TOMM22 encodes hTom22, a single-pass mitochondrial outer membrane receptor and scaffold subunit of the TOM complex. TOMM22 recognizes mitochondrial precursor proteins, helps transfer them toward the TOMM40 pore, and supports TOM complex assembly and stability; its transporter annotation is best interpreted as contribution to TOM complex protein import rather than standalone pore activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Correct as a TOM-complex entry step for matrix-destined mitochondrial preproteins. TOMM22 is a receptor/scaffold that recognizes precursors and transfers them toward the TOMM40 pore before downstream inner-membrane import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. |
| GO:0005742 mitochondrial outer membrane translocase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Human **TOMM22 (Q9NS69)** encodes **hTom22**, a **single-pass outer mitochondrial membrane** subunit of the TOM complex that acts as the **central receptor** and an **assembly-organizing scaffold**. file:human/TOMM22/TOMM22-deep-research-falcon.md 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability. |
| GO:0008320 protein transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as contribution to TOM complex protein transmembrane transporter activity. TOMM22 is the receptor/scaffold that transfers precursors toward the TOMM40 pore, not the pore-forming subunit by itself. Reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. file:human/TOMM22/TOMM22-deep-research-falcon.md The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Γ
** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct pathway family but too broad. TOMM22 specifically functions in TOM-complex mitochondrial protein import. Reason: Use mitochondrial protein import/localization and TOM complex terms rather than generic intracellular protein transport. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. |
| GO:0005515 protein binding | IPI PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership. Reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and |
| GO:0005515 protein binding | IPI PMID:25556234 New host factors important for respiratory syncytial virus (... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership. Reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership. Reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership. Reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and |
| GO:0030150 protein import into mitochondrial matrix | TAS PMID:10982837 Identification and functional analysis of human Tom22 for pr... | ACCEPT | Summary: Correct as a TOM-complex entry step for matrix-destined mitochondrial preproteins. TOMM22 is a receptor/scaffold that recognizes precursors and transfers them toward the TOMM40 pore before downstream inner-membrane import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Correct but broad. TOMM22 is specifically localized to the mitochondrial outer membrane/TOM complex. Reason: Prefer mitochondrial outer membrane and TOM complex annotations over generic mitochondrion. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0005741 mitochondrial outer membrane | EXP PMID:10982837 Identification and functional analysis of human Tom22 for pr... | ACCEPT | Summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0030150 protein import into mitochondrial matrix | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: Correct as a TOM-complex entry step for matrix-destined mitochondrial preproteins. TOMM22 is a receptor/scaffold that recognizes precursors and transfers them toward the TOMM40 pore before downstream inner-membrane import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. |
| GO:0005741 mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | KEEP AS NON CORE | Summary: Supported as a TOM-complex assembly/import pathway role, but TOMM22 is primarily the TOM receptor/scaffold rather than a general outer-membrane protein insertase. Reason: Keep as non-core because TOMM22 affects TOM assembly and insertion of TOM-related substrates, while the core function is preprotein receptor/scaffold activity. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability. file:human/TOMM22/TOMM22-deep-research-falcon.md Functional perturbation evidence supports a role for Tom22 as an assembly determinant and, in some contexts, a rate-limiting factor for full TOM complex formation. |
| GO:0140596 TOM complex | NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas... | ACCEPT | Summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Human **TOMM22 (Q9NS69)** encodes **hTom22**, a **single-pass outer mitochondrial membrane** subunit of the TOM complex that acts as the **central receptor** and an **assembly-organizing scaffold**. file:human/TOMM22/TOMM22-deep-research-falcon.md 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: Correct but broad. TOMM22 is specifically localized to the mitochondrial outer membrane/TOM complex. Reason: Prefer mitochondrial outer membrane and TOM complex annotations over generic mitochondrion. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0030943 mitochondrion targeting sequence binding | IDA PMID:35733257 Structural basis of Tom20 and Tom22 cytosolic domains as the... | MODIFY | Summary: Correct and core. TOMM22 functions as a major mitochondrial preprotein/targeting-signal binding receptor in the TOM complex. Reason: GO:0030943 (mitochondrion targeting sequence binding) is obsolete in the current GO release (consider GO:0140436 / GO:0008320). TOMM22 is the central TOM receptor for presequences, so the receptor MF GO:0140436 is the designated replacement. Proposed replacements: mitochondrial signal sequence receptor activity Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. file:human/TOMM22/TOMM22-deep-research-falcon.md The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Γ
** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Correct but very broad. TOMM22 is specifically a mitochondrial outer membrane TOM complex subunit. Reason: Use mitochondrial outer membrane/TOM complex annotations instead of generic membrane. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-5205661 | ACCEPT | Summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0016020 membrane | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | MARK AS OVER ANNOTATED | Summary: Correct but very broad. TOMM22 is specifically a mitochondrial outer membrane TOM complex subunit. Reason: Use mitochondrial outer membrane/TOM complex annotations instead of generic membrane. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic Ξ±-helical** protein. |
| GO:0008320 protein transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as contribution to TOM complex protein transmembrane transporter activity. TOMM22 is the receptor/scaffold that transfers precursors toward the TOMM40 pore, not the pore-forming subunit by itself. Reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. file:human/TOMM22/TOMM22-deep-research-falcon.md The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Γ
** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation. |
| GO:0005742 mitochondrial outer membrane translocase complex | IDA PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra... | ACCEPT | Summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Human **TOMM22 (Q9NS69)** encodes **hTom22**, a **single-pass outer mitochondrial membrane** subunit of the TOM complex that acts as the **central receptor** and an **assembly-organizing scaffold**. file:human/TOMM22/TOMM22-deep-research-falcon.md 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability. |
| GO:0005742 mitochondrial outer membrane translocase complex | IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Human **TOMM22 (Q9NS69)** encodes **hTom22**, a **single-pass outer mitochondrial membrane** subunit of the TOM complex that acts as the **central receptor** and an **assembly-organizing scaffold**. file:human/TOMM22/TOMM22-deep-research-falcon.md 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability. |
| GO:0008320 protein transmembrane transporter activity | TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ... | ACCEPT | Summary: Accepted as contribution to TOM complex protein transmembrane transporter activity. TOMM22 is the receptor/scaffold that transfers precursors toward the TOMM40 pore, not the pore-forming subunit by itself. Reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. file:human/TOMM22/TOMM22-deep-research-falcon.md The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Γ
** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation. |
| GO:0005515 protein binding | IPI PMID:14557246 AIP is a mitochondrial import mediator that binds to both im... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership. Reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as: file:human/TOMM22/TOMM22-deep-research-falcon.md 1) a **major preprotein-binding site** and transfer platform, and |
| GO:0070585 protein localization to mitochondrion | TAS PMID:14557246 AIP is a mitochondrial import mediator that binds to both im... | ACCEPT | Summary: Correct. TOMM22 is a central TOM-complex receptor/scaffold enabling localization/import of nuclear-encoded mitochondrial precursor proteins. Supporting Evidence: file:human/TOMM22/TOMM22-deep-research-falcon.md The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. file:human/TOMM22/TOMM22-deep-research-falcon.md TOMM22 functions as a **major preprotein-binding site** and **organizational scaffold** for the TOM complex, helping recognize mitochondrial precursor proteins and transfer them toward the **Tom40 import pore**. |
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Download this section (compressed HTML)Q: Which human mitochondrial precursor classes rely most directly on TOMM22 rather than TOMM20 or TOMM70 receptor engagement?
Q: How separable are TOMM22 precursor-receptor functions from its TOM complex assembly/stability role in human cells?
Experiment: Use TOMM22 cytosolic-domain and transmembrane/interface mutants in rescue cells, then compare precursor binding, TOM complex assembly by BN-PAGE, and import of presequence versus internal-signal substrates.
Hypothesis: TOMM22 targeting-sequence binding and TOM complex scaffold functions are separable.
Experiment: Titrate TOMM22 expression in human cells and measure TOM assembly intermediates, Tom40/Tom7 incorporation, and import flux for representative matrix, inner-membrane, and outer-membrane substrates.
Hypothesis: TOMM22 abundance can become rate-limiting for TOM complex assembly and mitochondrial protein import in high-biogenesis contexts.
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