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Q67207

- M2_I61A1

UniProt

Q67207 - M2_I61A1

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Protein
Matrix protein 2
Gene
M
Organism
Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
Status
Reviewed - Annotation score: 4 out of 5 - Protein inferred from homologyi

Functioni

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 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei37 – 371Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filter By similarity
Sitei41 – 411Seems to be involved in pH gating By similarity

GO - Molecular functioni

  1. hydrogen ion transmembrane transporter activity Source: InterPro
  2. ion channel activity Source: UniProtKB-KW

GO - Biological processi

  1. pore formation by virus in membrane of host cell Source: UniProtKB-KW
  2. protein oligomerization Source: UniProtKB-KW
  3. suppression by virus of host autophagy Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Viral ion channel

Keywords - Biological processi

Host-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix protein 2
Alternative name(s):
Proton channel protein M2
Gene namesi
Name:M
OrganismiInfluenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
Taxonomic identifieri383533 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000007769: Genome

Subcellular locationi

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222Virion surface Reviewed prediction
Add
BLAST
Transmembranei23 – 4321Helical; Reviewed prediction
Add
BLAST
Topological domaini44 – 9754Intravirion Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. integral to membrane of host cell Source: UniProtKB-KW
  4. virion membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9797Matrix protein 2
PRO_0000326342Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi17 – 17Interchain (with C-17) By similarity
Disulfide bondi19 – 19Interchain (with C-19) By similarity
Glycosylationi20 – 201N-linked (GlcNAc...); by host Reviewed prediction
Lipidationi50 – 501S-palmitoyl cysteine; by host By similarity
Modified residuei64 – 641Phosphoserine; by host By similarity
Modified residuei82 – 821Phosphoserine; by host By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Interactioni

Subunit structurei

Homotetramer; composed of two disulfide-linked dimers held together by non-covalent interactions. May interact with matrix protein 1 By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ67207.
SMRiQ67207. Positions 23-60.

Family & Domainsi

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

InterProiIPR002089. Flu_M2.
[Graphical view]
PfamiPF00599. Flu_M2. 1 hit.
[Graphical view]
ProDomiPD001031. Flu_M2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Note: Only the first 9 residues are shared by the 2 isoforms.

Isoform M2 (identifier: Q67207-1) [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

MSLLTEVETP TRSEWGCRCN DSSDPLVAAA SIIGILHLIL WILDRLFFKC   50
IYRRFKYGLK RGPSTEGVPE SMREEYRQKQ QSAVDVDDGH FVNIELE 97
Length:97
Mass (Da):11,177
Last modified:November 1, 1996 - v1
Checksum:i1A85B514B27EE25E
GO
Isoform M1 (identifier: Q89562-1) [UniParc]FASTAAdd to Basket

The sequence of this isoform can be found in the external entry Q89562.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:252
Mass (Da):27,856
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti95 – 951E → V.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M63519 Genomic RNA. Translation: AAA43343.1.
CY032214 Viral cRNA. Translation: ACD85156.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M63519 Genomic RNA. Translation: AAA43343.1 .
CY032214 Viral cRNA. Translation: ACD85156.1 .

3D structure databases

ProteinModelPortali Q67207.
SMRi Q67207. Positions 23-60.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

InterProi IPR002089. Flu_M2.
[Graphical view ]
Pfami PF00599. Flu_M2. 1 hit.
[Graphical view ]
ProDomi PD001031. Flu_M2. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
ProtoNeti Search...

Publicationsi

  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].

Entry informationi

Entry nameiM2_I61A1
AccessioniPrimary (citable) accession number: Q67207
Secondary accession number(s): B3EUQ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 56 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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