P05780 (M2_I33A0) 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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1)) [Complete proteome]

Taxonomic identifier

381518 [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	Evidence at protein level

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 By similarity. May interact with matrix protein 1.
Subcellular location	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
Domain	Cytoplasmic tail plays an important role in virion assembly and morphogenesis. Ref.6
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 Glycoprotein Lipoprotein Palmitate Phosphoprotein
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-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: 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
Molecule processing
	Chain	1 – 97	97	Matrix protein 2		PRO_0000078894
Regions
	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
Sites
	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
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Isoform M2 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 1B5A86F9E0CD71DE	FASTA	97	11,313
	10 20 30 40 50 60 MSLLTEVETP IRNEWGCRCN DSSDPLVIAA NIIGILHLIL WILDRLFFKC IYRRFKYGLK 70 80 90 RGPSTEGVPE SMREEYRKEQ QNAVDVDDGH FVNIELE
	Isoform M1 [UniParc]. See P05777.		–	–

References

[1]	"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.
[2]	"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]. Strain: A/WSN/33.
[3]	"Specific changes in the M1 protein during adaptation of influenza virus to mouse." Ward A.C. 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.
[4]	"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.
[5]	"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. Strain: A/WSN/33.
[6]	"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.
[7]	"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.
[8]	"Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data." Lear J.D. FEBS Lett. 552:17-22(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"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.
[10]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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
ProteinModelPortal	P05780.
SMR	P05780. Positions 23-60.
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_I33A0

Accession

Primary (citable) accession number: P05780
Secondary accession number(s): Q67182

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	May 1, 2013
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program