Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

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

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:10469659

Different import pathways through the mitochondrial intermembrane space for inner membrane proteins.

Tim9p-Tim10p and Tim8p-Tim13p complexes each mediate import of different subsets of inner membrane proteins, transferring them to TIM22, TIM23, or other sites.

PMID:10648604

Tim18p, a new subunit of the TIM22 complex that mediates insertion of imported proteins into the yeast mitochondrial inner membrane.

Tim18p is an additional subunit of the TIM22 complex; its deletion is synthetically lethal with ts mutations in Tim9p or Tim10p.

PMID:11483513

Functional reconstitution of the import of the yeast ADP/ATP carrier mediated by the TIM10 complex.

Tim9 and Tim10 purified from E. coli form a complex identical in size to the endogenous complex. The reconstituted TIM10 complex restores AAC import in tim10-ts mitochondria.

PMID:11867522

The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier.

Mature Tim9-Tim10 complex in the IMS contains disulfide bonds, not zinc; zinc coordination occurs only during cytoplasmic transit.

PMID:12138093

Assembly of Tim9 and Tim10 into a functional chaperone.

The reconstituted Tim9-Tim10 hexameric complex binds the ADP/ATP carrier substrate and displays chaperone activity in refolding firefly luciferase.

PMID:16823961

Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.

TIM9 identified by mass spectrometry in purified yeast mitochondria as part of comprehensive proteomics.

PMID:19037098

Structural and functional requirements for activity of the Tim9-Tim10 complex in mitochondrial protein import.

Crystal structure of yeast Tim9-Tim10 hexamer at 2.5A. Tim9 N-terminal region required for efficient substrate trapping; Tim9 plays an important functional (not just structural) role.

PMID:19037698

The Dutch multicenter experience of the endo-sponge treatment for anastomotic leakage after colorectal surgery.

NOTE: This PMID appears to be a data entry error in the GOA. It is about colorectal surgery, not mitochondrial biology. The intended reference is likely PMID:19037098.

PMID:24769239

Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae.

TIM9 identified in quantitative proteomic analysis of yeast mitochondria under different growth conditions.

PMID:30358795

The cellular economy of the Saccharomyces cerevisiae zinc proteome.

TIM9 identified as a potential zinc-binding protein by bioinformatic analysis of the CX3C motif, but mature IMS form uses disulfide bonds.

PMID:9495346

Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5.

Tim10 and Tim12 interact with carrier protein precursors and facilitate translocation across the outer membrane; they form a complex with Tim22 for inner membrane insertion.

PMID:9822593

Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins.

Tim9p identified as essential partner of Tim10p in a soluble 70 kDa IMS complex. Tim9p cross-links to partly translocated carrier proteins. A fraction associates with the inner membrane 300 kDa TIM22 complex.

PMID:9889188

Tim9, a new component of the TIM22.54 translocase in mitochondria.

Tim9 independently identified as essential component of TIM22.54 machinery. The TIM9.10 complex mediates partial translocation of carrier proteins; the TIM9.10.12 complex assists further translocation via TIM22.54.

Reactome:R-SCE-1252259

TIM9:TIM10 binds hydrophobic proteins

Reactome:R-SCE-1252260

MIA40:ERV1 oxidizes cysteine residues to cystine disulfide bonds

UniProt:O74700

UniProtKB entry for TIM9_YEAST

Mitochondrial intermembrane chaperone; participates in import and insertion of multi-pass transmembrane proteins into the inner membrane and transfer of beta-barrel precursors to SAM complex.

file:yeast/TIM9/TIM9-deep-research-falcon.md

Falcon deep research on TIM9 (Edison Scientific Literature)

Tim9 is a small TIM family soluble IMS chaperone (holdase) whose primary role is chaperone-like binding and transfer of hydrophobic precursors, not catalysis or transport.

"Tim9 is best viewed as a **specialized, soluble IMS holdase chaperone**"
Tim9 is located in the mitochondrial intermembrane space, between TOM-mediated entry and TIM22-mediated inner-membrane insertion.

"Tim9 is located in the **mitochondrial IMS**"
Tim9 forms the canonical Tim9-Tim10 heterohexamer (3:3 stoichiometry, ~70 kDa soluble complex) and a Tim9-Tim10-Tim12 (3:2:1) docking complex linked to TIM22.

"Tim9:Tim10 complex stoichiometry is **3:3**; the TIM22-associated complex is **Tim9–Tim10–Tim12 = 3:2:1**; the soluble Tim9/Tim10 complex is about **~70 kDa**"
Tim9 acts as a chaperone/escort factor that prevents aggregation of hydrophobic precursors in the aqueous IMS and transfers them from TOM to TIM22.

"Tim9 acts as a **chaperone/escort factor** that prevents aggregation of hydrophobic precursors in the aqueous IMS and transfers them from **TOM** to **TIM22**."
Within the complex, Tim10 provides the key substrate-binding elements; Tim9 alone does not bind the AAC carrier (consistent with UniProt noting Tim9 has a strong structural role relative to Tim10).

"Biochemical substrate-binding evidence indicates that **Tim10** (alone) can bind the **ATP/ADP carrier (AAC)** similarly to the Tim9–Tim10 complex, whereas **Tim9 alone does not bind AAC**, supporting a model where Tim10 provides key substrate-binding elements within the complex"
The Tim9-Tim10 complex recognizes hydrophobic clients through a hydrophobic cleft formed by chaperone helices.

"TIM9·10 recognizes hydrophobic clients primarily through a **hydrophobic cleft** formed by chaperone helices"
Small TIMs including Tim9 can also assist trafficking of some outer-membrane beta-barrel proteins toward the SAM complex.

"Small TIMs can also assist trafficking of some outer-membrane β-barrel proteins toward the SAM complex"
Tim9 is itself imported via TOM and oxidatively folded in the IMS by the MIA pathway, which introduces the two intramolecular disulfides in its conserved CX3C motifs (rather than stable metal coordination in the mature form).

"Small TIM proteins (including Tim9) are imported through TOM and undergo oxidative folding in the IMS via the **MIA (mitochondrial import and assembly) pathway**, which introduces disulfides in the conserved CX3C motifs"
Tim9 and Tim10 assemble into an essential heterohexameric Tim9/10 complex; unassembled small TIMs can be degraded by Yme1, with assembly being protective.

"Tim9 and Tim10 assemble into an essential heterohexameric Tim9/10 complex** that chaperones hydrophobic preproteins from TOM to TIM22"
Conserved-residue mutants tim9-19 (E52G) and tim9-3 (V40A + S60P) abolish a detectable Tim9-Tim10 heterohexamer, linking these residues to complex integrity and import function.

"tim9-19 (E52G)** and **tim9-3 (V40A + S60P)** show **no detectable Tim9–Tim10 heterohexamer** in detergent-solubilized mitochondria"