Q9WV57 · MPEG1_RAT

  • Protein
    Macrophage-expressed gene 1 protein
  • Gene
    Mpeg1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Pore-forming protein involved in both innate and adaptive immunity. Plays a central role in antigen cross-presentation in dendritic cells by forming a pore in antigen-containing compartments, thereby promoting delivery of antigens for cross-presentation. Also involved in innate immune response following bacterial infection; shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria. Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol. Required for the antibacterial activity of reactive oxygen species and nitric oxide.

Macrophage-expressed gene 1 protein, processed form

Pore-forming protein that plays a central role in antigen cross-presentation in dendritic cells by mediating delivery of antigens for cross-presentation. Dendritic cells bridge innate and adaptive immunity by capturing exogenous antigens on MHC class-I molecules and presenting them to naive CD8+ T-cells. Acts by forming a pore in antigen-containing compartments, promoting the release of antigens into the cytosol, enabling generation of MHCI:peptide complexes and T-cell priming.

Activity regulation

Forms arc- and ring-shaped pre-pores on top of the membrane at neutral to slightly acidic pH conditions and converts to pores upon acidification. Undergoes transition from the pre-pore to the pore in a processive clockwise hand-over-hand process. In the pore state, 2 alpha-helical regions refold into transmembrane hairpins (TMH1 and TMH2) in each protomer that form in the ensemble complex giant beta-barrel transmembrane pores.

Features

Showing features for site.

TypeIDPosition(s)Description
Site352-353Cleavage; by LGMN
Site357-358Cleavage; by LGMN
Site359-360Cleavage; by LGMN
Site628-629Cleavage; by trypsin

GO annotations

AspectTerm
Cellular Componentcytoplasmic vesicle
Cellular Componentendolysosome
Cellular Componentphagocytic vesicle
Cellular Componentphagocytic vesicle membrane
Cellular Componentphagolysosome membrane
Molecular Functionpore-forming activity
Molecular Functionwide pore channel activity
Biological Processadaptive immune response
Biological Processantibacterial innate immune response
Biological Processantigen processing and presentation of exogenous peptide antigen
Biological Processantigen processing and presentation of exogenous peptide antigen via MHC class I
Biological Processdefense response to bacterium
Biological Processdefense response to Gram-negative bacterium
Biological Processdefense response to Gram-positive bacterium
Biological Processdendritic cell antigen processing and presentation

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      Mpeg1

Organism names

  • Taxonomic identifier
  • Strains
    • Brown Norway
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q9WV57

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasmic vesicle membrane
; Multi-pass membrane protein
Note: Bacterial infection induces translocation of the cytoplasmic vesicles to bacterium-containing phagocytic vesicles and fusing of the vesicles.

Macrophage-expressed gene 1 protein, processed form

Cytoplasmic vesicle, phagosome membrane
; Multi-pass membrane protein
Note: Proteolytically processed in lysosomes, leading to its maturation and forms pores in the membrane of antigen-containing phagosomes.

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane113-120Beta stranded
Transmembrane127-132Beta stranded
Transmembrane235-244Beta stranded
Transmembrane248-256Beta stranded
Transmembrane654-674Helical

Keywords

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-19
ChainPRO_000032414520-714Macrophage-expressed gene 1 protein
Disulfide bond34↔70
Glycosylation185N-linked (GlcNAc...) asparagine
Glycosylation269N-linked (GlcNAc...) asparagine
Disulfide bond350↔369
ChainPRO_0000459025353-629Macrophage-expressed gene 1 protein, processed form
Glycosylation375N-linked (GlcNAc...) asparagine
Disulfide bond385↔394
Disulfide bond432↔446
Disulfide bond436↔442
Disulfide bond531↔569
Disulfide bond554↔574

Post-translational modification

Proteolytically processed in two steps to generate the Macrophage-expressed gene 1 protein, processed form: cleaved by trypsin in proximity of the helical transmembrane domain releases the ectodomain into the lysosomal lumen to orient the pore-forming domain toward the endogenous membranes, and processed by the asparagine endopeptidase (LGMN). Proteolytic processing in antigen-containing vesicles is pH-dependent.
Monoubiquitinated in response to bacterial infection; ubiquitination is required for vesicular localization and antibacterial activity and can be blocked by bacterial cell cycle inhibiting factor (cif).

Keywords

Proteomic databases

PTM databases

Interaction

Subunit

Homooligomer; predominantly forms a homooligomeric arc-shaped pore complex instead of complete rings of 16 subunits.

Structure

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain30-345MACPF
Region410-653P2
Region690-714Disordered

Domain

The MACPF domain includes the central machinery of pore formation: acidification causes a significant structural rearrangement, leading to oligomerization and deployment of the transmembrane beta-strands (named TMH1 and TMH2) that enter the membrane as amphipathic beta-hairpins.
The P2 region contains beta-hairpins to interact with target membranes.

Sequence similarities

Belongs to the MPEG1 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    714
  • Mass (Da)
    78,527
  • Last updated
    2008-03-18 v2
  • Checksum
    3235512C40B9DF35
MNSFMAIALIWMMIACAEADKPLRDPGMTGFQTCKDTLKLPVLEVLPGGGWDNLRNIDMGRVIDLTYTNCKTTEDGQYIIPDEVYTIPQKESNLEMNSEIRDSWVNYQSTTSFSINTELSLFSKVNGKFSTEFQRMKTLQVKDQAVTTRVQVRNRIYTVKNSPTSELSFGFTNALMDICDQLEKNQTKMATYLAELLVLNYGTHVITSVDAGAALVQEDHIRSSFLLDNQNSENTVTASAGIAFLNIVNFKVETDHTSQTLLTKSYLSNRTNSRVQSFGGIPFYPGITLETWQKGITNHLVAIDRAGLPLHFFIKPDKLPGLPGGLVKKLSKTVETAVRHYYTFNTHPGCTNVDSPNFNFQANMEDDSCDAKVTNFTFGGLYQECTELSGDALCQNLEQKNLLTGDFSCPSGYTPVHLLSQTHEEGYSRLECKKKCTLKIFCKTVCEDVFRVAKAQFRAYWCVATGQVPDNSGLLFGGLFTDKSINPMTNAQSCPAGYIPLNLFESLKVCVSLDYELGYKFSVPFGGFFSCIMGNPLVNSDTAKDIGAPSLKKCPGGFSQHLAVISDGCQVSYCVKAGIFTGGSLLPVRLPPYTKPPLMSQVATNTVIVTSSETARSWIKDPQTNQWKLGEPLELHKAMTVIHGDGNGMSGGEAAGVTLGVIIALGIVITLAIYSTRKYKKEKEYQEIEEQESLVGSFATDASPPNGEQDPCPA

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I6AL73A0A8I6AL73_RATMpeg1721

Sequence caution

The sequence AAD38417.1 differs from that shown. Reason: Frameshift

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AABR03005343
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AF156540
EMBL· GenBank· DDBJ
AAD38417.1
EMBL· GenBank· DDBJ
mRNA Frameshift

Genome annotation databases

Similar Proteins

Disclaimer

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