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P05780

- M2_I33A0

UniProt

P05780 - M2_I33A0

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Protein

Matrix protein 2

Gene

M

Organism
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Status
Reviewed - Annotation score: 5 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 (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)LengthDescriptionGraphical viewFeature identifierActions
Sitei37 – 371Essential for channel activity, seems to be protonated during channel activation, and may play a role in the channel gating and selectivityBy similarity
Sitei41 – 411Seems to be involved in pH gatingBy 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/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
Taxonomic identifieri381518 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000000834: Genome

Subcellular locationi

Virion membrane 1 Publication. Host apical cell membrane 1 Publication; Single-pass type III membrane protein 1 Publication
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).

GO - Cellular componenti

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

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi74 – 763EEY → AAA: Loss of infectivity, and modification of virion morphology. 1 Publication
Mutagenesisi77 – 793RKE → AAA: Loss of infectivity, and modification of virion morphology. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9797Matrix protein 2PRO_0000078894Add
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
Lipidationi50 – 501S-palmitoyl cysteine; by hostBy similarity
Modified residuei64 – 641Phosphoserine; by hostBy 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 (By similarity). May interact with matrix protein 1.By similarity

Structurei

3D structure databases

ProteinModelPortaliP05780.
SMRiP05780. Positions 23-60.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222Virion surfaceSequence AnalysisAdd
BLAST
Topological domaini44 – 9754IntravirionSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei23 – 4321Helical; Signal-anchor for type III membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Domaini

Cytoplasmic tail plays an important role in virion assembly and morphogenesis.1 Publication

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: P05780-1) [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 DSSDPLVIAA NIIGILHLIL WILDRLFFKC
60 70 80 90
IYRRFKYGLK RGPSTEGVPE SMREEYRKEQ QNAVDVDDGH FVNIELE
Length:97
Mass (Da):11,313
Last modified:November 1, 1988 - v1
Checksum:i1B5A86F9E0CD71DE
GO
Isoform M1 (identifier: P05777-1) [UniParc]FASTAAdd to Basket

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.
Length:252
Mass (Da):27,864
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti34 – 341G → E in AAA91324. (PubMed:7710364)Curated
Sequence conflicti55 – 551F → L in AAA43274. (PubMed:3414185)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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

ProteinModelPortali P05780.
SMRi P05780. 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. "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.

Entry informationi

Entry nameiM2_I33A0
AccessioniPrimary (citable) accession number: P05780
Secondary accession number(s): Q67182
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: November 1, 1988
Last modified: October 29, 2014
This is version 93 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