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Matrix protein 2



Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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.UniRule annotation


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

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)DescriptionActionsGraphical viewLength
Sitei37Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filterUniRule annotation1
Sitei41Seems to be involved in pH gatingUniRule annotation1

GO - Molecular functioni

GO - Biological processi


Molecular functionIon channel, Viral ion channel
Biological processHost-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-168255 Influenza Life Cycle
R-HSA-168275 Entry of Influenza Virion into Host Cell via Endocytosis
R-HSA-168288 Fusion of the Influenza Virion to the Host Cell Endosome
R-HSA-168298 Release
R-HSA-168302 Budding
R-HSA-168303 Packaging of Eight RNA Segments
R-HSA-168316 Assembly of Viral Components at the Budding Site
R-HSA-168336 Uncoating of the Influenza Virion
R-HSA-168874 Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus
R-HSA-192823 Viral mRNA Translation

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix protein 2UniRule annotation
Alternative name(s):
Proton channel protein M2UniRule annotation
Gene namesi
Name:MUniRule annotation
OrganismiInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Taxonomic identifieri211044 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeAlphainfluenzavirus
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
  • UP000116373 Componenti: Genome
  • UP000170967 Componenti: Genome
  • UP000009255 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type III membrane protein UniRule annotation
  • 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).UniRule annotation


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22Virion surfaceUniRule annotationAdd BLAST22
Transmembranei23 – 43Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST21
Topological domaini44 – 97IntravirionUniRule annotationAdd BLAST54

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Chemistry databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000788901 – 97Matrix protein 2Add BLAST97

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi17Interchain (with C-17)UniRule annotation
Disulfide bondi19Interchain (with C-19)UniRule annotation
Glycosylationi20N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi50S-palmitoyl cysteine; by hostUniRule annotation1
Modified residuei64Phosphoserine; by hostUniRule annotation1
Modified residuei82Phosphoserine; by hostUniRule annotation1
Modified residuei93Phosphoserine; by hostUniRule annotation1

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.UniRule annotation

Binary interactionsi

Show more details

Protein-protein interaction databases

IntActiP06821, 104 interactors


Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni3 – 5Combined sources3
Beta strandi6 – 8Combined sources3

3D structure databases


Family & Domainsi


Cytoplasmic tail plays an important role in virion assembly and morphogenesis.UniRule annotation

Sequence similaritiesi

Belongs to the influenza viruses matrix protein M2 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases


Family and domain databases

HAMAPiMF_04069 INFV_M2, 1 hit
InterProiView protein in InterPro
IPR002089 Flu_M2
PfamiView protein in Pfam
PF00599 Flu_M2, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD001031 Flu_M2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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
60 70 80 90
Mass (Da):11,045
Last modified:November 1, 1988 - v1
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.
Mass (Da):27,893

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27A → I in ABD77677 (Ref. 5) 1
Sequence conflicti30A → S in ABD77677 (Ref. 5) 1
Sequence conflicti54R → L in ABD77677 (Ref. 5) 1
Sequence conflicti61G → R in ABD77677 (Ref. 5) 1
Sequence conflicti77R → Q in ABD77677 (Ref. 5) 1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti10P → H in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H. 1
Natural varianti10P → L in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L. 1
Natural varianti27A → 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. 1
Natural varianti39I → 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. 1

Sequence databases

Select the link destinations:
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


Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiM2_I34A1
AccessioniPrimary (citable) accession number: P06821
Secondary accession number(s): A4GXH7
, Q20N37, Q5UAV4, Q5UAV5, Q5UAV6, Q84105, Q8JUU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1988
Last modified: May 23, 2018
This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program


Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome


  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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