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
//