ID VME1_SARS2 Reviewed; 222 AA.
AC P0DTC5;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 1.
DT 09-APR-2025, entry version 27.
DE RecName: Full=Membrane protein {ECO:0000255|HAMAP-Rule:MF_04202};
DE Short=M;
DE AltName: Full=E1 glycoprotein {ECO:0000255|HAMAP-Rule:MF_04202};
DE AltName: Full=Matrix glycoprotein {ECO:0000255|HAMAP-Rule:MF_04202};
DE AltName: Full=Membrane glycoprotein {ECO:0000255|HAMAP-Rule:MF_04202};
GN ORFNames=M;
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 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).
RN [3]
RP INTERACTION WITH S PROTEIN, AND 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 [4]
RP GLYCOSYLATION AT ASN-5, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=38666819; DOI=10.3390/biology13040207;
RA Schwarze M., Volke D., Rojas Echeverri J.C., Schick R., Lakowa N.,
RA Gruenewald T., Wolf J., Borte S., Scholz M., Krizsan A., Hoffmann R.;
RT "Influence of Mutations and N-Glycosylation Sites in the Receptor-Binding
RT Domain (RBD) and the Membrane Protein of SARS-CoV-2 Variants of Concern on
RT Antibody Binding in ELISA.";
RL Biology 13:1-21(2024).
RN [5] {ECO:0007744|PDB:8CTK}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.52 ANGSTROMS), TOPOLOGY, AND
RP GLYCOSYLATION AT ASN-5.
RX PubMed=36264056; DOI=10.7554/elife.81702;
RA Dolan K.A., Dutta M., Kern D.M., Kotecha A., Voth G.A., Brohawn S.G.;
RT "Structure of SARS-CoV-2 M protein in lipid nanodiscs.";
RL Elife 11:1-16(2022).
RN [6] {ECO:0007744|PDB:7VGR, ECO:0007744|PDB:7VGS}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS), SUBUNIT, MUTAGENESIS OF
RP 42-ARG--ARG-44, AND GLYCOSYLATION AT ASN-5.
RX PubMed=35931673; DOI=10.1038/s41467-022-32019-3;
RA Zhang Z., Nomura N., Muramoto Y., Ekimoto T., Uemura T., Liu K., Yui M.,
RA Kono N., Aoki J., Ikeguchi M., Noda T., Iwata S., Ohto U., Shimizu T.;
RT "Structure of SARS-CoV-2 membrane protein essential for virus assembly.";
RL Nat. Commun. 13:1-12(2022).
CC -!- FUNCTION: Component of the viral envelope that plays a central role in
CC virus morphogenesis and assembly via its interactions with other viral
CC proteins (By similarity). Regulates the localization of S protein at
CC cis-Golgi, the place of virus budding (PubMed:33229438). May act by
CC binding cytoplasmic c-terminus of S (PubMed:33229438).
CC {ECO:0000255|HAMAP-Rule:MF_04202, ECO:0000255|PROSITE-ProRule:PRU01275,
CC ECO:0000269|PubMed:33229438}.
CC -!- SUBUNIT: Homomultimer (PubMed:35931673). Interacts with envelope E
CC protein in the budding compartment of the host cell, which is located
CC between endoplasmic reticulum and the Golgi complex (By similarity).
CC Forms a complex with S proteins (PubMed:33229438). Interacts with
CC nucleocapsid N protein. This interaction probably participates in RNA
CC packaging into the virus (PubMed:35931673). Interacts with the
CC accessory proteins 3a and 7a (By similarity).
CC {ECO:0000250|UniProtKB:P59596, ECO:0000255|HAMAP-Rule:MF_04202,
CC ECO:0000269|PubMed:33229438, ECO:0000269|PubMed:35931673}.
CC -!- INTERACTION:
CC P0DTC5; P0DTD8: 7b; NbExp=4; IntAct=EBI-25475853, EBI-25475914;
CC P0DTC5; P0DTC4: E; NbExp=5; IntAct=EBI-25475853, EBI-25475850;
CC P0DTC5; P0DTC5: M; NbExp=4; IntAct=EBI-25475853, EBI-25475853;
CC P0DTC5; P0DTC9: N; NbExp=6; IntAct=EBI-25475853, EBI-25475856;
CC P0DTC5; Q9BYX4: IFIH1; Xeno; NbExp=3; IntAct=EBI-25475853, EBI-6115771;
CC P0DTC5; Q7Z434: MAVS; Xeno; NbExp=11; IntAct=EBI-25475853, EBI-995373;
CC P0DTC5; O00487: PSMD14; Xeno; NbExp=2; IntAct=EBI-25475853, EBI-722193;
CC P0DTC5; Q9UHD2: TBK1; Xeno; NbExp=10; IntAct=EBI-25475853, EBI-356402;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04202}; Multi-pass membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04202}. Host Golgi apparatus membrane {ECO:0000255|HAMAP-
CC Rule:MF_04202, ECO:0000269|PubMed:33060197}; Multi-pass membrane
CC protein {ECO:0000255|HAMAP-Rule:MF_04202}. Host membrane
CC {ECO:0000269|PubMed:33060197}; Multi-pass membrane protein.
CC Note=Largely embedded in the lipid bilayer. {ECO:0000255|HAMAP-
CC Rule:MF_04202}.
CC -!- PTM: Glycosylated at N-terminus by host. {ECO:0000269|PubMed:35931673,
CC ECO:0000269|PubMed:36264056, ECO:0000269|PubMed:38666819}.
CC -!- POLYMORPHISM: Variant Delta/B.1.617.2 belongs to a lineage first
CC isolated in India (October 2020) and is also called G/478K.V1. It has
CC an estimated 97% increase of transmissibility. {ECO:0000305}.
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 M protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04202}.
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DR EMBL; MN908947; QHD43419.1; -; Genomic_RNA.
DR RefSeq; YP_009724393.1; NC_045512.2.
DR PDB; 7VGR; EM; 2.70 A; A/B=1-222.
DR PDB; 7VGS; EM; 2.80 A; A/B=1-222.
DR PDB; 8CME; X-ray; 2.26 A; C/F/I=176-190.
DR PDB; 8CTK; EM; 3.52 A; A/B=1-222.
DR PDB; 9BF9; X-ray; 3.40 A; G=177-189.
DR PDB; 9CTU; EM; 3.03 A; A/B=1-222.
DR PDB; 9CTW; EM; 3.01 A; A/B=1-222.
DR PDBsum; 7VGR; -.
DR PDBsum; 7VGS; -.
DR PDBsum; 8CME; -.
DR PDBsum; 8CTK; -.
DR PDBsum; 9BF9; -.
DR PDBsum; 9CTU; -.
DR PDBsum; 9CTW; -.
DR EMDB; EMD-26993; -.
DR EMDB; EMD-31977; -.
DR EMDB; EMD-31978; -.
DR EMDB; EMD-45919; -.
DR EMDB; EMD-45921; -.
DR SMR; P0DTC5; -.
DR BioGRID; 4383846; 2341.
DR IntAct; P0DTC5; 270.
DR MINT; P0DTC5; -.
DR TCDB; 1.A.117.1.2; the coronavirus membrane matrix-protein (m-protein) family.
DR GlyGen; P0DTC5; 1 site.
DR iPTMnet; P0DTC5; -.
DR ABCD; P0DTC5; 10 sequenced antibodies.
DR DNASU; 43740571; -.
DR GeneID; 43740571; -.
DR KEGG; vg:43740571; -.
DR AGR; RefSeq:YP_009724393; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-HSA-9694322; Virion Assembly and Release.
DR Reactome; R-HSA-9694594; Maturation of protein M.
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-9733458; Induction of Cell-Cell Fusion.
DR Reactome; R-HSA-9754560; SARS-CoV-2 modulates autophagy.
DR Reactome; R-HSA-9755779; SARS-CoV-2 targets host intracellular signalling and regulatory pathways.
DR SIGNOR; P0DTC5; -.
DR PRO; PR:P0DTC5; -.
DR Proteomes; UP000464024; Genome.
DR GO; GO:0044178; C:host cell Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0019031; C:viral envelope; 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:0140311; F:protein sequestering activity; IDA:UniProt.
DR GO; GO:0039660; F:structural constituent of virion; IEA:UniProtKB-UniRule.
DR GO; GO:0039545; P:symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IDA:UniProt.
DR CDD; cd21569; SARS-like-CoV_M; 1.
DR HAMAP; MF_04202; BETA_CORONA_M; 1.
DR InterPro; IPR002574; M_CoV.
DR InterPro; IPR044361; M_SARS-like-CoV.
DR Pfam; PF01635; CoV_M; 1.
DR PROSITE; PS51927; COV_M; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Host Golgi apparatus; Host membrane;
KW Host-virus interaction; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Viral envelope protein; Viral immunoevasion;
KW Viral matrix protein; Virion.
FT CHAIN 1..222
FT /note="Membrane protein"
FT /id="PRO_0000449652"
FT TOPO_DOM 2..16
FT /note="Virion surface"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TRANSMEM 17..36
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TOPO_DOM 37..44
FT /note="Intravirion"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TRANSMEM 45..70
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TOPO_DOM 71..75
FT /note="Virion surface"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TRANSMEM 76..105
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:36264056"
FT TOPO_DOM 106..222
FT /note="Intravirion"
FT /evidence="ECO:0000269|PubMed:36264056"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:35931673,
FT ECO:0000269|PubMed:36264056, ECO:0000269|PubMed:38666819"
FT VARIANT 3
FT /note="D -> G (in strain: Omicron/BA.1)"
FT /evidence="ECO:0000305"
FT VARIANT 3
FT /note="D -> N (in strain: Omicron/BA.5, Omicron/BQ.1.1)"
FT /evidence="ECO:0000305"
FT VARIANT 19
FT /note="Q -> E (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, Omicron/EG.5.1)"
FT /evidence="ECO:0000305"
FT VARIANT 63
FT /note="A -> T (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, Omicron/EG.5.1)"
FT /evidence="ECO:0000305"
FT VARIANT 82
FT /note="I -> T (in strain: Eta/B.1.525 and Delta/B.1.617.2)"
FT /evidence="ECO:0000305"
FT MUTAGEN 42..44
FT /note="RNR->ANA: Partial loss of N-RNA binding."
FT /evidence="ECO:0000269|PubMed:35931673"
FT HELIX 11..36
FT /evidence="ECO:0007829|PDB:7VGR"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:7VGR"
FT HELIX 44..70
FT /evidence="ECO:0007829|PDB:7VGR"
FT HELIX 77..105
FT /evidence="ECO:0007829|PDB:7VGR"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 117..135
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:7VGR"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:7VGR"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:7VGR"
SQ SEQUENCE 222 AA; 25147 MW; ED44D84C3BB9A6DB CRC64;
MADSNGTITV EELKKLLEQW NLVIGFLFLT WICLLQFAYA NRNRFLYIIK LIFLWLLWPV
TLACFVLAAV YRINWITGGI AIAMACLVGL MWLSYFIASF RLFARTRSMW SFNPETNILL
NVPLHGTILT RPLLESELVI GAVILRGHLR IAGHHLGRCD IKDLPKEITV ATSRTLSYYK
LGASQRVAGD SGFAAYSRYR IGNYKLNTDH SSSSDNIALL VQ
//