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A4GCK9

- M2_I43A0

UniProt

A4GCK9 - M2_I43A0

Protein

Matrix protein 2

Gene

M2

Organism
Influenza A virus (strain A/USA:Iowa/1943 H1N1)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi
  1. Functioni

    Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation By similarity.By similarity

    Enzyme regulationi

    The M2 protein from most influenza A strains is inhibited by amantadine and rimantadine, resulting in viral uncoating incapacity. Emergence of amantadine-resistant variants is usually rapid.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei37 – 371Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filterBy similarity
    Sitei41 – 411Seems to be involved in pH gatingBy similarity

    GO - Molecular functioni

    1. hydrogen ion transmembrane transporter activity Source: InterPro

    GO - Biological processi

    1. suppression by virus of host autophagy Source: UniProtKB-KW

    Keywords - Molecular functioni

    Ion channel

    Keywords - Biological processi

    Host-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Matrix protein 2
    Gene namesi
    Name:M2
    OrganismiInfluenza A virus (strain A/USA:Iowa/1943 H1N1)
    Taxonomic identifieri425563 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000008432: Genome

    Subcellular locationi

    Virion membrane By similarity. Host apical cell membrane By similarity; Single-pass type III membrane protein By similarity
    Note: Abundantly expressed at the apical plasma membrane in infected polarized epithelial cells, in close proximity to budding and assembled virions. Minor component of virions (only 16-20 molecules/virion) By similarity.By similarity

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host cell membrane, Host membrane, Membrane, Virion

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 9797Matrix protein 2PRO_0000372921Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi17 – 17Interchain (with C-17)By similarity
    Disulfide bondi19 – 19Interchain (with C-19)By similarity
    Glycosylationi20 – 201N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi50 – 501S-palmitoyl cysteine; by hostBy similarity
    Modified residuei64 – 641Phosphoserine; by hostBy similarity
    Modified residuei82 – 821Phosphoserine; by hostBy similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

    Interactioni

    Subunit structurei

    Homotetramer; composed of two disulfide-linked dimers held together by non-covalent interactions. May interact with matrix protein 1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliA4GCK9.
    SMRiA4GCK9. Positions 23-60.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2222Virion surfaceSequence AnalysisAdd
    BLAST
    Topological domaini44 – 9754IntravirionSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei23 – 4321Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domaini

    Cytoplasmic tail plays an important role in virion assembly and morphogenesis.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Family and domain databases

    InterProiIPR002089. Flu_M2.
    [Graphical view]
    PfamiPF00599. Flu_M2. 1 hit.
    [Graphical view]
    ProDomiPD001031. Flu_M2. 1 hit.
    [Graphical view] [Entries sharing at least one domain]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Note: Only the first 9 residues are shared by the 2 isoforms.

    Isoform M2 (identifier: A4GCK9-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSLLTEVETP IRNEWGCRCN DSSDPLVVAA SIIGILHLIL WILDRLFFKC   50
    IYRLFKHGLK RGPSTEGVPE SMREEYRKEQ QSAVDADDSH FVNIELE 97
    Length:97
    Mass (Da):11,178
    Last modified:April 17, 2007 - v1
    Checksum:i3CD02057E22994A4
    GO
    Isoform M1 (identifier: A4GCL0-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry A4GCL0.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:252
    Mass (Da):27,833
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CY020462 Viral cRNA. Translation: ABO38375.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CY020462 Viral cRNA. Translation: ABO38375.1 .

    3D structure databases

    ProteinModelPortali A4GCK9.
    SMRi A4GCK9. Positions 23-60.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    InterProi IPR002089. Flu_M2.
    [Graphical view ]
    Pfami PF00599. Flu_M2. 1 hit.
    [Graphical view ]
    ProDomi PD001031. Flu_M2. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. The NIAID Influenza Genome Sequencing Consortium
      Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

    Entry informationi

    Entry nameiM2_I43A0
    AccessioniPrimary (citable) accession number: A4GCK9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 5, 2009
    Last sequence update: April 17, 2007
    Last modified: October 1, 2014
    This is version 31 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    When the channel is activated, one or more imidazole moities of His-37 probably become bi-protonated.

    Keywords - Technical termi

    Complete proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3