TOMM7 is a small single-pass mitochondrial outer membrane TOM complex subunit. It is not the TOM pore or a standalone transporter; instead it regulates TOM core assembly, stability, and oligomeric organization, and it has a supported mitochondrial quality-control role in PINK1 stabilization/activation and PINK1-Parkin mitophagy signaling after mitochondrial depolarization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005742 mitochondrial outer membrane translocase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct phylogenetic inference. TOMM7 is a conserved small TOM subunit in the mitochondrial outer membrane translocase complex. Supporting Evidence: file:human/TOMM7/TOMM7-deep-research-falcon.md TOMM7 is an **outer mitochondrial membrane** subunit of the TOM machinery. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct UniProt-derived localization. TOMM7 is a single-pass outer mitochondrial membrane TOM subunit. |
| GO:0005742 mitochondrial outer membrane translocase complex | IEA GO_REF:0000002 | ACCEPT | Summary: Correct InterPro-derived annotation. TOMM7 is a Tom7-family small TOM complex subunit. |
| GO:0030150 protein import into mitochondrial matrix | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Correct as a broad TOM pathway consequence but not TOMM7's most specific role. TOMM7 regulates TOM complex assembly/stability and supports import indirectly through the TOM complex. Reason: Matrix import is one route through TOM; TOMM7's core role is TOM complex regulation. |
| GO:0005515 protein binding | IPI PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra... | REMOVE | Summary: Protein binding is too generic. The relevant result is TOMM7 insertion and assembly into the TOM complex, captured by TOM complex and assembly terms. Reason: Protein binding is uninformative for TOMM7 function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Histone crosslinking protein binding is not part of the curated TOMM7 mitochondrial outer membrane/TOM function. Reason: Protein binding is uninformative and likely unrelated to TOMM7 core function. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Generic OpenCell protein binding does not capture TOMM7's function as a regulatory/structural TOM complex subunit. Reason: Protein binding is uninformative; complex and process annotations are more appropriate. |
| GO:0030150 protein import into mitochondrial matrix | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | KEEP AS NON CORE | Summary: Broad but valid for the TOM import pathway. TOMM7 contributes indirectly through TOM complex organization rather than acting as the matrix-import motor or pore. Reason: Matrix import is a TOM pathway outcome but not TOMM7's most specific function. |
| GO:0005741 mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct localization. TOMM7 is a small outer mitochondrial membrane subunit of the TOM machinery. |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | MODIFY | Summary: The broad TOM biology is related, but TOMM7 is not an independent insertase. The specific supported role is TOM complex assembly/stability and oligomeric-state regulation. Reason: Replace outer membrane insertion with TOM complex assembly/stability. Proposed replacements: mitochondrial outer membrane translocase complex assembly |
| GO:0140596 TOM complex | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct and specific. TOMM7 is a TOM core/holo complex subunit adjacent to TOM40/TOM22 and the other small Tom proteins. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM7 is specifically a mitochondrial outer membrane TOM complex subunit. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0005742 mitochondrial outer membrane translocase complex | TAS PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | ACCEPT | Summary: Accepted. The TOMM7/PINK1-Parkin evidence is consistent with TOMM7 acting at the TOM complex. |
| GO:0031647 regulation of protein stability | IMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | ACCEPT | Summary: Accepted for the PINK1 context. TOMM7 is required for efficient PINK1 stabilization/activation at the TOM complex after mitochondrial depolarization. |
| GO:1903749 positive regulation of protein localization to mitochondrion | IMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | ACCEPT | Summary: Accepted as a PINK1-related annotation. TOMM7 supports PINK1 accumulation at damaged mitochondria/TOM after depolarization. |
| GO:1905091 positive regulation of type 2 mitophagy | IMP PMID:24270810 High-content genome-wide RNAi screens identify regulators of... | ACCEPT | Summary: Accepted. TOMM7 enables PINK1 stabilization/activation at TOM and downstream Parkin recruitment, supporting PINK1-Parkin mitophagy signaling. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-5205661 | ACCEPT | Summary: Accepted. Reactome places TOMM7 at the mitochondrial outer membrane in TOM/PINK1 pathway context. |
| GO:0005739 mitochondrion | IDA PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM7 is specifically an outer membrane TOM complex subunit. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0005742 mitochondrial outer membrane translocase complex | IDA PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra... | ACCEPT | Summary: Accepted. PMID:12198123 directly addresses insertion and assembly of human TOM7 into the TOM complex. |
| GO:0008320 protein transmembrane transporter activity | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | REMOVE | Summary: TOMM7 is not the TOM protein-conducting pore. Its role is regulatory and structural within the TOM complex rather than direct transporter activity. Reason: TOMM7 regulates TOM complex assembly/stability but does not independently enable protein transmembrane transporter activity. |
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Download this section (compressed HTML)Q: Which TOMM7 structural features separately control TOM oligomeric stability and PINK1 arrest/activation at the TOM complex?
Q: Why do different TOMM7 disease alleles produce selective developmental, metabolic, or cerebrovascular phenotypes despite retention of mitochondrial localization?
Experiment: Compare endogenous TOMM7 knockout/rescue with p.W25R and p.P29L alleles for TOM complex assembly, TOMM40/TOMM22 interaction, import of representative mitochondrial precursors, PINK1 stabilization, Parkin recruitment, and endothelial/iPSC metabolic phenotypes.
Hypothesis: TOMM7 disease variants selectively weaken TOMM7-TOMM40/TOMM22 interactions, altering TOM assembly and PINK1 signaling without uniformly abolishing import.
Type: endogenous rescue, TOM assembly assay, and mitophagy assay
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