ATP5ME (ATP5I) encodes subunit e of mitochondrial F1F0 ATP synthase (complex V). It is a small accessory subunit of the membrane F(o) domain and assembles with the stator-stalk subunits b and g. Subunit e stabilizes ATP synthase dimers and higher oligomers, which bend the inner membrane at cristae ridges. Its loss in human cells destabilizes oligomers, leaves assembly intermediates, alters mitochondrial morphology and inhibits oxidative phosphorylation. It has been implicated as a target through which biguanides such as metformin affect complex V.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: Protein binding (IPI) with FOS, from a large-scale Y2H screen. A mitochondrial inner-membrane F(o) subunit binding this partner has no established functional meaning. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SPG21, from the HuRI binary Y2H map. A mitochondrial inner-membrane F(o) subunit binding this partner has no established functional meaning. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with CIDEB, from the HuRI binary Y2H map. A mitochondrial inner-membrane F(o) subunit binding this partner has no established functional meaning. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:38884001 Mapping adipocyte interactome networks by HaloTag-enrichment... | REMOVE | Summary: Protein binding (IPI) with FOS, from an adipocyte HaloTag pull-down mass-spectrometry screen. A mitochondrial inner-membrane F(o) subunit binding this partner has no established functional meaning. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). Detected in the high-confidence mitochondrial proteome. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001752424 SUPPORTS TRANSFER Mitochondrial complex V subunit family. Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005739 mitochondrion | IC PMID:12110673 A functionally active human F1F0 ATPase can be purified by i... | ACCEPT | Summary: Mitochondrion (IC). Inferred from membership in complex V. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrion (IDA). Human Protein Atlas immunofluorescence. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrion (IEA). UniProt subcellular location or ARBA rule. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial inner membrane (IEA). UniProt subcellular location or ARBA rule. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep... | ACCEPT | Summary: Mitochondrial inner membrane (NAS). ComplexPortal statement. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-164832 | ACCEPT | Summary: Mitochondrial inner membrane (TAS). UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. The Reactome event is 'ATPase synthesizes ATP'. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-164834 | ACCEPT | Summary: Mitochondrial inner membrane (TAS). UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. The Reactome event is 'Enzyme-bound ATP is released'. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-164840 | ACCEPT | Summary: Mitochondrial inner membrane (TAS). UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. The Reactome event is 'ADP and Pi bind to ATPase'. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-8949580 | ACCEPT | Summary: Mitochondrial inner membrane (TAS). UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. The Reactome event is 'F1Fo ATP synthase dimerizes'. Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0015078 proton transmembrane transporter activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Proton transmembrane transporter activity (IEA, InterPro ATP synthase subunit e family). UniProt describes the membrane proton channel as the whole F(o) domain, built from subunits c, a, 8, e, f, g, k and j. The activity is a property of that assembled sector. The subunit e evidence is about dimer and oligomer stability (loss of e removes its partner subunit g and destabilizes dimers), not about proton conduction. For an accessory subunit, contributes_to rotary ATP synthase activity is the right statement; an unqualified 'enables' transporter activity overstates it. Over-annotation. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] [PMID:42138716 "ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology."] [PMID:42138716 "The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A)."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, PMID:42138716 ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology. PMID:42138716 The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A). |
| GO:0015986 proton motive force-driven ATP synthesis | IEA GO_REF:0000002 | ACCEPT | Summary: Proton motive force-driven atp synthesis (IEA). As a complex V subunit that stabilizes ATP synthase dimers, subunit e takes part in oxidative ATP synthesis. Its knockout inhibits OXPHOS. Core process. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:42138716 "We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:42138716 We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis. |
| GO:0015986 proton motive force-driven ATP synthesis | NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep... | ACCEPT | Summary: Proton motive force-driven atp synthesis (NAS). As a complex V subunit that stabilizes ATP synthase dimers, subunit e takes part in oxidative ATP synthesis. Its knockout inhibits OXPHOS. Core process. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:42138716 "We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:42138716 We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis. |
| GO:0016020 membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Membrane (IEA). UniProt subcellular location or ARBA rule. UniProt places subunit e in the mitochondrial inner membrane, in the F(o) domain of complex V. Correct but generic; Accepted. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane. file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, |
| GO:0042776 proton motive force-driven mitochondrial ATP synthesis | IBA GO_REF:0000033 | ACCEPT | Summary: Proton motive force-driven mitochondrial atp synthesis (IBA). As a complex V subunit that stabilizes ATP synthase dimers, subunit e takes part in oxidative ATP synthesis. Its knockout inhibits OXPHOS. Core process. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:42138716 "We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001752424 SUPPORTS TRANSFER Mitochondrial ATP synthesis; consistent with the subunit's complex membership. Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:42138716 We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis. |
| GO:0042776 proton motive force-driven mitochondrial ATP synthesis | IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i... | ACCEPT | Summary: Proton motive force-driven mitochondrial atp synthesis (IDA). As a complex V subunit that stabilizes ATP synthase dimers, subunit e takes part in oxidative ATP synthesis. Its knockout inhibits OXPHOS. Core process. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:42138716 "We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:42138716 We demonstrate that ATP5I interacts with a biguanide analogue in vitro, and disabling its expression by CRISPR-Cas9 in pancreatic cancer cells leads to the same phenotype as biguanide-treated cells, including mitochondrial morphology alterations, reduction of the NAD+/NADH ratio, inhibition of oxidative phosphorylation (OXPHOS), rescue of respiration by uncouplers, and a compensatory increase in glycolysis. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Protein-containing complex binding (IEA, rat ortholog projection). Subunit e is a constituent of complex V; it stabilizes dimers and keeps its partner subunit g, rather than binding the complex as a separate entity. Complex membership is captured by GO:0045259, and the dimer-stabilizing role by the core function. This binding term adds nothing; over-annotation. Reason: [PMID:26297831 "When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex)."] [PMID:42138716 "The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A)."] [PMID:42138716 "ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology."] Supporting Evidence: PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex). PMID:42138716 The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A). PMID:42138716 ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology. |
| GO:0045259 proton-transporting ATP synthase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Proton-transporting ATP synthase complex (IBA). Subunit e is a membrane subunit of the F(o) domain of complex V. It co-purifies with immunocaptured human F1F0, and it assembles into the stator-stalk 'b-e-g' subcomplex. Core. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:26297831 "When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex)."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001752424 SUPPORTS TRANSFER Complex V subunit e family node; human ATP5ME (P56385) is itself an experimentally annotated member. Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex). |
| GO:0045259 proton-transporting ATP synthase complex | IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i... | ACCEPT | Summary: Proton-transporting ATP synthase complex (IDA). Subunit e is a membrane subunit of the F(o) domain of complex V. It co-purifies with immunocaptured human F1F0, and it assembles into the stator-stalk 'b-e-g' subcomplex. Core. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:26297831 "When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex)."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex). |
| GO:0045259 proton-transporting ATP synthase complex | IEA GO_REF:0000107 | ACCEPT | Summary: Proton-transporting ATP synthase complex (IEA). Subunit e is a membrane subunit of the F(o) domain of complex V. It co-purifies with immunocaptured human F1F0, and it assembles into the stator-stalk 'b-e-g' subcomplex. Core. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:26297831 "When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex)."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex). |
| GO:0045259 proton-transporting ATP synthase complex | NAS PMID:26297831 Assembly of human mitochondrial ATP synthase through two sep... | ACCEPT | Summary: Proton-transporting ATP synthase complex (NAS). Subunit e is a membrane subunit of the F(o) domain of complex V. It co-purifies with immunocaptured human F1F0, and it assembles into the stator-stalk 'b-e-g' subcomplex. Core. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:26297831 "When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex)."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:26297831 When expression of d-subunit, a stator stalk component, was knocked-down, human cells could not form ATP synthase holocomplex and instead accumulated two subcomplexes, one containing a central rotor shaft plus catalytic subunits (F1-c-ring) and the other containing stator stalk components ("b-e-g" complex). |
| GO:0046933 proton-transporting ATP synthase activity, rotational mechanism | IBA GO_REF:0000033 | ACCEPT | Summary: Contributes to proton-transporting ATP synthase activity, rotational mechanism (IBA). The contributes_to qualifier fits: subunit e is part of the complex whose rotary activity is measured on the immunocaptured enzyme, but it is not a catalytic or proton-channel subunit itself. Core. Reason: [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:12110673 "The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001752424 SUPPORTS TRANSFER contributes_to transfer within the subunit e family; appropriate for a non-catalytic subunit. Supporting Evidence: PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:12110673 The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive. file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex |
| GO:0046933 proton-transporting ATP synthase activity, rotational mechanism | IDA PMID:12110673 A functionally active human F1F0 ATPase can be purified by i... | ACCEPT | Summary: Contributes to proton-transporting ATP synthase activity, rotational mechanism (IDA). The contributes_to qualifier fits: subunit e is part of the complex whose rotary activity is measured on the immunocaptured enzyme, but it is not a catalytic or proton-channel subunit itself. Core. Reason: [PMID:12110673 "The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection."] [PMID:12110673 "The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive."] [file:human/ATP5ME/ATP5ME-uniprot.txt "CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex"] Supporting Evidence: PMID:12110673 The immunoprecipitated F(1)F(0) contained a full complement of subunits that were identified with specific antibodies against five of the subunits (alpha, beta, OSCP, d, and IF(1)) and by MALDI-TOF and/or LC/MS/MS for all subunits except subunit c, which could not be resolved by these methods because of the limits of detection. PMID:12110673 The captured complex V displayed ATP hydrolysis activity that was fully oligomycin and inhibitor protein IF(1)-sensitive. file:human/ATP5ME/ATP5ME-uniprot.txt CC -!- FUNCTION: Subunit e, of the mitochondrial membrane ATP synthase complex |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Proton transmembrane transport (IEA, GO_REF:0000108). This row is inferred mechanically from the GO:0015078 transporter-activity row, which is marked over-annotated, and so it shares that basis. Subunit e's process role is captured by the accepted ATP synthesis rows. Over-annotation, consistent with the source MF row. Reason: [file:human/ATP5ME/ATP5ME-uniprot.txt "CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8,"] [PMID:42138716 "ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology."] Supporting Evidence: file:human/ATP5ME/ATP5ME-uniprot.txt CC a membrane F(0) domain - the membrane proton channel (subunits c, a, 8, PMID:42138716 ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology. |
| GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly | IMP PMID:42138716 The role of ATP synthase subunit e (ATP5I) in mediating the ... | NEW | Summary: Mitochondrial proton-transporting ATP synthase complex assembly (NEW, IMP). In ATP5I-knockout human cells, partner subunit g is lost, OSCP falls, dimeric and monomeric ATP synthase become scarce, and vestigial assembly intermediates accumulate. Re-expressing ATP5I restores the missing subunits. As a structural F(o) subunit at the dimer-forming membrane region, subunit e does part of the work of building the complete, oligomer-competent enzyme. This matches the in-repo ATP5MD (subunit k) review, which proposes the same term on similar evidence. GOA does not yet carry it for any F(o) accessory subunit. Reason: [PMID:42138716 "The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A)."] [PMID:42138716 "This increase in assembly intermediates of the F₁F₀-ATP synthase upon metformin treatment mimics the phenotype of ATP5I knockout cells, where, in addition, the dimeric and monomeric forms of the enzyme are also scarce (Figure 2G)."] [PMID:42138716 "Notably, metformin disrupts F₁F₀-ATP synthase oligomerization, leading to the accumulation of vestigial assembly intermediates in pancreatic and osteosarcoma cancer cells, a phenotype also observed upon ATP5I inactivation in pancreatic cancer cells."] Supporting Evidence: PMID:42138716 The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A). PMID:42138716 This increase in assembly intermediates of the F₁F₀-ATP synthase upon metformin treatment mimics the phenotype of ATP5I knockout cells, where, in addition, the dimeric and monomeric forms of the enzyme are also scarce (Figure 2G). PMID:42138716 Notably, metformin disrupts F₁F₀-ATP synthase oligomerization, leading to the accumulation of vestigial assembly intermediates in pancreatic and osteosarcoma cancer cells, a phenotype also observed upon ATP5I inactivation in pancreatic cancer cells. |
| GO:0005198 structural molecule activity | IMP PMID:42138716 The role of ATP synthase subunit e (ATP5I) in mediating the ... | NEW | Summary: Structural molecule activity (NEW, IMP). Subunit e has no catalytic role. In ATP5I-knockout human cells its partner subunit g is lost and ATP synthase dimers and monomers become scarce, so its activity is structural: holding the dimer-forming F(o) membrane region together. This matches the subunit-level MF used in the ATP5MD (subunit k) review; the complex-level activity is captured by contributes_to GO:0046933. Reason: [PMID:42138716 "ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology."] [PMID:42138716 "The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A)."] [PMID:42138716 "This increase in assembly intermediates of the F₁F₀-ATP synthase upon metformin treatment mimics the phenotype of ATP5I knockout cells, where, in addition, the dimeric and monomeric forms of the enzyme are also scarce (Figure 2G)."] Supporting Evidence: PMID:42138716 ATP5I maintains the stability of F₁F₀-ATP synthase dimers, which is crucial for shaping cristae morphology. PMID:42138716 The results show that all ATP5I knockout clones (ATP5I KO) did not express ATP5I or its partner ATP5L (subunit g in yeast) and had lower levels of ATP5O (oligomycin sensitivity-conferring protein, OSCP in yeast) (Figure 2A). PMID:42138716 This increase in assembly intermediates of the F₁F₀-ATP synthase upon metformin treatment mimics the phenotype of ATP5I knockout cells, where, in addition, the dimeric and monomeric forms of the enzyme are also scarce (Figure 2G). |
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Download this section (compressed HTML)Q: Should dimer-stabilizing F(o) subunits (e, g, k) carry a cristae formation (GO:0042407) term? None does in GOA, although loss of subunit e destabilizes oligomers and alters cristae; complex assembly (GO:0033615) is proposed here and in the ATP5MD review.
Experiment: Use cryo-ET of ATP5ME-knockout mitochondria to quantify ATP synthase dimer rows and cristae curvature, and test whether metformin binding to subunit e directly loosens dimer contacts in purified complex V.
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