MTX2 (metaxin-2) is a non-enzymatic mitochondrial outer membrane metaxin-family factor that partners with MTX1 in the mammalian SAM machinery. Its best-supported core role is mitochondrial outer membrane protein biogenesis/organization, especially SAM-mediated integration and assembly of beta-barrel outer membrane proteins, with additional links to MICOS/MIB architecture, mitochondrial transport, apoptosis, and MTX2-associated mandibuloacral dysplasia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045040 protein insertion into mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Correct phylogenetic inference. MTX2 is an MTX1 partner in the SAM machinery supporting integration/assembly of beta-barrel proteins into the mitochondrial outer membrane. Supporting Evidence: file:human/MTX2/MTX2-deep-research-falcon.md The **mitochondrial Sorting and Assembly Machinery (SAM)** is an OMM pathway that supports the **correct integration of Ξ²-barrel proteins into the OMM**. |
| GO:0070096 mitochondrial outer membrane translocase complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as a SAM/metaxin assembly function. MTX2 supports the organization and assembly of outer membrane translocase components and beta-barrel proteins. |
| GO:0001401 SAM complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. MTX2 is a metaxin component of the mammalian SAM machinery with MTX1 and SAMM50. |
| GO:0001401 SAM complex | IEA GO_REF:0000002 | ACCEPT | Summary: Correct InterPro-derived annotation. The Falcon synthesis supports MTX2 as a SAM/metaxin factor at the mitochondrial outer membrane. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Correct but too general. MTX2 is specifically localized to the mitochondrial outer membrane and SAM machinery. Reason: Subsumed by mitochondrial outer membrane and SAM complex annotations. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct UniProt-derived localization. MTX2 is an outer mitochondrial membrane metaxin protein facing the cytosolic compartment. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Proteome-scale protein binding is too generic to capture MTX2 function. The supported biology is MTX2 partnership with MTX1 in SAM/metaxin outer membrane protein biogenesis. Reason: Protein binding is uninformative; use SAM complex and assembly terms instead. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binary-interactome protein binding does not represent MTX2's curated mitochondrial outer membrane/SAM function. Reason: Protein binding is uninformative; complex membership captures the supported function. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Correct but less specific than the mitochondrial outer membrane/SAM localization. Reason: Subsumed by mitochondrial outer membrane and SAM complex annotations. |
| GO:0001401 SAM complex | IPI PMID:17510655 Conserved roles of Sam50 and metaxins in VDAC biogenesis. | ACCEPT | Summary: Accepted. Conserved Sam50/metaxin evidence supports MTX2 as part of the SAM machinery for VDAC/beta-barrel biogenesis. |
| GO:0005741 mitochondrial outer membrane | NAS PMID:31387448 Mitochondria-hubs for regulating cellular biochemistry: emer... | ACCEPT | Summary: Accepted. MTX2 is consistently described as a mitochondrial outer membrane metaxin/SAM component. |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:31387448 Mitochondria-hubs for regulating cellular biochemistry: emer... | ACCEPT | Summary: Accepted as the core SAM/metaxin process: correct integration and assembly of beta-barrel proteins into the mitochondrial outer membrane. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: High-throughput mitochondrial proteome evidence supports mitochondrial localization, but this is less specific than the outer membrane/SAM annotation. Reason: Subsumed by mitochondrial outer membrane and SAM complex annotations. |
| GO:0006839 mitochondrial transport | IMP PMID:32917887 Loss of MTX2 causes mandibuloacral dysplasia and links mitoc... | KEEP AS NON CORE | Summary: Valid but broad disease-mechanism annotation. MTX2 loss disrupts mitochondrial function and transport/biogenesis, but the more precise core process is SAM-mediated outer membrane protein insertion and assembly. Reason: Broad process term; retained as a disease-relevant non-core phenotype/process. |
| GO:0001401 SAM complex | HDA PMID:26477565 Evolution and structural organization of the mitochondrial c... | ACCEPT | Summary: Accepted. High-throughput complex evidence is consistent with MTX2 in SAM-associated mitochondrial outer membrane assemblies. |
| GO:0007007 inner mitochondrial membrane organization | IC PMID:26477565 Evolution and structural organization of the mitochondrial c... | KEEP AS NON CORE | Summary: Supported as a secondary consequence/context of SAM-MICOS/MIB bridging and mitochondrial architecture effects, but not the primary MTX2 function. Reason: MIB/MICOS-associated architecture is secondary to the core SAM role. |
| GO:0140275 MIB complex | HDA PMID:26477565 Evolution and structural organization of the mitochondrial c... | KEEP AS NON CORE | Summary: Supported as an additional SAM-MICOS/MIB-associated context. Keep as non-core because the strongest MTX2 function is SAM/metaxin outer membrane protein biogenesis. Reason: MIB complex association is secondary to the primary SAM/metaxin role. |
| GO:0005739 mitochondrion | IDA PMID:25997101 QIL1 is a novel mitochondrial protein required for MICOS com... | MARK AS OVER ANNOTATED | Summary: Correct but too general for MTX2, which localizes to the mitochondrial outer membrane and SAM machinery. Reason: Subsumed by mitochondrial outer membrane and SAM complex annotations. |
| GO:0005741 mitochondrial outer membrane | TAS PMID:10381257 Metaxin 1 interacts with metaxin 2, a novel related protein ... | ACCEPT | Summary: Accepted. MTX2 was identified as an MTX1-interacting protein associated with the mammalian mitochondrial outer membrane. |
| GO:0006839 mitochondrial transport | TAS PMID:10381257 Metaxin 1 interacts with metaxin 2, a novel related protein ... | KEEP AS NON CORE | Summary: Broad but directionally correct for metaxin biology. The more specific function is outer membrane protein biogenesis/insertion through SAM. Reason: Broad process term; more specific SAM-mediated insertion terms exist. |
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Download this section (compressed HTML)Q: Which MTX2-MTX1 interfaces are required for SAM-mediated beta-barrel insertion versus broader SAM-MICOS/MIB architecture?
Q: How do pathogenic MTX2 splice or null variants alter SAM composition, MTX1 stability, and mitochondrial outer membrane protein assembly in patient cells?
Experiment: Perform endogenous MTX2 knockout/rescue and patient-variant rescue in human cells, then measure MTX1 stability, SAM complex assembly, VDAC/TOM40 import, mitochondrial network morphology, and apoptosis/respiration phenotypes.
Hypothesis: MTX2 stabilizes MTX1-containing SAM assemblies required for beta-barrel outer membrane protein biogenesis.
Type: endogenous rescue and mitochondrial import/assembly assay
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