TIMM17A

GO Term	Evidence	Action	Reason
GO:0008320 protein transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Correct as a contributes_to molecular-function annotation. TIMM17A is a TIM23 core subunit that contributes to the protein-conducting import channel/cavity rather than acting as a standalone transporter. Supporting Evidence: file:human/TIMM17A/TIMM17A-deep-research-falcon.md TIMM17A is an integral mitochondrial inner membrane component of the TIM23 core
GO:0030150 protein import into mitochondrial matrix	IBA GO_REF:0000033	ACCEPT	Summary: Correct core biological process. TIM23 imports presequence-containing precursors into the matrix, and TIMM17A contributes to the TIM23 translocation path.
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex	IBA GO_REF:0000033	ACCEPT	Summary: Correct complex annotation. TIMM17A is a core subunit of a human TIM23 variant with TIMM23 and ROMO1.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct UniProt-derived localization. TIMM17A is an integral mitochondrial inner membrane protein with conserved Tim17-family transmembrane topology.
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex	IEA GO_REF:0000002	ACCEPT	Summary: Correct InterPro-derived annotation. TIMM17A belongs to the Tim17/Tim23 family and is part of the TIM23 inner membrane translocase.
GO:0008320 protein transmembrane transporter activity	IEA GO_REF:0000002	ACCEPT	Summary: Correct when interpreted as a TIM23 subunit contribution to the protein-conducting channel/cavity.
GO:0030150 protein import into mitochondrial matrix	IEA GO_REF:0000002	ACCEPT	Summary: Correct InterPro-derived process annotation for the TIM23 presequence pathway. TIMM17A contributes to import of matrix-destined precursors.
GO:0005743 mitochondrial inner membrane	NAS PMID:10339406 Genetic and structural characterization of the human mitocho...	ACCEPT	Summary: Correct. The foundational human TIM23 study places Tim17-A in the mitochondrial inner membrane translocase.
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex	NAS PMID:10339406 Genetic and structural characterization of the human mitocho...	ACCEPT	Summary: Correct. TIMM17A is a human TIM23 core component and is consistently described in recent TIM23 architecture studies.
GO:0006886 intracellular protein transport	NAS PMID:10339406 Genetic and structural characterization of the human mitocho...	MODIFY	Summary: The annotation captures protein transport but is too broad. The specific TIMM17A process is mitochondrial matrix import through TIM23. Reason: Replace broad intracellular protein transport with mitochondrial matrix import. Proposed replacements: protein import into mitochondrial matrix
GO:0030150 protein import into mitochondrial matrix	TAS PMID:10339406 Genetic and structural characterization of the human mitocho...	ACCEPT	Summary: Correct. TIMM17A is a TIM23 translocase subunit involved in matrix import of presequence-containing precursors.
GO:0005739 mitochondrion	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: Correct but too general. TIMM17A is specifically localized to the mitochondrial inner membrane and TIM23 complex. Reason: Subsumed by mitochondrial inner membrane and TIM23 complex annotations.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	MARK AS OVER ANNOTATED	Summary: High-throughput mitochondrial proteome evidence supports mitochondrial localization, but the term is less specific than the inner membrane/TIM23 localization. Reason: Subsumed by mitochondrial inner membrane and TIM23 complex annotations.
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex	IDA PMID:30598479 ROMO1 is a constituent of the human presequence translocase ...	ACCEPT	Summary: Accepted. ROMO1/TIM23 complex studies recovered TIM17A in authentic human TIM23 assemblies.
GO:0005743 mitochondrial inner membrane	IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b...	ACCEPT	Summary: Correct localization for TIMM17A as an integral TIM23 inner membrane subunit.
GO:0005743 mitochondrial inner membrane	IDA PMID:10339406 Genetic and structural characterization of the human mitocho...	ACCEPT	Summary: Correct localization from the foundational human TIM23 characterization.
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex	IDA PMID:10339406 Genetic and structural characterization of the human mitocho...	ACCEPT	Summary: Correct complex annotation from the foundational human TIM23 characterization and supported by recent TIM23 architecture literature.

Deep Research

Falcon

(TIMM17A-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 16 citations 2026-05-11T12:29:26.503316

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.

Comprehensive research report: Human TIMM17A (UniProt Q99595)—functional annotation and current understanding

0) Target verification and nomenclature

The literature summarized here is explicitly matched to the UniProt entry Q99595, annotated as mitochondrial import inner membrane translocase subunit Tim17-A, encoded by the human gene TIMM17A (Tim17a). A 2024 peer‑reviewed study on the human core TIM23 complex explicitly identifies TIMM17A as UniProt Q99595 and places it in the Tim17/Tim22/Tim23 family (pfam Tim17; IPR005678) (maruszczak2024structurepredictionanalysis pages 2-3). Human TIMM17A is distinct from the paralog TIMM17B, which forms an alternative TIM23 core variant and shares ~76% sequence identity (maruszczak2024structurepredictionanalysis pages 3-5).

1) Key concepts and definitions (current understanding)

1.1 The TIM23 “presequence” pathway

Most mitochondrial proteins are nuclear‑encoded and must be imported post‑translationally. The TIM23 complex (translocase of the inner membrane 23) is the central inner‑membrane translocase for presequence‑containing precursor proteins. A 2024 TIM23 disease‑focused mini‑review estimates that TIM23 mediates import of ~60% of the mitochondrial proteome, including the majority of matrix proteins and many inner‑membrane proteins, plus a subset of intermembrane space (IMS) proteins (jain2024hotspotsfordiseasecausing pages 2-4).

1.2 TIM23 functional modes: motor vs sorting

TIM23 is described as operating in at least two coupled modes:
* TIM23MOTOR: association of the TIM23 core with the PAM (presequence translocase‑associated motor) to drive matrix import (ATP‑dependent mtHsp70 pulling plus inner‑membrane potential). (jain2024hotspotsfordiseasecausing pages 2-4, chaudhuri2020tim17updatesa pages 6-8)
* TIM23SORT: association with factors such as Tim21 and Mgr2 (yeast) to favor lateral insertion/sorting of some inner‑membrane proteins and certain IMS sorting events. (jain2024hotspotsfordiseasecausing pages 2-4, chaudhuri2020tim17updatesa pages 6-8)

Human complexes are discussed in analogous terms, with TIMM17 paralogs contributing to different assemblies (jain2024hotspotsfordiseasecausing pages 2-4).

1.3 What TIMM17A is (molecular role)

TIMM17A is an integral mitochondrial inner membrane component of the TIM23 core (maruszczak2024structurepredictionanalysis pages 2-3, chaudhuri2020tim17updatesa pages 6-8). Tim17 family reviews describe a conserved four‑transmembrane helix topology, classically with both N‑ and C‑termini in the IMS (chaudhuri2020tim17updatesa pages 8-10). TIMM17A does not catalyze an enzymatic reaction; rather, it contributes to the protein‑conducting import channel/cavity and/or its regulation within TIM23 (maruszczak2024structurepredictionanalysis pages 2-3, sim2023structuralbasisof pages 1-4).

2) TIMM17A complex membership, interaction partners, and localization

2.1 Core complex membership and paralog specialization (TIMM17A vs TIMM17B)

Humans have two Tim17 orthologs, TIMM17A and TIMM17B, which form two pools/variants of the TIM23 core complex in combination with TIMM23 (maruszczak2024structurepredictionanalysis pages 2-3, maruszczak2024structurepredictionanalysis pages 1-2). The variants are predicted to be highly similar structurally (maruszczak2024structurepredictionanalysis pages 3-5, maruszczak2024structurepredictionanalysis pages 9-11).

A 2024 Genes mini‑review further describes human TIM23 “motor” assemblies in which TIMM17A defines translocase A together with DNAJC15, while TIMM17B isoforms pair with DNAJC19 to define other assemblies (translocases B1/B2) (jain2024hotspotsfordiseasecausing pages 2-4). In review literature, translocase‑B is described as constitutive/essential for normal function, while translocase‑A (TIMM17A‑linked) is dispensable under normal conditions but important for oncogenic proliferation contexts (chaudhuri2020tim17updatesa pages 6-8).

2.2 ROMO1 as a human TIM23 constituent (quantitative evidence)

A key human‑cell biochemical study defined ROMO1 as a constituent of the human presequence translocase and recovered TIM17A in TIM23/TIM21/TIM50 purifications by SILAC‑MS, placing TIMM17A within authentic human TIM23 complexes (richter2019romo1isa pages 1-2).

Importantly, the same work provides quantitative complex‑association measurements: approximately 25% of mitochondrial ROMO1 co‑isolated with TIM23‑FLAG, and ~50% of ROMO1 co‑isolated with TIM21‑FLAG (richter2019romo1isa pages 2-4). These results support ROMO1 as a stable, though dynamic, component of TIM23 assemblies that include TIM17A/B, TIM50, TIM44, and TIM21 (richter2019romo1isa pages 2-4).

3) Mechanistic function: what TIMM17A does in preprotein import

3.1 Revised channel model: Tim17 cavity as central translocation route

A major conceptual shift in 2023–2024 TIM23 biology is the growing structural/biochemical evidence that Tim17, rather than Tim23, provides much of the polypeptide translocation path.

A 2023 cryo‑EM study of the TIM23 complex (in yeast) reports that Tim17 and Tim23 form a stable 1:1 heterodimer in an idle state and identifies a laterally open cavity in Tim17, with Mgr2 positioned at this lateral opening; the authors propose enclosure of the Tim17 cavity provides a plausible route for polypeptide translocation (sim2023structuralbasisof pages 1-4). The same source argues against interpreting Tim23 as the sole/primary aqueous channel because prior electrophysiology often relied on refolded Tim23 preparations and lacks gold‑standard native‑membrane patch clamp validation (sim2023structuralbasisof pages 1-4).

Human‑focused modeling reinforces this reinterpretation: a 2024 structure‑prediction analysis emphasizes that recent structural and biochemical work places Tim17 as having a primary role in translocation, forming a cavity large enough to accommodate translocating proteins (maruszczak2024structurepredictionanalysis pages 1-2).

3.2 TIMM17A structural features relevant to substrate handling

The 2024 human TIM23 architecture analysis attributes conserved features to TIMM17A that are relevant to presequence import: an IMS‑exposed acidic patch that could attract positively charged presequences, a hydrophobic cavity lining conducive to polypeptide passage, and an intramolecular disulfide bond described as essential for function (maruszczak2024structurepredictionanalysis pages 2-3). These features are consistent with a role in guiding positively charged presequences into a membrane‑embedded import cavity (maruszczak2024structurepredictionanalysis pages 2-3).

3.3 Substrate classes (what is imported) and where TIMM17A acts

TIM23 imports presequence‑containing precursors destined to the matrix and many destined to the inner membrane, with some IMS sorting, representing a large fraction of mitochondrial proteins (~60% as above) (jain2024hotspotsfordiseasecausing pages 2-4). TIMM17A acts at the inner membrane as part of the translocation pore/cavity and as a platform for mode switching between motor‑driven matrix import and lateral sorting modes, through interactions with accessory factors (jain2024hotspotsfordiseasecausing pages 2-4, sim2023structuralbasisof pages 1-4).

4) Regulation of TIMM17A abundance and activity (stress, proteolysis, and signaling)

4.1 YME1L‑dependent proteolytic control of TIMM17A

Multiple sources support protease‑mediated regulation of TIMM17A, particularly via the i‑AAA protease YME1L.

A high‑impact 2019 Nature study demonstrates that cellular stresses that inhibit mTORC1 (including nutrient limitation and hypoxia) can induce acute, YME1L‑dependent proteolysis of TIMM17A among a set of substrates, linking mitochondrial membrane lipid composition and nutrient signaling to regulated degradation of inner‑membrane proteins (macvicar2019lipidsignallingdrives pages 3-4). The authors also reconstituted TIMM17A proteolysis in liposomes as an ATP‑dependent YME1L activity (with an inactive catalytic mutant control), supporting a direct proteolytic mechanism (macvicar2019lipidsignallingdrives pages 3-4). The study provides quantitative experimental context including immunoblot quantification for TIMM17A under hypoxia with n=3 independent experiments and points to public proteomics/transcriptomics datasets (PRIDE: PXD011750, PXD014405; GEO: GSE133753) for deeper quantitative evaluation (macvicar2019lipidsignallingdrives pages 10-14).

A 2024 Biochemical Society Transactions mini‑review synthesizes these findings, stating that Tim17A is a stress‑induced degradation substrate of YME1L in human cells, and that TIMM17A and TIMM23 are down‑regulated under hypoxia in WT but not Yme1l−/− contexts (kan2024roleofyme1 pages 3-4).

4.2 Coupling of import and proteostasis via ROMO1–YME1L feedback

ROMO1 was identified as a TIM23 constituent required for efficient import of the YME1L protease itself; ROMO1 is also short‑lived and accumulates in YME1L knockout cells, indicating YME1L‑dependent ROMO1 turnover (richter2019romo1isa pages 9-11). This creates a plausible feedback loop in which import machinery composition affects import of quality‑control proteases, and proteases in turn remodel the import machinery (richter2019romo1isa pages 9-11, kan2024roleofyme1 pages 3-4). TIM17A is listed among known YME1L substrates, reinforcing the link between import channel composition and proteolytic remodeling (richter2019romo1isa pages 2-4).

4.3 Protein import machinery as a stress‑signaling hub (2023 perspective)

A 2023 review frames mitochondrial protein import as a signaling hub, where import impairment triggers proteostatic and metabolic responses beyond mitochondria (maruszczak2024structurepredictionanalysis pages 1-2). Within that context, TIMM17A is specifically mentioned as an import component subject to stress‑linked remodeling (including cleavage/turnover of TIMM17A as part of adaptive responses) (maruszczak2024structurepredictionanalysis pages 2-3).

5) Recent developments (prioritize 2023–2024)

5.1 2023: Cryo‑EM structure revises the “Tim23 channel” assumption

The 2023 Nature cryo‑EM work is widely treated as a mechanistic inflection point, presenting a Tim17‑centered cavity model and explicitly questioning whether prior Tim23‑only channel models reflect the native state (sim2023structuralbasisof pages 1-4).

5.2 2024: Human TIM23 core architecture modeling, TIMM17A vs TIMM17B comparison

A 2024 FEBS Open Bio study provides a human‑focused structural interpretation: TIMM17A (UniProt Q99595) and TIMM17B form two predicted human TIM23 core variants with TIMM23 and ROMO1 and show high structural conservation relative to yeast TIM23 (maruszczak2024structurepredictionanalysis pages 2-3, maruszczak2024structurepredictionanalysis pages 3-5). It also compiles functional distinctions discussed in the literature, including the idea that TIMM17B may be more “housekeeping” whereas TIMM17A may contribute to regulated remodeling and stress/cancer contexts (maruszczak2024structurepredictionanalysis pages 3-5).

5.3 2024: Disease mutation landscape review of TIM23 complex

A 2024 Genes mini‑review synthesizes pathogenic‑variant hotspots across TIM23 components and places TIMM17A within the landscape of TIM23 motor/sorting assemblies, emphasizing that Tim17 can act as the channel for TIM23 motor activity and summarizing evidence linking high TIMM17A expression with adverse outcomes in breast cancer (jain2024hotspotsfordiseasecausing pages 2-4, jain2024hotspotsfordiseasecausing pages 11-12).

6) Current applications and real‑world implementations

6.1 Variant interpretation and mitochondrial disease mechanisms

Although TIMM17A itself is not emphasized as a dominant monogenic disease hotspot in the TIM23 complex compared with other components (e.g., Tim50/PAM factors discussed elsewhere), TIM23 dysfunction is a clinically important mechanism in mitochondrial disease, and mechanistic mapping of TIM23 substrate classes (matrix vs lateral insertion) can directly inform phenotypic interpretation (jain2024hotspotsfordiseasecausing pages 2-4). Human TIM23 biology is also increasingly approached using proteomics to map downstream consequences of reduced import and altered translocase composition (macvicar2019lipidsignallingdrives pages 10-14).

6.2 Cancer biology and biomarker hypotheses

Review sources cite clinical associations that high TIMM17A expression is linked with adverse pathological/clinical outcomes and aggressiveness in human breast cancer (jain2024hotspotsfordiseasecausing pages 11-12). Separately, translocase‑A (TIMM17A‑linked) is described as dispensable for normal mitochondrial function but required for oncogenic proliferation in review literature, suggesting a potential vulnerability axis in cancer metabolism/biogenesis (chaudhuri2020tim17updatesa pages 6-8).

6.3 Experimental and systems applications

The 2019 YME1L study explicitly provides public quantitative datasets (PRIDE proteomics and GEO transcriptomics) that can be mined to evaluate TIMM17A abundance and remodeling across hypoxia/nutrient conditions, enabling reproducible integrative functional annotation (macvicar2019lipidsignallingdrives pages 10-14).

7) Expert opinions and analysis (authoritative interpretations)

A consistent theme across recent expert syntheses is that TIM23 is not a static pore but a dynamic translocation system whose core architecture is conserved yet whose functional specificity can be tuned by paralog choice (TIMM17A vs TIMM17B) and accessory subunits (ROMO1/TIM21/PAM). The 2024 human structure‑prediction study explicitly frames an open problem: TIMM17A‑ and TIMM17B‑containing cores are nearly identical structurally, so differences likely arise from regulatory factors and context‑specific remodeling rather than gross architectural differences (maruszczak2024structurepredictionanalysis pages 9-11). The 2023 cryo‑EM work similarly emphasizes unresolved mechanistic gaps (e.g., initial presequence engagement with the Tim17 cavity and dynamics during translocation) despite clearer structural grounding (sim2023structuralbasisof pages 1-4).

8) Key statistics and quantitative data (from recent/primary evidence)

TIM23 is reported to import ~60% of the mitochondrial proteome (matrix + many inner‑membrane proteins; some IMS proteins) (jain2024hotspotsfordiseasecausing pages 2-4).
In human‑cell purifications, ROMO1 co‑isolates at approximately 25% with TIM23‑FLAG and ~50% with TIM21‑FLAG, consistent with ROMO1 as a TIM23 constituent interacting with TIM21 and the TIM23 core that includes TIM17A/B (richter2019romo1isa pages 2-4, richter2019romo1isa media 2e38f9b5).
Hypoxia/HIF1α and nutrient signaling regulate YME1L‑dependent remodeling including TIMM17A abundance; quantitative immunoblotting context includes n=3 independent experiments and linked public omics datasets for reanalysis (macvicar2019lipidsignallingdrives pages 10-14).

9) Visual evidence (human TIM23 composition and ROMO1 association)

Richter et al. provide a schematic of the human TIM23 presequence translocase including TIM17A/B and ROMO1 and quantitative ROMO1 co‑purification with TIM23 and TIM21 (richter2019romo1isa media 2e38f9b5).

10) Summary functional annotation (concise)

TIMM17A (UniProt Q99595) encodes an integral mitochondrial inner membrane protein of the TIM23 presequence translocase. It participates in import of nuclear‑encoded, presequence‑containing precursor proteins into the mitochondrial matrix and for inner‑membrane insertion, acting as a core translocation component (channel/cavity) within TIM23 motor assemblies and coordinating with accessory factors (TIM21/ROMO1/PAM) that tune sorting versus matrix import. Its abundance is stress‑regulated, notably via YME1L‑dependent proteolysis in response to nutrient/hypoxia signaling, providing a mechanism to remodel mitochondrial biogenesis/import capacity. (maruszczak2024structurepredictionanalysis pages 2-3, jain2024hotspotsfordiseasecausing pages 2-4, sim2023structuralbasisof pages 1-4, macvicar2019lipidsignallingdrives pages 3-4)

Embedded evidence table

Aspect	Key points	Best recent source(s) with year/URL/DOI
Identity	Human TIMM17A encodes mitochondrial import inner membrane translocase subunit Tim17-A; UniProt Q99595. It is one of two human Tim17 paralogs (TIMM17A, TIMM17B) in the Tim17/Tim22/Tim23 family and a core subunit of the TIM23 presequence translocase. TIMM17A and TIMM17B share ~76% sequence identity. (maruszczak2024structurepredictionanalysis pages 2-3, maruszczak2024structurepredictionanalysis pages 3-5)	Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840
Subcellular localization / topology	TIMM17A is a mitochondrial inner membrane protein. Tim17-family proteins show a conserved 4-transmembrane-helix topology with both N- and C-termini in the intermembrane space; TIMM17A is tightly anchored in the inner membrane as part of the import channel machinery. (chaudhuri2020tim17updatesa pages 8-10, chaudhuri2020tim17updatesa pages 6-8)	Chaudhuri et al., 2020, Biomolecules, https://doi.org/10.3390/biom10121643, DOI: 10.3390/biom10121643
Complex membership	TIMM17A forms one of the two human core TIM23 variants with TIMM23 and ROMO1; the human core also associates with TIM44, TIM50, TIM21, and mtHsp70-linked motor components. Human TIM23 assemblies can be described as translocase-A (TIMM17A-containing; linked with DNAJC15) versus translocase-B (TIMM17B-containing; linked with DNAJC19 isoforms). (maruszczak2024structurepredictionanalysis pages 2-3, jain2024hotspotsfordiseasecausing pages 2-4, richter2019romo1isa pages 1-2, richter2019romo1isa pages 2-4, richter2019romo1isa media 2e38f9b5)	Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840; Jain et al., 2024, Genes, https://doi.org/10.3390/genes15121534, DOI: 10.3390/genes15121534; Richter et al., 2019, J Cell Biol, https://doi.org/10.1083/jcb.201806093, DOI: 10.1083/jcb.201806093
Key interaction partners	Best-supported partners include TIMM23 (stable Tim17–Tim23 core), ROMO1 (human Mgr2-like subunit), TIM50, TIM21, TIM44, and HSP70/PAM-related factors in the import motor. Quantitatively, ~25% of mitochondrial ROMO1 co-isolated with TIM23-FLAG, and ~50% co-isolated with TIM21-FLAG in human-cell purifications, supporting ROMO1’s association with the human TIM23 machinery. (maruszczak2024structurepredictionanalysis pages 1-2, richter2019romo1isa pages 2-4, richter2019romo1isa media 2e38f9b5)	Richter et al., 2019, J Cell Biol, https://doi.org/10.1083/jcb.201806093, DOI: 10.1083/jcb.201806093; Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840
Mechanistic role	Current model places Tim17/TIMM17A at the center of the translocation path: recent structural work argues Tim17 forms a laterally open cavity/channel large enough to accommodate translocating polypeptides, while Tim23 is more constrained and likely has a more regulatory/architectural role. Conserved TIMM17A features include an IMS acidic patch that can attract positively charged presequences, a hydrophobic cavity lining, and an intramolecular disulfide bond important for function. (maruszczak2024structurepredictionanalysis pages 2-3, maruszczak2024structurepredictionanalysis pages 1-2, sim2023structuralbasisof pages 1-4)	Sim et al., 2023, Nature, https://doi.org/10.1038/s41586-023-06239-6, DOI: 10.1038/s41586-023-06239-6; Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840
Functional distinction vs TIMM17B	TIMM17A- and TIMM17B-containing human TIM23 complexes are predicted to be structurally very similar, but functional specialization is reported: TIMM17B is often described as the more housekeeping/canonical import variant, whereas TIMM17A has a more specialized/regulatory role and is linked to translocase-A and oncogenic proliferation contexts. (maruszczak2024structurepredictionanalysis pages 3-5, chaudhuri2020tim17updatesa pages 8-10, chaudhuri2020tim17updatesa pages 6-8)	Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840; Chaudhuri et al., 2020, Biomolecules, https://doi.org/10.3390/biom10121643, DOI: 10.3390/biom10121643
Regulation / proteolysis	TIMM17A is regulated by mitochondrial quality-control proteases. It is reported as a YME1L substrate, and stress-adaptive remodeling of import can include selective turnover of TIMM17A to reduce mitochondrial import and alter metabolic state. In ROMO1 studies, ROMO1 itself is also short-lived and YME1L-regulated, linking TIMM17A-containing TIM23 assemblies to proteostatic control. (maruszczak2024structurepredictionanalysis pages 2-3, richter2019romo1isa pages 1-2, richter2019romo1isa pages 9-11, richter2019romo1isa pages 2-4)	Richter et al., 2019, J Cell Biol, https://doi.org/10.1083/jcb.201806093, DOI: 10.1083/jcb.201806093; Maruszczak et al., 2024, FEBS Open Bio, https://doi.org/10.1002/2211-5463.13840, DOI: 10.1002/2211-5463.13840
Disease / cancer associations	No recurrent monogenic TIMM17A disease hotspot is established in current TIM23 disease reviews, but high TIMM17A expression has been associated with adverse outcomes and aggressiveness in breast cancer. Broader TIM23-complex dysfunction is clinically important in mitochondrial disease, and TIMM17A-containing translocase-A has been described as required for oncogenic cell proliferation in review literature. (jain2024hotspotsfordiseasecausing pages 2-4, jain2024hotspotsfordiseasecausing pages 11-12, chaudhuri2020tim17updatesa pages 6-8)	Jain et al., 2024, Genes, https://doi.org/10.3390/genes15121534, DOI: 10.3390/genes15121534; Chaudhuri et al., 2020, Biomolecules, https://doi.org/10.3390/biom10121643, DOI: 10.3390/biom10121643

Table: This table summarizes the verified identity, localization, complex membership, mechanism, regulation, and disease relevance of human TIMM17A. It highlights the most useful recent sources for interpreting TIMM17A as a core TIM23 presequence-translocase subunit.

References

(maruszczak2024structurepredictionanalysis pages 2-3): Klaudia K. Maruszczak, Piotr Draczkowski, Artur Wnorowski, and Agnieszka Chacinska. Structure prediction analysis of human core tim23 complex reveals conservation of the protein translocation mechanism. FEBS Open Bio, 14:1656-1667, Jun 2024. URL: https://doi.org/10.1002/2211-5463.13840, doi:10.1002/2211-5463.13840. This article has 13 citations and is from a peer-reviewed journal.
(maruszczak2024structurepredictionanalysis pages 3-5): Klaudia K. Maruszczak, Piotr Draczkowski, Artur Wnorowski, and Agnieszka Chacinska. Structure prediction analysis of human core tim23 complex reveals conservation of the protein translocation mechanism. FEBS Open Bio, 14:1656-1667, Jun 2024. URL: https://doi.org/10.1002/2211-5463.13840, doi:10.1002/2211-5463.13840. This article has 13 citations and is from a peer-reviewed journal.
(jain2024hotspotsfordiseasecausing pages 2-4): Sahil Jain, Eyal Paz, and Abdussalam Azem. Hotspots for disease-causing mutations in the mitochondrial tim23 import complex. Genes, 15:1534, Nov 2024. URL: https://doi.org/10.3390/genes15121534, doi:10.3390/genes15121534. This article has 1 citations.
(chaudhuri2020tim17updatesa pages 6-8): Minu Chaudhuri, Chauncey Darden, Fidel Soto Gonzalez, Ujjal K. Singha, Linda Quinones, and Anuj Tripathi. Tim17 updates: a comprehensive review of an ancient mitochondrial protein translocator. Biomolecules, 10:1643, Dec 2020. URL: https://doi.org/10.3390/biom10121643, doi:10.3390/biom10121643. This article has 24 citations.
(chaudhuri2020tim17updatesa pages 8-10): Minu Chaudhuri, Chauncey Darden, Fidel Soto Gonzalez, Ujjal K. Singha, Linda Quinones, and Anuj Tripathi. Tim17 updates: a comprehensive review of an ancient mitochondrial protein translocator. Biomolecules, 10:1643, Dec 2020. URL: https://doi.org/10.3390/biom10121643, doi:10.3390/biom10121643. This article has 24 citations.
(sim2023structuralbasisof pages 1-4): Sue Im Sim, Yuanyuan Chen, Diane L. Lynch, James C. Gumbart, and Eunyong Park. Structural basis of mitochondrial protein import by the tim23 complex. Nature, 621:620-626, Jun 2023. URL: https://doi.org/10.1038/s41586-023-06239-6, doi:10.1038/s41586-023-06239-6. This article has 105 citations and is from a highest quality peer-reviewed journal.
(maruszczak2024structurepredictionanalysis pages 1-2): Klaudia K. Maruszczak, Piotr Draczkowski, Artur Wnorowski, and Agnieszka Chacinska. Structure prediction analysis of human core tim23 complex reveals conservation of the protein translocation mechanism. FEBS Open Bio, 14:1656-1667, Jun 2024. URL: https://doi.org/10.1002/2211-5463.13840, doi:10.1002/2211-5463.13840. This article has 13 citations and is from a peer-reviewed journal.
(maruszczak2024structurepredictionanalysis pages 9-11): Klaudia K. Maruszczak, Piotr Draczkowski, Artur Wnorowski, and Agnieszka Chacinska. Structure prediction analysis of human core tim23 complex reveals conservation of the protein translocation mechanism. FEBS Open Bio, 14:1656-1667, Jun 2024. URL: https://doi.org/10.1002/2211-5463.13840, doi:10.1002/2211-5463.13840. This article has 13 citations and is from a peer-reviewed journal.
(richter2019romo1isa pages 1-2): Frank Richter, Sven Dennerlein, Miroslav Nikolov, Daniel C. Jans, Nataliia Naumenko, Abhishek Aich, Thomas MacVicar, Andreas Linden, Stefan Jakobs, Henning Urlaub, Thomas Langer, and Peter Rehling. Romo1 is a constituent of the human presequence translocase required for yme1l protease import. The Journal of Cell Biology, 218:598-614, Dec 2019. URL: https://doi.org/10.1083/jcb.201806093, doi:10.1083/jcb.201806093. This article has 74 citations.
(richter2019romo1isa pages 2-4): Frank Richter, Sven Dennerlein, Miroslav Nikolov, Daniel C. Jans, Nataliia Naumenko, Abhishek Aich, Thomas MacVicar, Andreas Linden, Stefan Jakobs, Henning Urlaub, Thomas Langer, and Peter Rehling. Romo1 is a constituent of the human presequence translocase required for yme1l protease import. The Journal of Cell Biology, 218:598-614, Dec 2019. URL: https://doi.org/10.1083/jcb.201806093, doi:10.1083/jcb.201806093. This article has 74 citations.
(macvicar2019lipidsignallingdrives pages 3-4): Thomas MacVicar, Yohsuke Ohba, Hendrik Nolte, Fiona Carola Mayer, Takashi Tatsuta, Hans-Georg Sprenger, Barbara Lindner, Yue Zhao, Jiahui Li, Christiane Bruns, Marcus Krüger, Markus Habich, Jan Riemer, Robin Schwarzer, Manolis Pasparakis, Sinika Henschke, Jens C. Brüning, Nicola Zamboni, and Thomas Langer. Lipid signalling drives proteolytic rewiring of mitochondria by yme1l. Nature, 575:361-365, Nov 2019. URL: https://doi.org/10.1038/s41586-019-1738-6, doi:10.1038/s41586-019-1738-6. This article has 207 citations and is from a highest quality peer-reviewed journal.
(macvicar2019lipidsignallingdrives pages 10-14): Thomas MacVicar, Yohsuke Ohba, Hendrik Nolte, Fiona Carola Mayer, Takashi Tatsuta, Hans-Georg Sprenger, Barbara Lindner, Yue Zhao, Jiahui Li, Christiane Bruns, Marcus Krüger, Markus Habich, Jan Riemer, Robin Schwarzer, Manolis Pasparakis, Sinika Henschke, Jens C. Brüning, Nicola Zamboni, and Thomas Langer. Lipid signalling drives proteolytic rewiring of mitochondria by yme1l. Nature, 575:361-365, Nov 2019. URL: https://doi.org/10.1038/s41586-019-1738-6, doi:10.1038/s41586-019-1738-6. This article has 207 citations and is from a highest quality peer-reviewed journal.
(kan2024roleofyme1 pages 3-4): Kwan Ting Kan, Joel Wilcock, and Hui Lu. Role of yme1 in mitochondrial protein homeostasis: from regulation of protein import, oxphos function to lipid synthesis and mitochondrial dynamics. Biochemical Society Transactions, 52:1539-1548, Jun 2024. URL: https://doi.org/10.1042/bst20240450, doi:10.1042/bst20240450. This article has 9 citations and is from a peer-reviewed journal.
(richter2019romo1isa pages 9-11): Frank Richter, Sven Dennerlein, Miroslav Nikolov, Daniel C. Jans, Nataliia Naumenko, Abhishek Aich, Thomas MacVicar, Andreas Linden, Stefan Jakobs, Henning Urlaub, Thomas Langer, and Peter Rehling. Romo1 is a constituent of the human presequence translocase required for yme1l protease import. The Journal of Cell Biology, 218:598-614, Dec 2019. URL: https://doi.org/10.1083/jcb.201806093, doi:10.1083/jcb.201806093. This article has 74 citations.
(jain2024hotspotsfordiseasecausing pages 11-12): Sahil Jain, Eyal Paz, and Abdussalam Azem. Hotspots for disease-causing mutations in the mitochondrial tim23 import complex. Genes, 15:1534, Nov 2024. URL: https://doi.org/10.3390/genes15121534, doi:10.3390/genes15121534. This article has 1 citations.
(richter2019romo1isa media 2e38f9b5): Frank Richter, Sven Dennerlein, Miroslav Nikolov, Daniel C. Jans, Nataliia Naumenko, Abhishek Aich, Thomas MacVicar, Andreas Linden, Stefan Jakobs, Henning Urlaub, Thomas Langer, and Peter Rehling. Romo1 is a constituent of the human presequence translocase required for yme1l protease import. The Journal of Cell Biology, 218:598-614, Dec 2019. URL: https://doi.org/10.1083/jcb.201806093, doi:10.1083/jcb.201806093. This article has 74 citations.

Citations

maruszczak2024structurepredictionanalysis pages 2-3
maruszczak2024structurepredictionanalysis pages 3-5
jain2024hotspotsfordiseasecausing pages 2-4
sim2023structuralbasisof pages 1-4
maruszczak2024structurepredictionanalysis pages 1-2
macvicar2019lipidsignallingdrives pages 3-4
macvicar2019lipidsignallingdrives pages 10-14
jain2024hotspotsfordiseasecausing pages 11-12
maruszczak2024structurepredictionanalysis pages 9-11
https://doi.org/10.1002/2211-5463.13840,
https://doi.org/10.3390/biom10121643,
https://doi.org/10.3390/genes15121534,
https://doi.org/10.1083/jcb.201806093,
https://doi.org/10.1038/s41586-023-06239-6,
https://doi.org/10.1038/s41586-019-1738-6,
https://doi.org/10.1042/bst20240450,

📄 View Raw YAML

id: Q99595
gene_symbol: TIMM17A
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TIMM17A is an integral mitochondrial inner membrane subunit of the human TIM23
  presequence translocase. It contributes to the TIM23 protein-conducting
  channel/cavity for import of presequence-containing mitochondrial precursors,
  especially matrix-destined proteins, and participates in TIM23 complex
  organization and regulated remodeling of mitochondrial protein import.
existing_annotations:
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    summary: >-
      Correct as a contributes_to molecular-function annotation. TIMM17A is a
      TIM23 core subunit that contributes to the protein-conducting import
      channel/cavity rather than acting as a standalone transporter.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    supported_by:
    - reference_id: file:human/TIMM17A/TIMM17A-deep-research-falcon.md
      supporting_text: "TIMM17A is an **integral mitochondrial inner membrane** component of the **TIM23 core**"
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Correct core biological process. TIM23 imports presequence-containing
      precursors into the matrix, and TIMM17A contributes to the TIM23
      translocation path.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Correct complex annotation. TIMM17A is a core subunit of a human TIM23
      variant with TIMM23 and ROMO1.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      Correct UniProt-derived localization. TIMM17A is an integral mitochondrial
      inner membrane protein with conserved Tim17-family transmembrane topology.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      Correct InterPro-derived annotation. TIMM17A belongs to the Tim17/Tim23
      family and is part of the TIM23 inner membrane translocase.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0008320
    label: protein transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      Correct when interpreted as a TIM23 subunit contribution to the
      protein-conducting channel/cavity.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      Correct InterPro-derived process annotation for the TIM23 presequence
      pathway. TIMM17A contributes to import of matrix-destined precursors.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: NAS
  original_reference_id: PMID:10339406
  review:
    summary: >-
      Correct. The foundational human TIM23 study places Tim17-A in the
      mitochondrial inner membrane translocase.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: NAS
  original_reference_id: PMID:10339406
  review:
    summary: >-
      Correct. TIMM17A is a human TIM23 core component and is consistently
      described in recent TIM23 architecture studies.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: NAS
  original_reference_id: PMID:10339406
  review:
    summary: >-
      The annotation captures protein transport but is too broad. The specific
      TIMM17A process is mitochondrial matrix import through TIM23.
    action: MODIFY
    reason: Replace broad intracellular protein transport with mitochondrial matrix import.
    proposed_replacement_terms:
    - id: GO:0030150
      label: protein import into mitochondrial matrix
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: TAS
  original_reference_id: PMID:10339406
  review:
    summary: >-
      Correct. TIMM17A is a TIM23 translocase subunit involved in matrix import
      of presequence-containing precursors.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      Correct but too general. TIMM17A is specifically localized to the
      mitochondrial inner membrane and TIM23 complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: Subsumed by mitochondrial inner membrane and TIM23 complex annotations.
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  review:
    summary: >-
      High-throughput mitochondrial proteome evidence supports mitochondrial
      localization, but the term is less specific than the inner membrane/TIM23
      localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Subsumed by mitochondrial inner membrane and TIM23 complex annotations.
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: IDA
  original_reference_id: PMID:30598479
  review:
    summary: >-
      Accepted. ROMO1/TIM23 complex studies recovered TIM17A in authentic human
      TIM23 assemblies.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:20053669
  review:
    summary: >-
      Correct localization for TIMM17A as an integral TIM23 inner membrane
      subunit.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:10339406
  review:
    summary: >-
      Correct localization from the foundational human TIM23 characterization.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: IDA
  original_reference_id: PMID:10339406
  review:
    summary: >-
      Correct complex annotation from the foundational human TIM23
      characterization and supported by recent TIM23 architecture literature.
    action: ACCEPT
    additional_reference_ids:
    - file:human/TIMM17A/TIMM17A-deep-research-falcon.md
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings:
  - statement: InterPro2GO assigns TIM23 complex membership and protein transmembrane
      transporter activity based on the Tim17/Tim23 family signature.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: PAINT/IBA phylogenetic propagation supports TIM23 complex membership
      and matrix import activity for TIMM17A across Tim17 orthologs.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings:
  - statement: UniProt subcellular location vocabulary maps TIMM17A to the mitochondrial
      inner membrane.
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings:
  - statement: Curated immunofluorescence data place TIMM17A in mitochondria.
- id: PMID:10339406
  title: Genetic and structural characterization of the human mitochondrial inner
    membrane translocase.
  findings:
  - statement: Two human TIM17 genes (TIM17a/TIM17b) were cloned and shown to encode
      proteins essentially identical except for their C termini.
    supporting_text: In contrast to yeast, two TIM17 genes were found to be expressed
      in humans.
  - statement: hTim23 is organized into two distinct TIM23 complexes of native mass
      ~110 kDa in the inner membrane, one containing hTim17a and one containing
      hTim17b.
    supporting_text: hTim23 is organized into two distinct complexes in the inner
      membrane, one containing hTim17a and one containing hTim17b.
  - statement: TIM23.17 preprotein translocase organization is conserved between
      yeast and humans.
    supporting_text: We suggest that the structural organization of TIM23.17 preprotein
      translocases is conserved from low to high eukaryotes.
- id: PMID:20053669
  title: Role of Magmas in protein transport and human mitochondria biogenesis.
  findings:
  - statement: Human Magmas (PAM16 ortholog) is essential for protein translocation
      across the mitochondrial inner membrane and forms a stable subcomplex with
      DnaJC19/Pam18 tethered to TIM23.
    supporting_text: Human Magmas shows a complete growth complementation of Deltapam16
      yeast cells at all temperatures.
  - statement: Magmas peripherally associates with the inner mitochondrial membrane
      and is tethered to the TIM23 complex in yeast and humans, supporting the
      TIM23-dependent matrix import pathway in which TIMM17A participates.
    supporting_text: Magmas forms a stable subcomplex with J-protein Pam18 or DnaJC19
      through its C-terminal region and is tethered to TIM23 complex of yeast and
      humans.
- id: PMID:30598479
  title: ROMO1 is a constituent of the human presequence translocase required for
    YME1L protease import.
  findings:
  - statement: Mass-spectrometry definition of the human TIM23 complex constituents
      recovers TIMM17A in authentic human TIM23 assemblies and identifies ROMO1
      as a new translocase subunit.
    supporting_text: Here, we define the constituents of the human TIM23 complex
      using mass spectrometry and identified ROMO1 as a new translocase constituent
      with an exceptionally short half-life.
  - statement: ROMO1 is dispensable for general presequence-pathway import but is
      specifically required for YME1L import; this defines a regulatory layer on
      the TIM23/TIMM17A-dependent inner membrane import system.
    supporting_text: While ROMO1 is dispensable for general protein import along
      the presequence pathway, we show that it participates in the dynamics of
      TIM21 during respiratory chain biogenesis and is specifically required for
      import of YME1L.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: TIMM17A is a known short-lived subunit of the TIM23-PAM presequence
      import system, identified within the high-confidence human mitochondrial proteome
      (MitoCoP) with characterised turnover dynamics.
    supporting_text: Not only the TIM23-PAM import system contains the known short-lived
      subunits TIMM17A (Opalińska et al., 2018; Rainbolt et al., 2013) and ROMO1 (Richter
      et al., 2019), but also the PAM import motor system consists of proteins of
      different half-lives.
- id: file:human/TIMM17A/TIMM17A-deep-research-falcon.md
  title: Falcon deep research report for human TIMM17A
  findings:
  - statement: TIMM17A is an integral mitochondrial inner membrane component of
      the TIM23 core presequence translocase.
    supporting_text: "TIMM17A is an **integral mitochondrial inner membrane** component\
      \ of the **TIM23 core**"
  - statement: TIM23 imports presequence-containing precursors destined for the
      mitochondrial matrix and many destined for the inner membrane.
    supporting_text: "TIM23 imports **presequence‑containing precursors** destined\
      \ to the **matrix** and many destined to the **inner membrane**"
  - statement: TIMM17A acts at the inner membrane as part of the translocation
      pore/cavity rather than as a stand-alone enzyme.
    supporting_text: "TIMM17A acts at the **inner membrane** as part of the translocation\
      \ pore/cavity"
core_functions:
- description: >-
    TIMM17A contributes to the TIM23 presequence translocase channel/cavity at
    the mitochondrial inner membrane, supporting import of presequence-containing
    nuclear-encoded precursors into the matrix and sorting through TIM23.
  supported_by:
  - reference_id: file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    supporting_text: "TIMM17A is an **integral mitochondrial inner membrane** component of the **TIM23 core**"
  - reference_id: file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    supporting_text: "TIM23 imports **presequence‑containing precursors** destined to the **matrix** and many destined to the **inner membrane**"
  - reference_id: file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    supporting_text: "TIMM17A acts at the **inner membrane** as part of the translocation pore/cavity"
  contributes_to_molecular_function:
    id: GO:0008320
    label: protein transmembrane transporter activity
  directly_involved_in:
  - id: GO:0030150
    label: protein import into mitochondrial matrix
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  in_complex:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
proposed_new_terms: []
suggested_questions:
- question: >-
    Which TIMM17A-specific surfaces distinguish translocase-A regulation from
    TIMM17B-containing housekeeping TIM23 complexes?
  experts: []
- question: >-
    How does YME1L-dependent TIMM17A turnover remodel the substrate spectrum of
    human TIM23 under hypoxia or nutrient stress?
  experts: []
suggested_experiments:
- hypothesis: >-
    TIMM17A-specific structural features tune TIM23 matrix import and stress
    remodeling independently of core TIM23 assembly.
  description: >-
    Use endogenous TIMM17A knockout/rescue with TIMM17A/TIMM17B swap and
    structure-guided mutants, then assay TIM23 complex composition, matrix
    precursor import, YME1L-dependent turnover, and stress-dependent proteome
    remodeling.
  experiment_type: endogenous rescue and mitochondrial import assay

Gene Description

Existing Annotations Review

Core Functions

TIMM17A contributes to the TIM23 presequence translocase channel/cavity at the mitochondrial inner membrane, supporting import of presequence-containing nuclear-encoded precursors into the matrix and sorting through TIM23.