severe acute
RT   respiratory syndrome.";
RL   Science 300:1394-1399(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Tor2;
RX   PubMed=12730501; DOI=10.1126/science.1085953;
RA   Marra M.A., Jones S.J.M., Astell C.R., Holt R.A., Brooks-Wilson A.,
RA   Butterfield Y.S.N., Khattra J., Asano J.K., Barber S.A., Chan S.Y.,
RA   Cloutier A., Coughlin S.M., Freeman D., Girn N., Griffith O.L., Leach S.R.,
RA   Mayo M., McDonald H., Montgomery S.B., Pandoh P.K., Petrescu A.S.,
RA   Robertson A.G., Schein J.E., Siddiqui A., Smailus D.E., Stott J.M.,
RA   Yang G.S., Plummer F., Andonov A., Artsob H., Bastien N., Bernard K.,
RA   Booth T.F., Bowness D., Czub M., Drebot M., Fernando L., Flick R.,
RA   Garbutt M., Gray M., Grolla A., Jones S., Feldmann H., Meyers A.,
RA   Kabani A., Li Y., Normand S., Stroher U., Tipples G.A., Tyler S.,
RA   Vogrig R., Ward D., Watson B., Brunham R.C., Krajden M., Petric M.,
RA   Skowronski D.M., Upton C., Roper R.L.;
RT   "The genome sequence of the SARS-associated coronavirus.";
RL   Science 300:1399-1404(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate CUHK-Su10, and Isolate CUHK-W1;
RX   PubMed=12853594; DOI=10.1056/nejm200307103490216;
RA   Tsui S.K.W., Chim S.S.C., Lo Y.M.D.;
RT   "Coronavirus genomic-sequence variations and the epidemiology of the severe
RT   acute respiratory syndrome.";
RL   N. Engl. J. Med. 349:187-188(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate HKU-39849;
RX   PubMed=12876307; DOI=10.1177/15353702-0322807-13;
RA   Zeng F.Y., Chan C.W., Chan M.N., Chen J.D., Chow K.Y.C., Hon C.C.C.,
RA   Hui R.K.H., Li J., Li V.Y.Y., Wang C.Y., Wang P.Y., Guan Y., Zheng B.,
RA   Poon L.L.M., Chan K.H., Yuen K.Y., Peiris J.S.M., Leung F.C.;
RT   "The complete genome sequence of severe acute respiratory syndrome
RT   coronavirus strain HKU-39849 (HK-39).";
RL   Exp. Biol. Med. 228:866-873(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate BJ01, Isolate BJ02, Isolate BJ03, Isolate BJ04, and
RC   Isolate GD01;
RA   Qin E., Zhu Q., Yu M., Fan B., Chang G., Si B., Yang B., Peng W., Jiang T.,
RA   Liu B., Deng Y., Liu H., Zhang Y., Wang C., Li Y., Gan Y., Li X., Lu F.,
RA   Tan G., Yang R., Cao W.S., Wang J., Chen W., Cong L., Deng Y., Dong W.,
RA   Han Y., Hu W., Lei M., Li C., Li G., Li G., Li H., Li S., Li S., Li W.,
RA   Li W., Lin W., Liu J., Liu Z., Lu H., Ni P., Qi Q., Sun Y., Tang L.,
RA   Tong Z., Wang J., Wang X., Wu Q., Xi Y., Xu Z., Yang L., Ye C., Ye J.,
RA   Zhang B., Zhang F., Zhang J., Zhang X., Zhou J., Yang H.;
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate TW1;
RA   Yeh S.-H., Kao C.-L., Tsai C.-Y., Liu C.-J., Chen D.-S., Chen P.-J.;
RT   "The complete genome of SARS coronavirus clone TW1.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate FRA;
RA   Eickmann M., Becker S., Klenk H.-D., Doerr H.W., Stadler K., Censini S.,
RA   Guidotti S., Masignani V., Scarselli M., Mora M., Donati C., Han J.,
RA   Song H.C., Abrignani S., Covacci A., Rappuoli R.;
RT   "SARS virus is a close relative of type II coronaviruses.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Frankfurt 1;
RA   Thiel V., Hertzig T., Putics A., Ivanov K.A., Schelle B., Bayer S.,
RA   Scheiner B., Weinand H., Weissbrich B., Ziebuhr J.;
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Shanghai QXC1;
RA   Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y.;
RT   "Analysis of SARS coronavirus genome in Shanghai isolates.";
RL   Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Taiwan TC1, Isolate Taiwan TC2, and Isolate Taiwan TC3;
RA   Chang J.-G.C., Lin T.-H., Chen C.-M., Lin C.-S., Chan W.-L., Shih M.-C.;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate TWH, Isolate TWJ, Isolate TWK, Isolate TWS, and Isolate TWY;
RA   Shu H.Y., Wu K.M., Tsai S.F.;
RT   "The complete genome of SARS coronavirus TWH.";
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate HSR 1;
RA   Canducci F., Clementi M., Poli G., Vicenzi E.;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [13]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate AS;
RA   Balotta C., Corvasce S., Violin M., Galli M., Moroni M., Vigevani G.M.,
RA   Ruan Y.J., Salemi M.;
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16103185; DOI=10.1128/jvi.79.17.11335-11342.2005;
RA   Pewe L., Zhou H., Netland J., Tangudu C., Olivares H., Shi L., Look D.,
RA   Gallagher T., Perlman S.;
RT   "A severe acute respiratory syndrome-associated coronavirus-specific
RT   protein enhances virulence of an attenuated murine coronavirus.";
RL   J. Virol. 79:11335-11342(2005).
RN   [15]
RP   SUBCELLULAR LOCATION.
RC   STRAIN=Isolate CUHK-W1;
RX   PubMed=16310783; DOI=10.1016/j.febslet.2005.11.007;
RA   Geng H., Liu Y.-M., Chan W.S., Lo A.W.-I., Au D.M.-Y., Waye M.M.-Y.,
RA   Ho Y.-Y.;
RT   "The putative protein 6 of the severe acute respiratory syndrome-associated
RT   coronavirus: expression and functional characterization.";
RL   FEBS Lett. 579:6763-6768(2005).
RN   [16]
RP   SUBCELLULAR LOCATION.
RX   PubMed=17108045; DOI=10.1128/jvi.01515-06;
RA   Tangudu C., Olivares H., Netland J., Perlman S., Gallagher T.;
RT   "Severe acute respiratory syndrome coronavirus protein 6 accelerates murine
RT   coronavirus infections.";
RL   J. Virol. 81:1220-1229(2007).
RN   [17]
RP   INTERACTION WITH NSP8, AND SUBCELLULAR LOCATION.
RX   PubMed=17532020; DOI=10.1016/j.virol.2007.04.029;
RA   Kumar P., Gunalan V., Liu B., Chow V.T., Druce J., Birch C., Catton M.,
RA   Fielding B.C., Tan Y.J., Lal S.K.;
RT   "The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with
RT   its ORF6 accessory protein.";
RL   Virology 366:293-303(2007).
RN   [18]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=17596301; DOI=10.1128/jvi.01012-07;
RA   Frieman M., Yount B., Heise M., Kopecky-Bromberg S.A., Palese P.,
RA   Baric R.S.;
RT   "Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1
RT   function by sequestering nuclear import factors on the rough endoplasmic
RT   reticulum/Golgi membrane.";
RL   J. Virol. 81:9812-9824(2007).
RN   [19]
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF 49-TYR--LEU-52 AND 53-ASP--GLU-56.
RX   PubMed=22026976; DOI=10.1186/1756-0500-4-446;
RA   Gunalan V., Mirazimi A., Tan Y.J.;
RT   "A putative diacidic motif in the SARS-CoV ORF6 protein influences its
RT   subcellular localization and suppression of expression of co-transfected
RT   expression constructs.";
RL   BMC Res. Notes 4:446-446(2011).
RN   [20]
RP   INTERACTION WITH PROTEIN ORF9B, AND SUBCELLULAR LOCATION.
RX   PubMed=22820404; DOI=10.1016/j.virusres.2012.07.012;
RA   Calvo E., DeDiego M.L., Garcia P., Lopez J.A., Perez-Brena P., Falcon A.;
RT   "Severe acute respiratory syndrome coronavirus accessory proteins 6 and 9b
RT   interact in vivo.";
RL   Virus Res. 169:282-288(2012).
CC   -!- FUNCTION: Disrupts cell nuclear import complex formation by tethering
CC       karyopherin alpha 2 and karyopherin beta 1 to the membrane. Retention
CC       of import factors at the ER/Golgi membrane leads to a loss of transport
CC       into the nucleus. Thereby prevents STAT1 nuclear translocation in
CC       response to interferon signaling, thus blocking the expression of
CC       interferon stimulated genes (ISGs) that display multiple antiviral
CC       activities. {ECO:0000269|PubMed:17596301}.
CC   -!- SUBUNIT: Interacts with host KPNA2 (PubMed:17596301). May interact with
CC       nsp8 (PubMed:17532020). Interacts with protein ORF9b (PubMed:22820404).
CC       {ECO:0000269|PubMed:17532020, ECO:0000269|PubMed:17596301,
CC       ECO:0000269|PubMed:22820404}.
CC   -!- INTERACTION:
CC       P59634; Q13561: DCTN2; Xeno; NbExp=2; IntAct=EBI-25489038, EBI-715074;
CC   -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:17108045, ECO:0000269|PubMed:17532020,
CC       ECO:0000269|PubMed:17596301}. Host Golgi apparatus membrane
CC       {ECO:0000269|PubMed:17108045, ECO:0000269|PubMed:17596301}. Host
CC       cytoplasm {ECO:0000269|PubMed:22820404}. Note=Localizes to virus-
CC       induced vesicular structures called double membrane vesicles.
CC       {ECO:0000269|PubMed:17108045, ECO:0000269|PubMed:17596301,
CC       ECO:0000269|PubMed:22026976}.
CC   -!- SIMILARITY: Belongs to the coronaviruses accessory protein 6 family.
CC       {ECO:0000305}.
DR   EMBL; AY278741; AAP13448.1; -; Genomic_RNA.
DR   EMBL; AY274119; AAP41042.1; -; Genomic_RNA.
DR   EMBL; AY282752; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278554; AAP13572.1; -; Genomic_RNA.
DR   EMBL; AY278491; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278487; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278488; AAP30035.1; -; Genomic_RNA.
DR   EMBL; AY278489; AAP51232.1; -; Genomic_RNA.
DR   EMBL; AY278490; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY279354; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY291451; AAP37022.1; -; Genomic_RNA.
DR   EMBL; AY310120; AAP50490.1; -; Genomic_RNA.
DR   EMBL; AY291315; AAP33702.1; -; Genomic_RNA.
DR   EMBL; AY463059; AAR86791.1; -; Genomic_RNA.
DR   EMBL; AY338174; AAQ01602.1; -; Genomic_RNA.
DR   EMBL; AY338175; AAQ01614.1; -; Genomic_RNA.
DR   EMBL; AY348314; AAP97887.1; -; Genomic_RNA.
DR   EMBL; AP006557; BAC81353.1; -; Genomic_RNA.
DR   EMBL; AP006558; BAC81367.1; -; Genomic_RNA.
DR   EMBL; AP006559; BAC81381.1; -; Genomic_RNA.
DR   EMBL; AP006560; BAC81395.1; -; Genomic_RNA.
DR   EMBL; AP006561; BAC81409.1; -; Genomic_RNA.
DR   EMBL; AY323977; AAP72979.1; -; Genomic_RNA.
DR   EMBL; AY427439; AAQ94065.1; -; Genomic_RNA.
DR   RefSeq; NP_828856.1; NC_004718.3.
DR   BioGRID; 4383919; 13.
DR   IntAct; P59634; 2.
DR   GeneID; 1489673; -.
DR   KEGG; vg:1489673; -.
DR   SIGNOR; P59634; -.
DR   Proteomes; UP000000354; Genome.
DR   Proteomes; UP000103670; Genome.
DR   Proteomes; UP000109640; Genome.
DR   Proteomes; UP000116947; Genome.
DR   Proteomes; UP000121636; Genome.
DR   Proteomes; UP000131569; Genome.
DR   Proteomes; UP000131955; Genome.
DR   Proteomes; UP000137377; Genome.
DR   Proteomes; UP000138690; Genome.
DR   Proteomes; UP000143093; Genome.
DR   Proteomes; UP000145651; Genome.
DR   Proteomes; UP000146108; Genome.
DR   Proteomes; UP000146181; Genome.
DR   Proteomes; UP000146296; Genome.
DR   Proteomes; UP000148194; Genome.
DR   Proteomes; UP000153467; Genome.
DR   Proteomes; UP000160648; Genome.
DR   Proteomes; UP000164441; Genome.
DR   Proteomes; UP000172416; Genome.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW.
DR   InterPro; IPR022736; NS6_bCoV.
DR   Pfam; PF12133; Sars6; 1.
PE   1: Evidence at protein level;
KW   Host cytoplasm; Host endoplasmic reticulum; Host Golgi apparatus;
KW   Host membrane; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host STAT1 by virus; Interferon antiviral system evasion;
KW   Membrane; Reference proteome; Viral immunoevasion; Virulence.
FT   CHAIN           1..63
FT                   /note="ORF6 protein"
FT                   /id="PRO_0000106134"
FT   REGION          54..63
FT                   /note="Critical for disrupting nuclear import"
FT                   /evidence="ECO:0000269|PubMed:17596301"
FT   VARIANT         32..63
FT                   /note="IISSIVRQLFKPLTKKNYSELDDEEPMELDYP -> NKFNSETII (in
FT                   strain: Isolate TWJ)"
FT   VARIANT         57
FT                   /note="P -> L (in strain: Isolate GD01, Isolate BJ01,
FT                   Isolate BJ02, Isolate BJ03 and Isolate BJ04)"
FT   MUTAGEN         49..52
FT                   /note="YSEL->AAAA: No effect in the suppression of nuclear
FT                   gene expression."
FT                   /evidence="ECO:0000269|PubMed:22026976"
FT   MUTAGEN         53..56
FT                   /note="DDEE->AAAA: Reduction in the suppression of nuclear
FT                   gene expression."
FT                   /evidence="ECO:0000269|PubMed:22026976"
SQ   SEQUENCE   63 AA;  7527 MW;  70C9150941C759BF CRC64;
     MFHLVDFQVT IAEILIIIMR TFRIAIWNLD VIISSIVRQL FKPLTKKNYS ELDDEEPMEL
     DYP
//