TOMM70 is a cytosol-facing mitochondrial outer membrane TOM receptor/adaptor. Its primary role is to dock Hsp70/Hsp90-bound hydrophobic mitochondrial precursor proteins, especially internal-signal/carrier-type substrates, and deliver them to the TOM translocation machinery. It also has supported non-core signaling roles in MAVS/IRF3 antiviral responses and PINK1/Parkin-linked mitochondrial quality control.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005741 mitochondrial outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. Supporting Evidence: file:human/TOMM70/TOMM70-deep-research-falcon.md TOMM70 is anchored in the **outer mitochondrial membrane (OMM)** with its receptor domain facing the cytosol. |
| GO:0008320 protein transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as TOMM70 contribution to TOM-dependent protein transmembrane transport. TOMM70 is a receptor/adaptor, not the pore-forming subunit, but it contributes to the TOM complex import activity. Supporting Evidence: file:human/TOMM70/TOMM70-deep-research-falcon.md TOMM70 is best understood as a **surface receptor/adaptor** of the **TOM (translocase of the outer membrane)** import gateway |
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Broadly valid as a TOM-pathway outcome, but TOMM70 is best described as an outer-membrane receptor/adaptor rather than the matrix import pore or motor. Reason: Matrix import is one TOM-dependent route; TOMM70 has a more specific receptor/adaptor role for chaperone-bound precursors. |
| GO:0030943 mitochondrion targeting sequence binding | IBA GO_REF:0000033 | MODIFY | Summary: Supported. TOMM70 recognizes mitochondrial precursor proteins, especially hydrophobic internal-signal substrates delivered by Hsp70/Hsp90 chaperones. Reason: GO:0030943 (mitochondrion targeting sequence binding) is obsolete in the current GO release (consider GO:0140436 / GO:0008320). TOMM70 is a TOM receptor recognizing (mainly internal) mitochondrial targeting signals of chaperone-delivered precursors; GO:0140436 is defined as binding a mitochondrial targeting sequence and is the designated receptor replacement. Proposed replacements: mitochondrial signal sequence receptor activity Supporting Evidence: file:human/TOMM70/TOMM70-deep-research-falcon.md Cytosolic **Hsp70/Hsp90** chaperones bind newly synthesized hydrophobic precursors to prevent aggregation and **deliver them to TOMM70** |
| GO:0045039 protein insertion into mitochondrial inner membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reasonable as a pathway-level consequence for carrier/internal-signal precursor delivery, but TOMM70 does not catalyze inner membrane insertion itself. Reason: TOMM70 acts upstream at the outer membrane before substrates are handed to downstream inner-membrane import machinery. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005515 protein binding | IPI PMID:32353859 A SARS-CoV-2 protein interaction map reveals targets for dru... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:32728199 SARS-CoV-2 Orf9b suppresses type I interferon responses by t... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:33060197 Comparative host-coronavirus protein interaction networks re... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:33845483 Multilevel proteomics reveals host perturbations by SARS-CoV... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:33990585 Crystal structure of SARS-CoV-2 Orf9b in complex with human ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: The interaction is documented, but generic protein binding should be superseded by specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:34232536 Interactomes of SARS-CoV-2 and human coronaviruses reveal ho... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:34502139 Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting ... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:34942634 Evolution of enhanced innate immune evasion by SARS-CoV-2. | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0030150 protein import into mitochondrial matrix | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Broadly valid as a TOM-pathway outcome, but TOMM70 is best described as an outer-membrane receptor/adaptor rather than the matrix import pore or motor. Reason: Matrix import is one TOM-dependent route; TOMM70 has a more specific receptor/adaptor role for chaperone-bound precursors. |
| GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development | IEA GO_REF:0000107 | REMOVE | Summary: Automatic orthology transfer is not supported by the TOMM70 literature synthesis as a direct function of this gene product. Reason: Developmental/thyroxine response terms overreach beyond TOMM70's demonstrated receptor/adaptor and signaling roles. |
| GO:0097068 response to thyroxine | IEA GO_REF:0000107 | REMOVE | Summary: Automatic orthology transfer is not supported by the TOMM70 literature synthesis as a direct function of this gene product. Reason: Developmental/thyroxine response terms overreach beyond TOMM70's demonstrated receptor/adaptor and signaling roles. |
| GO:1903749 positive regulation of protein localization to mitochondrion | IEA GO_REF:0000107 | ACCEPT | Summary: Supported broad process annotation. TOMM70 promotes mitochondrial localization/import of precursor proteins through its receptor/adaptor role. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0030150 protein import into mitochondrial matrix | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | KEEP AS NON CORE | Summary: Broadly valid as a TOM-pathway outcome, but TOMM70 is best described as an outer-membrane receptor/adaptor rather than the matrix import pore or motor. Reason: Matrix import is one TOM-dependent route; TOMM70 has a more specific receptor/adaptor role for chaperone-bound precursors. |
| GO:0005741 mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | MODIFY | Summary: The annotation captures mitochondrial protein import context but overstates TOMM70 as an outer-membrane insertase. Reason: TOMM70 is a receptor/adaptor for precursor targeting/import, not the SAM/outer-membrane insertion machinery. Proposed replacements: protein localization to mitochondrion |
| GO:0140596 TOM complex | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct and specific. TOMM70 is a TOM-complex receptor component rather than an independent pore-forming subunit. |
| GO:0005741 mitochondrial outer membrane | EXP PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | EXP PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | EXP PMID:33723040 Toxoplasma gondii association with host mitochondria require... | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0005515 protein binding | IPI PMID:35391620 The role of the individual TOM subunits in the association o... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: The interaction is documented, but generic protein binding should be superseded by specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | ACCEPT | Summary: Accepted. TOMM70 functions as a receptor/adaptor for chaperone-bound mitochondrial precursor proteins and also as a MAVS-linked signaling scaffold. Supporting Evidence: file:human/TOMM70/TOMM70-deep-research-falcon.md TOMM70 is best understood as a **surface receptor/adaptor** of the **TOM (translocase of the outer membrane)** import gateway |
| GO:0031966 mitochondrial membrane | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | MARK AS OVER ANNOTATED | Summary: Correct but too broad. The specific supported localization is mitochondrial outer membrane, not generic mitochondrial membrane. Reason: Subsumed by mitochondrial outer membrane annotations. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-5205661 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-9685281 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-9709663 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-9709787 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-9709842 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-9709852 | ACCEPT | Summary: Correct localization. TOMM70 is an outer mitochondrial membrane TOM receptor/adaptor with a cytosol-facing TPR receptor domain. |
| GO:0002218 activation of innate immune response | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | KEEP AS NON CORE | Summary: Supported in the antiviral MAVS/IRF3 literature, but this is a context-specific signaling role rather than TOMM70's core mitochondrial import function. Reason: Non-core signaling/adaptor role in antiviral innate immune response. |
| GO:0002230 positive regulation of defense response to virus by host | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | KEEP AS NON CORE | Summary: Supported in the antiviral MAVS/IRF3 literature, but this is a context-specific signaling role rather than TOMM70's core mitochondrial import function. Reason: Non-core signaling/adaptor role in antiviral innate immune response. |
| GO:0005515 protein binding | IPI PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005515 protein binding | IPI PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005739 mitochondrion | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0005739 mitochondrion | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0032728 positive regulation of interferon-beta production | IDA PMID:20628368 Tom70 mediates activation of interferon regulatory factor 3 ... | KEEP AS NON CORE | Summary: Supported in the antiviral MAVS/IRF3 literature, but this is a context-specific signaling role rather than TOMM70's core mitochondrial import function. Reason: Non-core signaling/adaptor role in antiviral innate immune response. Supporting Evidence: file:human/TOMM70/TOMM70-deep-research-falcon.md TOMM70 is described as participating in antiviral innate immune signaling by acting as a **receptor/scaffold for MAVS-associated signaling** |
| GO:0042981 regulation of apoptotic process | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | KEEP AS NON CORE | Summary: Supported for Sendai virus-induced TOMM70/Hsp90/IRF3/BAX apoptosis context, but it is a secondary signaling phenotype. Reason: Context-specific antiviral/apoptosis role rather than primary mitochondrial import function. |
| GO:0098586 cellular response to virus | IDA PMID:25609812 Tom70 mediates Sendai virus-induced apoptosis on mitochondri... | KEEP AS NON CORE | Summary: Supported in the antiviral MAVS/IRF3 literature, but this is a context-specific signaling role rather than TOMM70's core mitochondrial import function. Reason: Non-core signaling/adaptor role in antiviral innate immune response. |
| GO:0005742 mitochondrial outer membrane translocase complex | ISS GO_REF:0000024 | ACCEPT | Summary: Correct complex annotation. TOMM70 associates with the TOM import machinery and acts as a receptor/adaptor at the outer membrane translocase. |
| GO:0008320 protein transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as TOMM70 contribution to TOM-dependent protein transmembrane transport. TOMM70 is a receptor/adaptor, not the pore-forming subunit, but it contributes to the TOM complex import activity. |
| GO:0030150 protein import into mitochondrial matrix | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Broadly valid as a TOM-pathway outcome, but TOMM70 is best described as an outer-membrane receptor/adaptor rather than the matrix import pore or motor. Reason: Matrix import is one TOM-dependent route; TOMM70 has a more specific receptor/adaptor role for chaperone-bound precursors. |
| GO:0030943 mitochondrion targeting sequence binding | ISS GO_REF:0000024 | MODIFY | Summary: Supported. TOMM70 recognizes mitochondrial precursor proteins, especially hydrophobic internal-signal substrates delivered by Hsp70/Hsp90 chaperones. Reason: GO:0030943 (mitochondrion targeting sequence binding) is obsolete in the current GO release (consider GO:0140436 / GO:0008320). TOMM70 is a TOM receptor recognizing (mainly internal) mitochondrial targeting signals of chaperone-delivered precursors; GO:0140436 is defined as binding a mitochondrial targeting sequence and is the designated receptor replacement. Proposed replacements: mitochondrial signal sequence receptor activity |
| GO:0045039 protein insertion into mitochondrial inner membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reasonable as a pathway-level consequence for carrier/internal-signal precursor delivery, but TOMM70 does not catalyze inner membrane insertion itself. Reason: TOMM70 acts upstream at the outer membrane before substrates are handed to downstream inner-membrane import machinery. |
| GO:0070585 protein localization to mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Supported broad process annotation. TOMM70 promotes mitochondrial localization/import of precursor proteins through its receptor/adaptor role. |
| GO:0005515 protein binding | IPI PMID:23911537 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role... | REMOVE | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: Replace generic protein binding curation with specific adaptor, receptor, TOM complex, and pathway annotations. |
| GO:0005739 mitochondrion | IDA PMID:20531390 Suppression of the novel ER protein Maxer by mutant ataxin-1... | MARK AS OVER ANNOTATED | Summary: Correct but too general. TOMM70 is specifically an outer mitochondrial membrane TOM receptor/adaptor. Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations. |
| GO:0070062 extracellular exosome | HDA PMID:18570454 Proteomic analysis of exosomes from human neural stem cells ... | REMOVE | Summary: High-throughput extracellular exosome detection is not supported as TOMM70 functional localization and conflicts with the mitochondrial outer membrane synthesis. Reason: Likely high-throughput carryover/noise for an outer mitochondrial membrane TOM receptor. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Correct but too broad. The specific supported localization is mitochondrial outer membrane, not generic membrane. Reason: Subsumed by mitochondrial outer membrane annotations. |
| GO:0005742 mitochondrial outer membrane translocase complex | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: Correct complex annotation. TOMM70 associates with the TOM import machinery and acts as a receptor/adaptor at the outer membrane translocase. |
| GO:0008320 protein transmembrane transporter activity | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: Accepted as TOMM70 contribution to TOM-dependent protein transmembrane transport. TOMM70 is a receptor/adaptor, not the pore-forming subunit, but it contributes to the TOM complex import activity. |
| GO:0005515 protein binding | IPI PMID:12526792 Molecular chaperones Hsp90 and Hsp70 deliver preproteins to ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM70. The informative functions are chaperone-bound precursor receptor/adaptor activity, TOM association, and context-specific MAVS/PINK1 signaling. Reason: The interaction is documented, but generic protein binding should be superseded by specific adaptor, receptor, TOM complex, and pathway annotations. |
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Download this section (compressed HTML)Q: Which mammalian TOMM70 substrates require direct chaperone docking versus direct precursor contacts?
Q: How are TOMM70 import, MAVS signaling, and PINK1/Parkin quality-control roles separated by post-translational regulation?
Experiment: Compare import of carrier-type substrates and presequence substrates in TOMM70 knockout or knockdown cells rescued with wild-type versus chaperone-docking-defective TOMM70 variants.
Hypothesis: TOMM70 TPR-domain mutants that disrupt Hsp70/Hsp90 docking selectively impair carrier/internal-signal precursor import while preserving TOM core assembly.
Experiment: Assay MAVS-induced IRF3 activation and mitochondrial precursor import in parallel for TOMM70 interface mutants.
Hypothesis: TOMM70 antiviral signaling can be separated from its import receptor activity by mutating MAVS/Hsp90 signaling interfaces outside the precursor handoff surface.
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