ARMCX1 (ALEX1) is a eutherian-specific armadillo-repeat protein of the X-linked ARMCX cluster, which arose from the ancestral gene ARMC10. It has an N-terminal transmembrane segment with a predicted mitochondrial outer-membrane targeting sequence, localizes to mitochondria, and binds the mitochondrial transport adaptor MIRO1. In mouse retinal ganglion cells Armcx1 enhances mitochondrial transport and promotes neuronal survival and axon regeneration after injury, effects that depend on its mitochondrial localization. After traumatic brain injury in mice, Armcx1 supports mitochondrial transport and neuronal survival. ARMCX1 expression is lost in many carcinomas. In lung adenocarcinoma cells it has been reported to recruit the E3 ligase FBXW7 for c-Myc degradation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with COIL, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with ZBTB8A, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with TFIP11, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding (IPI) with TFIP11, from a yeast two-hybrid study of variant effects. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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 CEP70, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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 GPKOW, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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 ZBTB8A, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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 PICK1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. 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 | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). Mouse Armcx1 is mitochondria-localized, and its neuroprotective and regenerative effects depend on that localization. This row infers the location from the ARMC10/ARMCX family node. Core location. Reason: [PMID:28009275 "In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition."] [PMID:28009275 "We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001038987 SUPPORTS TRANSFER ARMC10/ARMCX node; seeded by mouse Armcx1, Armcx2, Armcx3 and Armcx6, human ARMC10, and human ARMCX1 itself. Mitochondrial localization is shared across the family (PMID:22569362). Supporting Evidence: PMID:28009275 In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. PMID:28009275 We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrion (IDA). Mouse Armcx1 is mitochondria-localized, and its neuroprotective and regenerative effects depend on that localization. This row is the Human Protein Atlas antibody staining of human ARMCX1 (GO_REF:0000052), the only direct human localization evidence. Core location. Reason: This row is the Human Protein Atlas antibody staining of human ARMCX1 (GO_REF:0000052), the only direct human localization evidence. [PMID:28009275 "In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition."] Supporting Evidence: PMID:28009275 In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrion (IEA). Mouse Armcx1 is mitochondria-localized, and its neuroprotective and regenerative effects depend on that localization. This row derives from UniProt's ARBA and SubCell mappings. Core location. Reason: [PMID:28009275 "In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition."] [PMID:28009275 "We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization."] Supporting Evidence: PMID:28009275 In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. PMID:28009275 We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrion (ISS). Mouse Armcx1 is mitochondria-localized, and its neuroprotective and regenerative effects depend on that localization. This row transfers the mouse Armcx1 localization. Core location. Reason: [PMID:28009275 "In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition."] [PMID:28009275 "We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9CX83 SUPPORTS TRANSFER Mouse Armcx1 (UniProtKB:Q9CX83, MGI:1925498); donor EXP mitochondrion (PMID:28009275, PMID:22569362). Supporting Evidence: PMID:28009275 In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. PMID:28009275 We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial outer membrane (IEA). Armcx1 has a putative outer-membrane targeting sequence flanking its transmembrane segment, binds the outer-membrane adaptor Miro1, and is described as an outer-membrane protein of neurons. Accepted. Reason: [PMID:28009275 "Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D)"] [PMID:28009275 "Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex."] [PMID:37454781 "Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport."] Supporting Evidence: PMID:28009275 Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D) PMID:28009275 Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex. PMID:37454781 Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial outer membrane (ISS). Armcx1 has a putative outer-membrane targeting sequence flanking its transmembrane segment, binds the outer-membrane adaptor Miro1, and is described as an outer-membrane protein of neurons. Accepted. Reason: [PMID:28009275 "Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D)"] [PMID:28009275 "Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex."] [PMID:37454781 "Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9CX83 SUPPORTS TRANSFER Mouse Armcx1 (UniProtKB:Q9CX83, MGI:1925498); mitochondrial localization with a predicted outer-membrane targeting sequence (PMID:28009275). Supporting Evidence: PMID:28009275 Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D) PMID:28009275 Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex. PMID:37454781 Armcx1 is highly expressed in the brain and is located in the mitochondrial outer membrane of neurons, where it mediates mitochondrial transport. |
| GO:0019896 axonal transport of mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Axonal transport of mitochondrion (IBA). The node's seed is mouse Armcx3, which regulates neuronal mitochondrial trafficking through the Kinesin/Miro/Trak2 complex. Mouse Armcx1 itself binds Miro1, the adaptor that couples mitochondria to the Trak-kinesin motor, and enhances mitochondrial transport in retinal ganglion cell axons. Armcx1 knockdown after brain injury impairs mitochondrial transport and lowers Miro1. Participation rather than regulation is chosen because Armcx1 sits on the transported organelle and engages the transport adaptor, as Miro and TRAK do, although the papers describe its effect as controlling the motile pool. Accepted. Reason: [PMID:22569362 "Furthermore, we demonstrate that Armcx3 expression levels regulate mitochondrial dynamics and trafficking in neurons, and that Alex3 interacts with the Kinesin/Miro/Trak2 complex in a Ca(2+)-dependent manner."] [PMID:28009275 "Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex."] [PMID:28009275 "Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs)."] [PMID:38492796 "In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001038987 SUPPORTS TRANSFER ARMC10/ARMCX node; for this term the only seed is mouse Armcx3 (MGI:1918953). Mouse Armcx1 has its own transport evidence (PMID:28009275). Supporting Evidence: PMID:22569362 Furthermore, we demonstrate that Armcx3 expression levels regulate mitochondrial dynamics and trafficking in neurons, and that Alex3 interacts with the Kinesin/Miro/Trak2 complex in a Ca(2+)-dependent manner. PMID:28009275 Co-immunoprecipitation using Armcx1-HA and Miro1-Myc showed that Armcx1 interacted with Miro1 (Figure 1H), the protein linking mitochondria to the Trak1-Kinesin motor complex. PMID:28009275 Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs). PMID:38492796 In addition, inhibition of Armcx1 expression further led to impaired mitochondrial transport, abnormal morphology, reduced ATP levels, aggravation of neuronal apoptosis and neurological dysfunction, and decrease Miro1 expression. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Axon cytoplasm (IEA, a GO inter-ontology inference from the axonal transport process). Axonal mitochondria, with ARMCX1 on their outer membrane, lie within the axon cytoplasm, so the term is not wrong. It is derivative of the process row and less precise than the outer-membrane location; kept as non-core. Reason: [PMID:28009275 "Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D)"] [PMID:28009275 "Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs)."] Supporting Evidence: PMID:28009275 Similar to other members of the Armcx cluster, Armcx1 has a putative mitochondrial outer membrane-targeting sequence flanking the trans-membrane (TM) domain (Figure 1D) PMID:28009275 Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs). |
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Experiment: Map ARMCX1 binding partners on mitochondria by proximity labelling in neurons, and test whether its tumour-suppressor activity needs mitochondrial targeting.
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