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Q67186 (M2_I88A5) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 54. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Matrix protein 2
Alternative name(s):
Proton channel protein M2
Gene names
OrganismInfluenza A virus (strain A/Swine/Iowa/17672/1988 H1N1)
Taxonomic identifier380341 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length97 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)


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.

Enzyme regulation

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.

Subunit structure

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

Subcellular location

Virion membrane By similarity. Host apical cell membrane; 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.


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


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

Sequence similarities

Belongs to the influenza viruses matrix protein M2 family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Only the first 9 residues are shared by the 2 isoforms.
Isoform M2 (identifier: Q67186-1)

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.
Isoform M1 (identifier: Q67187-1)

The sequence of this isoform can be found in the external entry Q67187.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9797Matrix protein 2


Topological domain1 – 2222Virion surface Potential
Transmembrane23 – 4321Helical; Potential
Topological domain44 – 9754Intravirion Potential


Site371Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filter By similarity
Site411Seems to be involved in pH gating By similarity

Amino acid modifications

Modified residue641Phosphoserine; by host By similarity
Lipidation501S-palmitoyl cysteine; by host By similarity
Disulfide bond17Interchain (with C-17) By similarity
Disulfide bond19Interchain (with C-19) By similarity


Sequence LengthMass (Da)Tools
Isoform M2 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 178457AD324E0DB4

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Isoform M1 [UniParc].

See Q67187.


[1]"Evolutionary analysis of the influenza A virus M gene with comparison of the M1 and M2 proteins."
Ito T., Gorman O.T., Kawaoka Y., Bean W.J., Webster R.G.
J. Virol. 65:5491-5498(1991) [PubMed] [Europe PMC] [Abstract]


Sequence databases

M63522 Genomic RNA. Translation: AAA43317.1.

3D structure databases

SMRQ67186. Positions 23-60.

Protocols and materials databases


Family and domain databases

InterProIPR002089. Flu_M2.
[Graphical view]
PfamPF00599. Flu_M2. 1 hit.
[Graphical view]
ProDomPD001031. Flu_M2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Entry information

Entry nameM2_I88A5
AccessionPrimary (citable) accession number: Q67186
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 54 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents


Index of protein domains and families