ARMCX2 (ALEX2) is a eutherian-specific armadillo-repeat protein of the X-linked ARMCX cluster, which arose from the ancestral gene ARMC10. Like its relatives it has an N-terminal transmembrane segment and is mitochondrial, appearing in the high-confidence human mitochondrial proteome. It is expected to share the family's role in regulating mitochondrial dynamics and axonal transport, although ARMCX2 itself has not been tested. Its transcript is broadly expressed, and its promoter becomes methylated in chemoresistant ovarian cancer.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). The ARMCX family, including mouse Armcx2, localizes to mitochondria, and human ARMCX2 is in the high-confidence human 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:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] 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:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). The ARMCX family, including mouse Armcx2, localizes to mitochondria, and human ARMCX2 is in the high-confidence human mitochondrial proteome. Core location. Reason: [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] 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. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Mitochondrion (IEA). The ARMCX family, including mouse Armcx2, localizes to mitochondria, and human ARMCX2 is in the high-confidence human mitochondrial proteome. Core location. Reason: [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] Supporting Evidence: PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrion (ISS). The ARMCX family, including mouse Armcx2, localizes to mitochondria, and human ARMCX2 is in the high-confidence human mitochondrial proteome. Core location. Reason: [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q6A058 SUPPORTS TRANSFER Mouse Armcx2, the ortholog; donor EXP mitochondrion (PMID:22569362). Supporting Evidence: PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial outer membrane (IEA). ARMCX3, the paralog donor, is an integral outer-membrane protein. ARMCX2 shares the N-terminal transmembrane segment that targets ARMCX proteins to mitochondria, so the outer-membrane placement is expected; accepted. Reason: [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] Supporting Evidence: PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. |
| GO:0005741 mitochondrial outer membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial outer membrane (ISS). ARMCX3, the paralog donor, is an integral outer-membrane protein. ARMCX2 shares the N-terminal transmembrane segment that targets ARMCX proteins to mitochondria, so the outer-membrane placement is expected; accepted. Reason: [PMID:19304657 "Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane."] [PMID:22569362 "Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q8BHS6 SUPPORTS TRANSFER Mouse Armcx3, a paralog, not the ortholog. Donor IDA/EXP for the outer membrane (PMID:19304657, PMID:22569362). The transfer relies on the shared N-terminal transmembrane anchor of the ARMCX family; ARMCX2 itself has no direct outer-membrane assay. Supporting Evidence: PMID:19304657 Biochemical analyses indicate that ARMCX3 is an integral membrane protein of the mitochondrial outer membrane. PMID:22569362 Here we show a new protein family that localizes to the mitochondria and controls mitochondrial dynamics. |
| GO:0019896 axonal transport of mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Axonal transport of mitochondrion (IBA). The only seed is mouse Armcx3, which regulates neuronal mitochondrial trafficking through the Kinesin/Miro/Trak2 complex. Family members ARMC10 and Armcx1 have independent transport evidence. ARMCX2 has not been tested, but nothing suggests it has lost the family function; accepted as an inherited role. 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:22569362 "The Armcx cluster is unique to Eutherian mammals and evolved from a single ancestor gene (Armc10)."] 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). ARMC10 (PMID:24722288) and Armcx1 (PMID:28009275) independently regulate mitochondrial transport; ARMCX2 has no direct data. 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:22569362 The Armcx cluster is unique to Eutherian mammals and evolved from a single ancestor gene (Armc10). |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Axon cytoplasm (IEA, inferred from the axonal transport process). ARMCX proteins sit on the mitochondrial outer membrane 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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Experiment: Measure mitochondrial motility in neurons after ARMCX2 knockdown or overexpression, alongside ARMCX1 and ARMCX3.
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