TOMM40

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0030943 mitochondrion targeting sequence binding	IBA GO_REF:0000033	MODIFY	Summary: TOMM40 forms the channel that translocates presequence-containing precursors. The beta-barrel pore interacts with targeting sequences during translocation. Well supported by yeast Tom40 studies and human data (PMID:15644312). Reason: GO:0030943 (mitochondrion targeting sequence binding) is obsolete in the current GO release (consider GO:0140436 / GO:0008320). TOMM40 is the beta-barrel import channel, not a receptor; its engagement of targeting sequences during passage is part of its protein-conducting channel activity, so the row maps to GO:0008320 rather than the receptor MF GO:0140436. TOMM40 already carries GO:0008320, so this MODIFY folds the row into that existing annotation and asserts nothing new; the signal-recognition content of the obsoleted term is not carried over, because for a channel it is not a separate activity. Proposed replacements: transmembrane protein transporter activity
GO:0030150 protein import into mitochondrial matrix	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: TOMM40 is the central channel through which matrix-destined preproteins pass. However, TOMM40 is involved in ALL mitochondrial import pathways, not only matrix import. This annotation captures only one pathway (TOM-TIM23-PAM). Reason: Matrix import is one of several import routes through the TOM channel.
GO:0005742 mitochondrial outer membrane translocase complex	IBA GO_REF:0000033	ACCEPT	Summary: TOMM40 is the defining channel subunit of the TOM complex. Directly demonstrated in human cells by co-immunoprecipitation and BN-PAGE (PMID:12198123, PMID:15644312, PMID:18331822).
GO:0008320 protein transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: TOMM40 is the protein-conducting channel of the outer membrane. This MF term accurately describes its core molecular function. Supporting Evidence: file:human/TOMM40/TOMM40-deep-research-falcon.md Primary molecular function: Tom40 (TOMM40 product) is a β‑barrel translocation pore in the mitochondrial outer membrane that enables import of nuclear-encoded mitochondrial precursor proteins into mitochondria as part of the TOM complex.
GO:0008320 protein transmembrane transporter activity	IEA GO_REF:0000002	ACCEPT	Summary: Redundant with IBA annotation for the same term. InterPro-based inference is correct — TOMM40 has protein transmembrane transporter activity.
GO:0030150 protein import into mitochondrial matrix	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Redundant with IBA for same term. Correct but captures only one of several import pathways through TOM. Reason: Matrix import is one specific pathway; TOMM40 serves all import routes.
GO:0055085 transmembrane transport	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Very generic parent term. The more specific GO:0008320 (protein transmembrane transporter activity) is already annotated and more informative. Reason: Too general; subsumed by more specific annotations.
GO:0005515 protein binding	IPI PMID:31412244 TOM40 Targets Atg2 to Mitochondria-Associated ER Membranes f...	REMOVE	Summary: PMID:31412244 shows TOM40 targets Atg2 to MAM for phagophore expansion. Protein binding is uninformative per curation guidelines. The actual function is recruitment of ATG2A to ER-mitochondria contact sites. Reason: Protein binding is uninformative. The interaction with ATG2A represents a non-core MAM/autophagy function.
GO:0030150 protein import into mitochondrial matrix	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Redundant with IBA and IEA for same term. Correct but non-core — matrix import is one of many pathways served by the TOM channel.
GO:0005739 mitochondrion	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: Correct but too general — TOMM40 specifically localizes to the mitochondrial outer membrane. The more specific CC term GO:0005741 is already annotated. Reason: Subsumed by more specific mitochondrial outer membrane annotation.
GO:0005741 mitochondrial outer membrane	EXP PMID:15644312 Dissection of the mitochondrial import and assembly pathway ...	ACCEPT	Summary: Humphries et al. 2005 demonstrated TOMM40 localization to the outer membrane by subcellular fractionation and protease protection assays. Core CC.
GO:0005741 mitochondrial outer membrane	EXP PMID:31206022 BAP31 regulates mitochondrial function via interaction with ...	ACCEPT	Summary: Namba 2019 confirmed TOMM40 at OM via immunofluorescence and co-IP. Redundant with PMID:15644312 evidence for same term.
GO:0030150 protein import into mitochondrial matrix	IMP PMID:15644312 Dissection of the mitochondrial import and assembly pathway ...	KEEP AS NON CORE	Summary: Humphries et al. showed depletion of TOMM40 compromises protein import. However, this is expected for the general import channel. Non-core because TOMM40 serves all import routes, not specifically matrix import.
GO:0005741 mitochondrial outer membrane	NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas...	ACCEPT	Summary: Kato & Mihara 2008 identified Tom5 and Tom6 in the human TOM complex and confirmed Tom40 as an outer membrane component. Redundant with EXP evidence.
GO:0045040 protein insertion into mitochondrial outer membrane	NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas...	MODIFY	Summary: This term refers to insertion of proteins INTO the outer membrane (e.g., alpha-helical or beta-barrel proteins). TOMM40 itself is inserted into the OM but does not catalyze insertion of others — that is the role of SAM (for beta-barrels) and MTCH2/MIM (for alpha-helical proteins). TOMM40 facilitates translocation THROUGH the outer membrane, not insertion into it. Reason: TOMM40 is a translocation channel, not an insertase. It translocates proteins across the OM, not into the OM lipid bilayer. Proposed replacements: protein transmembrane transporter activity
GO:0140596 TOM complex	NAS PMID:18331822 Identification of Tom5 and Tom6 in the preprotein translocas...	ACCEPT	Summary: Kato & Mihara confirmed TOMM40 in the human TOM complex via immuno-isolation. GO:0140596 (TOM complex) is a more specific CC term than GO:0005742 (mitochondrial outer membrane translocase complex). Both are correct.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	MARK AS OVER ANNOTATED	Summary: High-throughput mitochondrial proteome confirms TOMM40 as mitochondrial. Too general — more specific OM annotation exists. Reason: Subsumed by mitochondrial outer membrane annotation.
GO:0005515 protein binding	IPI PMID:31206022 BAP31 regulates mitochondrial function via interaction with ...	REMOVE	Summary: Namba 2019 showed TOMM40 interacts with BCAP31 at ER-mitochondria contact sites. Protein binding is uninformative per guidelines. Reason: Protein binding is uninformative. The BCAP31 interaction is a non-core MAM function.
GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site	IDA PMID:31206022 BAP31 regulates mitochondrial function via interaction with ...	KEEP AS NON CORE	Summary: Namba 2019 demonstrated TOMM40 localizes to MAM via interaction with BCAP31. This is a secondary localization beyond its primary OM residence. The MAM function (facilitating Complex I assembly) is a non-core role. Reason: MAM localization is secondary to the core TOM complex function.
GO:0070585 protein localization to mitochondrion	IGI PMID:31206022 BAP31 regulates mitochondrial function via interaction with ...	KEEP AS NON CORE	Summary: Namba 2019 showed BAP31-TOMM40 complex mediates NDUFS4 translocation to mitochondria. This is a specific aspect of TOMM40 general import function. The term is quite general but captures TOMM40 role in protein localization. Reason: General term; the specific Complex I assembly role via BAP31 is non-core.
GO:0005743 mitochondrial inner membrane	IDA PMID:24746669 Cyclin B1/Cdk1 coordinates mitochondrial respiration for cel...	REMOVE	Summary: PMID:24746669 is about Cyclin B1/Cdk1 and mitochondrial respiration. TOMM40 is an outer membrane beta-barrel protein. Inner membrane localization is incorrect — TOMM40 may contact the IM via supercomplex formation with TIM complexes, but it is not an IM resident protein. Reason: TOMM40 is an outer membrane protein. Inner membrane annotation is incorrect; likely an artifact of co-fractionation.
GO:0005515 protein binding	IPI PMID:27554484 Tim29 is a novel subunit of the human TIM22 translocase and ...	REMOVE	Summary: Kang et al. 2016 showed TIMM29 interacts with TOMM40, linking TIM22 to TOM complex. Protein binding is uninformative per guidelines. Reason: Protein binding is uninformative. The TIM22-TOM interaction via TIMM29 is better captured by TOM complex CC annotation.
GO:0005741 mitochondrial outer membrane	TAS Reactome:R-HSA-5205661	ACCEPT	Summary: Reactome pathway for PINK1 recruitment to mitochondria. Confirms TOMM40 at the outer membrane. Redundant with direct experimental evidence.
GO:0016020 membrane	IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ...	MARK AS OVER ANNOTATED	Summary: Extremely generic CC term. TOMM40 is specifically in the mitochondrial outer membrane (GO:0005741), which is already well-annotated. Reason: Too general; subsumed by mitochondrial outer membrane.
GO:0008320 protein transmembrane transporter activity	ISS GO_REF:0000024	ACCEPT	Summary: Ortholog-based transfer of transporter activity. Correct and redundant with IBA evidence for same term.
GO:0005739 mitochondrion	IMP NOT PMID:11745481 Genetic identity and differential expression of p38.5 (Hayma...	REMOVE	Summary: PMID:11745481 (Das et al. 2001) identified TOMM40 as p38.5/Haymaker and reported differential expression in malignant cells. The NOT annotation for mitochondrion localization is incorrect — TOMM40 is definitively a mitochondrial protein. This may reflect early confusion about the gene identity. Reason: The NOT\|mitochondrion annotation contradicts overwhelming evidence that TOMM40 is a core mitochondrial outer membrane protein.
GO:0005741 mitochondrial outer membrane	ISS PMID:10980201 Characterization of rat TOM40, a central component of the pr...	ACCEPT	Summary: Based on rat Tom40 characterization (Suzuki et al. 2000). Correct — outer membrane localization is conserved.
GO:0005742 mitochondrial outer membrane translocase complex	IDA PMID:12198123 Insertion and assembly of human tom7 into the preprotein tra...	ACCEPT	Summary: Johnston et al. 2002 identified TOMM40 in the ~380 kDa TOM complex by BN-PAGE and supershift analysis. Direct experimental evidence for TOM complex membership.
GO:0005742 mitochondrial outer membrane translocase complex	IDA PMID:15644312 Dissection of the mitochondrial import and assembly pathway ...	ACCEPT	Summary: Humphries et al. 2005 confirmed TOMM40 in TOM complex by BN-PAGE. Redundant with PMID:12198123 but independent confirmation.
GO:0008320 protein transmembrane transporter activity	TAS PMID:15644312 Dissection of the mitochondrial import and assembly pathway ...	ACCEPT	Summary: Humphries et al. described TOMM40 as the channel-forming subunit essential for protein import. Core MF annotation.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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