TOMM5

UniProt ID: Q8N4H5
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TOMM5 is a very small single-pass mitochondrial outer membrane subunit of the TOM translocase core. It is a structural/regulatory accessory component, not an enzyme or independent receptor, and supports TOM core organization, stability, and biogenesis around TOMM40.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005742 mitochondrial outer membrane translocase complex
IBA
GO_REF:0000033 		ACCEPT
Summary: Correct phylogenetic inference. TOMM5 is a conserved small Tom subunit of the TOM core complex.
Supporting Evidence:
file:human/TOMM5/TOMM5-deep-research-falcon.md
TOMM5 is a component of the TOM machinery embedded in the **mitochondrial outer membrane** as part of the detergent-stable TOM **core complex**
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Correct UniProt-derived localization. Human structural and review evidence place TOMM5 in the mitochondrial outer membrane TOM core.
GO:0005742 mitochondrial outer membrane translocase complex
IEA
GO_REF:0000002 		ACCEPT
Summary: Correct InterPro-derived complex annotation. TOMM5 is a small subunit of the mitochondrial TOM translocase complex.
GO:0005739 mitochondrion
IDA
GO_REF:0000052 		MARK AS OVER ANNOTATED
Summary: Correct but 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
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		ACCEPT
Summary: Kato and Mihara identified human Tom5 in the outer membrane TOM preprotein translocase complex; this matches the Falcon synthesis of structural evidence.
GO:0045040 protein insertion into mitochondrial outer membrane
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		MODIFY
Summary: TOMM5 supports TOM organization and biogenesis, but the evidence does not support TOMM5 as an independent insertase for outer membrane proteins. TOM complex assembly is the more precise process annotation.
Reason: Replace the insertion term with TOM complex assembly/stability, which is the small Tom5 subunit role supported by structural and ortholog evidence.
GO:0140596 TOM complex
NAS
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		ACCEPT
Summary: Correct and specific. TOMM5 is a detergent-stable TOM core subunit adjacent to TOMM40, TOMM6, TOMM7, and TOMM22.
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		MARK AS OVER ANNOTATED
Summary: High-throughput mitochondrial proteome data support mitochondrial localization, but the term is too general for a TOM outer membrane core subunit.
Reason: Subsumed by mitochondrial outer membrane and TOM complex annotations.
GO:0005741 mitochondrial outer membrane
TAS
Reactome:R-HSA-5205661 		ACCEPT
Summary: Reactome places TOMM5 at the mitochondrial outer membrane in TOM/PINK1 pathway context. This agrees with the TOM core localization.
GO:0070585 protein localization to mitochondrion
IC
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		KEEP AS NON CORE
Summary: Correct as a broad process annotation for a TOM complex subunit, but TOMM5's more specific role is structural support of TOM core assembly and organization.
Reason: Broad process term; the synthesized core function emphasizes TOM complex assembly/stability.
GO:0005742 mitochondrial outer membrane translocase complex
IDA
PMID:18331822
Identification of Tom5 and Tom6 in the preprotein translocas... 		ACCEPT
Summary: Direct evidence from Kato and Mihara supports human TOMM5 membership in the mitochondrial outer membrane translocase complex. A cryo-EM structure of the endogenous TOM-VDAC array (PMID:40080546; PDB 9EIH/9EII/9EIJ) independently resolves TOM5 within the assembled TOM core complex.
Supporting Evidence:
PMID:40080546
TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and

Core Functions

TOMM5 is a structural/regulatory small Tom subunit that contributes to the TOM core translocase by stabilizing TOMM40-containing assemblies and likely assisting TOM biogenesis.

Directly Involved In:
mitochondrial outer membrane translocase complex assembly
Cellular Locations:
mitochondrial outer membrane
In Complex:
TOM complex
Supporting Evidence:
  • file:human/TOMM5/TOMM5-deep-research-falcon.md
    TOMM5 is **not an enzyme** and has **no known catalytic reaction or substrate specificity** in the enzyme/transporter sense.
  • file:human/TOMM5/TOMM5-deep-research-falcon.md
    TOMM5 is a component of the TOM machinery embedded in the **mitochondrial outer membrane** as part of the detergent-stable TOM **core complex**
  • file:human/TOMM5/TOMM5-deep-research-falcon.md
    Mechanistically, TOMM5 is best annotated as an **accessory structural/regulatory subunit** that supports TOM complex organization and likely assists biogenesis/assembly

References

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Suggested Questions for Experts

Q: Which Tom5 contacts in the human TOM core are essential for TOMM40 assembly versus precursor routing?

Q: How much of TOMM5 function in human cells can be separated from conserved yeast Tom5 roles in late Tom40 assembly at SAM?

Suggested Experiments

Experiment: Use endogenous TOMM5 depletion/rescue with structure-guided mutants and measure TOMM40 assembly intermediates, mature TOM complex abundance, and import of representative mitochondrial precursor classes.

Hypothesis: TOMM5 promotes stable TOM core biogenesis by contacting TOMM40 during or after TOMM40 assembly.

Type: endogenous rescue and mitochondrial import assay

Deep Research

Falcon

(TOMM5-deep-research-falcon.md)

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