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P06821 (M2_I34A1) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix protein 2
Alternative name(s):
Proton channel protein M2
Gene names
Name:M
OrganismInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1) [Reference proteome]
Taxonomic identifier211044 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length97 AA.
Sequence statusComplete.
Protein existenceInferred 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 processHost-virus interaction
Hydrogen ion transport
Inhibition of host autophagy by virus
Ion transport
Transport
   Cellular componentHost cell membrane
Host membrane
Membrane
Virion
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionIon channel
Viral ion channel
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processfusion of virus membrane with host plasma membrane

Traceable author statement. Source: Reactome

intracellular transport of viral protein in host cell

Traceable author statement. Source: Reactome

pore formation by virus in membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

protein oligomerization

Inferred from electronic annotation. Source: UniProtKB-KW

receptor-mediated endocytosis of virus by host cell

Traceable author statement. Source: Reactome

suppression by virus of host autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

uncoating of virus

Traceable author statement. Source: Reactome

viral entry into host cell

Traceable author statement. Source: Reactome

viral genome packaging

Traceable author statement. Source: Reactome

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral release from host cell

Traceable author statement. Source: Reactome

viral transcription

Traceable author statement. Source: Reactome

virion assembly

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

endosome lumen

Traceable author statement. Source: Reactome

extracellular region

Traceable author statement. Source: Reactome

host cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

integral to membrane of host cell

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionhydrogen ion transmembrane transporter activity

Inferred from electronic annotation. Source: InterPro

ion channel activity

Inferred from electronic annotation. Source: UniProtKB-KW

transporter activity

Traceable author statement. Source: Reactome

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: P06821-1)

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: P03485-1)

The sequence of this isoform can be found in the external entry P03485.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9797Matrix protein 2
PRO_0000078890

Regions

Topological domain1 – 2222Virion surface Potential
Transmembrane23 – 4321Helical; Signal-anchor for type III membrane protein; Potential
Topological domain44 – 9754Intravirion Potential

Sites

Site371Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filter By similarity
Site411Seems to be involved in pH gating By similarity

Amino acid modifications

Modified residue641Phosphoserine; by host By similarity
Modified residue821Phosphoserine; by host By similarity
Modified residue931Phosphoserine; by host By similarity
Lipidation501S-palmitoyl cysteine; by host By similarity
Glycosylation201N-linked (GlcNAc...); by host Potential
Disulfide bond17Interchain (with C-17) By similarity
Disulfide bond19Interchain (with C-19) By similarity

Natural variations

Natural variant101P → H in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.
Natural variant101P → L in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L.
Natural variant271A → T in strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.
Natural variant391I → T in strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.

Experimental info

Sequence conflict271A → I in ABD77677. Ref.5
Sequence conflict301A → S in ABD77677. Ref.5
Sequence conflict541R → L in ABD77677. Ref.5
Sequence conflict611G → R in ABD77677. Ref.5
Sequence conflict771R → Q in ABD77677. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform M2 [UniParc].

Last modified November 1, 1988. Version 1.
Checksum: 85858F6E84A97AB8

FASTA9711,045
        10         20         30         40         50         60 
MSLLTEVETP IRNEWGCRCN GSSDPLAIAA NIIGILHLIL WILDRLFFKC IYRRFKYGLK 

        70         80         90 
GGPSTEGVPK SMREEYRKEQ QSAVDADDGH FVSIELE 

« Hide

Isoform M1 [UniParc].

See P03485.

References

[1]"Cloning of influenza cDNA into M13: the sequence of the RNA segment encoding the A/PR/8/34 matrix protein."
Winter G., Fields S.
Nucleic Acids Res. 8:1965-1974(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Plasmid-only rescue of influenza A virus vaccine candidates."
Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P.
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]"Influenza type a virus escape mutants emerge in vivo in the presence of antibodies to the ectodomain of matrix protein 2."
Zharikova D., Mozdzanowska K., Feng J., Zhang M., Gerhard W.
J. Virol. 79:6644-6654(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: A/Puerto Rico/8/34/Mount Sinai/Wi, A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H and A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L.
[5]"The NIAID influenza genome sequencing project."
Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. expand/collapse author list , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[6]"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.
[7]"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.
[8]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V01099 Genomic RNA. Translation: CAA24283.1. Sequence problems.
AF389121 Genomic RNA. Translation: AAM75162.1.
EF467824 Genomic RNA. Translation: ABO21713.1.
AY768951 mRNA. Translation: AAV41244.1.
AY768952 mRNA. Translation: AAV41245.1.
AY768953 mRNA. Translation: AAV41246.1.
CY009445 Genomic RNA. Translation: ABD77677.1.
RefSeqNP_040979.2. NC_002016.1.

3D structure databases

ProteinModelPortalP06821.
SMRP06821. Positions 23-60.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP06821. 12 interactions.

Chemistry

ChEMBLCHEMBL1932894.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID956528.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Family and domain databases

InterProIPR002089. Flu_M2.
[Graphical view]
PfamPF00599. Flu_M2. 1 hit.
[Graphical view]
ProDomPD001031. Flu_M2. 1 hit.
[Graphical view] [Entries sharing at least one domain]
ProtoNetSearch...

Entry information

Entry nameM2_I34A1
AccessionPrimary (citable) accession number: P06821
Secondary accession number(s): A4GXH7 expand/collapse secondary AC list , Q20N37, Q5UAV4, Q5UAV5, Q5UAV6, Q84105, Q8JUU3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1988
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families