TOMM6

UniProt ID: Q96B49
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TOMM6 is a small single-pass mitochondrial outer membrane subunit of the TOM translocase core. It is not an independent transporter or enzyme; instead it helps organize and stabilize the TOMM40/TOMM22-containing import channel, including anchoring/positioning TOMM22 and supporting TOM core assembly and oligomerization.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: TOMM6 is a mitochondrial protein, but the annotation is less specific than the well-supported mitochondrial outer membrane/TOM complex localization.
Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations.
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Correct UniProt-derived localization. Falcon research summarizes TOMM6 as a single-pass outer mitochondrial membrane component of the TOM core.
Supporting Evidence:
file:human/TOMM6/TOMM6-deep-research-falcon.md
Human TOMM6 is an OMM component of TOM.
GO:0005742 mitochondrial outer membrane translocase complex
IEA
GO_REF:0000002 		ACCEPT
Summary: Correct complex-level annotation. TOMM6 is one of the small Tom subunits of the TOM core with TOMM40, TOMM22, TOMM5, and TOMM7.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: Generic binary-interactome protein binding does not capture TOMM6's specific role as a structural/regulatory TOM core subunit.
Reason: Protein binding is uninformative for TOMM6; the curated function is TOM complex organization at the mitochondrial outer membrane.
GO:0005739 mitochondrion
IDA
GO_REF:0000052 		MARK AS OVER ANNOTATED
Summary: Correct but too general. TOMM6 is specifically an outer membrane TOM core subunit.
Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations.
GO:0005741 mitochondrial outer membrane
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		ACCEPT
Summary: Kato and Mihara identified human Tom6 in the outer membrane TOM preprotein translocase complex; this agrees with structural/review evidence summarized by Falcon.
GO:0045040 protein insertion into mitochondrial outer membrane
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		MODIFY
Summary: The broad direction of the annotation is related to TOMM6 biology, but TOMM6 is not itself an insertase. Evidence better supports a role in TOM core assembly, stability, and oligomerization.
Reason: Replace the insertion process with TOM complex assembly/stability, which better matches the small Tom6 subunit role.
GO:0140596 TOM complex
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		ACCEPT
Summary: Correct specific complex annotation. TOMM6 is a small TOM core subunit positioned against TOMM40 and coupled to TOMM22 in structural models.
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		MARK AS OVER ANNOTATED
Summary: High-throughput mitochondrial proteomics supports mitochondrial localization, but this is less specific than the mitochondrial outer membrane/TOM complex annotations.
Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations.
GO:0005741 mitochondrial outer membrane
TAS
Reactome:R-HSA-5205661 		ACCEPT
Summary: Reactome places TOMM6 at the mitochondrial outer membrane in TOM/PINK1 pathway context. This matches the structural TOM core localization.

Core Functions

TOMM6 is a structural/regulatory small Tom subunit that stabilizes and organizes the mitochondrial TOM core, supporting TOMM40/TOMM22-dependent mitochondrial protein import and TOM complex assembly.

Directly Involved In:
mitochondrial outer membrane translocase complex assembly
Cellular Locations:
mitochondrial outer membrane
In Complex:
TOM complex
Supporting Evidence:
  • file:human/TOMM6/TOMM6-deep-research-falcon.md
    In this framework, **TOMM6** is best defined as an **auxiliary structural/regulatory subunit** that supports **assembly, stability, and oligomerization** of the TOM core
  • file:human/TOMM6/TOMM6-deep-research-falcon.md
    Human TOMM6 is an OMM component of TOM.
  • file:human/TOMM6/TOMM6-deep-research-falcon.md
    TOMM6 is not itself the pore; rather it supports the protein import pathway by maintaining TOM structural integrity and assembly state.

References

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Suggested Questions for Experts

Q: Which human TOMM6 surfaces are required for TOMM22 anchoring versus general TOMM40 core stabilization?

Q: Does endogenous TOMM6 depletion preferentially impair assembly of new TOM complexes or the import activity of pre-existing TOM complexes?

Suggested Experiments

Experiment: Introduce TOMM6 point mutants in residues predicted to contact TOMM40 or TOMM22, then measure TOM complex assembly by blue-native PAGE/cryo-EM and mitochondrial precursor import using endogenous rescue assays.

Hypothesis: TOMM6 promotes TOM core assembly by stabilizing TOMM40-TOMM22 contacts.

Type: structure-guided mutagenesis and import assay

Deep Research

Falcon

(TOMM6-deep-research-falcon.md)

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