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P06821

- M2_I34A1

UniProt

P06821 - M2_I34A1

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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

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
Complete GO annotation...

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-KW
  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: InterPro
Complete GO annotation...

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

        10         20         30         40         50
MSLLTEVETP IRNEWGCRCN GSSDPLAIAA NIIGILHLIL WILDRLFFKC
60 70 80 90
IYRRFKYGLK GGPSTEGVPK SMREEYRKEQ QSAVDADDGH FVSIELE
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 29, 2014
This is version 103 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