Gene Ontology annotation through association of InterPro records with GO terms

InterPro2GO mapping assigns TOM complex membership to TOMM6 based on the Tom6 (IPR029182) / PF15184 family signature.

Annotation inferences using phylogenetic trees

PAINT/IBA phylogenetic propagation supports mitochondrial localization for TOMM6 across the Tom6 family.

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

UniProt subcellular location annotation places TOMM6 in the mitochondrial outer membrane.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

Curated immunofluorescence localization places TOMM6 in mitochondria.

PMID:18331822

Identification of Tom5 and Tom6 in the preprotein translocase complex of human mitochondrial outer membrane.

Human Tom5 and Tom6 were immuno-isolated as associated subunits of the TOM preprotein translocase from HeLa cells expressing hTom22-FLAG.

"We immuno-isolated the TOM complex from HeLa cells expressing hTom22-FLAG and identified the human counterparts of Tom5 and Tom6, together with the other components including Tom7."
Tom6 is associated with Tom40 in the mammalian TOM complex.

"These small Tom proteins are associated with Tom40 in the TOM complex."
Small Tom proteins (Tom5/Tom6/Tom7) maintain the structural integrity of the human TOM complex, with double knockdown impairing precursor import.

"Matrix import of preprotein was affected by double knockdown of any combination of small Tom proteins. These results indicate that human small Tom proteins maintain the structural integrity of the TOM complex."

PMID:32296183

A reference map of the human binary protein interactome.

TOMM6 appears in the high-throughput Y2H-based HuRI binary protein interactome map; this is generic protein-binding evidence and does not by itself define the specific role of TOMM6 in the TOM core.

PMID:34800366

Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.

TOMM6 is included in the high-confidence quantitative human mitochondrial proteome supporting mitochondrial localization.

Reactome:R-HSA-5205661

Pink1 is recruited from the cytoplasm to the mitochondria

Reactome places TOMM6 at the mitochondrial outer membrane as part of the TOM complex in the PINK1 recruitment pathway.

file:human/TOMM6/TOMM6-deep-research-falcon.md

Falcon deep research report for human TOMM6

TOMM6 is an α-helical single-pass outer mitochondrial membrane protein that participates in the TOM translocase together with TOMM40 (pore) and TOMM22 (receptor).

"Tom6/TOMM6 as an α-helical single-pass outer mitochondrial membrane (OMM) protein that participates in the TOM (translocase of the outer membrane) protein-import machinery together with TOMM40 (pore) and TOMM22 (core receptor/adaptor)."
TOMM6 functions as an auxiliary structural/regulatory subunit supporting assembly, stability, and oligomerization of the TOM core rather than as a stand-alone transporter.

"**TOMM6** is best defined as an **auxiliary structural/regulatory subunit** that supports **assembly, stability, and oligomerization** of the TOM core rather than directly binding and transporting substrates as a stand-alone importer."
TOMM6 contacts the Tom40 β-barrel (around β13–β15) primarily via hydrophobic interactions and helps anchor TOMM22 to the TOMM40 pore.

"Tom6 contacts the **Tom40 β-barrel**, especially around the **β13–β15** region, primarily via hydrophobic interactions."
siRNA targeting of small TOMM proteins (TOMM5/6/7) destabilizes TOM complex proteins, consistent with an assembly/stability role.

"siRNA targeting of the small TOMM proteins (TOMM5/6/7) destabilizes TOM complex proteins, supporting an assembly/stability role."
TOMM6 is positioned on the exterior of the Tom40 β-barrel as a single-pass α-helical membrane protein, consistent with an accessory structural role.

"Tom6 as a **single-pass α-helical membrane protein** (single transmembrane segment) positioned on the exterior of the Tom40 β-barrel, consistent with an accessory structural role."