EMRE (CG17680) encodes the Drosophila essential MCU regulator, a small single-pass protein of the inner mitochondrial membrane and a metazoan-specific subunit of the mitochondrial calcium uniporter. As in other animals, fly MCU cannot conduct calcium without EMRE; EMRE's transmembrane helix associates with the MCU pore and stabilizes its open state, and in mammals its acidic C-terminal tail also couples the pore to the MICU gatekeepers. Loss of EMRE abolishes fast mitochondrial calcium uptake, and co-overexpression of EMRE with MCU causes MICU1-suppressible tissue loss, while EMRE null flies are viable with a shortened lifespan.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005262 calcium channel activity | IMP PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: EMRE loss abolishes fast mitochondrial calcium uptake (contributes_to calcium channel activity). Reason: EMRE does not form the pore but is required for MCU to conduct calcium; contributes_to calcium channel activity is exactly the right representation for this subunit. Supporting Evidence: PMID:31042479 As with MCU1, analysis of these EMRE mutants revealed that they all exhibit no fast mitochondrial Ca2+ uptake |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to mitochondrial inner membrane. Reason: EMRE is a single-pass inner mitochondrial membrane subunit of the uniporter. Supporting Evidence: file:DROME/EMRE/EMRE-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of inner membrane location from human EMRE/SMDT1 (Q9H4I9). Reason: Conserved topology; core location. Supporting Evidence: file:DROME/EMRE/EMRE-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | NAS PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: Author statement locating the uniporter components in the inner membrane. Reason: Core location of the uniporter subunit. Supporting Evidence: file:DROME/EMRE/EMRE-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0006851 mitochondrial calcium ion transmembrane transport | IMP PMID:27099988 Dual functions of a small regulatory subunit in the mitochon... | MODIFY | Summary: Fly MCU requires EMRE to transport calcium in a reconstitution assay. Reason: Correct but general; the measured transport is calcium uptake into mitochondria, captured by the child term GO:0036444 calcium import into the mitochondrion, which EMRE already carries. Proposed replacements: calcium import into the mitochondrion Supporting Evidence: PMID:27099988 metazoan MCU homologues from C. elegans and D. melanogaster require EMRE to transport Ca2+ |
| GO:0006851 mitochondrial calcium ion transmembrane transport | IMP PMID:28726639 Mitochondrial calcium uniporter in Drosophila transfers calc... | MODIFY | Summary: EMRE is required for Drosophila MCU calcium channel activity. Reason: Correct but general; refine to GO:0036444 calcium import into the mitochondrion, already annotated to EMRE. Proposed replacements: calcium import into the mitochondrion Supporting Evidence: PMID:28726639 Drosophila MCU contains evolutionarily conserved structures and requires essential MCU regulator (EMRE) for its calcium channel activities |
| GO:0036444 calcium import into the mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of calcium import into the mitochondrion, with fly EMRE (FB:FBgn0062440) and human EMRE (Q9H4I9) among donors via PTN002141638. Reason: Core process; the fly gene's own experimental data are part of the evidence for the node. Supporting Evidence: PMID:31042479 While loss of pore-forming MCU or EMRE abolishes fast mitochondrial Ca2+ uptake |
| GO:0036444 calcium import into the mitochondrion | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (EMRE family) mapping to calcium import into the mitochondrion. Reason: Correct core process, confirmed by fly mutants. Supporting Evidence: PMID:31042479 EMRE mutations prevent mitochondrial Ca2+ uptake equivalent to the inhibitor ruthenium red |
| GO:0036444 calcium import into the mitochondrion | IMP PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: EMRE null mutants lack fast mitochondrial calcium uptake. Reason: Direct mutant evidence for the core process. Supporting Evidence: PMID:31042479 As with MCU1, analysis of these EMRE mutants revealed that they all exhibit no fast mitochondrial Ca2+ uptake |
| GO:0036444 calcium import into the mitochondrion | NAS PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: Author statement (NAS) for EMRE in mitochondrial calcium uptake. Reason: Duplicate of the IMP row; core process. Supporting Evidence: PMID:31042479 While loss of pore-forming MCU or EMRE abolishes fast mitochondrial Ca2+ uptake |
| GO:0045089 positive regulation of innate immune response | HMP PMID:19520911 Genome-wide RNAi screen identifies genes involved in intesti... | MARK AS OVER ANNOTATED | Summary: Genome-wide RNAi screen hit for susceptibility to intestinal Serratia marcescens infection. Reason: Positive regulation of the innate immune response is a mechanistic claim that a survival screen cannot support: reduced survival after infection does not show that EMRE modulates immune signalling, and could reflect general fitness or epithelial homeostasis effects of altered mitochondrial calcium handling. By contrast, the companion row GO:0050829 defense response to Gram-negative bacterium is close to a restatement of the screen phenotype and is kept as non-core. The gene is not discussed in the cached text (the hits are in supplementary tables). Supporting Evidence: PMID:19520911 tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity |
| GO:0050829 defense response to Gram-negative bacterium | HMP PMID:19520911 Genome-wide RNAi screen identifies genes involved in intesti... | KEEP AS NON CORE | Summary: Genome-wide RNAi screen hit for susceptibility to Gram-negative intestinal infection. Reason: Reflects the screen phenotype (altered survival after Serratia infection); plausible as an indirect requirement but not a core role of a uniporter subunit, and not followed up. Supporting Evidence: PMID:19520911 We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. |
| GO:0051560 mitochondrial calcium ion homeostasis | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial calcium ion homeostasis (fly EMRE FB:FBgn0062440, human Q9H4I9, C. elegans donors) via PTN002141638. Reason: As an essential uniporter subunit, EMRE controls matrix calcium entry; same treatment as for MCU. |
| GO:0051560 mitochondrial calcium ion homeostasis | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (EMRE family) mapping to mitochondrial calcium ion homeostasis. Reason: Consistent with EMRE's essential role in uniporter calcium uptake. |
| GO:0051560 mitochondrial calcium ion homeostasis | IMP PMID:27099988 Dual functions of a small regulatory subunit in the mitochon... | ACCEPT | Summary: EMRE is required for fly MCU-mediated mitochondrial calcium transport. Reason: Supports EMRE control of matrix calcium entry. Supporting Evidence: PMID:27099988 metazoan MCU homologues from C. elegans and D. melanogaster require EMRE to transport Ca2+ |
| GO:0051560 mitochondrial calcium ion homeostasis | NAS PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: Author statement (NAS) linking EMRE to mitochondrial calcium homeostasis. Reason: Consistent with the uniporter's role in matrix calcium uptake. Supporting Evidence: PMID:31042479 Mitochondrial Ca2+ uptake is an important mediator of metabolism and cell death. |
| GO:1990246 uniplex complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of uniplex complex membership (human EMRE Q9H4I9 and other donors). Reason: EMRE is an obligate subunit of the metazoan uniplex; uniplex complex is accepted for all fly uniporter subunits. Supporting Evidence: PMID:31042479 Co-expression of either MICU1-A or MICU1-B with MCU and EMRE prevented the MCU:EMRE phenotype (Figure 5B). |
| GO:1990246 uniplex complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (EMRE family) mapping to uniplex complex. Reason: Correct complex membership. |
| GO:1990246 uniplex complex | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of uniplex complex from human EMRE (Q9H4I9). Reason: Correct complex membership. |
| GO:1990246 uniplex complex | NAS PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: Author statement (NAS) placing EMRE in the uniporter. Reason: Core complex membership. Supporting Evidence: PMID:31042479 This includes loss-of-function mutants for MCU, EMRE, MICU1, and MICU3 (Drosophila lack MCUb and MICU2) |
| GO:1990246 uniplex complex | TAS PMID:31042479 Comprehensive Genetic Characterization of Mitochondrial Ca(2... | ACCEPT | Summary: Traceable author statement placing EMRE in the uniporter. Reason: Core complex membership; duplicate of the NAS row. Supporting Evidence: PMID:31042479 Here, we report a comprehensive genetic characterization of all known uniporter components conserved in Drosophila. |
Loading supporting content…
Download this section (compressed HTML)Q: Does Drosophila EMRE, like human EMRE, bind MICU1 through its C-terminal acidic tail to keep the MCU pore under gatekeeper control?
Experiment: Express EMRE lacking the C-terminal acidic tail in EMRE null flies and measure low-calcium leak through the uniporter in isolated mitochondria.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)