ARMC10 (SVH) is a 343-residue armadillo-repeat protein with a single N-terminal transmembrane segment, the vertebrate ancestor of the eutherian ARMCX genes. It sits on the mitochondrial outer membrane, associates with MIRO1/2 and TRAK2 of the mitochondrial trafficking machinery and controls the number of moving mitochondria in neurons. AMPK phosphorylates it at S45, and ARMC10 is required for AMPK-induced mitochondrial fission. Mouse ArmC10 binds the myeloid growth factor oncomodulin with high affinity and mediates oncomodulin-driven axon regeneration. The SVH-B splice isoform binds p53 and suppresses its transcriptional activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). ARMC10 localizes to mitochondria in neurons and HEK293T cells and is in the high-confidence human mitochondrial proteome; core location, refined by the outer membrane rows. 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)."] [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion 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). file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). ARMC10 localizes to mitochondria in neurons and HEK293T cells and is in the high-confidence human mitochondrial proteome; core location, refined by the outer membrane rows. Reason: [PMID:24722288 "We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain."] [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion 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, human ARMCX1, and human ARMC10 itself. Mitochondrial localization is shared across the family, and ARMC10 has its own mitochondrial evidence (PMID:24722288). Supporting Evidence: PMID:24722288 We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrion (IDA). ARMC10 localizes to mitochondria in neurons and HEK293T cells and is in the high-confidence human mitochondrial proteome; core location, refined by the outer membrane rows. Reason: [PMID:24722288 "We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain."] [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane"] Supporting Evidence: PMID:24722288 We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | ACCEPT | Summary: Mitochondrion (IEA). ARMC10 localizes to mitochondria in neurons and HEK293T cells and is in the high-confidence human mitochondrial proteome; core location, refined by the outer membrane rows. Reason: [PMID:24722288 "We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain."] [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane"] Supporting Evidence: PMID:24722288 We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane |
| GO:0005741 mitochondrial outer membrane | EXP PMID:27184847 APEX Fingerprinting Reveals the Subcellular Localization of ... | ACCEPT | Summary: Mitochondrial outer membrane (EXP). APEX proximity labelling placed ARMC10 (isoform SVH-B) in the outer membrane; ARMC10 also co-immunoprecipitates with MIRO1/2 and TRAK2 of the trafficking complex on the outer membrane. Core location. Reason: [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane"] [PMID:27184847 "Using APEX labeling of specific proteins, we uncovered subcellular localization at sub-compartmental resolution and successfully elucidated the membrane protein topology of HMOX1 and sub-mitochondrial localization of recently identified mitochondrial proteins."] [PMID:24722288 "Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies."] [PMID:24722288 "Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b)."] Supporting Evidence: file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane PMID:27184847 Using APEX labeling of specific proteins, we uncovered subcellular localization at sub-compartmental resolution and successfully elucidated the membrane protein topology of HMOX1 and sub-mitochondrial localization of recently identified mitochondrial proteins. PMID:24722288 Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies. PMID:24722288 Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b). |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial outer membrane (IEA). APEX proximity labelling placed ARMC10 (isoform SVH-B) in the outer membrane; ARMC10 also co-immunoprecipitates with MIRO1/2 and TRAK2 of the trafficking complex on the outer membrane. Core location. Reason: [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane"] [PMID:27184847 "Using APEX labeling of specific proteins, we uncovered subcellular localization at sub-compartmental resolution and successfully elucidated the membrane protein topology of HMOX1 and sub-mitochondrial localization of recently identified mitochondrial proteins."] [PMID:24722288 "Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies."] [PMID:24722288 "Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b)."] Supporting Evidence: file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane PMID:27184847 Using APEX labeling of specific proteins, we uncovered subcellular localization at sub-compartmental resolution and successfully elucidated the membrane protein topology of HMOX1 and sub-mitochondrial localization of recently identified mitochondrial proteins. PMID:24722288 Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies. PMID:24722288 Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b). |
| GO:0005783 endoplasmic reticulum | IDA PMID:12839973 A specific splicing variant of SVH, a novel human armadillo ... | KEEP AS NON CORE | Summary: Endoplasmic reticulum (IDA). The original SVH study placed all four overexpressed splice variants in the ER. Later work places endogenous ARMC10 on mitochondria, so the ER is at most a minor or overexpression-dependent location; kept as non-core. Reason: [PMID:12839973 "Four variants of SVH, SVH-A, -B, -C, and -D, resulting from alternative splicing in the coding region of the SVH transcript, were observed and were all localized in endoplasmic reticulum (ER)."] [PMID:24722288 "We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain."] Supporting Evidence: PMID:12839973 Four variants of SVH, SVH-A, -B, -C, and -D, resulting from alternative splicing in the coding region of the SVH transcript, were observed and were all localized in endoplasmic reticulum (ER). PMID:24722288 We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Endoplasmic reticulum membrane (IEA). The original SVH study placed all four overexpressed splice variants in the ER. Later work places endogenous ARMC10 on mitochondria, so the ER is at most a minor or overexpression-dependent location; kept as non-core. Reason: [PMID:12839973 "Four variants of SVH, SVH-A, -B, -C, and -D, resulting from alternative splicing in the coding region of the SVH transcript, were observed and were all localized in endoplasmic reticulum (ER)."] [PMID:24722288 "We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain."] Supporting Evidence: PMID:12839973 Four variants of SVH, SVH-A, -B, -C, and -D, resulting from alternative splicing in the coding region of the SVH transcript, were observed and were all localized in endoplasmic reticulum (ER). PMID:24722288 We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. |
| GO:0019896 axonal transport of mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Axonal transport of mitochondrion (IBA). The IBA is seeded by mouse Armcx3, a retrotransposed eutherian copy of Armc10. ARMC10 itself co-immunoprecipitates with MIRO1/2 and TRAK2 (but not KIF5) and sets the number of moving mitochondria in neuronal axons, so the transfer holds for the ancestral gene; accepted. Reason: [PMID:24722288 "Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies."] [PMID:24722288 "Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b)."] [PMID:24722288 "In contrast, we did not detect co-immunoprecipitation of the Armc10-GFP protein with KIF5C, KIF5A or KIF5B in transfected HEK293T cells (Figure 6b and not shown)."] [PMID:24722288 "Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria."] [PMID:24722288 "Two days later, axons from transfected neurons were identified and recorded for 15 min, and mitochondrial dynamics were quantified using kymographs."] 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). Armcx genes arose by retrotransposition of Armc10 mRNA, and ARMC10 has its own trafficking evidence (PMID:24722288). Supporting Evidence: PMID:24722288 Co-immunoprecipitation experiments in HEK293T cells transfected with Armc10-GFP and either Miro1-myc or Miro2-myc cDNAs revealed that Miro proteins were detected by WB in lysates immunoprecipitated with anti-GFP antibodies. PMID:24722288 Co-immunoprecipitation experiments with the mitochondrial adaptor protein Trak2 also revealed co-association with the Armc10 protein (Figure 6b). PMID:24722288 Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. PMID:24722288 Two days later, axons from transfected neurons were identified and recorded for 15 min, and mitochondrial dynamics were quantified using kymographs. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Axon cytoplasm (IEA, inferred from the axonal transport process). ARMC10 sits on the mitochondrial outer membrane of axonal mitochondria rather than in the cytosol; the location is derivative of the process row. Kept as non-core. Reason: [PMID:24722288 "Two days later, axons from transfected neurons were identified and recorded for 15 min, and mitochondrial dynamics were quantified using kymographs."] [file:human/ARMC10/ARMC10-uniprot.txt "CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane"] Supporting Evidence: PMID:24722288 Two days later, axons from transfected neurons were identified and recorded for 15 min, and mitochondrial dynamics were quantified using kymographs. file:human/ARMC10/ARMC10-uniprot.txt CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion outer membrane |
| GO:0090141 positive regulation of mitochondrial fission | IMP PMID:30631047 Global phosphoproteomic analysis reveals ARMC10 as an AMPK s... | NEW | Summary: Positive regulation of mitochondrial fission (NEW, IDA, human cells). AMPK phosphorylates ARMC10 at S45. ARMC10 overexpression promotes mitochondrial fission, and its knockout in U2OS cells prevents AMPK-induced fission, placing ARMC10 between AMPK and the fission machinery. The effect is context-dependent. In neurons, Armc10 overexpression gave slightly larger mitochondria and protected against amyloid-beta-induced fragmentation. The term describes the AMPK-stimulated setting in U2OS cells. Reason: [PMID:30631047 "We validated one uncharacterized protein, ARMC10, and demonstrated that the S45 site of ARMC10 can be phosphorylated by AMPK both in vitro and in vivo."] [PMID:30631047 "Moreover, ARMC10 overexpression was sufficient to promote mitochondrial fission, whereas ARMC10 knockout prevented AMPK-mediated mitochondrial fission."] [PMID:24722288 "Armc10-overexpressing neurons displayed slightly larger mitochondria than control neurons."] Supporting Evidence: PMID:30631047 We validated one uncharacterized protein, ARMC10, and demonstrated that the S45 site of ARMC10 can be phosphorylated by AMPK both in vitro and in vivo. PMID:30631047 Moreover, ARMC10 overexpression was sufficient to promote mitochondrial fission, whereas ARMC10 knockout prevented AMPK-mediated mitochondrial fission. PMID:24722288 Armc10-overexpressing neurons displayed slightly larger mitochondria than control neurons. |
| GO:0005634 nucleus | ISO PMID:24722288 The Armc10/SVH gene: genome context, regulation of mitochond... | NEW | Summary: Nucleus (NEW, ISO from mouse Armc10). In developing and adult neurons, Armc10 immunostaining is prominent in nuclei as well as on mitochondria, a bimodal localization shared with Armcx3. A nuclear pool would also be consistent with the reported SVH-B-p53 interaction. Non-core relative to the mitochondrial role. Reason: [PMID:24722288 "In most developing and adult neurons, Armc10 signals were prominent in neuronal nuclei and fainter staining was detected in neuronal perikarya and in the neuropil."] [PMID:24722288 "The above data indicate that, as with the Armcx3 protein, Armc10 is widely expressed in the nervous system, where it shows a mainly bimodal localisation in mitochondria and the cell nucleus."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9D0L7 SUPPORTS TRANSFER Mouse Armc10 (MGI:1914461); nuclear and mitochondrial immunostaining in neurons (PMID:24722288). Supporting Evidence: PMID:24722288 In most developing and adult neurons, Armc10 signals were prominent in neuronal nuclei and fainter staining was detected in neuronal perikarya and in the neuropil. PMID:24722288 The above data indicate that, as with the Armcx3 protein, Armc10 is widely expressed in the nervous system, where it shows a mainly bimodal localisation in mitochondria and the cell nucleus. |
| GO:0038023 signaling receptor activity | ISO PMID:37556559 The oncomodulin receptor ArmC10 enables axon regeneration in... | NEW | Summary: Signaling receptor activity (NEW, ISO from mouse Armc10). Mouse ArmC10 binds the growth factor oncomodulin with high affinity (surface plasmon resonance), and oncomodulin acts through ArmC10 to drive axon regeneration in vivo. How a mitochondrial outer-membrane protein acts as a cell-surface receptor is unresolved; see suggested_questions. Reason: [PMID:37556559 "Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm."] [PMID:37556559 "Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9D0L7 SUPPORTS TRANSFER Mouse Armc10 (MGI:1914461); receptor evidence from PMID:37556559, which also reports ArmC10 expression and oncomodulin responses in human iPSC-derived sensory neurons and monocytes. Supporting Evidence: PMID:37556559 Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm. PMID:37556559 Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models. |
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Download this section (compressed HTML)Q: The SVH-B isoform binds p53 and suppresses its transcriptional activity in hepatoma cells (PMID:17904127). Is this relevant to endogenous ARMC10 at mitochondria?
Q: How does ARMC10, a single-pass mitochondrial outer-membrane protein, act as a cell-surface receptor for oncomodulin? Is a distinct isoform or pool at the plasma membrane?
Q: Does S45 phosphorylation by AMPK change ARMC10's binding to MIRO/TRAK2 or to fission factors such as MFF or DRP1?
Experiment: Express phospho-dead S45A and phospho-mimetic S45D ARMC10 in ARMC10-knockout cells and measure fission and mitochondrial motility under AMPK activation.
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