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Protein

Matrix protein 2

Gene

M2

Organism
Influenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
Status
Reviewed-Annotation score: 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).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)DescriptionActionsGraphical viewLength
Sitei37Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filterBy similarity1
Sitei41Seems to be involved in pH gatingBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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
Gene namesi
Name:M2
OrganismiInfluenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
Taxonomic identifieri518998 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008081 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22Virion surfaceSequence analysisAdd BLAST22
Transmembranei23 – 43Helical; Signal-anchor for type III membrane proteinSequence analysisAdd BLAST21
Topological domaini44 – 97IntravirionSequence analysisAdd BLAST54

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003729161 – 97Matrix protein 2Add BLAST97

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi17Interchain (with C-17)By similarity
Disulfide bondi19Interchain (with C-19)By similarity
Glycosylationi20N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi50S-palmitoyl cysteine; by hostBy similarity1
Modified residuei64Phosphoserine; by hostBy similarity1
Modified residuei82Phosphoserine; by hostBy similarity1
Modified residuei93Phosphoserine; by hostBy similarity1

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliB4URD7.
ModBaseiSearch...
MobiDBiSearch...

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. AlignAdd to basket

Note: Only the first 9 residues are shared by the 2 isoforms.
Isoform M2 (identifier: B4URD7-1) [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

        10         20         30         40         50
MSLLTEVETP IRNEWGCRCN GSSDPLTIAA NIIGILHLTL WILDRLFFKC
60 70 80 90
IYRRFKYGLK GGPSTEGVPK SMREEYRKEQ QSAVDADDGH FVSIELE
Length:97
Mass (Da):11,063
Last modified:September 23, 2008 - v1
Checksum:iC495837284B47BD4
GO
Isoform M1 (identifier: B4URD8-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry B4URD8.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:252
Mass (Da):27,893
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY034125 Viral cRNA. Translation: ACF54589.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY034125 Viral cRNA. Translation: ACF54589.1.

3D structure databases

ProteinModelPortaliB4URD7.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]
ProtoNetiSearch...

Entry informationi

Entry nameiM2_I06A0
AccessioniPrimary (citable) accession number: B4URD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: September 23, 2008
Last modified: October 5, 2016
This is version 35 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.