M2_I34A0
ID M2_I34A0 Reviewed; 97 AA.
AC P03492; Q76V61;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 02-JUN-2021, entry version 115.
DE RecName: Full=Matrix protein 2 {ECO:0000255|HAMAP-Rule:MF_04069};
DE AltName: Full=Proton channel protein M2 {ECO:0000255|HAMAP-Rule:MF_04069};
GN Name=M {ECO:0000255|HAMAP-Rule:MF_04069};
OS Influenza A virus (strain A/Fowl plague virus/Rostock/8/1934 H7N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=392810;
OH NCBI_TaxID=8782; Aves.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6292344; DOI=10.1099/0022-1317-58-1-211;
RA McCauley J.W., Mahy B.W.J., Inglis S.C.;
RT "Nucleotide sequence of fowl plague virus RNA segment 7.";
RL J. Gen. Virol. 58:211-215(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2053297; DOI=10.1016/0042-6822(91)90118-u;
RA Schultz U., Fitch W.M., Ludwig S., Mandler J., Scholtissek C.;
RT "Evolution of pig influenza viruses.";
RL Virology 183:61-73(1991).
RN [3]
RP PALMITOYLATION AT CYS-50.
RX PubMed=2219738; DOI=10.1016/0042-6822(90)90272-s;
RA Sugrue R.J., Belshe R.B., Hay A.J.;
RT "Palmitoylation of the influenza A virus M2 protein.";
RL Virology 179:51-56(1990).
RN [4]
RP FUNCTION, AND DISULFIDE BONDS.
RX PubMed=1989386; DOI=10.1016/0042-6822(91)90075-m;
RA Sugrue R.J., Hay A.J.;
RT "Structural characteristics of the M2 protein of influenza A viruses:
RT evidence that it forms a tetrameric channel.";
RL Virology 180:617-624(1991).
RN [5]
RP REVIEW.
RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012;
RA Nayak D.P., Hui E.K., Barman S.;
RT "Assembly and budding of influenza virus.";
RL Virus Res. 106:147-165(2004).
RN [6]
RP REVIEW.
RX PubMed=12972146; DOI=10.1016/s0014-5793(03)00778-6;
RA Lear J.D.;
RT "Proton conduction through the M2 protein of the influenza A virus; a
RT quantitative, mechanistic analysis of experimental data.";
RL FEBS Lett. 552:17-22(2003).
RN [7]
RP REVIEW.
RX PubMed=12972147; DOI=10.1016/s0014-5793(03)00779-8;
RA Wu Y., Voth G.A.;
RT "Computational studies of proton transport through the M2 channel.";
RL FEBS Lett. 552:23-27(2003).
CC -!- FUNCTION: Forms a proton-selective ion channel that is necessary for
CC the efficient release of the viral genome during virus entry. After
CC attaching to the cell surface, the virion enters the cell by
CC endocytosis. Acidification of the endosome triggers M2 ion channel
CC activity. The influx of protons into virion interior is believed to
CC disrupt interactions between the viral ribonucleoprotein (RNP), matrix
CC protein 1 (M1), and lipid bilayers, thereby freeing the viral genome
CC from interaction with viral proteins and enabling RNA segments to
CC migrate to the host cell nucleus, where influenza virus RNA
CC transcription and replication occur. Also plays a role in viral
CC proteins secretory pathway. Elevates the intravesicular pH of normally
CC acidic compartments, such as trans-Golgi network, preventing newly
CC formed hemagglutinin from premature switching to the fusion-active
CC conformation. {ECO:0000255|HAMAP-Rule:MF_04069,
CC ECO:0000269|PubMed:1989386}.
CC -!- ACTIVITY REGULATION: The M2 protein from most influenza A strains is
CC inhibited by amantadine and rimantadine, resulting in viral uncoating
CC incapacity. Emergence of amantadine-resistant variants is usually
CC rapid.
CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers held
CC together by non-covalent interactions. May interact with matrix protein
CC 1. {ECO:0000255|HAMAP-Rule:MF_04069}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04069}. Host apical cell membrane {ECO:0000255|HAMAP-
CC Rule:MF_04069}; Single-pass type III membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_04069}. Note=Abundantly expressed at the
CC apical plasma membrane in infected polarized epithelial cells, in close
CC proximity to budding and assembled virions. Minor component of virions
CC (only 16-20 molecules/virion). {ECO:0000255|HAMAP-Rule:MF_04069}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Only the first 9 residues are shared by the 2 isoforms.;
CC Name=M2;
CC IsoId=P03492-1; Sequence=Displayed;
CC Name=M1;
CC IsoId=P03488-1; Sequence=External;
CC -!- DOMAIN: Cytoplasmic tail plays an important role in virion assembly and
CC morphogenesis. {ECO:0000255|HAMAP-Rule:MF_04069}.
CC -!- MISCELLANEOUS: When the channel is activated, one or more imidazole
CC moieties of His-37 probably become bi-protonated. {ECO:0000255|HAMAP-
CC Rule:MF_04069}.
CC -!- SIMILARITY: Belongs to the influenza viruses matrix protein M2 family.
CC {ECO:0000255|HAMAP-Rule:MF_04069}.
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DR EMBL; X05905; CAA29335.1; -; Genomic_RNA.
DR EMBL; M55474; AAA43257.1; -; Genomic_RNA.
DR EMBL; M55475; AAA43259.1; -; Genomic_RNA.
DR PIR; A04085; MFIV2F.
DR SMR; P03492; -.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0044385; C:integral to membrane of host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-UniRule.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IEA:UniProtKB-UniRule.
DR GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-UniRule.
DR GO; GO:0039521; P:suppression by virus of host autophagy; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04069; INFV_M2; 1.
DR InterPro; IPR002089; Flu_M2.
DR Pfam; PF00599; Flu_M2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Host cell membrane;
KW Host membrane; Host-virus interaction; Hydrogen ion transport;
KW Inhibition of host autophagy by virus; Ion channel; Ion transport;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Signal-anchor;
KW Transmembrane; Transmembrane helix; Transport; Viral ion channel; Virion.
FT CHAIN 1..97
FT /note="Matrix protein 2"
FT /id="PRO_0000078881"
FT TOPO_DOM 1..22
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT TRANSMEM 23..43
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT TOPO_DOM 44..97
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT REGION 60..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 67..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 37
FT /note="Essential for channel activity, possibly by being
FT protonated during channel activation, and by forming the
FT channel gate and the selective filter"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT SITE 41
FT /note="Seems to be involved in pH gating"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT MOD_RES 64
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT MOD_RES 82
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT LIPID 50
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069,
FT ECO:0000269|PubMed:2219738"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT DISULFID 17
FT /note="Interchain (with C-17)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069,
FT ECO:0000269|PubMed:1989386"
FT DISULFID 19
FT /note="Interchain (with C-19)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04069,
FT ECO:0000269|PubMed:1989386"
SQ SEQUENCE 97 AA; 11226 MW; E6885CCAF3D09941 CRC64;
MSLLTEVETP TRNGWECRCN DSSDPLIIAA SIIGILHLIL WILNRLFFKC IYRRLKYGLK
RGPSTEGVPE SMREEYRQEQ QSAVDVDDGH FVNIELE
