TOMM22

UniProt ID: Q9NS69
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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 Å** 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 α-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 α-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 α-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 α-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 α-helical** protein.
GO:0030943 mitochondrion targeting sequence binding
IDA
PMID:35733257
Structural basis of Tom20 and Tom22 cytosolic domains as the... 		ACCEPT
Summary: Correct and core. TOMM22 functions as a major mitochondrial preprotein/targeting-signal binding receptor in the TOM complex.
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 Å** 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 α-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 α-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 α-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 Å** 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 Å** 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**.

Core Functions

TOMM22 is the central receptor/scaffold subunit of the mitochondrial outer membrane TOM complex, binding mitochondrial precursor proteins and transferring them toward the TOMM40 pore while stabilizing TOM complex assembly.

Molecular Function:
mitochondrion targeting sequence binding
Directly Involved In:
protein localization to mitochondrion protein import into mitochondrial matrix
Cellular Locations:
mitochondrial outer membrane
In Complex:
TOM 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
    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
    2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
  • file:human/TOMM22/TOMM22-deep-research-falcon.md
    hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10982837
Identification and functional analysis of human Tom22 for protein import into mitochondria.
PMID:12198123
Insertion and assembly of human tom7 into the preprotein translocase complex of the outer mitochondrial membrane.
PMID:14557246
AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins.
PMID:15644312
Dissection of the mitochondrial import and assembly pathway for human Tom40.
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocase complex of human mitochondrial outer membrane.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:25556234
New host factors important for respiratory syncytial virus (RSV) replication revealed by a novel microfluidics screen for interactors of matrix (M) protein.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
PMID:35733257
Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.
Reactome:R-HSA-5205661
Pink1 is recruited from the cytoplasm to the mitochondria
file:human/TOMM22/TOMM22-deep-research-falcon.md
Falcon deep research report for human TOMM22

Suggested Questions for Experts

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?

Suggested Experiments

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.

Deep Research

Falcon

(TOMM22-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 18 citations 2026-05-11T16:43:40.301411

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human TOMM22 (UniProt Q9NS69) — Functional Annotation and Current Understanding

1) Target verification (identity and disambiguation)

The UniProt accession Q9NS69 corresponds to human TOMM22 (TOM22), annotated as the mitochondrial import receptor subunit TOM22 homolog (hTom22) and a member of the Tom22 family. Multiple independent human-mitochondria studies and reviews explicitly define Tom22/TOMM22 as a receptor/core subunit of the translocase of the outer mitochondrial membrane (TOM) complex, consistent with the UniProt description and expected domain/family context (Tom22 family single-pass α-helical subunit). (pitt2021abiochemicaland pages 6-9, su2024structureofthe pages 1-3, haastrup2024mitochondrialtranslocasetomm22 pages 1-3)

2) Key concepts and definitions (current understanding)

2.1 The TOM complex and why TOMM22 is central

The TOM complex is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria. In the human system, precursor proteins (carrying N-terminal presequences or internal targeting signals) are recognized by TOM receptors Tom20, Tom22, and Tom70, and then translocated through the Tom40 pore. (su2024structureofthe pages 1-3)

Within this machinery, TOMM22/hTom22 is described as the central receptor of the TOM complex, functioning both as:
1) a major preprotein-binding site and transfer platform, and
2) an organizational scaffold required for correct TOM complex assembly and stability. (pitt2021abiochemicaland pages 6-9)

A quantitative estimate summarized in a structural/biochemical review is that ~1100 proteins out of ~1500 proteins imported by the TOM complex rely on hTom22 for import—emphasizing its broad client range and centrality among TOM receptors. (pitt2021abiochemicaland pages 13-15)

2.2 Subcellular localization and topology

hTom22 is an outer mitochondrial membrane (OMM) component and is structurally a single-pass amphipathic α-helical protein. Cryo-EM-based descriptions place Tom22 between two Tom40 β-barrels, where it forms a key part of the dimeric interface and provides stabilizing support to Tom40. (pitt2021abiochemicaland pages 6-9)

The protein contains a conserved proline that introduces a kink in the transmembrane helix. In available human TOM structures, substantial portions of Tom22 are not resolved (notably residues 1–61 and 119–142 in the cited review’s summary of structural work), implying flexible/disordered regions that may contribute to receptor function and interactions. (pitt2021abiochemicaland pages 6-9)

A major conceptual update in the current understanding is that the human Tom22 IMS-facing region appears mechanistically distinct from fungal Tom22: the review notes that human Tom22 lacks the acidic patch in the IMS region implicated in the fungal “acid chain hypothesis,” and instead contains a glutamine-rich domain. This is interpreted as evidence that some mechanistic features of mitochondrial targeting and translocation characterized in fungi may not directly translate to humans. (pitt2021abiochemicaland pages 6-9)

2.3 Complex composition and receptor cooperation

A 2024 cryo-EM study focused on receptor positioning describes the TOM complex as comprising seven subunits (Tom40, Tom20, Tom22, Tom70, Tom5, Tom6, Tom7) and supports a model in which different receptors can function simultaneously to ensure efficient translocation of precursors. This work obtained a human TOM holo complex containing an intact Tom20 receptor at ~6 Å resolution, in which Tom20 is stabilized by extensive interactions with Tom22, Tom40, and Tom6. (Su et al., 2024; published online 26 Jul 2024; https://doi.org/10.1093/pnasnexus/pgae269) (su2024structureofthe pages 1-3)

3) Molecular function and pathways

3.1 Primary function: receptor/scaffold for mitochondrial protein import

The best-supported primary function of TOMM22 is as a central receptor/scaffold enabling mitochondrial protein import via the TOM complex. Functional evidence summarized in the Cells review includes perturbation experiments showing that hTom22 knockdown increases levels of stable hTOM assembly intermediates, consistent with a requirement for Tom22 in Tom40/TOM assembly; conversely, Tom22 overexpression supports the interpretation that Tom22 can be rate-limiting for assembly of complete TOM complexes and can promote integration of other subunits (e.g., Tom7) in a human cell context. (Pitt & Buchanan, 2021; 11 May 2021; https://doi.org/10.3390/cells10051164) (pitt2021abiochemicaland pages 6-9)

3.2 Interaction partners (TOM complex and beyond)

Within TOM, Tom22 is positioned to interact closely with Tom40 and other core subunits; receptor-level cooperation includes Tom22 interactions with Tom20 (supported by cross-linking mass spectrometry evidence reported in the review, although not fully resolved structurally). (pitt2021abiochemicaland pages 6-9)

Beyond canonical import, Tom22 is repeatedly described as having a broad interactome that includes proteins involved in apoptosis, mitochondrial dynamics, and metabolic functions. The review highlights functional interactions relevant to:
- Apoptosis via Bax (see below) (pitt2021abiochemicaland pages 13-15)
- Mitochondrial morphology/dynamics (review summary of Tom22 perturbation phenotypes) (pitt2021abiochemicaland pages 15-16)
- Steroidogenesis via a larger metabolic protein complex involving 3βHSD2 and other components (pitt2021abiochemicaland pages 13-15)

These broader interactions are consistent with an emerging view of import machinery components as integration points for stress and signaling, as emphasized by a 2023 review essay describing mitochondrial protein import as a signaling hub connecting mitochondrial and cellular homeostasis. (Lionaki et al., 2023; accepted 2 Jan 2023; https://doi.org/10.1002/bies.202200160) (lionaki2023mitochondrialproteinimport pages 1-2)

4) Recent developments (prioritizing 2023–2024)

4.1 Structural biology (2024): receptor organization within human TOM

The 2024 PNAS Nexus study (Su et al.) reports a human TOM holo complex cryo-EM structure including intact Tom20 at ~6 Å and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation. This work strengthens a receptor-cooperation model in which Tom22 is physically positioned to stabilize receptor arrangement and facilitate precursor delivery to Tom40. (26 Jul 2024; https://doi.org/10.1093/pnasnexus/pgae269) (su2024structureofthe pages 1-3)

4.2 Cancer biology (2024): TOMM22 overexpression in pancreatic cancer

A 2024 Molecular Cancer Research article reports that TOMM22 mRNA/protein is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and is inversely correlated with disease outcomes. Functionally, in pancreatic cancer cell models, TOMM22 silencing decreased whereas forced overexpression increased growth and malignant potential. The authors further report that TOMM22 overexpression increased import of several mitochondrial proteins (including respiration-associated proteins) and was associated with increased complex I (RCI) activity, NAD+/NADH ratio, oxygen consumption rate, mitochondrial membrane potential, and ATP production; complex I inhibition reduced ATP and suppressed malignant phenotypes, linking TOMM22-driven import changes to bioenergetics and growth. (Haastrup et al., 1 Feb 2024 issue date; final article context indicates Feb 2024, with PMC availability noted Dec 2024; https://doi.org/10.1158/1541-7786.MCR-23-0138) (haastrup2024mitochondrialtranslocasetomm22 pages 1-3)

Interpretation: this study supports the hypothesis that, in at least some tumors, increased TOMM22 can act as a functional enabler of mitochondrial biogenesis/respiratory capacity via increased import capacity, rather than being a passive marker of mitochondrial abundance. (haastrup2024mitochondrialtranslocasetomm22 pages 1-3)

4.3 Import machinery as a stress-signaling node (2023)

A 2023 review essay frames mitochondrial protein import as a regulatable signaling hub, where impairment of import induces adaptive responses inside and outside mitochondria (proteostasis and metabolic responses). While not Tom22-specific, it supports an expert consensus that TOM components (including receptor subunits like Tom22) should be considered in a systems context where changes in import efficiency can engage broader stress/quality-control pathways. (Lionaki et al., 2023; https://doi.org/10.1002/bies.202200160) (lionaki2023mitochondrialproteinimport pages 1-2)

5) Current applications and real-world implementations

5.1 Biomarker and therapeutic targeting concepts in oncology

The pancreatic cancer study explicitly proposes TOMM22 as having potential for early diagnostic/prognostic biomarker development and therapeutic targeting in PDAC, based on tumor overexpression, correlation with outcomes, and functional causality in cell models (gain- and loss-of-function) linked to mitochondrial import and OXPHOS-related readouts. (Haastrup et al., 2024; https://doi.org/10.1158/1541-7786.MCR-23-0138) (haastrup2024mitochondrialtranslocasetomm22 pages 1-3)

Separately, a structural/biochemical review highlights that Tom22 participates in apoptosis-related interactions (notably with Bax), and discusses the concept that targeting TOM-complex components and their interactions could be a viable strategy in disease contexts where mitochondrial dysfunction is causal. (Pitt & Buchanan, 2021; https://doi.org/10.3390/cells10051164) (pitt2021abiochemicaland pages 13-15)

5.2 Mechanistic disease models (yeast) for noncanonical substrates

A primary research study in yeast mitochondria provides direct evidence that Tom22 can act as a receptor for amyloid-β (Aβ): Aβ binding is reported to be mediated mainly by Tom22 rather than Tom20, and Aβ residues 25–42 were identified as critical for interaction. The authors propose that cytosolic Aβ is recognized by Tom22 and then transferred to Tom40 for translocation. While this is a yeast model, it is frequently used as a tractable platform to dissect TOM-mediated uptake mechanisms relevant to Alzheimer’s-disease-associated mitochondrial Aβ accumulation. (Hu et al., 2018; https://doi.org/10.1074/jbc.ra118.002713) (hu2018mitochondrialaccumulationof pages 1-2)

6) Expert opinions and analysis (authoritative synthesis)

6.1 Essentiality and assembly control

The Cells review argues that the “structural reliance” of the core TOM complex on Tom22 is consistent with impaired viability observed when Tom22 is deficient (as discussed across model systems and mammalian contexts). The same review synthesizes perturbation evidence supporting Tom22 as an assembly organizer and potential rate-limiting component for complete TOM biogenesis under some conditions. (Pitt & Buchanan, 2021; https://doi.org/10.3390/cells10051164) (pitt2021abiochemicaland pages 13-15, pitt2021abiochemicaland pages 6-9)

6.2 Apoptosis interface (Bax)

A key expert-level point emphasized in the review is that Tom22 is not merely an import receptor but also participates in Bax-mediated apoptosis: inhibition of Tom22–Bax interactions (e.g., via antibody blocking or Tom22 knockdown) is reported to inhibit Bax-mediated apoptosis, suggesting Tom22 can be an actionable node coupling mitochondrial surface machinery to apoptotic execution pathways. (Pitt & Buchanan, 2021; https://doi.org/10.3390/cells10051164) (pitt2021abiochemicaland pages 13-15)

7) Relevant statistics and quantitative data (from recent/authoritative sources)

  • Mitochondrial proteome scale (mammals): mammalian mitochondria may contain up to ~1500 proteins, and only about ~1% are encoded by mitochondrial DNA, implying extensive reliance on nuclear-encoded precursor import. (Lionaki et al., 2023; https://doi.org/10.1002/bies.202200160) (lionaki2023mitochondrialproteinimport pages 1-2)
  • Tom22-dependent import breadth: ~1100 of ~1500 TOM-imported proteins are summarized as relying on hTom22 for import (review synthesis). (Pitt & Buchanan, 2021; https://doi.org/10.3390/cells10051164) (pitt2021abiochemicaland pages 13-15)
  • Structural parameters: human TOM structural work summarized in the Cells review includes a human TOM core at ~3.4 Å (review summary) and an observed tetrameric form at ~8.5 Å (review summary). (pitt2021abiochemicaland pages 11-12)
  • 2024 cryo-EM holo complex resolution: the Tom20-containing human TOM holo complex was resolved at ~6 Å. (Su et al., 2024; https://doi.org/10.1093/pnasnexus/pgae269) (su2024structureofthe pages 1-3)
  • Noncanonical substrate determinant: in the yeast Aβ study, Aβ residues 25–42 were implicated in Tom22-mediated interaction. (Hu et al., 2018; https://doi.org/10.1074/jbc.ra118.002713) (hu2018mitochondrialaccumulationof pages 1-2)

8) Visual evidence (figures) supporting TOMM22 placement and features

The following extracted figures visually summarize Tom22’s placement within the TOM complex and highlight its structural features/interactome in a review context. (pitt2021abiochemicaland media a23c1074, pitt2021abiochemicaland media 096ec19a, pitt2021abiochemicaland media 626e7aa4)

9) Consolidated functional annotation (narrative conclusion)

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. Its core role is to coordinate recognition/transfer of mitochondrial precursor proteins from receptor engagement toward passage through the Tom40 pore, and structural work positions Tom22 at the Tom40 dimer interface with a conserved kinked helix and flexible terminal regions. 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. Beyond canonical import, authoritative synthesis highlights Tom22 as an interaction hub relevant to apoptosis (e.g., Bax-related mechanisms) and metabolic processes (e.g., steroidogenic complexes), consistent with recent frameworks that mitochondrial protein import machinery participates in broader stress-signaling networks. Recent 2024 work advances receptor-level structural organization of the human TOM holo complex and provides disease-context evidence in which TOMM22 overexpression can enhance import-linked respiratory phenotypes and tumor aggressiveness in pancreatic cancer, supporting ongoing interest in TOMM22 as a biomarker and potential therapeutic target. (pitt2021abiochemicaland pages 6-9, pitt2021abiochemicaland pages 13-15, su2024structureofthe pages 1-3, haastrup2024mitochondrialtranslocasetomm22 pages 1-3, lionaki2023mitochondrialproteinimport pages 1-2)

Summary Table

Category Summary
Identity TOMM22 encodes the human mitochondrial import receptor subunit TOM22 homolog (hTom22), the central receptor of the TOM complex; this matches UniProt Q9NS69 and the Tom22 family assignment. It is a conserved TOM core component distinct from TOM20/TOM70 receptor subunits. (pitt2021abiochemicaland pages 6-9, su2024structureofthe pages 1-3, haastrup2024mitochondrialtranslocasetomm22 pages 1-3)
Localization/topology hTom22 localizes to the outer mitochondrial membrane as a single-pass amphipathic α-helical protein. Structural work places it between the two Tom40 β-barrels, forming the dimeric interface and stabilizing the complex. Human Tom22 contains a conserved proline-induced kink; the N-terminal cytosolic and C-terminal IMS regions are partly unresolved/flexible in structures, and the human IMS region is glutamine-rich rather than carrying the fungal acidic patch. (pitt2021abiochemicaland pages 6-9, pitt2021abiochemicaland pages 11-12)
Molecular function 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. It participates in import of precursors with N-terminal presequences or contributes to handling broader precursor classes together with Tom20/Tom70. (pitt2021abiochemicaland pages 6-9, su2024structureofthe pages 1-3, haastrup2024mitochondrialtranslocasetomm22 pages 1-3)
Complex membership Human TOM complex contains Tom40, Tom20, Tom22, Tom70, Tom5, Tom6, and Tom7. Tom22 is part of the core TOM complex with Tom40/Tom5/Tom6/Tom7; cryo-EM studies resolved human TOM core structures at ~3.4 Å and a TOM holo complex containing intact Tom20 at ~6 Å. Tom22 is important for assembly state organization, while Tom6 stabilizes and Tom7 destabilizes TOM partly through effects linked to Tom22. (pitt2021abiochemicaland pages 11-12, su2024structureofthe pages 1-3, pitt2021abiochemicaland pages 6-9)
Interaction partners Key partners include Tom40, Tom20, Tom6, Tom7, and likely Tom70 within the import machinery. Outside canonical import, reported interactors include Bax (apoptosis), PINK1/Parkin pathway components, Mfn1, mito BKCa channel, 3βHSD2, P450C11AS, and StAR in steroidogenic contexts. Cross-linked MS supports a Tom20–Tom22 interaction even where density is unresolved. (pitt2021abiochemicaland pages 23-24, pitt2021abiochemicaland pages 15-16, pitt2021abiochemicaland pages 13-15, pitt2021abiochemicaland pages 6-9)
Regulation/quality control Tom22 is a rate-limiting factor for complete TOM assembly in some cell systems; knockdown increases stable TOM assembly intermediates, whereas overexpression promotes assembly and Tom7 integration. Reviews also note regulation through phosphorylation and quality-control pathways including Yme1-mediated degradation and import-stress signaling/mitophagy links. (pitt2021abiochemicaland pages 6-9, pitt2021abiochemicaland pages 23-24)
Disease/phenotypes Reduced or defective Tom22 impairs viability and mitochondrial homeostasis; zebrafish tom22 mutants show hepatocyte apoptosis and abnormal liver organization. In human disease biology, Tom22 contributes to Bax-mediated apoptosis, has been implicated in Parkinson’s disease-related import dysfunction, and is discussed in mitochondrial stress, steroidogenesis, and metabolic disease contexts. HIV-1 protease has been reported to cleave Tom22 in apoptosis-related models. (pitt2021abiochemicaland pages 13-15, pitt2021abiochemicaland pages 23-24, pitt2021abiochemicaland pages 15-16, su2024structureofthe pages 1-3)
Recent 2023-2024 developments/applications 2024 cryo-EM work further defined receptor organization in the human TOM holo complex, supporting simultaneous action of Tom20/Tom22/Tom70 during import. 2024 pancreatic cancer data showed TOMM22 overexpression promotes aggressive growth by enhancing mitochondrial protein import, respiration-associated functions, membrane potential, and ATP production, highlighting biomarker/therapeutic potential. Reviews from 2023 emphasize TOM components, including Tom22, as signaling hubs in mitochondrial import stress responses. (su2024structureofthe pages 1-3, haastrup2024mitochondrialtranslocasetomm22 pages 1-3, lionaki2023mitochondrialproteinimport pages 1-2)
Quantitative data Mammalian mitochondria contain up to ~1500 proteins, with only ~1% mtDNA-encoded; a review estimates ~1100 of ~1500 TOM-imported proteins rely on hTom22 for import. Structural resolutions cited for human TOM include ~3.4 Å for the core complex and ~6 Å for the Tom20-containing holo complex; lower-resolution tetrameric TOM has been observed at ~8.5 Å. In the Aβ study, residues 25–42 were critical for Tom22-mediated recognition in yeast. (pitt2021abiochemicaland pages 13-15, pitt2021abiochemicaland pages 11-12, lionaki2023mitochondrialproteinimport pages 1-2, su2024structureofthe pages 1-3, hu2018mitochondrialaccumulationof pages 1-2)

Table: This table summarizes the key functional annotation for human TOMM22/ hTom22, including its identity, topology, role in the mitochondrial TOM complex, major interaction partners, disease links, and recent 2023-2024 developments. It is useful as a compact evidence-backed reference for narrative gene annotation.

References

  1. (pitt2021abiochemicaland pages 6-9): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  2. (su2024structureofthe pages 1-3): Jiayue Su, Xuyang Tian, Ziyi Wang, Jiawen Yang, Shan Sun, and Sen-Fang Sui. Structure of the intact tom20 receptor in the human translocase of the outer membrane complex. PNAS Nexus, Jun 2024. URL: https://doi.org/10.1093/pnasnexus/pgae269, doi:10.1093/pnasnexus/pgae269. This article has 12 citations and is from a peer-reviewed journal.

  3. (haastrup2024mitochondrialtranslocasetomm22 pages 1-3): Mary Oluwadamilola Haastrup, Kunwar Somesh Vikramdeo, Shashi Anand, Mohammad Aslam Khan, James Elliot Carter, Seema Singh, Ajay Pratap Singh, and Santanu Dasgupta. Mitochondrial translocase tomm22 is overexpressed in pancreatic cancer and promotes aggressive growth by modulating mitochondrial protein import and function. Molecular cancer research : MCR, 22:197-208, Oct 2024. URL: https://doi.org/10.1158/1541-7786.mcr-23-0138, doi:10.1158/1541-7786.mcr-23-0138. This article has 10 citations.

  4. (pitt2021abiochemicaland pages 13-15): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  5. (pitt2021abiochemicaland pages 15-16): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  6. (lionaki2023mitochondrialproteinimport pages 1-2): Eirini Lionaki, Ilias Gkikas, and Nektarios Tavernarakis. Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond. BioEssays, Jan 2023. URL: https://doi.org/10.1002/bies.202200160, doi:10.1002/bies.202200160. This article has 14 citations and is from a peer-reviewed journal.

  7. (hu2018mitochondrialaccumulationof pages 1-2): Wenxin Hu, Zhiming Wang, and Hongjin Zheng. Mitochondrial accumulation of amyloid β (aβ) peptides requires tomm22 as a main aβ receptor in yeast. Journal of Biological Chemistry, 293:12681-12689, Aug 2018. URL: https://doi.org/10.1074/jbc.ra118.002713, doi:10.1074/jbc.ra118.002713. This article has 51 citations and is from a domain leading peer-reviewed journal.

  8. (pitt2021abiochemicaland pages 11-12): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  9. (pitt2021abiochemicaland media a23c1074): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  10. (pitt2021abiochemicaland media 096ec19a): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  11. (pitt2021abiochemicaland media 626e7aa4): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

  12. (pitt2021abiochemicaland pages 23-24): Ashley S. Pitt and Susan K. Buchanan. A biochemical and structural understanding of tom complex interactions and implications for human health and disease. Cells, 10:1164, May 2021. URL: https://doi.org/10.3390/cells10051164, doi:10.3390/cells10051164. This article has 46 citations.

Citations

  1. su2024structureofthe pages 1-3
  2. pitt2021abiochemicaland pages 6-9
  3. pitt2021abiochemicaland pages 13-15
  4. pitt2021abiochemicaland pages 15-16
  5. lionaki2023mitochondrialproteinimport pages 1-2
  6. hu2018mitochondrialaccumulationof pages 1-2
  7. pitt2021abiochemicaland pages 11-12
  8. pitt2021abiochemicaland pages 23-24
  9. https://doi.org/10.1093/pnasnexus/pgae269
  10. https://doi.org/10.3390/cells10051164
  11. https://doi.org/10.1002/bies.202200160
  12. https://doi.org/10.1158/1541-7786.MCR-23-0138
  13. https://doi.org/10.1074/jbc.ra118.002713
  14. https://doi.org/10.3390/cells10051164,
  15. https://doi.org/10.1093/pnasnexus/pgae269,
  16. https://doi.org/10.1158/1541-7786.mcr-23-0138,
  17. https://doi.org/10.1002/bies.202200160,
  18. https://doi.org/10.1074/jbc.ra118.002713,

📄 View Raw YAML

 
id: Q9NS69
gene_symbol: TOMM22
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
- term:
    id: GO:0005742
    label: mitochondrial outer membrane translocase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Å** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Correct pathway family but too broad. TOMM22 specifically functions in TOM-complex mitochondrial protein import.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Use mitochondrial protein import/localization and TOM complex terms rather than generic intracellular protein transport.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12198123
  review:
    summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 'Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as:'
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25556234
  review:
    summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 'Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as:'
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 'Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as:'
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 'Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as:'
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: TAS
  original_reference_id: PMID:10982837
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: Correct but broad. TOMM22 is specifically localized to the mitochondrial outer membrane/TOM complex.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Prefer mitochondrial outer membrane and TOM complex annotations over generic mitochondrion.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: EXP
  original_reference_id: PMID:10982837
  review:
    summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:15644312
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: NAS
  original_reference_id: PMID:18331822
  review:
    summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0045040
    label: protein insertion into mitochondrial outer membrane
  evidence_type: NAS
  original_reference_id: PMID:18331822
  review:
    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.
    action: KEEP_AS_NON_CORE
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    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.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0140596
    label: TOM complex
  evidence_type: NAS
  original_reference_id: PMID:18331822
  review:
    summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  review:
    summary: Correct but broad. TOMM22 is specifically localized to the mitochondrial outer membrane/TOM complex.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Prefer mitochondrial outer membrane and TOM complex annotations over generic mitochondrion.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0030943
    label: mitochondrion targeting sequence binding
  evidence_type: IDA
  original_reference_id: PMID:35733257
  review:
    summary: Correct and core. TOMM22 functions as a major mitochondrial preprotein/targeting-signal binding receptor in the TOM complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Å** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: Correct but very broad. TOMM22 is specifically a mitochondrial outer membrane TOM complex subunit.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Use mitochondrial outer membrane/TOM complex annotations instead of generic membrane.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5205661
  review:
    summary: Correct. TOMM22 is a single-pass mitochondrial outer membrane component of the TOM complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:15644312
  review:
    summary: Correct but very broad. TOMM22 is specifically a mitochondrial outer membrane TOM complex subunit.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Use mitochondrial outer membrane/TOM complex annotations instead of generic membrane.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Å** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation.
- term:
    id: GO:0005742
    label: mitochondrial outer membrane translocase complex
  evidence_type: IDA
  original_reference_id: PMID:12198123
  review:
    summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
- term:
    id: GO:0005742
    label: mitochondrial outer membrane translocase complex
  evidence_type: IDA
  original_reference_id: PMID:15644312
  review:
    summary: Correct. TOMM22 is a core receptor/scaffold subunit of the TOM complex / mitochondrial outer membrane translocase complex.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: TAS
  original_reference_id: PMID:15644312
  review:
    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.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Retain only as complex contribution; TOMM40 is the conducting pore, whereas TOMM22 provides receptor/scaffold function needed for import.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The 2024 PNAS Nexus study (Su et al.) reports a **human TOM holo complex cryo-EM structure** including intact Tom20 at **~6 Å** and explicitly frames Tom22 as one of the TOM receptors that recognize targeting signals and collaborate in translocation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14557246
  review:
    summary: Protein binding is too generic for TOMM22. The informative functions are precursor/targeting-sequence recognition and TOM complex scaffold membership.
    action: MARK_AS_OVER_ANNOTATED
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    reason: Documented interactions should be captured by TOM complex and targeting-sequence/preprotein receptor annotations rather than generic protein binding.
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 'Within this machinery, **TOMM22/hTom22** is described as the **central receptor** of the TOM complex, functioning both as:'
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 1) a **major preprotein-binding site** and transfer platform, and
- term:
    id: GO:0070585
    label: protein localization to mitochondrion
  evidence_type: TAS
  original_reference_id: PMID:14557246
  review:
    summary: Correct. TOMM22 is a central TOM-complex receptor/scaffold enabling localization/import of nuclear-encoded mitochondrial precursor proteins.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TOMM22/TOMM22-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: The **TOM complex** is the primary entry gate for most nucleus-encoded mitochondrial proteins into mitochondria.
    - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
      supporting_text: 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**.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10982837
  title: Identification and functional analysis of human Tom22 for protein import into mitochondria.
  findings: []
- id: PMID:12198123
  title: Insertion and assembly of human tom7 into the preprotein translocase complex of the outer mitochondrial membrane.
  findings: []
- id: PMID:14557246
  title: AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins.
  findings: []
- id: PMID:15644312
  title: Dissection of the mitochondrial import and assembly pathway for human Tom40.
  findings: []
- id: PMID:18331822
  title: Identification of Tom5 and Tom6 in the preprotein translocase complex of human mitochondrial outer membrane.
  findings: []
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
- id: PMID:25556234
  title: New host factors important for respiratory syncytial virus (RSV) replication revealed by a novel microfluidics screen for interactors of matrix (M) protein.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  findings: []
- id: PMID:35733257
  title: Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.
  findings: []
- id: Reactome:R-HSA-5205661
  title: Pink1 is recruited from the cytoplasm to the mitochondria
  findings: []
- id: file:human/TOMM22/TOMM22-deep-research-falcon.md
  title: Falcon deep research report for human TOMM22
  findings: []
core_functions:
- description: TOMM22 is the central receptor/scaffold subunit of the mitochondrial outer membrane TOM complex, binding mitochondrial precursor proteins and transferring them toward the TOMM40 pore while stabilizing TOM complex assembly.
  supported_by:
  - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
    supporting_text: 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**.
  - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
    supporting_text: 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**.
  - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
    supporting_text: 2) an **organizational scaffold** required for correct **TOM complex assembly** and stability.
  - reference_id: file:human/TOMM22/TOMM22-deep-research-falcon.md
    supporting_text: hTom22 is an **outer mitochondrial membrane (OMM)** component and is structurally a **single-pass amphipathic α-helical** protein.
  molecular_function:
    id: GO:0030943
    label: mitochondrion targeting sequence binding
  directly_involved_in:
  - id: GO:0070585
    label: protein localization to mitochondrion
  - id: GO:0030150
    label: protein import into mitochondrial matrix
  locations:
  - id: GO:0005741
    label: mitochondrial outer membrane
  in_complex:
    id: GO:0140596
    label: TOM complex
proposed_new_terms: []
suggested_questions:
- question: Which human mitochondrial precursor classes rely most directly on TOMM22 rather than TOMM20 or TOMM70 receptor engagement?
  experts: []
- question: How separable are TOMM22 precursor-receptor functions from its TOM complex assembly/stability role in human cells?
  experts: []
suggested_experiments:
- hypothesis: TOMM22 targeting-sequence binding and TOM complex scaffold functions are separable.
  description: 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 abundance can become rate-limiting for TOM complex assembly and mitochondrial protein import in high-biogenesis contexts.
  description: 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.