ID A0A2P0VFC5_9INFA Unreviewed; 97 AA. AC A0A2P0VFC5; DT 23-MAY-2018, integrated into UniProtKB/TrEMBL. DT 23-MAY-2018, sequence version 1. DT 05-DEC-2018, entry version 6. DE RecName: Full=Matrix protein 2 {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040803}; DE AltName: Full=Proton channel protein M2 {ECO:0000256|HAMAP-Rule:MF_04069}; GN Name=M2 {ECO:0000313|EMBL:ASW34431.1}; GN Synonyms=M {ECO:0000256|HAMAP-Rule:MF_04069}; OS Influenza A virus (A/chicken/Jordan/70/2004(H9N2)). OC Viruses; ssRNA viruses; ssRNA negative-strand viruses; OC Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=2027238 {ECO:0000313|EMBL:ASW34431.1}; RN [1] {ECO:0000313|EMBL:ASW34431.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/chicken/Jordan/70/2004 {ECO:0000313|EMBL:ASW34431.1}; RX PubMed=29524835; DOI=.1016/j.virol.2018.02.016; RA Chrzastek K., Lee D.H., Gharaibeh S., Zsak A., Kapczynski D.R.; RT "Characterization of H9N2 avian influenza viruses from the Middle East RT demonstrates heterogeneity at amino acid position 226 in the RT hemagglutinin and potential for transmission to mammals."; RL Virology 518:195-201(2018). CC -!- FUNCTION: Forms a proton-selective ion channel that is necessary CC for the efficient release of the viral genome during virus entry. CC After 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 CC to disrupt interactions between the viral ribonucleoprotein (RNP), CC matrix protein 1 (M1), and lipid bilayers, thereby freeing the CC viral genome from interaction with viral proteins and enabling RNA CC segments to migrate to the host cell nucleus, where influenza CC virus RNA transcription and replication occur. Also plays a role CC in viral proteins secretory pathway. Elevates the intravesicular CC pH of normally acidic compartments, such as trans-Golgi network, CC preventing newly formed hemagglutinin from premature switching to CC the fusion-active conformation. {ECO:0000256|HAMAP-Rule:MF_04069, CC ECO:0000256|SAAS:SAAS01040783}. CC -!- ACTIVITY REGULATION: The M2 protein from most influenza A strains CC is inhibited by amantadine and rimantadine, resulting in viral CC uncoating incapacity. Emergence of amantadine-resistant variants CC is usually rapid. {ECO:0000256|RuleBase:RU361247, CC ECO:0000256|SAAS:SAAS01073786}. CC -!- SUBUNIT: Homotetramer; composed of two disulfide-linked dimers CC held together by non-covalent interactions. May interact with CC matrix protein 1. {ECO:0000256|HAMAP-Rule:MF_04069, CC ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040791}. CC -!- SUBCELLULAR LOCATION: Host apical cell membrane CC {ECO:0000256|HAMAP-Rule:MF_04069, ECO:0000256|SAAS:SAAS01040793}; CC Single-pass type III membrane protein {ECO:0000256|HAMAP- CC Rule:MF_04069, ECO:0000256|SAAS:SAAS01040793}. Virion membrane CC {ECO:0000256|HAMAP-Rule:MF_04069}. Note=Abundantly expressed at CC the apical plasma membrane in infected polarized epithelial cells, CC in close proximity to budding and assembled virions. Minor CC component of virions (only 16-20 molecules/virion). CC {ECO:0000256|HAMAP-Rule:MF_04069}. CC -!- DOMAIN: Cytoplasmic tail plays an important role in virion CC assembly and morphogenesis. {ECO:0000256|HAMAP-Rule:MF_04069, CC ECO:0000256|RuleBase:RU361247}. CC -!- MISCELLANEOUS: When the channel is activated, one or more CC imidazole moities of His-37 probably become bi-protonated. CC {ECO:0000256|HAMAP-Rule:MF_04069}. CC -!- SIMILARITY: Belongs to the influenza viruses matrix protein M2 CC family. {ECO:0000256|HAMAP-Rule:MF_04069, CC ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040773}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation CC of 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; MF673314; ASW34431.1; -; Viral_cRNA. 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-UniRule. 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. DR ProDom; PD001031; Flu_M2; 1. PE 3: Inferred from homology; KW Disulfide bond {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|SAAS:SAAS01040795}; KW Host cell membrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040804}; KW Host membrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040762}; KW Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|SAAS:SAAS01040805}; KW Hydrogen ion transport {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040774}; KW Inhibition of host autophagy by virus {ECO:0000256|HAMAP- KW Rule:MF_04069, ECO:0000256|SAAS:SAAS01040755}; KW Ion channel {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040776}; KW Ion transport {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040807}; KW Lipoprotein {ECO:0000256|HAMAP-Rule:MF_04069}; KW Membrane {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040794, KW ECO:0000256|SAM:Phobius}; KW Palmitate {ECO:0000256|HAMAP-Rule:MF_04069}; KW Phosphoprotein {ECO:0000256|HAMAP-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, ECO:0000256|SAAS:SAAS01040784, KW ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040757, KW ECO:0000256|SAM:Phobius}; KW Transport {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040788}; KW Viral ion channel {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|SAAS:SAAS01040754}; KW Virion {ECO:0000256|HAMAP-Rule:MF_04069, KW ECO:0000256|RuleBase:RU361247, ECO:0000256|SAAS:SAAS01040766}. FT TOPO_DOM 1 22 Virion surface. {ECO:0000256|HAMAP-Rule: FT MF_04069}. FT TRANSMEM 26 48 Helical. {ECO:0000256|SAM:Phobius}. FT TOPO_DOM 44 97 Intravirion. {ECO:0000256|HAMAP-Rule: FT MF_04069}. FT SITE 37 37 Essential for channel activity, possibly FT by being protonated during channel FT activation, and by forming the channel FT gate and the selective filter. FT {ECO:0000256|HAMAP-Rule:MF_04069}. FT SITE 41 41 Seems to be involved in pH gating. FT {ECO:0000256|HAMAP-Rule:MF_04069}. FT MOD_RES 64 64 Phosphoserine; by host. FT {ECO:0000256|HAMAP-Rule:MF_04069}. FT LIPID 50 50 S-palmitoyl cysteine; by host. FT {ECO:0000256|HAMAP-Rule:MF_04069}. FT DISULFID 17 17 Interchain (with Cys-17). FT {ECO:0000256|HAMAP-Rule:MF_04069}. FT DISULFID 19 19 Interchain (with Cys-19). FT {ECO:0000256|HAMAP-Rule:MF_04069}. SQ SEQUENCE 97 AA; 11092 MW; 62A6D2FF6D732856 CRC64; MSLLTEVETL TRNAWGCRCS DSSDPLVVAA SIIGILHLIL WILDRLFFKC IYRRFKYGLK GGPSTEGVPE SMREEYRQEQ QNAVDVDDGH FVNIELE //