ID NS7A_SARS2 Reviewed; 121 AA.
AC P0DTC7;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 1.
DT 28-JUN-2023, entry version 16.
DE RecName: Full=ORF7a protein;
DE Short=ORF7a;
DE AltName: Full=Accessory protein 7a;
DE AltName: Full=Protein U122;
DE AltName: Full=Protein X4;
DE Flags: Precursor;
GN ORFNames=7a;
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 VARIANT ILE-14.
RC STRAIN=20B/501Y.V1, B.1.1.7, VOC-202012/01, and VUI-202012/01;
RX PubMed=33413740; DOI=10.2807/1560-7917.es.2020.26.1.2002106;
RA Leung K., Shum M.H., Leung G.M., Lam T.T., Wu J.T.;
RT "Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-
RT 2 in the United Kingdom, October to November 2020.";
RL Eurosurveillance 26:0-0(2021).
RN [3]
RP FUNCTION, UBIQUITINATION AT LYS-119, AND MUTAGENESIS OF LYS-2; LYS-32;
RP LYS-53; LYS-72; LYS-85; LYS-117 AND LYS-119.
RX PubMed=33473190; DOI=10.1038/s41423-020-00603-6;
RA Cao Z., Xia H., Rajsbaum R., Xia X., Wang H., Shi P.Y.;
RT "Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon
RT response.";
RL Cell. Mol. Immunol. 18:746-748(2021).
RN [4]
RP FUNCTION, INTERACTION WITH HOST BST2, AND SUBCELLULAR LOCATION.
RX PubMed=33930332; DOI=10.1016/j.molcel.2021.04.008;
RA Martin-Sancho L., Lewinski M.K., Pache L., Stoneham C.A., Yin X.,
RA Becker M.E., Pratt D., Churas C., Rosenthal S.B., Liu S., Weston S.,
RA De Jesus P.D., O'Neill A.M., Gounder A.P., Nguyen C., Pu Y., Curry H.M.,
RA Oom A.L., Miorin L., Rodriguez-Frandsen A., Zheng F., Wu C., Xiong Y.,
RA Urbanowski M., Shaw M.L., Chang M.W., Benner C., Hope T.J., Frieman M.B.,
RA Garcia-Sastre A., Ideker T., Hultquist J.F., Guatelli J., Chanda S.K.;
RT "Functional landscape of SARS-CoV-2 cellular restriction.";
RL Mol. Cell 81:2656-2668.e8(2021).
RN [5]
RP DISORDERED REGIONS.
RX PubMed=35108439; DOI=10.1111/febs.16379;
RA Quaglia F., Salladini E., Carraro M., Minervini G., Tosatto S.C.E.,
RA Le Mercier P.;
RT "SARS-CoV-2 variants preferentially emerge at intrinsically disordered
RT protein sites helping immune evasion.";
RL FEBS J. 289:4240-4250(2022).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 117-LYS--LYS-119.
RX PubMed=36574644; DOI=10.1073/pnas.2208525120;
RA Arshad N., Laurent-Rolle M., Ahmed W.S., Hsu J.C., Mitchell S.M.,
RA Pawlak J., Sengupta D., Biswas K.H., Cresswell P.;
RT "SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to
RT down-regulate MHC-I surface expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 120:e2208525120-e2208525120(2023).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 16-82, AND DISULFIDE BOND.
RA Nelson C.A., Minasov G., Shuvalova L., Fremont D.H.;
RT "STRUCTURE OF THE SARS-CoV-2 ORF7A ENCODED ACCESSORY PROTEIN.";
RL Submitted (MAR-2020) to the PDB data bank.
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 14-96.
RX PubMed=33615195; DOI=10.1016/j.isci.2021.102187;
RA Zhou Z., Huang C., Zhou Z., Huang Z., Su L., Kang S., Chen X., Chen Q.,
RA He S., Rong X., Xiao F., Chen J., Chen S.;
RT "Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor
RT for human CD14+ monocytes.";
RL IScience 24:102187-102187(2021).
CC -!- FUNCTION: Plays a role as antagonist of host tetherin (BST2),
CC disrupting its antiviral effect (PubMed:33930332). Acts by binding to
CC BST2 and sequestering it to perinuclear region, thereby preventing its
CC antiviral function at cell membrane (PubMed:33930332). May specifically
CC downregulate MHC-I allele HLA-A*02:01 (HLA-A2)(PubMed:36574644).
CC {ECO:0000269|PubMed:33930332, ECO:0000269|PubMed:36574644}.
CC -!- SUBUNIT: Interacts with host BST2 (PubMed:33930332). Interacts with the
CC spike glycoprotein (By similarity). Interacts with M protein (By
CC similarity). Interacts with E protein (By similarity). Interacts with
CC the ORF3a protein (By similarity). {ECO:0000250|UniProtKB:P59635,
CC ECO:0000269|PubMed:33930332}.
CC -!- INTERACTION:
CC P0DTC7; PRO_0000449625 [P0DTD1]: rep; NbExp=3; IntAct=EBI-25475903, EBI-25475871;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:33930332}. Virion {ECO:0000250|UniProtKB:P59635}.
CC Host endoplasmic reticulum membrane {ECO:0000269|PubMed:36574644};
CC Single-pass membrane protein {ECO:0000269|PubMed:36574644}. Host
CC endoplasmic reticulum-Golgi intermediate compartment membrane
CC {ECO:0000269|PubMed:36574644}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:36574644}. Host Golgi apparatus membrane
CC {ECO:0000269|PubMed:36574644}; Single-pass membrane protein
CC {ECO:0000269|PubMed:36574644}.
CC -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum localization
CC for type I membrane proteins. {ECO:0000250|UniProtKB:P59635}.
CC -!- PTM: Poly-ubiquitinated by host with K63-linked polyubiquitin chains.
CC {ECO:0000269|PubMed:33473190}.
CC -!- MISCELLANEOUS: Variant B.1.1.7 is also called Variant Of Concern (VOC)
CC 202012/01, Variant Under Investigation (VUI) 202012/01, or 20B/501Y.V1.
CC {ECO:0000305|PubMed:33413740}.
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DR EMBL; MN908947; QHD43421.1; -; Genomic_RNA.
DR PDB; 6W37; X-ray; 2.90 A; A=16-82.
DR PDB; 7CI3; X-ray; 2.20 A; A=14-96.
DR PDBsum; 6W37; -.
DR PDBsum; 7CI3; -.
DR SMR; P0DTC7; -.
DR BioGRID; 4383872; 1236.
DR IntAct; P0DTC7; 114.
DR iPTMnet; P0DTC7; -.
DR KEGG; vg:43740573; -.
DR Reactome; R-HSA-9694322; Virion Assembly and Release.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-9727281; Translation of Accessory Proteins.
DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR PRO; PR:P0DTC7; -.
DR Proteomes; UP000464024; Genome.
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:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; TAS:Reactome.
DR GO; GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR GO; GO:0039587; P:suppression by virus of host tetherin activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd21684; ORF7a_SARS-CoV-2-like; 1.
DR Gene3D; 2.60.40.1550; SARS coronavirus X4; 1.
DR InterPro; IPR044390; ORF7a_SARS-CoV-2-like.
DR InterPro; IPR014888; ORF7a_SARS-CoV-like.
DR InterPro; IPR044871; ORF7a_SARS-CoV-like_X4e.
DR InterPro; IPR036495; ORF7a_sf_CoV.
DR Pfam; PF08779; bCoV_NS7A; 1.
DR SUPFAM; SSF117066; Accessory protein X4 (ORF8, ORF7a); 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; Host cytoplasm;
KW Host endoplasmic reticulum; Host Golgi apparatus; Host membrane;
KW Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host MHC class I molecule presentation by virus;
KW Inhibition of host tetherin by virus; Isopeptide bond; Membrane;
KW Modulation of host cell cycle by virus; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation; Viral immunoevasion;
KW Virion.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..121
FT /note="ORF7a protein"
FT /evidence="ECO:0000255"
FT /id="PRO_0000449654"
FT TRANSMEM 96..116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 16..81
FT /note="X4e"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01267"
FT REGION 16..80
FT /note="Ig-like fold"
FT /evidence="ECO:0000305|PubMed:36574644"
FT REGION 83..95
FT /note="Disordered"
FT /evidence="ECO:0000305|PubMed:35108439"
FT MOTIF 117..119
FT /note="ER-retrieval motif"
FT /evidence="ECO:0000269|PubMed:36574644"
FT DISULFID 23..58
FT /evidence="ECO:0000269|PubMed:33615195, ECO:0000269|Ref.7"
FT DISULFID 35..67
FT /evidence="ECO:0000269|PubMed:33615195, ECO:0000269|Ref.7"
FT CROSSLNK 119
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:33473190"
FT VARIANT 14
FT /note="T -> I (in strain: Alpha/B.1.1.7)"
FT /evidence="ECO:0000305|PubMed:33413740"
FT VARIANT 82
FT /note="V -> A (in strain: Delta/B.1.617.2 and Kappa/
FT B.1.617.1 )"
FT /evidence="ECO:0000305"
FT VARIANT 120
FT /note="T -> I (in strain; Delta/B.1.617.2)"
FT /evidence="ECO:0000305"
FT MUTAGEN 2
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 32
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 53
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 72
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 85
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 117..119
FT /note="KRK->ARA: Complete loss of MHC-I retention in ER."
FT /evidence="ECO:0000269|PubMed:36574644"
FT MUTAGEN 117
FT /note="K->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:33473190"
FT MUTAGEN 119
FT /note="K->A: Complete loss of ubiquitination. Partial loss
FT of interferon pathway inhibition."
FT /evidence="ECO:0000269|PubMed:33473190"
FT STRAND 16..24
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:6W37"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:7CI3"
FT STRAND 72..80
FT /evidence="ECO:0007829|PDB:7CI3"
SQ SEQUENCE 121 AA; 13744 MW; 891E7EAB9E8A5BA9 CRC64;
MKIILFLALI TLATCELYHY QECVRGTTVL LKEPCSSGTY EGNSPFHPLA DNKFALTCFS
TQFAFACPDG VKHVYQLRAR SVSPKLFIRQ EEVQELYSPI FLIVAAIVFI TLCFTLKRKT
E
//