TIMM17A

UniProt ID: Q99595
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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 Review

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.
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.

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.

Directly Involved In:
protein import into mitochondrial matrix
Cellular Locations:
mitochondrial inner membrane
In Complex:
TIM23 mitochondrial import inner membrane translocase complex
Supporting Evidence:
  • file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    TIMM17A is an **integral mitochondrial inner membrane** component of the **TIM23 core**
  • file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    TIM23 imports **presequence‑containing precursors** destined to the **matrix** and many destined to the **inner membrane**
  • file:human/TIMM17A/TIMM17A-deep-research-falcon.md
    TIMM17A acts at the **inner membrane** as part of the translocation pore/cavity

References

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Suggested Questions for Experts

Q: Which TIMM17A-specific surfaces distinguish translocase-A regulation from TIMM17B-containing housekeeping TIM23 complexes?

Q: How does YME1L-dependent TIMM17A turnover remodel the substrate spectrum of human TIM23 under hypoxia or nutrient stress?

Suggested Experiments

Experiment: 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.

Hypothesis: TIMM17A-specific structural features tune TIM23 matrix import and stress remodeling independently of core TIM23 assembly.

Type: endogenous rescue and mitochondrial import assay

Deep Research

Falcon

(TIMM17A-deep-research-falcon.md)

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