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 02-DEC-2020, entry version 5. 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). 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 Golgi CC apparatus membrane {ECO:0000250|UniProtKB:P59632}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P59632}. Host cell membrane CC {ECO:0000250|UniProtKB:P59632}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P59632}. Secreted CC {ECO:0000250|UniProtKB:P59632}. Host cytoplasm CC {ECO:0000250|UniProtKB:P59632}. Note=The cell surface expressed protein CC can undergo endocytosis. The protein is secreted in association with CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 367. DR IntAct; P0DTC3; 367. DR GlyGen; P0DTC3; 2 sites. DR GeneID; 43740569; -. 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 Golgi apparatus; Host membrane; Membrane; Reference proteome; KW Secreted; 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 //