P05780 (M2_I33A0) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 88. History...
Names and origin
|Protein names||Recommended name:|
Matrix protein 2
Proton channel protein M2
|Organism||Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1)) [Complete proteome]|
|Taxonomic identifier||381518 [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||Evidence at protein level|
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 By similarity. May interact with matrix protein 1.
Virion membrane. Host apical cell membrane; Single-pass type III membrane protein. 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). Ref.5
Cytoplasmic tail plays an important role in virion assembly and morphogenesis. Ref.6
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.
|Biological process||Host-virus interaction|
Hydrogen ion transport
Inhibition of host autophagy by virus
|Cellular component||Host cell membrane|
|Coding sequence diversity||Alternative splicing|
|Molecular function||Ion channel|
Viral ion channel
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||suppression by virus of host autophagy|
Inferred from electronic annotation. Source: UniProtKB-KW
|Cellular_component||host cell plasma membrane|
Inferred from electronic annotation. Source: UniProtKB-SubCellintegral to membrane
Inferred from electronic annotation. Source: UniProtKB-KWvirion membrane
Inferred from electronic annotation. Source: UniProtKB-SubCell
|Molecular_function||hydrogen ion transmembrane transporter activity|
Inferred from electronic annotation. Source: InterPro
|Complete GO annotation...|
|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: P05780-1) |
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: P05777-1) |
The sequence of this isoform can be found in the external entry P05777.
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_0000078894|
|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, seems to be protonated during channel activation, and may play a role in the channel gating and selectivity 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|
|Lipidation||50||1||S-palmitoyl cysteine; by host By similarity|
|Glycosylation||20||1||N-linked (GlcNAc...); by host|
|Disulfide bond||17||Interchain (with C-17) By similarity|
|Disulfide bond||19||Interchain (with C-19) By similarity|
|Mutagenesis||74 – 76||3||EEY → AAA: Loss of infectivity, and modification of virion morphology. Ref.6|
|Mutagenesis||77 – 79||3||RKE → AAA: Loss of infectivity, and modification of virion morphology. Ref.6|
|Sequence conflict||34||1||G → E in AAA91324. Ref.3|
|Sequence conflict||55||1||F → L in AAA43274. Ref.2|
|||"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].
Strain: A/WS/33 and A/WSN/33.
|||"Nucleotide sequence of RNA segment 7 and the predicted amino sequence of M1 and M2 proteins of FPV/Weybridge (H7N7) and WSN (H1N1) influenza viruses."|
Markushin S., Ghiasi H., Sokolov N., Shilov A., Sinitsin B., Brown D., Klimov A., Nayak D.
Virus Res. 10:263-272(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Specific changes in the M1 protein during adaptation of influenza virus to mouse."|
Arch. Virol. 140:383-389(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA].
Strain: A/NWS/33 and A/WSN/33.
|||"Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface."|
Lamb R.A., Zebedee S.L., Richardson C.D.
Cell 40:627-633(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY.
|||"Expression of the influenza A virus M2 protein is restricted to apical surfaces of polarized epithelial cells."|
Hughey P.G., Compans R.W., Zebedee S.L., Lamb R.A.
J. Virol. 66:5542-5552(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
|||"The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly."|
Iwatsuki-Horimoto K., Horimoto T., Noda T., Kiso M., Maeda J., Watanabe S., Muramoto Y., Fujii K., Kawaoka Y.
J. Virol. 80:5233-5240(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, MUTAGENESIS OF 74-GLU--LYS-76 AND 77-ARG--GLU-79.
|||"Distinct domains of the influenza a virus M2 protein cytoplasmic tail mediate binding to the M1 protein and facilitate infectious virus production."|
McCown M.F., Pekosz A.
J. Virol. 80:8178-8189(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MATRIX PROTEIN 1.
|||"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.
|||"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.
|X08088 Genomic RNA. Translation: CAA30883.1.|
X08089 Genomic RNA. Translation: CAA30885.1.
M23922 Genomic RNA. Translation: AAA43274.1.
L25814 mRNA. Translation: AAA91322.1.
L25818 Genomic RNA. Translation: AAA91324.1.
3D structure databases
|SMR||P05780. 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: P05780|
Secondary accession number(s): Q67182
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families