M - Matrix protein 2 - Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)

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

Activity 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 key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	37	Essential for channel activity, possibly by being protonated during channel activation, and by forming the channel gate and the selective filterUniRule annotation		1
Siteⁱ	41	Seems to be involved in pH gatingUniRule annotation		1

GO - Molecular functionⁱ

ion channel activity Source: UniProtKB-UniRule
proton transmembrane transporter activity Source: UniProtKB-UniRule
transporter activity Source: Reactome

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

fusion of virus membrane with host plasma membrane Source: Reactome
intracellular transport of viral protein in host cell Source: Reactome
pore formation by virus in membrane of host cell Source: UniProtKB-UniRule
protein complex oligomerization Source: UniProtKB-UniRule
receptor-mediated endocytosis of virus by host cell Source: Reactome
suppression by virus of host autophagy Source: UniProtKB-UniRule
uncoating of virus Source: Reactome
viral budding from plasma membrane Source: Reactome
viral genome packaging Source: Reactome
virion assembly Source: Reactome
virion attachment to host cell Source: Reactome

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Ion channel, Viral ion channel
Biological process	Host-virus interaction, Hydrogen ion transport, Inhibition of host autophagy by virus, Ion transport, Transport

Enzyme and pathway databases

Reactomeⁱ	R-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

Reactomeⁱ

R-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 2UniRule annotation Alternative name(s): Proton channel protein M2UniRule annotation
Gene namesⁱ	Name:MUniRule annotation
Organismⁱ	Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Taxonomic identifierⁱ	211044 [NCBI]
Taxonomic lineageⁱ	Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Alphainfluenzavirus › Influenza A virus › H1N1 subtype
Virus hostⁱ	Aves [TaxID: 8782] Homo sapiens (Human) [TaxID: 9606] Sus scrofa (Pig) [TaxID: 9823]
Proteomesⁱ	UP000116373 Componentⁱ: Genome UP000170967 Componentⁱ: Genome UP000009255 Componentⁱ: Genome

Subcellular locationⁱ

Virion membrane
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04069
Host apical cell membrane
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04069
; Single-pass type III membrane protein
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04069

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 key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 22	Virion surfaceUniRule annotationAdd BLAST	22
Transmembraneⁱ	23 – 43	Helical; Signal-anchor for type III membrane proteinUniRule annotationAdd BLAST	21
Topological domainⁱ	44 – 97	IntravirionUniRule annotationAdd BLAST	54

GO - Cellular componentⁱ

cytosol Source: Reactome
endocytic vesicle membrane Source: Reactome
endoplasmic reticulum membrane Source: Reactome
endosome lumen Source: Reactome
extracellular region Source: Reactome
Golgi membrane Source: Reactome
host cell plasma membrane Source: UniProtKB-SubCell
integral component of membrane Source: UniProtKB-UniRule
integral to membrane of host cell Source: UniProtKB-UniRule
plasma membrane Source: Reactome
virion membrane Source: UniProtKB-SubCell

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechⁱ

Chemistry databases

ChEMBLⁱ	CHEMBL1932894

ChEMBLⁱ

CHEMBL1932894

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000078890	1 – 97	Matrix protein 2Add BLAST		97

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	17	Interchain (with C-17)UniRule annotation
Disulfide bondⁱ	19	Interchain (with C-19)UniRule annotation
Glycosylationⁱ	20	N-linked (GlcNAc...) asparagine; by hostUniRule annotation	1
Lipidationⁱ	50	S-palmitoyl cysteine; by hostUniRule annotation	1
Modified residueⁱ	64	Phosphoserine; by hostUniRule annotation	1
Modified residueⁱ	82	Phosphoserine; by hostUniRule annotation	1
Modified residueⁱ	93	Phosphoserine; by hostUniRule annotation	1

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

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
EIF2B4	Q9UI10	3	EBI-2547404,EBI-2340132	From Homo sapiens.
ZMPSTE24	O75844	2	EBI-2547404,EBI-1056377	From Homo sapiens.

Protein-protein interaction databases

ELMⁱ	P06821
IntActⁱ	P06821, 104 interactors

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Turnⁱ	3 – 5	Combined sources		3
Beta strandⁱ	6 – 8	Combined sources		3

Show more details

3D structure databases

ProteinModelPortalⁱ	P06821
SMRⁱ	P06821
ModBaseⁱ	Search...
MobiDBⁱ	Search...

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

KEGG Orthology (KO) More...KOⁱ	K19394
Database of Orthologous Groups More...OrthoDBⁱ	VOG090000KZ

Family and domain databases

HAMAPⁱ	MF_04069 INFV_M2, 1 hit
InterProⁱ	View protein in InterPro IPR002089 Flu_M2
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00599 Flu_M2, 1 hit
ProDomⁱ	View 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. Align Add to basket

Note: Only the first 9 residues are shared by the 2 isoforms.

Isoform M2 (identifier: P06821-1) [UniParc]FASTA Add 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]FASTA Add 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 key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	27	A → I in ABD77677 (Ref. 5)	1
Sequence conflictⁱ	30	A → S in ABD77677 (Ref. 5)	1
Sequence conflictⁱ	54	R → L in ABD77677 (Ref. 5)	1
Sequence conflictⁱ	61	G → R in ABD77677 (Ref. 5)	1
Sequence conflictⁱ	77	R → Q in ABD77677 (Ref. 5)	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱ	10	P → H in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10H.	1
Natural variantⁱ	10	P → L in strain: A/Puerto Rico/8/34/Mount Sinai/Wi-M2-P10L.	1
Natural variantⁱ	27	A → 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 variantⁱ	39	I → 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
NCBI Reference Sequences More...RefSeqⁱ	NP_040979.2, NC_002016.1 [P06821-1]

Genome annotation databases

GeneIDⁱ	956528
KEGGⁱ	vg:956528

Keywords - Coding sequence diversityⁱ

Alternative splicing

Protein	Similar proteins		Species	Score	Length	Source
P06821	Matrix protein 2		9INFA		97	UniRef100_P06821
Matrix protein 2		Influenza A virus (A/reassortant/CDC2005712034(California/07/2004 x Puerto Rico/8/1934)(H3N2))		97
Matrix protein 2		Influenza A virus (A/Puerto Rico/8-LVD3/1934(H1N1))		97
Matrix protein 2		Influenza A virus (A/Puerto Rico/8-LVD2/1934(H1N1))		97
Matrix protein 2		Influenza A virus (A/Puerto Rico/8-RG001A/1934(H1N1))		97
+5

Protein	Similar proteins		Species	Score	Length	Source
P06821	Matrix protein 2		I000X		97	UniRef90_P06821
Matrix protein 2		I06A0		97
Matrix protein 2		I36A0		97
Matrix protein 2		9INFA		97
Matrix protein 2		Influenza A virus (A/reassortant/CDC2005712034(California/07/2004 x Puerto Rico/8/1934)(H3N2))		97
+220

Protein	Similar proteins		Species	Score	Length	Source
P06821	Matrix protein 2		I000X		97	UniRef50_P06821
Matrix protein 2		I36A0		97
Matrix protein 2		I06A0		97
Matrix protein 2		I79A0		97
Matrix protein 2		I80A4		96
+61120

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
RefSeqⁱ	NP_040979.2, NC_002016.1 [P06821-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	5DLM	X-ray	2.20	X/Y	2-24	[»]
ProteinModelPortalⁱ	P06821
SMRⁱ	P06821
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

ELMⁱ	P06821
IntActⁱ	P06821, 104 interactors

Chemistry databases

ChEMBLⁱ	CHEMBL1932894

ChEMBLⁱ

CHEMBL1932894

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	956528
KEGGⁱ	vg:956528

Phylogenomic databases

KOⁱ	K19394
OrthoDBⁱ	VOG090000KZ

Enzyme and pathway databases

Reactomeⁱ	R-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

Reactomeⁱ

R-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

HAMAPⁱ	MF_04069 INFV_M2, 1 hit
InterProⁱ	View protein in InterPro IPR002089 Flu_M2
Pfamⁱ	View protein in Pfam PF00599 Flu_M2, 1 hit
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD001031 Flu_M2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	M2_I34A1
Accessionⁱ	P06821Primary (citable) accession number: P06821 Secondary accession number(s): A4GXH7 Q8JUU3
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
	Last sequence update:	November 1, 1988
	Last modified:	October 10, 2018
	This is version 123 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Viral Protein Annotation Program

UniProtKB

UniParc

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Supporting data

UniProtKB - P06821 (M2_I34A1)

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Matrix protein 2

M

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Sites

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

GO - Cellular componenti

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ