ARMC1 is a 282-residue protein with an N-terminal armadillo-motif helical domain, a heavy metal-associated-like domain that lacks metal-coordinating cysteines, and a conserved C-terminal domain that attaches it peripherally to the mitochondrial outer membrane, where the CTD contacts TMEM11 and MTCH2. It shuttles between the cytosol and mitochondria. On mitochondria it is recruited by the trafficking adaptor MIRO and assembles MIRO with the fission regulator MTFR (MTFR1L), stabilizing MTFR. The resulting complexes oppose retrograde mitochondrial movement. A separate complex with DNAJC11 releases ARMC1 to the cytosol. ARMC1 also co-purifies with MICOS/MIB components. Loss of ARMC1 fragments mitochondria and collapses them into the perinuclear region without affecting cristae or respiration.
| 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 MTFR1L, from the HI-II-14 binary yeast two-hybrid map. Generic protein binding carries no functional information. The MIRO-ARMC1-MTFR assembly role is captured by the NEW protein-macromolecule adaptor activity row. Removed under the 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:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | REMOVE | Summary: Protein binding (IPI) with MTFR1L, from a yeast two-hybrid isoform interactome. Generic protein binding carries no functional information. The MIRO-ARMC1-MTFR assembly role is captured by the NEW protein-macromolecule adaptor activity row. Removed under the 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:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Protein binding (IPI) with MTFR1L, from a yeast two-hybrid study of variant effects. Generic protein binding carries no functional information. The MIRO-ARMC1-MTFR assembly role is captured by the NEW protein-macromolecule adaptor activity row. Removed under the 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:31644573 Armadillo repeat-containing protein 1 is a dual localization... | REMOVE | Summary: Protein binding (IPI) with MTX1, from FLAG-ARMC1 immunoprecipitation from HEK293T mitochondria. Generic protein binding carries no functional information. ARMC1 co-purifies with MICOS/MIB components as a peripheral member, but no specific MF term captures this. Removed under the 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:31644573 Armadillo repeat-containing protein 1 is a dual localization... | REMOVE | Summary: Protein binding (IPI) with IMMT (MIC60), from FLAG-ARMC1 immunoprecipitation from HEK293T mitochondria. Generic protein binding carries no functional information. ARMC1 co-purifies with MICOS/MIB components as a peripheral member, but no specific MF term captures this. Removed under the 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:31644573 Armadillo repeat-containing protein 1 is a dual localization... | REMOVE | Summary: Protein binding (IPI) with MICOS10 (MIC10), from FLAG-ARMC1 immunoprecipitation from HEK293T mitochondria. Generic protein binding carries no functional information. ARMC1 co-purifies with MICOS/MIB components as a peripheral member, but no specific MF term captures this. Removed under the 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:31644573 Armadillo repeat-containing protein 1 is a dual localization... | REMOVE | Summary: Protein binding (IPI) with SAMM50, from FLAG-ARMC1 immunoprecipitation from HEK293T mitochondria. Generic protein binding carries no functional information. ARMC1 co-purifies with MICOS/MIB components as a peripheral member, but no specific MF term captures this. Removed under the 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 RNF24, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information. Removed under the 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:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with DNAJC11, from the BioPlex dual proteome-scale network. Generic protein binding carries no functional information. ARMC1 forms a distinct complex with DNAJC11 that promotes its release from mitochondria; no specific MF term captures this. Removed under the 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:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Protein binding (IPI) with DNAJC11, from the OpenCell endogenous-tagging interactome. Generic protein binding carries no functional information. ARMC1 forms a distinct complex with DNAJC11 that promotes its release from mitochondria; no specific MF term captures this. Removed under the 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:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Protein binding (IPI) with DNAJC11, from a multimodal cell map. Generic protein binding carries no functional information. ARMC1 forms a distinct complex with DNAJC11 that promotes its release from mitochondria; no specific MF term captures this. Removed under the 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:0005737 cytoplasm | EXP PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | ACCEPT | Summary: Cytoplasm (EXP). ARMC1 is dual-localized, with a cytosolic pool that DNAJC11 maintains by releasing it from mitochondria; core location. Reason: [PMID:31644573 "ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria."] [PMID:40203102 "We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig."] [PMID:40203102 "This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol."] Supporting Evidence: PMID:31644573 ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria. PMID:40203102 We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig. PMID:40203102 This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm (IEA). ARMC1 is dual-localized, with a cytosolic pool that DNAJC11 maintains by releasing it from mitochondria; core location. Reason: [PMID:31644573 "ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria."] [PMID:40203102 "We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig."] [PMID:40203102 "This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol."] Supporting Evidence: PMID:31644573 ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria. PMID:40203102 We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig. PMID:40203102 This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). ARMC1 associates with mitochondria in immunofluorescence and fractionation studies and in the high-confidence mitochondrial proteome; accepted, with the outer membrane row giving the precise site. 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:31644573 "ArmC1 associates with, but is not integrated into the OMM."] 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:31644573 ArmC1 associates with, but is not integrated into the OMM. |
| GO:0005739 mitochondrion | IDA PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | ACCEPT | Summary: Mitochondrion (IDA). ARMC1 associates with mitochondria in immunofluorescence and fractionation studies and in the high-confidence mitochondrial proteome; accepted, with the outer membrane row giving the precise site. Reason: [PMID:40203102 "We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig."] [PMID:31644573 "ArmC1 associates with, but is not integrated into the OMM."] Supporting Evidence: PMID:40203102 We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig. PMID:31644573 ArmC1 associates with, but is not integrated into the OMM. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrion (IEA). ARMC1 associates with mitochondria in immunofluorescence and fractionation studies and in the high-confidence mitochondrial proteome; accepted, with the outer membrane row giving the precise site. Reason: [PMID:40203102 "We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig."] [PMID:31644573 "ArmC1 associates with, but is not integrated into the OMM."] Supporting Evidence: PMID:40203102 We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig. PMID:31644573 ArmC1 associates with, but is not integrated into the OMM. |
| GO:0005741 mitochondrial outer membrane | EXP PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | ACCEPT | Summary: Mitochondrial outer membrane (EXP). ARMC1 associates peripherally with the outer membrane through its C-terminal domain, without integrating, and there it binds MIRO; core location. Reason: [PMID:31644573 "ArmC1 associates with, but is not integrated into the OMM."] [PMID:40203102 "In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution."] Supporting Evidence: PMID:31644573 ArmC1 associates with, but is not integrated into the OMM. PMID:40203102 In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial outer membrane (IEA). ARMC1 associates peripherally with the outer membrane through its C-terminal domain, without integrating, and there it binds MIRO; core location. Reason: [PMID:31644573 "ArmC1 associates with, but is not integrated into the OMM."] [PMID:40203102 "In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution."] Supporting Evidence: PMID:31644573 ArmC1 associates with, but is not integrated into the OMM. PMID:40203102 In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution. |
| GO:0005829 cytosol | IDA PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | ACCEPT | Summary: Cytosol (IDA). ARMC1 is dual-localized, with a cytosolic pool that DNAJC11 maintains by releasing it from mitochondria; core location. Reason: [PMID:31644573 "ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria."] [PMID:40203102 "We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig."] [PMID:40203102 "This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol."] Supporting Evidence: PMID:31644573 ArmC1, therefore, represents a novel peripheral component of the MICOS/MIB complex with an unusual localization to both cytosol and mitochondria, which might play a role in cellular distribution of mitochondria. PMID:40203102 We used these cell lines to further confirm the dual cytosolic and mitochondrial localization of WT F-ARMC1 using both immunofluorescence (fig. PMID:40203102 This is achieved through ARMC1 partitioning into a distinct complex with DNAJC11, which promotes ARMC1 release from mitochondria into the cytosol. |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | REMOVE | Summary: Metal ion binding (IEA, InterPro heavy metal-associated domain superfamily). ARMC1's HMA-like domain lacks the cysteines needed for metal coordination, and no metal binding has been reported. The mapping does not apply; removed. Reason: [PMID:40203102 "ARMC1 contains an N-terminal helical domain with an Armadillo motif, a heavy metal-associated–like (HMAL) domain that lacks cysteines in the positions required for metal coordination, and a short, conserved C-terminal domain (CTD) (fig."] Supporting Evidence: PMID:40203102 ARMC1 contains an N-terminal helical domain with an Armadillo motif, a heavy metal-associated–like (HMAL) domain that lacks cysteines in the positions required for metal coordination, and a short, conserved C-terminal domain (CTD) (fig. |
| GO:0048312 intracellular distribution of mitochondria | IMP PMID:31644573 Armadillo repeat-containing protein 1 is a dual localization... | ACCEPT | Summary: Intracellular distribution of mitochondria (IMP). ARMC1 knockout fragments mitochondria and reduces their motility. A later study shows ARMC1 loss collapses mitochondria into the perinuclear region, through loss of MIRO-MTFR complexes that oppose retrograde movement. Core process. Reason: [PMID:31644573 "Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility."] [PMID:40203102 "In dividing cells, especially in COS7 cells, deleting ARMC1 caused the distribution of mitochondria to “collapse” into the perinuclear region (Fig."] [PMID:40203102 "MTFR stability depends on ARMC1-mediated complex assembly, which specifically antagonizes excessive retrograde mitochondrial movement through competitive binding with TRAK2."] Supporting Evidence: PMID:31644573 Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. PMID:40203102 In dividing cells, especially in COS7 cells, deleting ARMC1 caused the distribution of mitochondria to “collapse” into the perinuclear region (Fig. PMID:40203102 MTFR stability depends on ARMC1-mediated complex assembly, which specifically antagonizes excessive retrograde mitochondrial movement through competitive binding with TRAK2. |
| GO:0030674 protein-macromolecule adaptor activity | IMP PMID:40203102 ARMC1 partitions between distinct complexes and assembles MI... | NEW | Summary: Protein-macromolecule adaptor activity (NEW, IMP; the D37R interface mutant loses MIRO and MTFR co-purification). ARMC1 binds MIRO directly and mediates assembly of a MIRO-MTFR complex, one MTFR with one MIRO. MTFR stability depends on this ARMC1-mediated assembly, and the resulting complex opposes excess retrograde mitochondrial movement. Reason: [PMID:40203102 "In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution."] [PMID:40203102 "In one complex, the mitochondrial trafficking adaptor MIRO recruits ARMC1, which mediates the assembly of a mitochondrial fission regulator (MTFR)."] [PMID:40203102 "MTFR stability depends on ARMC1-mediated complex assembly, which specifically antagonizes excessive retrograde mitochondrial movement through competitive binding with TRAK2."] Supporting Evidence: PMID:40203102 In this study, we report that ARMC1 directly interacts with MIRO and partitions between distinct OMM protein complexes, which is a critical determinant of mitochondrial distribution. PMID:40203102 In one complex, the mitochondrial trafficking adaptor MIRO recruits ARMC1, which mediates the assembly of a mitochondrial fission regulator (MTFR). PMID:40203102 MTFR stability depends on ARMC1-mediated complex assembly, which specifically antagonizes excessive retrograde mitochondrial movement through competitive binding with TRAK2. |
| GO:0050821 protein stabilization | IMP PMID:40203102 ARMC1 partitions between distinct complexes and assembles MI... | NEW | Summary: Protein stabilization (NEW, IMP). Without ARMC1, MTFR proteins are degraded by the ubiquitin-proteasome system. The MIRO/MTFR-binding-deficient D37R mutant fails to restore MTFR levels, while still binding DNAJC11. ARMC1 itself performs the stabilizing step by assembling MTFR into MIRO complexes. Reason: [PMID:40203102 "MTFR stability depends on ARMC1, and MIRO-MTFR complexes specifically antagonize retrograde mitochondrial movement."] [PMID:40203102 "We observed that MTFR down-regulation occurs through degradation via the ubiquitin-proteasome system, as inhibitors of proteasomes or the E1 ubiquitin-activating enzyme selectively stabilized MTFR (fig."] [PMID:40203102 "D37R F-ARMC1 failed to rescue MTFR levels (fig."] Supporting Evidence: PMID:40203102 MTFR stability depends on ARMC1, and MIRO-MTFR complexes specifically antagonize retrograde mitochondrial movement. PMID:40203102 We observed that MTFR down-regulation occurs through degradation via the ubiquitin-proteasome system, as inhibitors of proteasomes or the E1 ubiquitin-activating enzyme selectively stabilized MTFR (fig. PMID:40203102 D37R F-ARMC1 failed to rescue MTFR levels (fig. |
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Experiment: Track mitochondrial transport in ARMC1-knockout neurons rescued with MIRO-binding-deficient (D37R) or DNAJC11-binding-deficient ARMC1.
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