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Protein

Matrix protein 2

Gene

M

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed-Annotation score: 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)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, Viral ion channel

Keywords - Biological processi

Host-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-168255. Influenza Life Cycle.
R-HSA-168275. Entry of Influenza Virion into Host Cell via Endocytosis.
R-HSA-168288. Fusion of the Influenza Virion to the Host Cell Endosome.
R-HSA-168298. Release.
R-HSA-168302. Budding.
R-HSA-168303. Packaging of Eight RNA Segments.
R-HSA-168316. Assembly of Viral Components at the Budding Site.
R-HSA-168336. Uncoating of the Influenza Virion.
R-HSA-168874. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
R-HSA-192823. Viral mRNA Translation.

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/Puerto Rico/8/1934 H1N1)
Taxonomic identifieri211044 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000009255 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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1932894.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000788901 – 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

Protein-protein interaction databases

IntActiP06821. 12 interactors.

Structurei

Secondary structure

197
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni3 – 5Combined sources3
Beta strandi6 – 8Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DLMX-ray2.20X/Y2-24[»]
ProteinModelPortaliP06821.
SMRiP06821.
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

Phylogenomic databases

KOiK19394.

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: P06821-1) [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 GSSDPLAIAA NIIGILHLIL WILDRLFFKC
60 70 80 90
IYRRFKYGLK GGPSTEGVPK SMREEYRKEQ QSAVDADDGH FVSIELE
Length:97
Mass (Da):11,045
Last modified:November 1, 1988 - v1
Checksum:i85858F6E84A97AB8
GO
Isoform M1 (identifier: P03485-1) [UniParc]FASTAAdd to basket
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.
Length:252
Mass (Da):27,893
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti27A → I in ABD77677 (Ref. 5) Curated1
Sequence conflicti30A → S in ABD77677 (Ref. 5) Curated1
Sequence conflicti54R → L in ABD77677 (Ref. 5) Curated1
Sequence conflicti61G → R in ABD77677 (Ref. 5) Curated1
Sequence conflicti77R → Q in ABD77677 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti10P → H in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H. 1
Natural varianti10P → L in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L. 1
Natural varianti27A → 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. 1
Natural varianti39I → 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. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_040979.2. NC_002016.1. [P06821-1]

Genome annotation databases

GeneIDi956528.
KEGGivg:956528.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_040979.2. NC_002016.1. [P06821-1]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DLMX-ray2.20X/Y2-24[»]
ProteinModelPortaliP06821.
SMRiP06821.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP06821. 12 interactors.

Chemistry databases

ChEMBLiCHEMBL1932894.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi956528.
KEGGivg:956528.

Phylogenomic databases

KOiK19394.

Enzyme and pathway databases

ReactomeiR-HSA-168255. Influenza Life Cycle.
R-HSA-168275. Entry of Influenza Virion into Host Cell via Endocytosis.
R-HSA-168288. Fusion of the Influenza Virion to the Host Cell Endosome.
R-HSA-168298. Release.
R-HSA-168302. Budding.
R-HSA-168303. Packaging of Eight RNA Segments.
R-HSA-168316. Assembly of Viral Components at the Budding Site.
R-HSA-168336. Uncoating of the Influenza Virion.
R-HSA-168874. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
R-HSA-192823. Viral mRNA Translation.

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_I34A1
AccessioniPrimary (citable) accession number: P06821
Secondary accession number(s): A4GXH7
, Q20N37, Q5UAV4, Q5UAV5, Q5UAV6, Q84105, Q8JUU3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1988
Last modified: November 2, 2016
This is version 113 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, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.