ID VEMP_SARS2 Reviewed; 75 AA.
AC P0DTC4;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 1.
DT 27-MAR-2024, entry version 21.
DE RecName: Full=Envelope small membrane protein {ECO:0000255|HAMAP-Rule:MF_04204};
DE Short=E;
DE Short=sM protein {ECO:0000255|HAMAP-Rule:MF_04204};
GN Name=E {ECO:0000255|HAMAP-Rule:MF_04204}; ORFNames=4;
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;
OC Severe acute respiratory syndrome coronavirus.
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 FUNCTION, AND INTERACTION WITH HUMAN PALS1/MPP5.
RX PubMed=32891874; DOI=10.1016/j.micinf.2020.08.006;
RA De Maio F., Lo Cascio E., Babini G., Sali M., Della Longa S., Tilocca B.,
RA Roncada P., Arcovito A., Sanguinetti M., Scambia G., Urbani A.;
RT "Improved binding of SARS-CoV-2 Envelope protein to tight junction-
RT associated PALS1 could play a key role in COVID-19 pathogenesis.";
RL Microbes Infect. 22:592-597(2020).
RN [3]
RP TOPOLOGY.
RX PubMed=32898469; DOI=10.1098/rsob.200209;
RA Duart G., Garcia-Murria M.J., Grau B., Acosta-Caceres J.M.,
RA Martinez-Gil L., Mingarro I.;
RT "SARS-CoV-2 envelope protein topology in eukaryotic membranes.";
RL Open Biol. 10:200209-200209(2020).
RN [4]
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 [5]
RP STRUCTURE BY NMR OF 8-38, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=33177698; DOI=10.1038/s41594-020-00536-8;
RA Mandala V.S., McKay M.J., Shcherbakov A.A., Dregni A.J., Kolocouris A.,
RA Hong M.;
RT "Structure and drug binding of the SARS-CoV-2 envelope protein
RT transmembrane domain in lipid bilayers.";
RL Nat. Struct. Mol. Biol. 27:1202-1208(2020).
RN [6]
RP FUNCTION.
RX PubMed=33229438; DOI=10.1074/jbc.ra120.016175;
RA Boson B., Legros V., Zhou B., Siret E., Mathieu C., Cosset F.L.,
RA Lavillette D., Denolly S.;
RT "The SARS-CoV-2 Envelope and Membrane proteins modulate maturation and
RT retention of the Spike protein, allowing assembly of virus-like
RT particles.";
RL J. Biol. Chem. 296:100111-100111(2020).
RN [7] {ECO:0007744|PDB:7QCR, ECO:0007744|PDB:7QCS, ECO:0007744|PDB:7QCT}
RP X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 64-75, INTERACTION WITH HOST
RP PALS1/MPP5, INTERACTION WITH HOST TJP1/ZO1, INTERACTION WITH HOST LNX2,
RP INTERACTION WITH HOST PARD3, INTERACTION WITH HOST AFDN/MLLT4, AND
RP MUTAGENESIS OF PRO-71.
RX PubMed=35283834; DOI=10.3389/fmicb.2022.829094;
RA Zhu Y., Alvarez F., Wolff N., Mechaly A., Brule S., Neitthoffer B.,
RA Etienne-Manneville S., Haouz A., Boeda B., Caillet-Saguy C.;
RT "Interactions of Severe Acute Respiratory Syndrome Coronavirus 2 Protein E
RT With Cell Junctions and Polarity PSD-95/Dlg/ZO-1-Containing Proteins.";
RL Front. Microbiol. 13:829094-829094(2022).
CC -!- FUNCTION: Plays a central role in virus morphogenesis and assembly.
CC Acts as a viroporin and self-assembles in host membranes forming
CC pentameric protein-lipid pores that allow ion transport. Also plays a
CC role in the induction of apoptosis (By similarity). Regulates the
CC localization of S protein at cis-Golgi, the place of virus budding
CC (PubMed:33229438). May act by slowing down the cell secretory pathway
CC (PubMed:33229438). May interfere with tight-junction stability by
CC interacting with host MPP5. This would result in disruption of
CC epithelial barriers, thereby amplifying inflammatory processes
CC (PubMed:32891874). {ECO:0000255|HAMAP-Rule:MF_04204,
CC ECO:0000269|PubMed:33229438, ECO:0000303|PubMed:32891874}.
CC -!- SUBUNIT: Homopentamer (PubMed:33177698). Interacts via C-terminus PDM
CC domain with PDZ domain-containing host proteins such as PALS1/MPP5
CC (PubMed:32891874, PubMed:35283834), TJP1/ZO1 (PubMed:35283834), LNX2
CC (PubMed:35283834), PARD3 (PubMed:35283834), and AFDN/MLLT4
CC (PubMed:35283834). This may lead to disruption of tight junctions
CC between epithelial cells (PubMed:32891874). Interacts with membrane
CC protein M in the budding compartment of the host cell, which is located
CC between endoplasmic reticulum and the Golgi complex. Interacts with
CC Nucleoprotein (By similarity). {ECO:0000250|UniProtKB:P59637,
CC ECO:0000255|HAMAP-Rule:MF_04204, ECO:0000269|PubMed:33177698,
CC ECO:0000269|PubMed:35283834, ECO:0000303|PubMed:32891874}.
CC -!- INTERACTION:
CC P0DTC4; P0DTC4: E; NbExp=4; IntAct=EBI-25475850, EBI-25475850;
CC P0DTC4; P0DTC5: M; NbExp=3; IntAct=EBI-25475850, EBI-25475853;
CC P0DTC4; P0DTC9: N; NbExp=3; IntAct=EBI-25475850, EBI-25475856;
CC P0DTC4; O95429: BAG4; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-2949658;
CC P0DTC4; PRO_0000018590 [Q07021]: C1QBP; Xeno; NbExp=2; IntAct=EBI-25475850, EBI-14032968;
CC P0DTC4; Q8N3R9: PALS1; Xeno; NbExp=6; IntAct=EBI-25475850, EBI-2513978;
CC P0DTC4; O75360: PROP1; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-9027467;
CC P0DTC4; P61165: TMEM258; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-12019210;
CC P0DTC4; Q86VM9: ZC3H18; Xeno; NbExp=3; IntAct=EBI-25475850, EBI-1045965;
CC -!- SUBCELLULAR LOCATION: Host Golgi apparatus membrane {ECO:0000255|HAMAP-
CC Rule:MF_04204}; Single-pass type III membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04204, ECO:0000269|PubMed:32898469,
CC ECO:0000269|PubMed:33177698}. Note=The cytoplasmic tail functions as a
CC Golgi complex-targeting signal. {ECO:0000255|HAMAP-Rule:MF_04204}.
CC -!- POLYMORPHISM: Variant Omicron/BA.1 and BA.2 belong to a lineage first
CC isolated in South Africa (November 2021). {ECO:0000305}.
CC -!- POLYMORPHISM: Variant Omicron/BQ.1.1 belongs to a lineage first
CC isolated in Nigeria (November 2022). {ECO:0000305}.
CC -!- POLYMORPHISM: Variant Omicron/XBB.1.5 belongs to a lineage first
CC isolated in United States (November 2022). It is the result of
CC recombination between omicron BJ.1 and BM.1.1. Moreover XBB.1.5 do not
CC express ORF8. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the betacoronaviruses E protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04204}.
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DR EMBL; MN908947; QHD43418.1; -; Genomic_RNA.
DR PDB; 7K3G; NMR; -; A/B/C/D/E=8-38.
DR PDB; 7M4R; EM; 3.65 A; C=58-75.
DR PDB; 7NTK; X-ray; 1.90 A; C/E/G/H=68-75.
DR PDB; 7QCR; X-ray; 2.28 A; C/D=64-75.
DR PDB; 7QCS; X-ray; 2.80 A; C/D=64-75.
DR PDB; 7QCT; X-ray; 3.20 A; C/D=64-75.
DR PDB; 7TUQ; X-ray; 2.68 A; C=60-68.
DR PDB; 7TV0; X-ray; 2.60 A; E/G=53-64.
DR PDB; 8SUZ; NMR; -; A/B/C/D/E=8-38.
DR PDB; 8U1T; NMR; -; A/B=12-37.
DR PDBsum; 7K3G; -.
DR PDBsum; 7M4R; -.
DR PDBsum; 7NTK; -.
DR PDBsum; 7QCR; -.
DR PDBsum; 7QCS; -.
DR PDBsum; 7QCT; -.
DR PDBsum; 7TUQ; -.
DR PDBsum; 7TV0; -.
DR PDBsum; 8SUZ; -.
DR PDBsum; 8U1T; -.
DR BMRB; P0DTC4; -.
DR EMDB; EMD-23665; -.
DR SMR; P0DTC4; -.
DR BioGRID; 4383845; 1084.
DR IntAct; P0DTC4; 70.
DR MINT; P0DTC4; -.
DR TCDB; 1.A.65.1.7; the coronavirus viroporin e protein (viroporin e) family.
DR ABCD; P0DTC4; 9 sequenced antibodies.
DR AGR; RefSeq:YP_009724392; -.
DR Reactome; R-HSA-191650; Regulation of gap junction activity.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR Reactome; R-HSA-9694322; Virion Assembly and Release.
DR Reactome; R-HSA-9694493; Maturation of protein E.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-9694635; Translation of Structural Proteins.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-9705677; SARS-CoV-2 targets PDZ proteins in cell-cell junction.
DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion.
DR PRO; PR:P0DTC4; -.
DR Proteomes; UP000464024; Genome.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:UniProt.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005216; F:monoatomic ion channel activity; IDA:UniProt.
DR GO; GO:0039660; F:structural constituent of virion; IDA:UniProt.
DR GO; GO:0039709; P:cytoplasmic capsid assembly; IDA:UniProt.
DR GO; GO:0046760; P:viral budding from Golgi membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:InterPro.
DR CDD; cd21536; SARS-CoV-2_E; 1.
DR Gene3D; 6.10.250.1810; -; 1.
DR HAMAP; MF_04204; BETA_CORONA_E; 1.
DR InterPro; IPR043506; E_protein_bCoV.
DR InterPro; IPR003873; E_protein_CoV.
DR InterPro; IPR044377; E_SARS-CoV-2.
DR Pfam; PF02723; CoV_E; 1.
DR PROSITE; PS51926; COV_E; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Host Golgi apparatus; Host membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..75
FT /note="Envelope small membrane protein"
FT /id="PRO_0000449651"
FT TOPO_DOM 1..13
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000305|PubMed:32898469"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000269|PubMed:33177698, ECO:0000305|PubMed:32898469"
FT TOPO_DOM 35..75
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04204,
FT ECO:0000305|PubMed:32898469"
FT REGION 61..75
FT /note="Disordered"
FT /evidence="ECO:0000305|PubMed:35108439"
FT MOTIF 72..75
FT /note="PDZ-binding; required for interaction with human
FT MPP5"
FT /evidence="ECO:0000250|UniProtKB:P59637"
FT VARIANT 9
FT /note="T -> I (in strain: Omicron/BA.1, Omicron/BA.2,
FT Omicron/BA.2.12.1, Omicron/BA.2.75, Omicron/BA.4, Omicron/
FT BA.5, Omicron/BQ.1.1, Omicron/XBB.1.5)"
FT /evidence="ECO:0000305"
FT VARIANT 11
FT /note="T -> A (in strain: Omicron/XBB.1.5, Omicron/EG.5.1)"
FT /evidence="ECO:0000305"
FT VARIANT 21
FT /note="L -> F (in strain: Eta/B.1.525)"
FT /evidence="ECO:0000305"
FT VARIANT 71
FT /note="P -> L (in strain: Beta/B.1.351)"
FT /evidence="ECO:0000305"
FT MUTAGEN 71
FT /note="P->L: Complete loss of interaction with host PARD3
FT and MLLT4. Partial loss of interaction with host ZO1."
FT /evidence="ECO:0000269|PubMed:35283834"
FT HELIX 11..18
FT /evidence="ECO:0007829|PDB:7K3G"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:7K3G"
FT HELIX 22..36
FT /evidence="ECO:0007829|PDB:7K3G"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:7TV0"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:7QCT"
SQ SEQUENCE 75 AA; 8365 MW; 5C431BD2AA1B6B99 CRC64;
MYSFVSEETG TLIVNSVLLF LAFVVFLLVT LAILTALRLC AYCCNIVNVS LVKPSFYVYS
RVKNLNSSRV PDLLV
//