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Protein

Matrix protein 2

Gene

M

Organism
Influenza A virus (strain A/USSR/90/1977 H1N1)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

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.UniRule annotation

Miscellaneous

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

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 filterUniRule annotation1
Sitei41Seems to be involved in pH gatingUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Viral ion channel
Biological processHost-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

Protein family/group databases

TCDBi1.A.19.1.1. the type a influenza virus matrix-2 channel (m2-c) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix protein 2UniRule annotation
Alternative name(s):
Proton channel protein M2UniRule annotation
Gene namesi
Name:MUniRule annotation
OrganismiInfluenza A virus (strain A/USSR/90/1977 H1N1)
Taxonomic identifieri381516 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000007793 Componenti: Genome
  • UP000121508 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type III membrane protein UniRule annotation

  • 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).UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22Virion surfaceUniRule annotationAdd BLAST22
Transmembranei23 – 43Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST21
Topological domaini44 – 97IntravirionUniRule annotationAdd BLAST54

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000788931 – 97Matrix protein 2Add BLAST97

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi17Interchain (with C-17)UniRule annotation
Disulfide bondi19Interchain (with C-19)UniRule annotation
Glycosylationi20N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi50S-palmitoyl cysteine; by hostUniRule annotation1
Modified residuei64Phosphoserine; by hostUniRule annotation1

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.UniRule annotation

Structurei

Secondary structure

197
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 45Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NYJNMR-A/B/C/D22-46[»]
2H95NMR-A/B/C/D26-43[»]
ProteinModelPortaliP35938.
SMRiP35938.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35938.

Family & Domainsi

Domaini

Cytoplasmic tail plays an important role in virion assembly and morphogenesis.UniRule annotation

Sequence similaritiesi

Belongs to the influenza viruses matrix protein M2 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG090000KZ.

Family and domain databases

HAMAPiMF_04069. INFV_M2. 1 hit.
InterProiView protein in InterPro
IPR002089. Flu_M2.
PfamiView protein in Pfam
PF00599. Flu_M2. 1 hit.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD001031. Flu_M2. 1 hit.

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: P35938-1) [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 DSSDPLVVAA SIIGILHLIL WILDRLFFKC
60 70 80 90
IYRLFKHGLK RGPSTEGVPE SMREEYRKEQ QNAVDADDSH FVNIELE
Length:97
Mass (Da):11,205
Last modified:June 1, 1994 - v1
Checksum:i06E02057E22994BE
GO
Isoform M1 (identifier: P35937-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P35937.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:252
Mass (Da):27,819
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53029 Genomic RNA. Translation: CAB38716.1.
CY010373 Genomic RNA. Translation: ABD95352.1.
DQ508900 Genomic RNA. Translation: ABF21315.1.

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiM2_I77AB
AccessioniPrimary (citable) accession number: P35938
Secondary accession number(s): Q1WP08, Q67158, Q67159
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: June 7, 2017
This is version 99 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families