ID   NS7A_CVHSA              Reviewed;         122 AA.
AC   P59635; Q7TA11; Q7TA17;
DT   23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-APR-2003, sequence version 1.
DT   22-APR-2020, entry version 102.
DE   RecName: Full=Protein 7a;
DE   AltName: Full=Accessory protein 7a;
DE   AltName: Full=Protein U122;
DE   AltName: Full=Protein X4;
DE   Flags: Precursor;
GN   ORFNames=7a;
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 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   [10]
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   [11]
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   [12]
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   [13]
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   [14]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 32-122.
RC   STRAIN=Isolate Shanghai LY;
RA   Yuan Z., Zhang X., Hu Y., Lan S., Wang H., Zhou Z., Wen Y.;
RL   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [15]
RP   PEPTIDE SEQUENCE OF 16-29, SUBCELLULAR LOCATION, AND X-RAY CRYSTALLOGRAPHY
RP   (1.8 ANGSTROMS) OF 16-96.
RX   PubMed=15642263; DOI=10.1016/j.str.2004.10.010;
RA   Nelson C.A., Pekosz A., Lee C.A., Diamond M.S., Fremont D.H.;
RT   "Structure and intracellular targeting of the SARS-coronavirus Orf7a
RT   accessory protein.";
RL   Structure 13:75-85(2005).
RN   [16]
RP   INTERACTION WITH ACCESSORY PROTEIN 3A.
RX   PubMed=15194747; DOI=10.1128/jvi.78.13.6723-6734.2004;
RA   Tan Y.-J., Teng E., Shen S., Tan T.H.P., Goh P.-Y., Fielding B.C.,
RA   Ooi E.-E., Tan H.-C., Lim S.G., Hong W.;
RT   "A novel severe acute respiratory syndrome coronavirus protein, U274, is
RT   transported to the cell surface and undergoes endocytosis.";
RL   J. Virol. 78:6723-6734(2004).
RN   [17]
RP   SUBCELLULAR LOCATION, DI-LYSINE MOTIF, AND MUTAGENESIS OF 14-SER--TYR-18
RP   AND 118-LYS--LYS-120.
RX   PubMed=15220404; DOI=10.1128/jvi.78.14.7311-7318.2004;
RA   Fielding B.C., Tan Y.-J., Shuo S., Tan T.H.P., Ooi E.-E., Lim S.G.,
RA   Hong W., Goh P.-Y.;
RT   "Characterization of a unique group-specific protein (U122) of the severe
RT   acute respiratory syndrome coronavirus.";
RL   J. Virol. 78:7311-7318(2004).
RN   [18]
RP   FUNCTION.
RX   PubMed=15564512; DOI=10.1128/jvi.78.24.14043-14047.2004;
RA   Tan Y.-J., Fielding B.C., Goh P.-Y., Shen S., Tan T.H.P., Lim S.G.,
RA   Hong W.;
RT   "Overexpression of 7a, a protein specifically encoded by the severe acute
RT   respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent
RT   pathway.";
RL   J. Virol. 78:14043-14047(2004).
RN   [19]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH SPIKE GLYCOPROTEIN.
RX   PubMed=16840309; DOI=10.1128/jvi.00414-06;
RA   Huang C., Ito N., Tseng C.-T.K., Makino S.;
RT   "Severe acute respiratory syndrome coronavirus 7a accessory protein is a
RT   viral structural protein.";
RL   J. Virol. 80:7287-7294(2006).
RN   [20]
RP   SUBCELLULAR LOCATION.
RX   PubMed=17037516; DOI=10.1007/978-0-387-33012-9_20;
RA   Pekosz A., Schaecher S.R., Diamond M.S., Fremont D.H., Sims A.C.,
RA   Baric R.S.;
RT   "Structure, expression, and intracellular localization of the SARS-CoV
RT   accessory proteins 7a and 7b.";
RL   Adv. Exp. Med. Biol. 581:115-120(2006).
RN   [21]
RP   INTERACTION WITH M PROTEIN; E PROTEIN AND HUMAN SGT.
RX   PubMed=16580632; DOI=10.1016/j.bbrc.2006.03.091;
RA   Fielding B.C., Gunalan V., Tan T.H.P., Chou C.-F., Shen S., Khan S.,
RA   Lim S.G., Hong W., Tan Y.-J.;
RT   "Severe acute respiratory syndrome coronavirus protein 7a interacts with
RT   hSGT.";
RL   Biochem. Biophys. Res. Commun. 343:1201-1208(2006).
RN   [22]
RP   STRUCTURE BY NMR OF 16-99.
RX   PubMed=16328780; DOI=10.1007/s11373-005-9043-9;
RA   Haenel K., Stangler T., Stoldt M., Willbold D.;
RT   "Solution structure of the X4 protein coded by the SARS related coronavirus
RT   reveals an immunoglobulin like fold and suggests a binding activity to
RT   integrin I domains.";
RL   J. Biomed. Sci. 13:281-293(2006).
RN   [23]
RP   FUNCTION, AND INTERACTION WITH HOST ITGAL.
RX   PubMed=18020948; DOI=10.1515/bc.2007.157;
RA   Haenel K., Willbold D.;
RT   "SARS-CoV accessory protein 7a directly interacts with human LFA-1.";
RL   Biol. Chem. 388:1325-1332(2007).
RN   [24]
RP   FUNCTION.
RX   PubMed=20631126; DOI=10.1128/jvi.00748-10;
RA   Karjee S., Minhas A., Sood V., Ponia S.S., Banerjea A.C., Chow V.T.,
RA   Mukherjee S.K., Lal S.K.;
RT   "The 7a accessory protein of severe acute respiratory syndrome coronavirus
RT   acts as an RNA silencing suppressor.";
RL   J. Virol. 84:10395-10401(2010).
CC   -!- FUNCTION: Non-structural protein which is dispensable for virus
CC       replication in cell culture. May suppress small interfering RNA
CC       (siRNA). May bind to host ITGAL, thereby playing a role in attachment
CC       or modulation of leukocytes. {ECO:0000269|PubMed:15564512,
CC       ECO:0000269|PubMed:18020948, ECO:0000269|PubMed:20631126}.
CC   -!- SUBUNIT: Interacts with the spike glycoprotein, M protein, E protein
CC       and the accessory protein 3a. Interacts with human SGT. Interacts with
CC       host ITGAL. {ECO:0000269|PubMed:15194747, ECO:0000269|PubMed:16580632,
CC       ECO:0000269|PubMed:16840309, ECO:0000269|PubMed:18020948}.
CC   -!- SUBCELLULAR LOCATION: Virion. Host endoplasmic reticulum membrane;
CC       Single-pass membrane protein. Host endoplasmic reticulum-Golgi
CC       intermediate compartment membrane; Single-pass type I membrane protein.
CC       Host Golgi apparatus membrane; Single-pass membrane protein.
CC   -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum localization
CC       for type I membrane proteins. {ECO:0000250}.
DR   EMBL; AY278741; AAP13449.1; -; Genomic_RNA.
DR   EMBL; AY274119; AAP41043.1; -; Genomic_RNA.
DR   EMBL; AY282752; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278554; AAP13573.1; -; Genomic_RNA.
DR   EMBL; AY278491; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278487; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY278488; AAP30036.1; -; Genomic_RNA.
DR   EMBL; AY278489; AAP51233.1; -; Genomic_RNA.
DR   EMBL; AY278490; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY279354; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   EMBL; AY291451; AAP37023.1; -; Genomic_RNA.
DR   EMBL; AY310120; AAP50491.1; -; Genomic_RNA.
DR   EMBL; AY291315; AAP33703.1; -; Genomic_RNA.
DR   EMBL; AY338174; AAQ01603.1; -; Genomic_RNA.
DR   EMBL; AY338175; AAQ01615.1; -; Genomic_RNA.
DR   EMBL; AY348314; AAP97888.1; -; Genomic_RNA.
DR   EMBL; AP006557; BAC81354.1; -; Genomic_RNA.
DR   EMBL; AP006558; BAC81368.1; -; Genomic_RNA.
DR   EMBL; AP006559; BAC81382.1; -; Genomic_RNA.
DR   EMBL; AP006560; BAC81396.1; -; Genomic_RNA.
DR   EMBL; AP006561; BAC81410.1; -; Genomic_RNA.
DR   EMBL; AY323977; AAP72980.1; -; Genomic_RNA.
DR   EMBL; AY427439; AAQ94066.1; -; Genomic_RNA.
DR   EMBL; AY463059; AAP82982.2; -; Genomic_RNA.
DR   EMBL; AY322208; AAP82970.1; -; Genomic_RNA.
DR   RefSeq; NP_828857.1; NC_004718.3.
DR   PDB; 1XAK; X-ray; 1.80 A; A=14-96.
DR   PDB; 1YO4; NMR; -; A=16-99.
DR   PDBsum; 1XAK; -.
DR   PDBsum; 1YO4; -.
DR   SMR; P59635; -.
DR   ELM; P59635; -.
DR   IntAct; P59635; 8.
DR   PRIDE; P59635; -.
DR   GeneID; 1489674; -.
DR   KEGG; vg:1489674; -.
DR   EvolutionaryTrace; P59635; -.
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:0044165; C:host cell endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044173; C:host cell endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044177; C:host cell Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
DR   GO; GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR   GO; GO:0039587; P:suppression by virus of host tetherin activity; IDA:UniProtKB.
DR   Gene3D; 2.60.40.1550; -; 1.
DR   InterPro; IPR014888; SARS_X4.
DR   InterPro; IPR036495; SARS_X4_sf.
DR   Pfam; PF08779; SARS_X4; 1.
DR   SUPFAM; SSF117066; SSF117066; 1.
DR   PROSITE; PS51919; X4E; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond;
KW   G0/G1 host cell cycle checkpoint dysregulation by virus;
KW   Host endoplasmic reticulum; Host Golgi apparatus; Host membrane;
KW   Host-virus interaction; Membrane; Modulation of host cell cycle by virus;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix; Virion.
FT   SIGNAL          1..15
FT   CHAIN           16..122
FT                   /note="Protein 7a"
FT                   /id="PRO_0000037435"
FT   TOPO_DOM        16..96
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        97..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..122
FT                   /note="Intravirion"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          16..81
FT                   /note="X4e"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01267"
FT   MOTIF           118..122
FT                   /note="Di-lysine motif"
FT   DISULFID        23..58
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01267"
FT   DISULFID        35..67
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01267"
FT   VARIANT         38
FT                   /note="G -> A (in strain: Isolate Shanghai LY)"
FT   MUTAGEN         14..18
FT                   /note="SCELY->LLLLL: Complete loss of signal sequence
FT                   cleavage."
FT                   /evidence="ECO:0000269|PubMed:15220404"
FT   MUTAGEN         118..120
FT                   /note="KRK->ERE: Induces rapid exit from the endoplasmic
FT                   reticulum."
FT                   /evidence="ECO:0000269|PubMed:15220404"
FT   STRAND          16..24
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          27..32
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          34..37
FT                   /evidence="ECO:0000244|PDB:1YO4"
FT   STRAND          39..44
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   TURN            50..52
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          53..57
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          60..66
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          72..80
FT                   /evidence="ECO:0000244|PDB:1XAK"
FT   STRAND          82..84
FT                   /evidence="ECO:0000244|PDB:1YO4"
FT   STRAND          89..93
FT                   /evidence="ECO:0000244|PDB:1YO4"
FT   STRAND          95..97
FT                   /evidence="ECO:0000244|PDB:1YO4"
SQ   SEQUENCE   122 AA;  13941 MW;  6D8D8D949B0DB4B5 CRC64;
     MKIILFLTLI VFTSCELYHY QECVRGTTVL LKEPCPSGTY EGNSPFHPLA DNKFALTCTS
     THFAFACADG TRHTYQLRAR SVSPKLFIRQ EEVQQELYSP LFLIVAALVF LILCFTIKRK
     TE
//