Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P06821

- M2_I34A1

UniProt

P06821 - M2_I34A1

Protein

Matrix protein 2

Gene

M

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed - Annotation score: 5 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
    2. ion channel activity Source: UniProtKB-KW
    3. transporter activity Source: Reactome

    GO - Biological processi

    1. fusion of virus membrane with host plasma membrane Source: Reactome
    2. intracellular transport of viral protein in host cell Source: Reactome
    3. pore formation by virus in membrane of host cell Source: UniProtKB-KW
    4. protein oligomerization Source: UniProtKB-KW
    5. receptor-mediated endocytosis of virus by host cell Source: Reactome
    6. suppression by virus of host autophagy Source: UniProtKB-KW
    7. uncoating of virus Source: Reactome
    8. viral entry into host cell Source: Reactome
    9. viral genome packaging Source: Reactome
    10. viral life cycle Source: Reactome
    11. viral process Source: Reactome
    12. viral release from host cell Source: Reactome
    13. viral transcription Source: Reactome
    14. virion assembly Source: Reactome

    Keywords - Molecular functioni

    Ion channel, Viral ion channel

    Keywords - Biological processi

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

    Enzyme and pathway databases

    ReactomeiREACT_6145. Influenza Life Cycle.
    REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
    REACT_6212. Budding.
    REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
    REACT_6235. Packaging of Eight RNA Segments.
    REACT_6277. Assembly of Viral Components at the Budding Site.
    REACT_6321. Uncoating of the Influenza Virion.
    REACT_6326. Release.
    REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
    REACT_9491. Viral mRNA Translation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Matrix protein 2
    Alternative name(s):
    Proton channel protein M2
    Gene namesi
    Name:M
    OrganismiInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1)
    Taxonomic identifieri211044 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000009255: 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. cytosol Source: Reactome
    2. endocytic vesicle membrane Source: Reactome
    3. endoplasmic reticulum membrane Source: Reactome
    4. endosome lumen Source: Reactome
    5. extracellular region Source: Reactome
    6. Golgi membrane Source: Reactome
    7. host cell plasma membrane Source: UniProtKB-SubCell
    8. integral component of membrane Source: UniProtKB-KW
    9. integral to membrane of host cell Source: UniProtKB-KW
    10. plasma membrane Source: Reactome
    11. 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_0000078890Add
    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
    Modified residuei93 – 931Phosphoserine; 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

    Protein-protein interaction databases

    IntActiP06821. 12 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP06821.
    SMRiP06821. 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: P06821-1) [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 GSSDPLAIAA NIIGILHLIL WILDRLFFKC   50
    IYRRFKYGLK GGPSTEGVPK SMREEYRKEQ QSAVDADDGH FVSIELE 97
    Length:97
    Mass (Da):11,045
    Last modified:November 1, 1988 - v1
    Checksum:i85858F6E84A97AB8
    GO
    Isoform M1 (identifier: P03485-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry P03485.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:252
    Mass (Da):27,893
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti27 – 271A → I in ABD77677. 1 PublicationCurated
    Sequence conflicti30 – 301A → S in ABD77677. 1 PublicationCurated
    Sequence conflicti54 – 541R → L in ABD77677. 1 PublicationCurated
    Sequence conflicti61 – 611G → R in ABD77677. 1 PublicationCurated
    Sequence conflicti77 – 771R → Q in ABD77677. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti10 – 101P → H in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.
    Natural varianti10 – 101P → L in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L.
    Natural varianti27 – 271A → T in strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.
    Natural varianti39 – 391I → T in strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V01099 Genomic RNA. Translation: CAA24283.1. Sequence problems.
    AF389121 Genomic RNA. Translation: AAM75162.1.
    EF467824 Genomic RNA. Translation: ABO21713.1.
    AY768951 mRNA. Translation: AAV41244.1.
    AY768952 mRNA. Translation: AAV41245.1.
    AY768953 mRNA. Translation: AAV41246.1.
    CY009445 Genomic RNA. Translation: ABD77677.1.
    RefSeqiNP_040979.2. NC_002016.1. [P06821-1]

    Genome annotation databases

    GeneIDi956528.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V01099 Genomic RNA. Translation: CAA24283.1 . Sequence problems.
    AF389121 Genomic RNA. Translation: AAM75162.1 .
    EF467824 Genomic RNA. Translation: ABO21713.1 .
    AY768951 mRNA. Translation: AAV41244.1 .
    AY768952 mRNA. Translation: AAV41245.1 .
    AY768953 mRNA. Translation: AAV41246.1 .
    CY009445 Genomic RNA. Translation: ABD77677.1 .
    RefSeqi NP_040979.2. NC_002016.1. [P06821-1 ]

    3D structure databases

    ProteinModelPortali P06821.
    SMRi P06821. Positions 23-60.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P06821. 12 interactions.

    Chemistry

    ChEMBLi CHEMBL1932894.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 956528.

    Enzyme and pathway databases

    Reactomei REACT_6145. Influenza Life Cycle.
    REACT_6147. Entry of Influenza Virion into Host Cell via Endocytosis.
    REACT_6212. Budding.
    REACT_6215. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
    REACT_6235. Packaging of Eight RNA Segments.
    REACT_6277. Assembly of Viral Components at the Budding Site.
    REACT_6321. Uncoating of the Influenza Virion.
    REACT_6326. Release.
    REACT_6351. Fusion of the Influenza Virion to the Host Cell Endosome.
    REACT_9491. Viral mRNA Translation.

    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. "Cloning of influenza cDNA into M13: the sequence of the RNA segment encoding the A/PR/8/34 matrix protein."
      Winter G., Fields S.
      Nucleic Acids Res. 8:1965-1974(1980) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
      de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
      Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
    4. "Influenza type a virus escape mutants emerge in vivo in the presence of antibodies to the ectodomain of matrix protein 2."
      Zharikova D., Mozdzanowska K., Feng J., Zhang M., Gerhard W.
      J. Virol. 79:6644-6654(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L.
    5. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    6. "Assembly and budding of influenza virus."
      Nayak D.P., Hui E.K., Barman S.
      Virus Res. 106:147-165(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data."
      Lear J.D.
      FEBS Lett. 552:17-22(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    8. "Computational studies of proton transport through the M2 channel."
      Wu Y., Voth G.A.
      FEBS Lett. 552:23-27(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiM2_I34A1
    AccessioniPrimary (citable) accession number: P06821
    Secondary accession number(s): A4GXH7
    , Q20N37, Q5UAV4, Q5UAV5, Q5UAV6, Q84105, Q8JUU3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: November 1, 1988
    Last modified: October 1, 2014
    This is version 102 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, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3