ID   AP3A_SARS2              Reviewed;         275 AA.
AC   P0DTC3;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   22-APR-2020, sequence version 1.
DT   10-FEB-2021, entry version 6.
DE   RecName: Full=ORF3a protein;
DE            Short=ORF3a;
DE   AltName: Full=Accessory protein 3a;
DE   AltName: Full=Protein 3a;
DE   AltName: Full=Protein U274;
DE   AltName: Full=Protein X1;
GN   ORFNames=3a;
OS   Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC   Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC   Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC   Betacoronavirus; Sarbecovirus.
OX   NCBI_TaxID=2697049;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA   Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA   Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA   Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT   "A new coronavirus associated with human respiratory disease in China.";
RL   Nature 579:265-269(2020).
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=33060197; DOI=10.1126/science.abe9403;
RG   QCRG Structural Biology Consortium;
RG   Zoonomia Consortium;
RA   Gordon D.E., Hiatt J., Bouhaddou M., Rezelj V.V., Ulferts S., Braberg H.,
RA   Jureka A.S., Obernier K., Guo J.Z., Batra J., Kaake R.M., Weckstein A.R.,
RA   Owens T.W., Gupta M., Pourmal S., Titus E.W., Cakir M., Soucheray M.,
RA   McGregor M., Cakir Z., Jang G., O'Meara M.J., Tummino T.A., Zhang Z.,
RA   Foussard H., Rojc A., Zhou Y., Kuchenov D., Huettenhain R., Xu J.,
RA   Eckhardt M., Swaney D.L., Fabius J.M., Ummadi M., Tutuncuoglu B.,
RA   Rathore U., Modak M., Haas P., Haas K.M., Naing Z.Z.C., Pulido E.H.,
RA   Shi Y., Barrio-Hernandez I., Memon D., Petsalaki E., Dunham A.,
RA   Marrero M.C., Burke D., Koh C., Vallet T., Silvas J.A., Azumaya C.M.,
RA   Billesboelle C., Brilot A.F., Campbell M.G., Diallo A., Dickinson M.S.,
RA   Diwanji D., Herrera N., Hoppe N., Kratochvil H.T., Liu Y., Merz G.E.,
RA   Moritz M., Nguyen H.C., Nowotny C., Puchades C., Rizo A.N.,
RA   Schulze-Gahmen U., Smith A.M., Sun M., Young I.D., Zhao J., Asarnow D.,
RA   Biel J., Bowen A., Braxton J.R., Chen J., Chio C.M., Chio U.S.,
RA   Deshpande I., Doan L., Faust B., Flores S., Jin M., Kim K., Lam V.L.,
RA   Li F., Li J., Li Y.L., Li Y., Liu X., Lo M., Lopez K.E., Melo A.A.,
RA   Moss F.R. III, Nguyen P., Paulino J., Pawar K.I., Peters J.K.,
RA   Pospiech T.H. Jr., Safari M., Sangwan S., Schaefer K., Thomas P.V.,
RA   Thwin A.C., Trenker R., Tse E., Tsui T.K.M., Wang F., Whitis N., Yu Z.,
RA   Zhang K., Zhang Y., Zhou F., Saltzberg D., Hodder A.J., Shun-Shion A.S.,
RA   Williams D.M., White K.M., Rosales R., Kehrer T., Miorin L., Moreno E.,
RA   Patel A.H., Rihn S., Khalid M.M., Vallejo-Gracia A., Fozouni P.,
RA   Simoneau C.R., Roth T.L., Wu D., Karim M.A., Ghoussaini M., Dunham I.,
RA   Berardi F., Weigang S., Chazal M., Park J., Logue J., McGrath M.,
RA   Weston S., Haupt R., Hastie C.J., Elliott M., Brown F., Burness K.A.,
RA   Reid E., Dorward M., Johnson C., Wilkinson S.G., Geyer A., Giesel D.M.,
RA   Baillie C., Raggett S., Leech H., Toth R., Goodman N., Keough K.C.,
RA   Lind A.L., Klesh R.J., Hemphill K.R., Carlson-Stevermer J., Oki J.,
RA   Holden K., Maures T., Pollard K.S., Sali A., Agard D.A., Cheng Y.,
RA   Fraser J.S., Frost A., Jura N., Kortemme T., Manglik A., Southworth D.R.,
RA   Stroud R.M., Alessi D.R., Davies P., Frieman M.B., Ideker T., Abate C.,
RA   Jouvenet N., Kochs G., Shoichet B., Ott M., Palmarini M., Shokat K.M.,
RA   Garcia-Sastre A., Rassen J.A., Grosse R., Rosenberg O.S., Verba K.A.,
RA   Basler C.F., Vignuzzi M., Peden A.A., Beltrao P., Krogan N.J.;
RT   "Comparative host-coronavirus protein interaction networks reveal pan-viral
RT   disease mechanisms.";
RL   Science 0:0-0(2020).
CC   -!- FUNCTION: Forms homotetrameric potassium sensitive ion channels
CC       (viroporin) and may modulate virus release. Up-regulates expression of
CC       fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells.
CC       Induces apoptosis in cell culture. Downregulates the type 1 interferon
CC       receptor by inducing serine phosphorylation within the IFN alpha-
CC       receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1
CC       ubiquitination. {ECO:0000250|UniProtKB:P59632}.
CC   -!- SUBUNIT: Homotetramer composed of two homodimers linked non covalently.
CC       Interacts with M, S and E proteins. Also interacts with the accessory
CC       protein 7a. {ECO:0000250|UniProtKB:P59632}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P59632}. Host cell
CC       membrane {ECO:0000250|UniProtKB:P59632, ECO:0000269|PubMed:33060197};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:P59632}. Secreted
CC       {ECO:0000250|UniProtKB:P59632}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P59632, ECO:0000269|PubMed:33060197}. Host
CC       endosome {ECO:0000269|PubMed:33060197}. Note=The cell surface expressed
CC       protein can undergo endocytosis. The protein is secreted in association
CC       with membranous structures. {ECO:0000250|UniProtKB:P59632}.
CC   -!- DOMAIN: The second or the third transmembrane region are responsible
CC       for Golgi localization. {ECO:0000250|UniProtKB:P59632}.
CC   -!- PTM: Exists in both O-glycosylated and non-glycosylated forms. The
CC       glycosylated form is associated with the virion.
CC       {ECO:0000250|UniProtKB:P59632}.
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DR   EMBL; MN908947; QHD43417.1; -; Genomic_RNA.
DR   RefSeq; YP_009724391.1; NC_045512.2.
DR   PDB; 6XDC; EM; 2.90 A; A/B=1-275.
DR   PDBsum; 6XDC; -.
DR   SMR; P0DTC3; -.
DR   BioGRID; 4383868; 964.
DR   ComplexPortal; CPX-6098; SARS-CoV-2 3a complex.
DR   IntAct; P0DTC3; 367.
DR   GlyGen; P0DTC3; 2 sites.
DR   GeneID; 43740569; -.
DR   KEGG; vg:43740569; -.
DR   Reactome; R-HSA-9694322; Virion Assembly and Release.
DR   Reactome; R-HSA-9694614; Attachment and Entry.
DR   Reactome; R-HSA-9694635; Translation of structural proteins.
DR   Reactome; R-HSA-9694719; Maturation of protein 3a.
DR   PRO; PR:P0DTC3; -.
DR   Proteomes; UP000464024; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma 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:0005216; F:ion channel activity; IEA:InterPro.
DR   GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:InterPro.
DR   InterPro; IPR024407; Protein_3a_bCoV.
DR   Pfam; PF11289; bCoV_viroporin; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Glycoprotein; Host cell membrane; Host cytoplasm;
KW   Host endosome; Host membrane; Membrane; Reference proteome; Secreted;
KW   Transmembrane; Transmembrane helix; Virion.
FT   CHAIN           1..275
FT                   /note="ORF3a protein"
FT                   /id="PRO_0000449650"
FT   TRANSMEM        35..55
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        71..91
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        94..114
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   SITE            133
FT                   /note="Involved in polymerization"
FT                   /evidence="ECO:0000250|UniProtKB:P59632"
FT   CARBOHYD        32
FT                   /note="O-linked (GalNAc...) threonine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P59632"
FT   CARBOHYD        34
FT                   /note="O-linked (GalNAc...) threonine; by host"
FT                   /evidence="ECO:0000255"
FT   HELIX           44..60
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   HELIX           68..99
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   HELIX           103..133
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   HELIX           137..140
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          144..148
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          158..160
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          165..172
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          183..186
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          189..192
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          199..204
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          209..218
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   HELIX           220..223
FT                   /evidence="ECO:0000244|PDB:6XDC"
FT   STRAND          228..235
FT                   /evidence="ECO:0000244|PDB:6XDC"
SQ   SEQUENCE   275 AA;  31123 MW;  4688E6D477E031C4 CRC64;
     MDLFMRIFTI GTVTLKQGEI KDATPSDFVR ATATIPIQAS LPFGWLIVGV ALLAVFQSAS
     KIITLKKRWQ LALSKGVHFV CNLLLLFVTV YSHLLLVAAG LEAPFLYLYA LVYFLQSINF
     VRIIMRLWLC WKCRSKNPLL YDANYFLCWH TNCYDYCIPY NSVTSSIVIT SGDGTTSPIS
     EHDYQIGGYT EKWESGVKDC VVLHSYFTSD YYQLYSTQLS TDTGVEHVTF FIYNKIVDEP
     EEHVQIHTID GSSGVVNPVM EPIYDEPTTT TSVPL
//