Q67203 (M2_I81A4) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix protein 2

Alternative name(s):
Proton channel protein M2

Gene names

Name:

M

Organism

Influenza A virus (strain A/Swine/Ontario/2/1981 H1N1)

Taxonomic identifier

384501 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › Influenza A virus › H1N1 subtype

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	97 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

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

Ontologies

Keywords
Biological process	Host-virus interaction Hydrogen ion transport Inhibition of host autophagy by virus Ion transport Transport
Cellular component	Host cell membrane Host membrane Membrane Virion
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Ion channel Viral ion channel
PTM	Disulfide bond Lipoprotein Palmitate Phosphoprotein
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-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	hydrogen ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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: Q67203-1)

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: Q67204-1)

The sequence of this isoform can be found in the external entry Q67204.
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
Molecule processing
	Chain	1 – 97	97	Matrix protein 2		PRO_0000326376
Regions
	Topological domain	1 – 22	22	Virion surface Potential
	Transmembrane	23 – 43	21	Helical; Potential
	Topological domain	44 – 97	54	Intravirion Potential
Sites
	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
	Lipidation	50	1	S-palmitoyl cysteine; by host By similarity
	Disulfide bond	17		Interchain (with C-17) By similarity
	Disulfide bond	19		Interchain (with C-19) By similarity

Sequences

	Sequence		Length	Mass (Da)
	Isoform M2 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 2B48ACD86AB11DB4	FASTA	97	11,186
	10 20 30 40 50 60 MSLLTEVETP IRNEWGCRCN DSSDPLVAAA SIIGILHLIL WILDRLFFKC IYRRFKYGLK 70 80 90 RGPSTEGVPE SMREEYRQKQ QSAVDVDDGH FVNIVLE
	Isoform M1 [UniParc]. See Q67204.		–	–

References

[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] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M63520 Genomic RNA. Translation: AAA43337.1.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002089. Flu_M2. [Graphical view]
Pfam	PF00599. Flu_M2. 1 hit. [Graphical view]
ProDom	PD001031. Flu_M2. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...

Entry information

Entry name

M2_I81A4

Accession

Primary (citable) accession number: Q67203

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program