Yeast TOM22 (Mom22/Mas17/Mas22) encodes Tom22, a single-pass type II outer mitochondrial membrane protein that serves as the central receptor and organizing scaffold of the translocase of the outer mitochondrial membrane (TOM) complex. Together with Tom20 and Tom70, it forms the transit peptide receptor at the outer membrane surface, recognizes cytosolically synthesized mitochondrial preproteins, and transfers them toward the Tom40 translocation pore. Its cytosolic domain docks Tom20 and Tom70 to the general import pore (GIP) complex, its intermembrane space domain provides a trans binding site for presequences, and its transmembrane anchor is required to stabilize the higher-order TOM machinery and to control Tom40 channel gating. Tom22 also contributes to Tom40 biogenesis and Tom40 Ξ²-barrel insertion into the outer membrane through TOMβSAM handoff.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005742 mitochondrial outer membrane translocase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. Tom22 is a core receptor/scaffold subunit of the TOM (translocase of outer mitochondrial membrane) complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004364609 Β· PANTHER:PTN004364609 SUPPORTS TRANSFER Current PTHR12504 PAINT places GO:0005742 at PTN004364609 across opisthokont Tom22 orthologs, with yeast TOM22 among the experimental descendants. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. PMID:9774667 The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. |
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Correct as a TOM-entry step for matrix-destined mitochondrial preproteins. Tom22 is a receptor/scaffold that recognizes preproteins and transfers them toward the Tom40 pore for downstream TIM23/PAM-mediated matrix import. Tom22 also participates in non-matrix import routes, so this BP captures one of several TOM-mediated pathways. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004364609 Β· PANTHER:PTN004364609 SUPPORTS TRANSFER Current PTHR12504 PAINT places GO:0030150 at PTN004364609 for the conserved Tom22 receptor/scaffold contribution to mitochondrial preprotein import. Supporting Evidence: PMID:10519552 The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 PMID:10519552 Here we report the unexpected observation that a yeast strain can survive without Tom22, although it is strongly reduced in growth and the import of mitochondrial proteins. |
| GO:0008320 protein transmembrane transporter activity | IBA GO_REF:0000033 | REMOVE | Summary: Remove this historical IBA because current PTHR12504 PAINT does not carry GO:0008320 at PTN004364609. The contributes_to molecular-function claim remains biologically valid for yeast Tom22 and is still directly supported by the SGD IMP row from PMID:10519552. Reason: Upstream go-annotation issue #6466 raised the concern that "tom40 is the channel, we don't know the MF of tom22" and suggested removing this IBA propagation. Current PTHR12504 PAINT does not carry GO:0008320 at PTN004364609, so this GO_REF:0000033 row is now stale as a PAINT propagation and should not be accepted as-is. The same molecular-function contribution is annotated by SGD as an experimental IMP (PMID:10519552), and that direct row should be retained because (a) it carries the `contributes_to` qualifier, which indicates a subunit-level contribution to a complex-level activity, not a claim that Tom22 independently translocates substrate; (b) Tom22 is required for tight control of channel gating and the higher-order organisation that sustains import; and (c) the parallel human TOMM22 review reaches the same biological conclusion about the `contributes_to` semantics while still accepting its PTHR12504 IBA row. Tom40 should retain `enables GO:0008320` while Tom22 retains `contributes_to GO:0008320` through direct SGD support. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: PANTHER:PTN004364609 Β· PANTHER:PTN004364609 SOURCE STALE OR MISSING GOA retains this 2025 GO:0008320 IBA, but the current PTHR12504 PAINT snapshot does not carry GO:0008320 at PTN004364609. Supporting Evidence: PMID:10519552 In the absence of Tom22, the translocase dissociates into core complexes, representing the basic import units, but lacks a tight control of channel gating. PMID:10519552 Tom22 is a multifunctional protein that is required for the higher-level organization of the TOM machinery. 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 | IEA GO_REF:0000120 | ACCEPT | Summary: Correct. Tom22 is a single-pass type II mitochondrial outer membrane protein. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005742 mitochondrial outer membrane translocase complex | IEA GO_REF:0000002 | ACCEPT | Summary: Correct. Tom22 is a core subunit of the TOM/translocase complex. Supporting Evidence: PMID:9774667 The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct pathway family but too broad. Tom22 specifically functions in TOM-complex mitochondrial protein import, and more specific TOM/mitochondrial-import BPs are already annotated. Reason: Generic intracellular protein transport is far less informative than the existing TOM-mediated import annotations. Supporting Evidence: PMID:10519552 Mitochondrial preproteins are imported by a multisubunit translocase of the outer membrane (TOM), including receptor proteins and a general import pore. |
| GO:0030150 protein import into mitochondrial matrix | IEA GO_REF:0000002 | ACCEPT | Summary: Correct as a TOM-entry step for matrix-destined preproteins (duplicates the IBA/IMP annotations for the same term). Supporting Evidence: PMID:10519552 The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 |
| GO:0005515 protein binding | IPI PMID:11276259 Multistep assembly of the protein import channel of the mito... | REMOVE | Summary: Protein binding is too generic for Tom22. The biologically informative role here (Tom22 as the receptor that initiates Tom40 targeting/assembly) is already captured by mitochondrial outer membrane translocase complex and protein insertion into mitochondrial outer membrane annotations. Reason: Per project curation guidance, remove generic `protein binding` when the cited interaction has no more informative molecular-function replacement; specific complex membership and assembly roles are informative. Supporting Evidence: PMID:11276259 the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form the 250 kDa intermediate exposed to the intermembrane space. |
| GO:0005515 protein binding | IPI PMID:15797382 Mitochondrial presequence translocase: switching between TOM... | REMOVE | Summary: Protein binding is too generic. The Tom22βTim21 interaction documented in this paper is captured at the level of TOM-complex membership and PAM/presequence-translocase coupling annotations rather than generic protein binding. Reason: Generic `protein binding` does not convey the biological role, and the Tim21-Tom22 interaction does not support a specific Tom22 molecular function on its own. Supporting Evidence: PMID:10519552 Tom22 is a multifunctional protein that is required for the higher-level organization of the TOM machinery. |
| GO:0005515 protein binding | IPI PMID:16093310 Large-scale identification of yeast integral membrane protei... | REMOVE | Summary: Protein binding is too generic for Tom22. The Tom22βTom40 interaction is informatively captured by TOM-complex part_of annotations. Reason: Use TOM complex / outer-membrane translocase membership instead of generic protein binding. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. |
| GO:0005515 protein binding | IPI PMID:17635912 The mitochondrial TOM complex is required for tBid/Bax-induc... | REMOVE | Summary: Protein binding is too generic. The relevant interactions (Tom22 with Tom40 and with apoptotic regulators such as Bax in cross-species systems) are better captured by complex membership and process-level annotations. Reason: Generic `protein binding` does not convey the functional contribution, and the cross-species Bax interactions do not support a specific yeast Tom22 molecular-function replacement. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. |
| GO:0005515 protein binding | IPI PMID:22009199 The mitochondrial contact site complex, a determinant of mit... | REMOVE | Summary: Protein binding is too generic. The current GOA/IntAct row links this PMID to a Tom22-Tom40 IPI; the abstract itself foregrounds MICOS architecture and does not support a more specific Tom22 molecular-function term. Reason: Per project guidance, remove generic `protein binding`; TOM-complex and outer-membrane organisation annotations are more informative. Supporting Evidence: PMID:10519552 Tom22 is a multifunctional protein that is required for the higher-level organization of the TOM machinery. |
| GO:0005515 protein binding | IPI PMID:22198199 The cytosolic domain of human Tom22 modulates human Bax mito... | REMOVE | Summary: Protein binding is too generic for Tom22. Cross-species Tom22βBax interactions documented in this paper are captured at the level of TOM-complex membership and outer-membrane process annotations. Reason: Generic `protein binding` is uninformative, and the cross-species Bax interaction does not support a specific yeast Tom22 molecular-function replacement. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. |
| GO:0005515 protein binding | IPI PMID:23911324 Coupling of mitochondrial import and export translocases by ... | REMOVE | Summary: Protein binding is too generic. Tom22 interactions with Tom40, Tom20, and Sam50 captured here represent TOM/TOM-SAM supercomplex relationships best annotated at the complex-membership level. Reason: TOM and SAM/TOM-SAM coupling annotations are more informative than generic protein binding. Supporting Evidence: PMID:9774667 The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Protein binding is too generic. Large-scale interactome data implicating Tom22 with Tom40 and Tom20 corroborate TOM-complex membership annotations rather than supporting an independent informative MF. Reason: Generic `protein binding` is uninformative; use TOM-complex annotations. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. |
| GO:0005515 protein binding | IPI PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | REMOVE | Summary: Protein binding is too generic for Tom22. The Tom22βTom40 and Tom22βTom20 interactions documented in this study are already captured by TOM-complex membership annotations. Reason: Generic `protein binding` is uninformative; TOM-complex annotations carry the same information with more specificity. Supporting Evidence: PMID:9774667 The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct. Tom22 is an integral outer mitochondrial membrane component of the TOM complex. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005742 mitochondrial outer membrane translocase complex | IPI PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct. Tom22 is a core subunit of the TOM/GIP complex as demonstrated by this study. Supporting Evidence: PMID:9774667 The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. |
| GO:0045040 protein insertion into mitochondrial outer membrane | IDA PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct. Tom22 acts as a receptor required for targeting and assembly of Tom40 and other outer membrane import-machinery substrates into the OMM. Supporting Evidence: PMID:11276259 the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form the 250 kDa intermediate exposed to the intermembrane space. |
| GO:0045040 protein insertion into mitochondrial outer membrane | NAS PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct (duplicate of the IDA call from the same paper). Supporting Evidence: PMID:9774667 In mutant mitochondria lacking Tom6, the interaction between Tom22 and Tom40 is destabilized, leading to the dissociation of Tom22 and the generation of a subcomplex of approximately 100K containing Tom40, Tom7, and Tom5. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:16689936 Integral membrane proteins in the mitochondrial outer membra... | ACCEPT | Summary: Correct. Confirms Tom22 as an integral mitochondrial outer membrane protein in yeast. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | MARK AS OVER ANNOTATED | Summary: Correct but very broad. More specific mitochondrial outer membrane annotations are present. Reason: Tom22 is a single-pass outer-membrane protein; the specific GO:0005741 (mitochondrial outer membrane) annotations are more informative. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | MARK AS OVER ANNOTATED | Summary: Correct but very broad; more specific outer-membrane annotations exist. Reason: Prefer GO:0005741 mitochondrial outer membrane. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005741 mitochondrial outer membrane | HDA PMID:16407407 Proteomic analysis of the yeast mitochondrial outer membrane... | ACCEPT | Summary: Correct. Tom22 is an integral outer mitochondrial membrane protein. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0008320 protein transmembrane transporter activity | IMP PMID:10519552 Tom22 is a multifunctional organizer of the mitochondrial pr... | ACCEPT | Summary: Accepted as contribution to the TOM complex protein translocation activity. The IMP rests on tom22Ξ growth/import phenotypes plus a tight control of channel gating, demonstrating that Tom22 is required for the TOM complex to perform transmembrane protein translocation even though Tom40 is the conducting pore. Reason: Experimental annotation by SGD curator with the `contributes_to` qualifier, which is the correct semantic for a complex subunit that does not independently translocate substrate but is required for the activity of the complex that does. Upstream go-annotation issue #6466 raised concern about the IBA propagation of this term; this IMP is the source of the experimental support and aligns with that semantic. Supporting Evidence: PMID:10519552 The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 PMID:10519552 In the absence of Tom22, the translocase dissociates into core complexes, representing the basic import units, but lacks a tight control of channel gating. |
| GO:0005742 mitochondrial outer membrane translocase complex | IDA PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct. Direct demonstration that Tom22 is a core member of the TOM/GIP complex. Supporting Evidence: PMID:9774667 The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. |
| GO:0030150 protein import into mitochondrial matrix | IMP PMID:10519552 Tom22 is a multifunctional organizer of the mitochondrial pr... | ACCEPT | Summary: Correct. tom22Ξ mitochondria are strongly defective for preprotein import; matrix-destined preproteins use the TOM complex at the entry step, with Tom22 acting as the central receptor. Supporting Evidence: PMID:10519552 Here we report the unexpected observation that a yeast strain can survive without Tom22, although it is strongly reduced in growth and the import of mitochondrial proteins. |
| GO:0030150 protein import into mitochondrial matrix | IMP PMID:9774667 Preprotein translocase of the outer mitochondrial membrane: ... | ACCEPT | Summary: Correct. The TOM complex is the entry step for matrix-destined preproteins; Tom22 is one of two essential subunits of the GIP complex. Supporting Evidence: PMID:9774667 Besides the essential proteins Tom22 and Tom40, the GIP complex contains three small subunits, Tom5, Tom6, and Tom7. |
| GO:0045040 protein insertion into mitochondrial outer membrane | IMP PMID:12628251 Biogenesis of yeast mitochondrial cytochrome c: a unique rel... | ACCEPT | Summary: Correct. Tom22 is required for biogenesis of OMM/IMS substrates routed through the TOM machinery; cytochrome c levels are greatly reduced in tom22 mutants. Supporting Evidence: PMID:12628251 Mitochondria lacking the central receptor and organizing protein Tom22 contain greatly reduced levels of cytochrome c. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-SCE-1252255 | ACCEPT | Summary: Correct. Tom22 is an outer mitochondrial membrane component of the TOM complex. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-SCE-8953627 | ACCEPT | Summary: Correct. Tom22 in the MIB context is still anchored in the mitochondrial outer membrane. Supporting Evidence: PMID:9774667 The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). |
| GO:0140436 mitochondrial signal sequence receptor activity | TAS PMID:10519552 Tom22 is a multifunctional organizer of the mitochondrial pr... | NEW | Summary: Tom22 is the central preprotein receptor of the TOM complex, binding presequence-bearing precursors through both its cytosolic and its intermembrane space domains. This receptor activity is Tom22's core molecular function and is what GO:0140436 (the replacement for the obsolete GO:0030943) describes. GOA carries no row for either term on yeast TOM22, so the core function has no backing annotation without this proposal. Reason: Existing GOA lacks a signal-sequence receptor MF for Tom22. The same gap was filled with a NEW GO:0140436 row for human TIMM50 and worm tomm-22; yeast Tom22 is the canonical TOM presequence receptor. Supporting Evidence: PMID:10519552 The central receptor Tom22 binds preproteins through both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 |
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Download this section (compressed HTML)Q: Should the human TOMM22 contributes_to GO:0008320 IBA from PTN004364609 be marked stale to match yeast TOM22, now that the current PTHR12504 PAINT snapshot does not carry GO:0008320 at that node?
Q: How separable are Tom22's preprotein-receptor and TOM-complex scaffold functions in yeast, and does the IMS domain alone account for the trans presequence binding step?
Q: For the TOM-SAM handoff that inserts Tom40 Ξ²-barrels, which Tom22 surface is required, and is this distinct from the cytosolic Tom20/Tom70 docking surface?
Experiment: In purified reconstituted TOM proteoliposomes, compare preprotein translocation rates of Tom40-only vs. Tom22+Tom40 (and full TOM minus Tom22) at varying preprotein concentrations to quantify Tom22's kinetic contribution beyond gating.
Hypothesis: The `contributes_to` semantic on GO:0008320 reflects a genuine functional dependence of TOM-mediated transport on Tom22, not just a complex-membership artifact.
Component of the TOM (Translocase of Outer Membrane) complex; responsible for initial import of mitochondrially directed proteins; mediates interaction between TOM and TIM complexes and acts as receptor for precursor proteins; implicated in mitochondrial accumulation of amyloid beta peptides via direct interaction with amyloid beta peptide residues 25-42 followed by transfer to Tom40p and transport through the TOM channel
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