ID Q20QC9_9INFA Unreviewed; 97 AA. AC Q20QC9; DT 18-APR-2006, integrated into UniProtKB/TrEMBL. DT 18-APR-2006, sequence version 1. DT 22-FEB-2023, entry version 73. DE RecName: Full=Matrix protein 2 {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|RuleBase:RU361247}; DE AltName: Full=Proton channel protein M2 {ECO:0000256|HAMAP-Rule:MF_04069}; GN Name=M2 {ECO:0000313|EMBL:ABB88140.1}; GN Synonyms=M {ECO:0000256|HAMAP-Rule:MF_04069}; OS Influenza A virus (A/wedge-tailed shearwater/Western OS Australia/2576/1979(H15N9)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=352560 {ECO:0000313|EMBL:ABB88140.1, ECO:0000313|Proteomes:UP000103171}; RN [1] {ECO:0000313|EMBL:ABB88140.1, ECO:0000313|Proteomes:UP000103171} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=A/wedge-tailed shearwater/Western Australia/2576/1979 RC {ECO:0000313|EMBL:ABB88140.1}; RX PubMed=16439620; DOI=10.1126/science.1121586; RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., Finkelstein D.B., RA Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., Webster R.G., Hoffmann E., RA Krauss S., Zheng J., Zhang Z., Naeve C.W.; RT "Large-scale sequence analysis of avian influenza isolates."; RL Science 311:1576-1580(2006). 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:0000256|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. {ECO:0000256|RuleBase:RU361247}. CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers held CC together by non-covalent interactions. May interact with matrix protein CC 1. {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|RuleBase:RU361247}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000256|HAMAP- CC Rule:MF_04069}. Host apical cell membrane {ECO:0000256|HAMAP- CC Rule:MF_04069}; Single-pass type III membrane protein CC {ECO:0000256|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:0000256|HAMAP-Rule:MF_04069}. CC -!- DOMAIN: Cytoplasmic tail plays an important role in virion assembly and CC morphogenesis. {ECO:0000256|HAMAP-Rule:MF_04069, CC ECO:0000256|RuleBase:RU361247}. CC -!- MISCELLANEOUS: When the channel is activated, one or more imidazole CC moities of His-37 probably become bi-protonated. {ECO:0000256|HAMAP- CC Rule:MF_04069}. CC -!- SIMILARITY: Belongs to the influenza viruses matrix protein M2 family. CC {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|RuleBase:RU361247}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_04069}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CY005406; ABB88140.1; -; Other_RNA. DR SMR; Q20QC9; -. DR Proteomes; UP000103171; Genome. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. 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 Gene3D; 6.10.250.1640; -; 1. DR HAMAP; MF_04069; INFV_M2; 1. DR InterPro; IPR002089; Flu_M2. DR Pfam; PF00599; Flu_M2; 1. PE 3: Inferred from homology; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04069}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247}; KW Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04069}; KW Hydrogen ion transport {ECO:0000256|ARBA:ARBA00022781, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Inhibition of host autophagy by virus {ECO:0000256|HAMAP-Rule:MF_04069}; KW Ion channel {ECO:0000256|ARBA:ARBA00023303, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Ion transport {ECO:0000256|ARBA:ARBA00023065, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|RuleBase:RU361247}; KW Palmitate {ECO:0000256|ARBA:ARBA00023139, ECO:0000256|HAMAP-Rule:MF_04069}; KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Signal-anchor {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247}; KW Transmembrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247}; KW Transport {ECO:0000256|ARBA:ARBA00022448, ECO:0000256|HAMAP-Rule:MF_04069}; KW Viral ion channel {ECO:0000256|ARBA:ARBA00023039, ECO:0000256|HAMAP- KW Rule:MF_04069}; KW Virion {ECO:0000256|ARBA:ARBA00022844, ECO:0000256|HAMAP-Rule:MF_04069}. FT TOPO_DOM 1..22 FT /note="Virion surface" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT TRANSMEM 26..48 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT TOPO_DOM 44..97 FT /note="Intravirion" FT /evidence="ECO:0000256|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:0000256|HAMAP-Rule:MF_04069" FT SITE 41 FT /note="Seems to be involved in pH gating" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT MOD_RES 64 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT MOD_RES 82 FT /note="Phosphoserine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT LIPID 50 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT DISULFID 17 FT /note="Interchain (with Cys-17)" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" FT DISULFID 19 FT /note="Interchain (with Cys-19)" FT /evidence="ECO:0000256|HAMAP-Rule:MF_04069" SQ SEQUENCE 97 AA; 11158 MW; FF12EFFCB4370398 CRC64; MSLLTEVETP TRNGWECKCS DSSDPLVIAA SIIGILHLIL WILDRLFFKC IYRRLKYGLK RGPSTEGVPE SMREEYRQEQ QSAVDVDDGH FVNIELE //