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- M2_I50A0


P10921 - M2_I50A0

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Matrix protein 2



Influenza A virus (strain A/Fort Warren/1/1950 H1N1)
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi


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.


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

GO - Biological processi

  1. pore formation by virus in membrane of host cell Source: UniProtKB-KW
  2. protein oligomerization Source: UniProtKB-KW
  3. suppression by virus of host autophagy Source: UniProtKB-KW
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

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix protein 2
Alternative name(s):
Proton channel protein M2
Gene namesi
OrganismiInfluenza A virus (strain A/Fort Warren/1/1950 H1N1)
Taxonomic identifieri384525 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

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


Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222Virion surfaceSequence AnalysisAdd
Transmembranei23 – 4321Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
Topological domaini44 – 9754IntravirionSequence AnalysisAdd

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. integral to membrane of host cell Source: UniProtKB-KW
  4. virion membrane Source: UniProtKB-SubCell
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_0000078880Add

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 residuei89 – 891Phosphoserine; by hostBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein


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


3D structure databases

SMRiP10921. Positions 23-60.

Family & Domainsi


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: P10921-1) [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
60 70 80 90
Mass (Da):11,178
Last modified:July 1, 1989 - v1
Isoform M1 (identifier: P69275-1) [UniParc]FASTAAdd to Basket

The sequence of this isoform can be found in the external entry P69275.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Mass (Da):27,903

Sequence databases

Select the link destinations:
Links Updated
X08091 Genomic RNA. Translation: CAA30889.1.

Keywords - Coding sequence diversityi

Alternative splicing


Sequence databases

Select the link destinations:
Links Updated
X08091 Genomic RNA. Translation: CAA30889.1 .

3D structure databases

ProteinModelPortali P10921.
SMRi P10921. 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...


  1. "Nucleotide sequences of influenza A virus RNA segment 7: a comparison of five isolates."
    Zebedee S.L., Lamb R.A.
    Nucleic Acids Res. 17:2870-2870(1989) [PubMed] [Europe PMC] [Abstract]
  2. "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.
  3. "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.
  4. "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_I50A0
AccessioniPrimary (citable) accession number: P10921
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: January 7, 2015
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program



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


  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.