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
//