P10921 (M2_I50A0) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 84. History...
Names and origin
|Protein names||Recommended name:|
Matrix protein 2
Proton channel protein M2
|Organism||Influenza A virus (strain A/Fort Warren/1/1950 H1N1)|
|Taxonomic identifier||384525 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›|
|Virus host||Aves [TaxID: 8782]|
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
|Sequence length||97 AA.|
|Protein existence||Inferred 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.
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.
Homotetramer; composed of two disulfide-linked dimers held together by non-covalent interactions. May interact with matrix protein 1 By similarity.
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.
Belongs to the influenza viruses matrix protein M2 family.
|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: P10921-1) |
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: P69275-1) |
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.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 97||97||Matrix protein 2||PRO_0000078880|
|Topological domain||1 – 22||22||Virion surface Potential|
|Transmembrane||23 – 43||21||Helical; Signal-anchor for type III membrane protein; Potential|
|Topological domain||44 – 97||54||Intravirion Potential|
|Site||37||1||Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filter By similarity|
|Site||41||1||Seems to be involved in pH gating By similarity|
Amino acid modifications
|Modified residue||64||1||Phosphoserine; by host By similarity|
|Modified residue||82||1||Phosphoserine; by host By similarity|
|Modified residue||89||1||Phosphoserine; by host By similarity|
|Lipidation||50||1||S-palmitoyl cysteine; by host By similarity|
|Glycosylation||20||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||17||Interchain (with C-17) By similarity|
|Disulfide bond||19||Interchain (with C-19) By similarity|
|||"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]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"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.
|||"Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data."|
FEBS Lett. 552:17-22(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"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.
|X08091 Genomic RNA. Translation: CAA30889.1.|
3D structure databases
|SMR||P10921. Positions 23-60. |
Protocols and materials databases
Family and domain databases
|InterPro||IPR002089. Flu_M2. |
|Pfam||PF00599. Flu_M2. 1 hit. |
|ProDom||PD001031. Flu_M2. 1 hit. |
[Graphical view] [Entries sharing at least one domain]
|Accession||Primary (citable) accession number: P10921|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families