Q9WV57 · MPEG1_RAT
- ProteinMacrophage-expressed gene 1 protein
- GeneMpeg1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids714 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 352-353 | Cleavage; by LGMN | ||||
Sequence: NV | ||||||
Site | 357-358 | Cleavage; by LGMN | ||||
Sequence: NF | ||||||
Site | 359-360 | Cleavage; by LGMN | ||||
Sequence: NF | ||||||
Site | 628-629 | Cleavage; by trypsin | ||||
Sequence: KL |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasmic vesicle | |
Cellular Component | endolysosome | |
Cellular Component | phagocytic vesicle | |
Cellular Component | phagocytic vesicle membrane | |
Cellular Component | phagolysosome membrane | |
Molecular Function | pore-forming activity | |
Molecular Function | wide pore channel activity | |
Biological Process | adaptive immune response | |
Biological Process | antibacterial innate immune response | |
Biological Process | antigen processing and presentation of exogenous peptide antigen | |
Biological Process | antigen processing and presentation of exogenous peptide antigen via MHC class I | |
Biological Process | defense response to bacterium | |
Biological Process | defense response to Gram-negative bacterium | |
Biological Process | defense response to Gram-positive bacterium | |
Biological Process | dendritic cell antigen processing and presentation |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameMacrophage-expressed gene 1 protein
- Short namesMacrophage gene 1 protein; Mpg-1
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ9WV57
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 113-120 | Beta stranded | ||||
Sequence: FSINTELS | ||||||
Transmembrane | 127-132 | Beta stranded | ||||
Sequence: GKFSTE | ||||||
Transmembrane | 235-244 | Beta stranded | ||||
Sequence: TVTASAGIAF | ||||||
Transmembrane | 248-256 | Beta stranded | ||||
Sequence: VNFKVETDH | ||||||
Transmembrane | 654-674 | Helical | ||||
Sequence: AAGVTLGVIIALGIVITLAIY |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MNSFMAIALIWMMIACAEA | ||||||
Chain | PRO_0000324145 | 20-714 | Macrophage-expressed gene 1 protein | |||
Sequence: DKPLRDPGMTGFQTCKDTLKLPVLEVLPGGGWDNLRNIDMGRVIDLTYTNCKTTEDGQYIIPDEVYTIPQKESNLEMNSEIRDSWVNYQSTTSFSINTELSLFSKVNGKFSTEFQRMKTLQVKDQAVTTRVQVRNRIYTVKNSPTSELSFGFTNALMDICDQLEKNQTKMATYLAELLVLNYGTHVITSVDAGAALVQEDHIRSSFLLDNQNSENTVTASAGIAFLNIVNFKVETDHTSQTLLTKSYLSNRTNSRVQSFGGIPFYPGITLETWQKGITNHLVAIDRAGLPLHFFIKPDKLPGLPGGLVKKLSKTVETAVRHYYTFNTHPGCTNVDSPNFNFQANMEDDSCDAKVTNFTFGGLYQECTELSGDALCQNLEQKNLLTGDFSCPSGYTPVHLLSQTHEEGYSRLECKKKCTLKIFCKTVCEDVFRVAKAQFRAYWCVATGQVPDNSGLLFGGLFTDKSINPMTNAQSCPAGYIPLNLFESLKVCVSLDYELGYKFSVPFGGFFSCIMGNPLVNSDTAKDIGAPSLKKCPGGFSQHLAVISDGCQVSYCVKAGIFTGGSLLPVRLPPYTKPPLMSQVATNTVIVTSSETARSWIKDPQTNQWKLGEPLELHKAMTVIHGDGNGMSGGEAAGVTLGVIIALGIVITLAIYSTRKYKKEKEYQEIEEQESLVGSFATDASPPNGEQDPCPA | ||||||
Disulfide bond | 34↔70 | |||||
Sequence: CKDTLKLPVLEVLPGGGWDNLRNIDMGRVIDLTYTNC | ||||||
Glycosylation | 185 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 269 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 350↔369 | |||||
Sequence: CTNVDSPNFNFQANMEDDSC | ||||||
Chain | PRO_0000459025 | 353-629 | Macrophage-expressed gene 1 protein, processed form | |||
Sequence: VDSPNFNFQANMEDDSCDAKVTNFTFGGLYQECTELSGDALCQNLEQKNLLTGDFSCPSGYTPVHLLSQTHEEGYSRLECKKKCTLKIFCKTVCEDVFRVAKAQFRAYWCVATGQVPDNSGLLFGGLFTDKSINPMTNAQSCPAGYIPLNLFESLKVCVSLDYELGYKFSVPFGGFFSCIMGNPLVNSDTAKDIGAPSLKKCPGGFSQHLAVISDGCQVSYCVKAGIFTGGSLLPVRLPPYTKPPLMSQVATNTVIVTSSETARSWIKDPQTNQWKL | ||||||
Glycosylation | 375 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 385↔394 | |||||
Sequence: CTELSGDALC | ||||||
Disulfide bond | 432↔446 | |||||
Sequence: CKKKCTLKIFCKTVC | ||||||
Disulfide bond | 436↔442 | |||||
Sequence: CTLKIFC | ||||||
Disulfide bond | 531↔569 | |||||
Sequence: CIMGNPLVNSDTAKDIGAPSLKKCPGGFSQHLAVISDGC | ||||||
Disulfide bond | 554↔574 | |||||
Sequence: CPGGFSQHLAVISDGCQVSYC |
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
- PTM
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 30-345 | MACPF | ||||
Sequence: GFQTCKDTLKLPVLEVLPGGGWDNLRNIDMGRVIDLTYTNCKTTEDGQYIIPDEVYTIPQKESNLEMNSEIRDSWVNYQSTTSFSINTELSLFSKVNGKFSTEFQRMKTLQVKDQAVTTRVQVRNRIYTVKNSPTSELSFGFTNALMDICDQLEKNQTKMATYLAELLVLNYGTHVITSVDAGAALVQEDHIRSSFLLDNQNSENTVTASAGIAFLNIVNFKVETDHTSQTLLTKSYLSNRTNSRVQSFGGIPFYPGITLETWQKGITNHLVAIDRAGLPLHFFIKPDKLPGLPGGLVKKLSKTVETAVRHYYTFN | ||||||
Region | 410-653 | P2 | ||||
Sequence: PSGYTPVHLLSQTHEEGYSRLECKKKCTLKIFCKTVCEDVFRVAKAQFRAYWCVATGQVPDNSGLLFGGLFTDKSINPMTNAQSCPAGYIPLNLFESLKVCVSLDYELGYKFSVPFGGFFSCIMGNPLVNSDTAKDIGAPSLKKCPGGFSQHLAVISDGCQVSYCVKAGIFTGGSLLPVRLPPYTKPPLMSQVATNTVIVTSSETARSWIKDPQTNQWKLGEPLELHKAMTVIHGDGNGMSGGE | ||||||
Region | 690-714 | Disordered | ||||
Sequence: EQESLVGSFATDASPPNGEQDPCPA |
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length714
- Mass (Da)78,527
- Last updated2008-03-18 v2
- Checksum3235512C40B9DF35
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AL73 | A0A8I6AL73_RAT | Mpeg1 | 721 |
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AABR03005343 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AF156540 EMBL· GenBank· DDBJ | AAD38417.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |