ARMCX1

UniProt ID: Q9P291
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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).

Core Functions

Mitochondrial outer-membrane protein that enhances axonal mitochondrial transport and supports neuronal survival and regeneration after injury.

Supporting Evidence:
  • PMID:28009275
    Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs).
  • 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
    We further showed that the effects of Armcx1 on neuronal survival and axon regeneration were dependent on its mitochondrial localization.
  • PMID:28009275
    Armcx1 localizes to mitochondria and interacts with mitochondrial transport machinery

References

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Suggested Questions for Experts

Q: Mouse Armcx1 co-immunoprecipitates with Miro1. Does human ARMCX1 bind MIRO1 directly, does it also bind TRAK or kinesin, and how does a mitochondrial outer-membrane protein recruit FBXW7 to c-Myc?

Suggested Experiments

Experiment: Map ARMCX1 binding partners on mitochondria by proximity labelling in neurons, and test whether its tumour-suppressor activity needs mitochondrial targeting.

Deep Research

Affinage

(ARMCX1-deep-research-affinage.md)

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πŸ“š Additional Documentation

Notes

(ARMCX1-notes.md)

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