ID   M2_I80A2                Reviewed;          97 AA.
AC   Q2VC90;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2006, sequence version 1.
DT   02-JUN-2021, entry version 66.
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/Seal/Massachusetts/1/1980 H7N7).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=384493;
OH   NCBI_TaxID=8782; Aves.
OH   NCBI_TaxID=9796; Equus caballus (Horse).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9709; Phocidae (true seals).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=SC35M mouse-adapted;
RX   PubMed=16339318; DOI=10.1073/pnas.0507415102;
RA   Gabriel G., Dauber B., Wolff T., Planz O., Klenk H.D., Stech J.;
RT   "The viral polymerase mediates adaptation of an avian influenza virus to a
RT   mammalian host.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:18590-18595(2005).
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   -!- 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=Q2VC90-1; Sequence=Displayed;
CC       Name=M1;
CC         IsoId=Q2VC89-1; 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   -!- MISCELLANEOUS: SC35 was derived from A/Seal/Massachussetts/1/80 (H7N7)
CC       by serial passages in chicken embryo cells, thereby acquiring a
CC       multibasic cleavage site in its hemagglutinin (HA) and becoming 100%
CC       lethal for chickens. SC35 was then passaged 11 times in mouse lung,
CC       yielding the mouse-adapted variant SC35M.
CC   -!- SIMILARITY: Belongs to the influenza viruses matrix protein M2 family.
CC       {ECO:0000255|HAMAP-Rule:MF_04069}.
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DR   EMBL; DQ266100; ABB90274.1; -; Genomic_RNA.
DR   SMR; Q2VC90; -.
DR   Proteomes; UP000008576; Genome.
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   3: Inferred from homology;
KW   Alternative splicing; Disulfide bond; Host cell membrane; Host membrane;
KW   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_0000326369"
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..84
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        67..84
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   DISULFID        17
FT                   /note="Interchain (with C-17)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
FT   DISULFID        19
FT                   /note="Interchain (with C-19)"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04069"
SQ   SEQUENCE   97 AA;  11181 MW;  388722E068E1CD2B CRC64;
     MSLLTEVETP IRNGWECKCS DSSDPLVIAA SIIGILHLIL WILDHLFFKC IYRRLKYGLK
     RGPSTEGVPE SMREEYRQEQ QSAVDVDDSH FVNIELE