ARMCX3 (ALEX3) is a eutherian-specific armadillo-repeat protein of the X-linked ARMCX cluster, which arose from the ancestral gene ARMC10. It is an integral mitochondrial outer-membrane protein. In neurons, mouse Armcx3 regulates mitochondrial dynamics and trafficking, interacting in a Ca2+-dependent manner with the kinesin/MIRO/TRAK2 transport complex. It forms a complex with Galpha-q that lets G protein-coupled receptor signalling control mitochondrial trafficking, and CNS loss of Armcx3 causes neuronal death and motor deficits. Non-canonical Wnt/PKC signalling promotes its degradation. On the outer membrane it also binds the transcription factor Sox10 and enhances Sox10-dependent transcription.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | REMOVE | Summary: Protein binding (IPI) with MAF1, from a binary interactome-mapping yeast two-hybrid study. 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:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding (IPI) with MAF1, from the BioPlex affinity-purification network. 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 FAM25A, 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 EHHADH, 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:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with MAF1, from the BioPlex dual proteome-scale network. 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:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Nucleus (IEA, from mouse Armcx3). UniProt records cytoplasmic and nuclear pools by similarity to mouse Armcx3, whose donor rows are IDA/EXP from PMID:22569362; that full text is not cached. A mitochondria-to-nucleus signalling route via Sox10 has also been proposed. The established site of action is the mitochondrial outer membrane; kept as non-core. Reason: [file:human/ARMCX3/ARMCX3-uniprot.txt "CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus"] [PMID:23844091 "A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA nucleus (PMID:22569362). Supporting Evidence: file:human/ARMCX3/ARMCX3-uniprot.txt CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus PMID:23844091 A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nucleus (ISS, from mouse Armcx3). UniProt records cytoplasmic and nuclear pools by similarity to mouse Armcx3, whose donor rows are IDA/EXP from PMID:22569362; that full text is not cached. A mitochondria-to-nucleus signalling route via Sox10 has also been proposed. The established site of action is the mitochondrial outer membrane; kept as non-core. Reason: [file:human/ARMCX3/ARMCX3-uniprot.txt "CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus"] [PMID:23844091 "A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA nucleus (PMID:22569362). Supporting Evidence: file:human/ARMCX3/ARMCX3-uniprot.txt CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus PMID:23844091 A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm (IEA, from mouse Armcx3). UniProt records cytoplasmic and nuclear pools by similarity to mouse Armcx3, whose donor rows are IDA/EXP from PMID:22569362; that full text is not cached. A mitochondria-to-nucleus signalling route via Sox10 has also been proposed. The established site of action is the mitochondrial outer membrane; kept as non-core. Reason: [file:human/ARMCX3/ARMCX3-uniprot.txt "CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus"] [PMID:23844091 "A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Supporting Evidence: file:human/ARMCX3/ARMCX3-uniprot.txt CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus PMID:23844091 A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cytoplasm (ISS, from mouse Armcx3). UniProt records cytoplasmic and nuclear pools by similarity to mouse Armcx3, whose donor rows are IDA/EXP from PMID:22569362; that full text is not cached. A mitochondria-to-nucleus signalling route via Sox10 has also been proposed. The established site of action is the mitochondrial outer membrane; kept as non-core. Reason: [file:human/ARMCX3/ARMCX3-uniprot.txt "CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus"] [PMID:23844091 "A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor EXP cytoplasm (PMID:22569362). Supporting Evidence: file:human/ARMCX3/ARMCX3-uniprot.txt CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus PMID:23844091 A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). ARMCX3 is an integral mitochondrial outer-membrane protein, and human ARMCX3 is in the high-confidence mitochondrial proteome. Core location. Reason: [PMID:34800366 "We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Supporting Evidence: PMID:34800366 We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). ARMCX3 is an integral mitochondrial outer-membrane protein, and human ARMCX3 is in the high-confidence mitochondrial proteome. Core location. Reason: [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001038987 SUPPORTS TRANSFER ARMC10/ARMCX node; seeded by mouse Armcx1, Armcx2, Armcx3 and Armcx6 and by human ARMC10 and ARMCX1. Mitochondrial localization is shared across the family (PMID:22569362). Supporting Evidence: PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrion (IEA). ARMCX3 is an integral mitochondrial outer-membrane protein, and human ARMCX3 is in the high-confidence mitochondrial proteome. Core location. Reason: [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA mitochondrion (PMID:22569362). Supporting Evidence: PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrial outer membrane (IEA, from mouse Armcx3). Biochemical fractionation shows ARMCX3 is an integral outer-membrane protein, where it binds Sox10 and the Miro/Trak2 trafficking complex. Core location. Reason: [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] [PMID:19304657 "We extend this observation and demonstrate that, in the cytoplasm, Sox10 is peripherally associated with the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA/EXP outer membrane (PMID:19304657, PMID:22569362). Supporting Evidence: PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. PMID:19304657 We extend this observation and demonstrate that, in the cytoplasm, Sox10 is peripherally associated with the mitochondrial outer membrane. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial outer membrane (ISS, from mouse Armcx3). Biochemical fractionation shows ARMCX3 is an integral outer-membrane protein, where it binds Sox10 and the Miro/Trak2 trafficking complex. Core location. Reason: [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] [PMID:19304657 "We extend this observation and demonstrate that, in the cytoplasm, Sox10 is peripherally associated with the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA/EXP outer membrane (PMID:19304657, PMID:22569362). Supporting Evidence: PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. PMID:19304657 We extend this observation and demonstrate that, in the cytoplasm, Sox10 is peripherally associated with the mitochondrial outer membrane. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytosol (IEA, from mouse Armcx3). UniProt records cytoplasmic and nuclear pools by similarity to mouse Armcx3, whose donor rows are IDA/EXP from PMID:22569362; that full text is not cached. A mitochondria-to-nucleus signalling route via Sox10 has also been proposed. The established site of action is the mitochondrial outer membrane; kept as non-core. Reason: [file:human/ARMCX3/ARMCX3-uniprot.txt "CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus"] [PMID:23844091 "A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]."] [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3 (UniProtKB:Q8BHS6, MGI:1918953); donor IDA cytosol (PMID:22569362). Supporting Evidence: file:human/ARMCX3/ARMCX3-uniprot.txt CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q8BHS6}. Nucleus PMID:23844091 A recent report described Alex3 as a Sox10-interacting protein that localizes in the mitochondria of OBL21 cells and suggested a novel signaling cascade between mitochondria and the nucleus through a Sox10/Alex3 protein complex [11]. |
| GO:0019896 axonal transport of mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Axonal transport of mitochondrion (IBA). The node is seeded by mouse Armcx3 itself, whose levels regulate neuronal mitochondrial trafficking through the Kinesin/Miro/Trak2 complex. Armcx3 is also required for Galpha-q control of mitochondrial trafficking in neurons. Core process. 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:38320000 "By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of GΞ±q on mitochondrial trafficking and dendritic growth in neurons."] 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), the ortholog of the target. Donor IDA from PMID:22569362. 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:38320000 By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of GΞ±q on mitochondrial trafficking and dendritic growth in neurons. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Axon cytoplasm (IEA, inferred from the axonal transport process). ARMCX3 sits on the outer membrane of axonal mitochondria rather than free in the cytosol; this location is derivative of the process row. Kept as non-core. Reason: [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] [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."] Supporting Evidence: PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. 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. |
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Download this section (compressed HTML)Q: ARMCX3 enhances Sox10 transactivation without intrinsic transcriptional activity, while sitting on the mitochondrial outer membrane. Does it act by retaining or releasing Sox10 at mitochondria, rather than as a promoter-bound coactivator?
Q: Does ARMCX3 bridge Galpha-q to MIRO/TRAK2 directly, which would make it an adaptor, or is Galpha-q recruited through another subunit?
Experiment: Test direct binding among purified ARMCX3, Galpha-q and MIRO1, and map ARMCX3 mutants that separate Galpha-q from MIRO binding.
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