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P35938

- M2_I77AB

UniProt

P35938 - M2_I77AB

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Protein
Matrix protein 2
Gene
M
Organism
Influenza A virus (strain A/USSR/90/1977 H1N1)
Status
Reviewed - 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 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

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 2
Alternative name(s):
Proton channel protein M2
Gene namesi
Name:M
OrganismiInfluenza A virus (strain A/USSR/90/1977 H1N1)
Taxonomic identifieri381516 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000007793: 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; Signal-anchor for type III membrane protein; 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_0000078893Add
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 residuei89 – 891Phosphoserine; 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

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi23 – 4523

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NYJNMR-A/B/C/D22-46[»]
2H95NMR-A/B/C/D26-43[»]
ProteinModelPortaliP35938.
SMRiP35938. Positions 23-60.

Miscellaneous databases

EvolutionaryTraceiP35938.

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: 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

MSLLTEVETP IRNEWGCRCN DSSDPLVVAA SIIGILHLIL WILDRLFFKC   50
IYRLFKHGLK RGPSTEGVPE SMREEYRKEQ QNAVDADDSH FVNIELE 97
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:
EMBL
GenBank
DDBJ
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X53029 Genomic RNA. Translation: CAB38716.1 .
CY010373 Genomic RNA. Translation: ABD95352.1 .
DQ508900 Genomic RNA. Translation: ABF21315.1 .

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1NYJ NMR - A/B/C/D 22-46 [» ]
2H95 NMR - A/B/C/D 26-43 [» ]
ProteinModelPortali P35938.
SMRi P35938. Positions 23-60.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

TCDBi 1.A.19.1.1. the type a influenza virus matrix-2 channel (m2-c) family.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P35938.

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. "Primary structure of fragment 7 of the influenza virus A/USSR/90/77(H1N1) RNA."
    Samokhvalov E.I., Kongenov V.A., Chizhikov V.E., Blinov V.M., Yuferov V.P., Vasilenko S.K., Uryvaev L.V., Zhdanov V.M.
    Bioorg. Khim. 11:1080-1085(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Complete genome sequencing and analysis of selected influenza virus vaccine strains spanning six decades (1933-1999)."
    Mbawuike I.N., Zhang Y., Yamada R.E., Nino D., Bui H.-H., Sette A., Couch R.B.
    Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "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.
  5. "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.
  6. "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.
  7. "The closed state of a H+ channel helical bundle combining precise orientational and distance restraints from solid state NMR."
    Nishimura K., Kim S., Zhang L., Cross T.A.
    Biochemistry 41:13170-13177(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 22-46.

Entry informationi

Entry nameiM2_I77AB
AccessioniPrimary (citable) accession number: P35938
Secondary accession number(s): Q1WP08, Q67158, Q67159
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 85 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

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

External Data

Dasty 3

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