TIM10

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0042721 TIM22 mitochondrial import inner membrane insertion complex	IBA GO_REF:0000033	ACCEPT	Summary: TIM10 is a peripheral component of the TIM22 complex. The soluble TIM9-TIM10 complex docks onto the TIM22 inner membrane complex via TIM12 to deliver carrier precursors (PMID:9822593, PMID:9889188, PMID:12637749). Koehler et al. showed Tim10p is part of the 300 kDa TIM22 complex (PMID:9822593). Rehling et al. confirmed TIM10 as a component of the twin-pore TIM22 translocase (PMID:12637749). Reason: TIM10 is a bona fide component of the TIM22 complex. It forms part of the peripheral chaperone subcomplex (TIM9-TIM10-TIM12) that associates with the membrane-integral TIM22 complex. The IBA annotation is consistent with extensive experimental evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000113167 · PANTHER:PTN000113167 SUPPORTS TRANSFER Current PAINT retains the GO:0042721 IBD at this eukaryotic small-Tim node. SGD:S000000295 · TIM12 SUPPORTS TRANSFER Yeast Tim12 is a peripheral TIM22-pathway small-Tim component. SGD:S000003530 · TIM10 SUPPORTS TRANSFER Target TIM10 has direct complex-association evidence; its appearance as a seed is valid. UniProtKB:P62072 · TIMM10 SUPPORTS TRANSFER Human TIMM10 is the conserved orthologous small-Tim component. Supporting Evidence: PMID:9822593 A small fraction of Tim9p is bound to the outer face of the inner membrane in a 300 kDa complex whose other subunits include Tim54p, Tim22p, Tim12p and Tim10p. file:yeast/TIM10/TIM10-deep-research-falcon.md a TIM22-associated assembly often described as Tim9–Tim10–Tim12 (review-level stoichiometry cited as 3:2:1) that is positioned at the IMS face of TIM22 to receive precursors.
GO:0032977 membrane insertase activity	IBA GO_REF:0000033	MODIFY	Summary: GO:0032977 (membrane insertase activity) is defined as binding transmembrane domain-containing proteins and mediating their integration into a membrane. TIM10 does not itself insert proteins into the membrane. Rather, TIM10 escorts hydrophobic precursors across the IMS and delivers them to the TIM22 complex, which performs the actual membrane insertion (PMID:9430585, PMID:9495346). TIM10 functions as a chaperone/carrier in the aqueous IMS, not as an insertase. Reason: TIM10 does not have insertase activity. Tim22 is the insertase that mediates membrane-potential-dependent insertion of carrier proteins into the inner membrane. TIM10 is a soluble IMS chaperone that escorts precursors to TIM22. The correct molecular function is unfolded protein holdase activity (GO:0140309), which captures the escort/holdase function of TIM10. Koehler et al. explicitly stated that Tim10p was required to transport carrier precursors across the outer membrane, while Tim12p and Tim22p mediated insertion (PMID:9430585). Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000113167 · PANTHER:PTN000113167 SOURCE STALE OR MISSING GOA still carries GO:0032977 from this node, but the current cached PAINT table no longer contains an insertase IBD at PTN000113167. UniProtKB:P62072 · TIMM10 SOURCE BAD Human TIMM10 is a soluble small-Tim chaperone/carrier, not the membrane-embedded insertase; using it to seed insertase activity conflates delivery with insertion. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:9430585 Tim10p readily dissociated from the complex and was required to transport carrier precursors across the outer membrane; Tim12p was firmly bound to Tim22p and mediated the insertion of carriers into the inner membrane. PMID:9495346 Tim10 and Tim12 are found in a complex with Tim22, which takes over the precursor and mediates its membrane-potential-dependent insertion into the inner membrane. file:yeast/TIM10/TIM10-deep-research-falcon.md small Tim hexamers (Tim9·Tim10 and, for some clients, Tim8·Tim13) bind exposed hydrophobic segments to prevent aggregation and deliver substrates to the TIM22 machinery for membrane potential (Δψ)-dependent insertion.
GO:0045039 protein insertion into mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: TIM10 participates in the overall process of protein insertion into the mitochondrial inner membrane. While TIM10 itself does not perform the insertion step (that is Tim22), it is an essential component of the pathway that chaperones precursors across the IMS to the TIM22 insertase. Multiple studies have shown that loss of TIM10 function blocks carrier protein import and insertion (PMID:9430585, PMID:9495346, PMID:11483513). Reason: This biological process annotation is appropriate. TIM10 is directly involved in the protein insertion pathway even though it functions at the chaperoning step rather than the insertion step per se. The IBA annotation is well supported by extensive experimental evidence across multiple publications showing TIM10 is essential for this process. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000113167 · PANTHER:PTN000113167 SUPPORTS TRANSFER Current PAINT retains the GO:0045039 IBD at this conserved small-Tim node. SGD:S000000295 · TIM12 SUPPORTS TRANSFER Yeast Tim12 experimentally supports participation in the TIM22 pathway. SGD:S000003530 · TIM10 SUPPORTS TRANSFER Target experimental evidence validly grounds the ancestral process assertion. MGI:MGI:1353429 · mouse Timm10 SUPPORTS TRANSFER Mammalian ortholog evidence supports the conserved insertion pathway role. UniProtKB:P62072 · TIMM10 SUPPORTS TRANSFER Human TIMM10 supports conservation of the carrier-delivery pathway. WB:WBGene00006573 · worm tim-10 SUPPORTS TRANSFER Nematode ortholog evidence supports the conserved process assertion. Supporting Evidence: PMID:9430585 Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane. PMID:11483513 The reconstituted TIM10 complex not only facilitated passage of AAC across the outer membrane but also ensured its accurate membrane insertion. file:yeast/TIM10/TIM10-deep-research-falcon.md tim10-2 mitochondria: AAC import ~10-fold reduced in rate and ~5-fold reduced in yield (20 min), with accumulation of AAC precursors in ~500–600 kDa intermediates; import of presequence substrates remains largely normal.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: TIM10 is associated with the mitochondrial inner membrane as a peripheral membrane protein on the intermembrane space side. UniProt annotates TIM10 to the mitochondrion inner membrane as a peripheral membrane protein on the intermembrane side. This IEA annotation based on UniProt subcellular location mapping is supported by experimental data (PMID:10648604). Reason: TIM10 is indeed associated with the mitochondrial inner membrane as part of the 300 kDa TIM22 complex. A fraction of TIM10 is peripherally associated with the inner membrane via its interaction with TIM12/TIM22. The IEA is consistent with the IDA annotation to the same term (PMID:10648604). Supporting Evidence: PMID:10648604 The TIM22 complex contains the peripheral subunits Tim9p, Tim10p, and Tim12p and the integral membrane subunits Tim22p and Tim54p.
GO:0005758 mitochondrial intermembrane space	IEA GO_REF:0000044	ACCEPT	Summary: TIM10 is a soluble protein of the mitochondrial intermembrane space. This IEA annotation from UniProt subcellular location mapping is well supported by multiple experimental studies showing TIM10 resides in the IMS as part of the soluble 70 kDa TIM9-TIM10 complex (PMID:9889188, PMID:9822593). Reason: The mitochondrial IMS is the primary location of TIM10. The bulk of TIM10 exists as a soluble hexameric complex with TIM9 in the IMS. This is one of the most well-established features of TIM10 biology. Supporting Evidence: PMID:9889188 Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12. file:yeast/TIM10/TIM10-deep-research-falcon.md Tim10 is experimentally described as an IMS-localized protein functioning as a soluble component of the carrier import pathway rather than a matrix factor.
GO:0015031 protein transport	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: TIM10 is involved in protein transport, specifically transporting mitochondrial carrier proteins from the TOM complex across the IMS to the TIM22 complex. This IEA from UniProt keyword mapping is correct but overly general compared to the more specific GO:0045039 (protein insertion into mitochondrial inner membrane) annotations already present. Reason: This broad umbrella is correct and covers both TIM22-directed carrier delivery and the reported SAM-directed beta-barrel precursor route, but it is less informative than the reviewed pathway and carrier activities and is therefore non-core. Supporting Evidence: PMID:9430585 Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane.
GO:0042719 mitochondrial intermembrane space chaperone complex	IEA GO_REF:0000117	ACCEPT	Summary: TIM10 is a core component of the mitochondrial intermembrane space chaperone complex (the TIM9-TIM10 complex). This IEA from ARBA is well supported by multiple experimental IDA annotations to the same term (PMID:9822593, PMID:9889188). Reason: This IEA annotation is fully consistent with the experimentally determined localization of TIM10 as a subunit of the TIM9-TIM10 IMS chaperone complex. Supporting Evidence: PMID:9822593 Most of Tim9p is associated with Tim10p in a soluble 70 kDa complex. file:yeast/TIM10/TIM10-deep-research-falcon.md Tim9·Tim10 forms a soluble ~60–70 kDa hexameric assembly in the IMS.
GO:0045039 protein insertion into mitochondrial inner membrane	IEA GO_REF:0000117	ACCEPT	Summary: TIM10 is involved in the process of protein insertion into the mitochondrial inner membrane. This IEA from ARBA is consistent with multiple experimental IDA and IMP annotations to the same term (PMID:9430585, PMID:9495346, PMID:10648604, PMID:19037098). Reason: This IEA annotation correctly reflects TIM10 involvement in inner membrane protein insertion. It is redundant with the experimentally supported annotations to the same term, but acceptable as an independent IEA inference. Supporting Evidence: PMID:9430585 Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane.
GO:0046872 metal ion binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: TIM10 contains a twin CX3C zinc-finger-like motif with four conserved cysteines that can bind zinc. However, zinc binding occurs specifically during cytoplasmic transit to stabilize the reduced form and facilitate import into mitochondria. In the mitochondrial IMS, the mature protein forms disulfide bonds rather than coordinating zinc (PMID:9495346, UniProt). The IEA from UniProt keyword mapping to the general metal ion binding term is acceptable but the zinc binding is transient and context-dependent. Reason: TIM10 does bind metal ions (specifically zinc) via its CX3C motifs, though this occurs in the cytoplasm rather than in its functional IMS location. The IEA annotation to this general term is not wrong, but transient metal coordination during biogenesis is secondary to the mature IMS chaperone/carrier function. Supporting Evidence: PMID:9495346 Both proteins contain a zinc-finger-like motif with four cysteines and bind equimolar amounts of zinc ions.
GO:0005515 protein binding	IPI PMID:11483513 Functional reconstitution of the import of the yeast ADP/ATP...	MARK AS OVER ANNOTATED	Summary: This annotation records the physical interaction of TIM10 with TIM9 (O74700) as detected in PMID:11483513. Luciano et al. showed that Tim9 and Tim10 purified from E. coli can form a complex of the same size as the endogenous complex. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and should be replaced by more specific molecular function terms. The interaction between TIM10 and TIM9 is captured by the complex membership annotations (GO:0042719 and GO:0042721) and by the more informative unfolded protein holdase activity (GO:0140309) proposed as a replacement for GO:0051082. Supporting Evidence: PMID:11483513 Tim9 and Tim10 purified from Escherichia coli can form a complex of the same size as the endogenous complex from yeast mitochondria.
GO:0005515 protein binding	IPI PMID:12637749 Protein insertion into the mitochondrial inner membrane by a...	MARK AS OVER ANNOTATED	Summary: This annotation records the physical interaction of TIM10 with TIM18 (Q08749) as detected in PMID:12637749. The cached abstract establishes a purified TIM22 twin-pore translocase but does not name Tim10, Tim18, or their specific interaction; no evidence-matched quote for the IPI can therefore be supplied from this cache. Reason: Protein binding is uninformative, and the abstract-only cache cannot verify the partner-level assay. The independently established pathway relationship is better captured by TIM22 complex membership (GO:0042721); this does not assert that the curator's inaccessible full-text evidence was wrong.
GO:0005515 protein binding	IPI PMID:17882259 Shy1 couples Cox1 translational regulation to cytochrome c o...	MARK AS OVER ANNOTATED	Summary: This annotation records a physical interaction between TIM10 and TIM18 (Q08749) from PMID:17882259 (Shy1 couples Cox1 translational regulation to cytochrome c oxidase assembly). This is a large-scale interaction study. Reason: Protein binding is uninformative. This interaction is better captured by the complex membership annotations. The specific paper is about Shy1/Cox1 regulation and TIM10 interaction data from it is likely from a proteomics/interactomics dataset.
GO:0005515 protein binding	IPI PMID:23267104 Proteome-wide protein interaction measurements of bacterial ...	MARK AS OVER ANNOTATED	Summary: This annotation records a physical interaction of TIM10 with TIM12 (P32830) from PMID:23267104. Inspection of the cached full text verifies that the study is restricted to Escherichia coli proteins and contains no yeast, Tim10, or Tim12 mention, so the citation does not support this interaction. Reason: The cited full text is a verified identifier mismatch for this yeast interaction. The TIM10-TIM12 association is independently established and captured by complex membership annotations, but this generic protein-binding row overstates what its original reference supports. Supporting Evidence: PMID:9822593 A small fraction of Tim9p is bound to the outer face of the inner membrane in a 300 kDa complex whose other subunits include Tim54p, Tim22p, Tim12p and Tim10p.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: This annotation records a physical interaction of TIM10 with human MAGEA2B (P43356) from PMID:27107014 (an inter-species protein-protein interaction network). This is a cross-species interaction that likely has no physiological relevance for yeast TIM10 function. Reason: The intentionally cross-species interaction with human MAGEA2B has no physiological relevance to yeast TIM10 function. A generic protein-binding annotation derived from this heterologous assay should not be retained as yeast biology.
GO:0005515 protein binding	IPI PMID:27107014 An inter-species protein-protein interaction network across ...	REMOVE	Summary: This annotation records a physical interaction of TIM10 with human TEX11 (Q8IYF3-3) from PMID:27107014 (an inter-species protein-protein interaction network). This is a cross-species interaction that likely has no physiological relevance for yeast TIM10 function. Reason: The intentionally cross-species interaction with human TEX11 has no physiological relevance to yeast TIM10 function. A generic protein-binding annotation derived from this heterologous assay should not be retained as yeast biology.
GO:0005515 protein binding	IPI PMID:9495346 Carrier protein import into mitochondria mediated by the int...	MARK AS OVER ANNOTATED	Summary: This annotation records a physical interaction of TIM10 with TIM12 (P32830) from PMID:9495346. Sirrenberg et al. showed Tim10 and Tim12 interact sequentially with carrier precursors and form a complex with Tim22. Reason: Protein binding is uninformative. The TIM10-TIM12 interaction is better represented by the complex membership annotations (GO:0042721, GO:0042719). The more informative molecular function is protein transporter activity (GO:0140318) or unfolded protein holdase activity (GO:0140309). Supporting Evidence: PMID:9495346 Tim10 and Tim12 are found in a complex with Tim22, which takes over the precursor and mediates its membrane-potential-dependent insertion into the inner membrane.
GO:0005739 mitochondrion	IDA PMID:9889188 Tim9, a new component of the TIM22.54 translocase in mitocho...	ACCEPT	Summary: TIM10 localizes to mitochondria. Adam et al. (PMID:9889188) identified Tim9 as a mitochondrial intermembrane space component organized with Tim10 and Tim12, confirming mitochondrial localization of TIM10 by direct assay. Reason: TIM10 is a well-established mitochondrial protein. The IDA annotation is well supported, though GO:0005758 (mitochondrial intermembrane space) is more specific. Supporting Evidence: PMID:9889188 Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12.
GO:0005743 mitochondrial inner membrane	IDA PMID:10648604 Tim18p, a new subunit of the TIM22 complex that mediates ins...	ACCEPT	Summary: TIM10 is a peripheral membrane protein associated with the inner membrane as part of the TIM22 complex. Koehler et al. (PMID:10648604) showed the TIM22 complex contains peripheral subunits Tim9p, Tim10p, and Tim12p and integral membrane subunits Tim22p and Tim54p. Reason: TIM10 is peripherally associated with the mitochondrial inner membrane via its interaction with the TIM22 complex. This IDA annotation is experimentally well supported. Supporting Evidence: PMID:10648604 The TIM22 complex contains the peripheral subunits Tim9p, Tim10p, and Tim12p and the integral membrane subunits Tim22p and Tim54p.
GO:0005758 mitochondrial intermembrane space	IDA PMID:19037698 The Dutch multicenter experience of the endo-sponge treatmen...	ACCEPT	Summary: This annotation cites PMID:19037698, which is about "The Dutch multicenter experience of the endo-sponge treatment for anastomotic leakage after colorectal surgery" and has nothing to do with TIM10 or mitochondria. This is clearly a PMID error in the ComplexPortal annotation source. The intended reference was likely PMID:19037098 (Baker et al. 2009, about the Tim9-Tim10 complex structure) or another mitochondrial study. Despite the wrong reference, TIM10 IMS localization is well established. Reason: The annotation to GO:0005758 (mitochondrial intermembrane space) is correct for TIM10 -- it is one of the best-characterized IMS proteins. However, the cited PMID:19037698 is clearly wrong (it is an unrelated colorectal surgery paper). This is likely a PMID transcription error; the correct reference is probably PMID:19037098 (Baker et al. 2009, Mol Biol Cell). The localization itself is supported by multiple other references (PMID:9889188, PMID:9822593). Supporting Evidence: PMID:9889188 Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12. PMID:19037098 The Tim9-Tim10 complex plays an essential role in mitochondrial protein import by chaperoning select hydrophobic precursor proteins across the intermembrane space.
GO:0045039 protein insertion into mitochondrial inner membrane	IDA PMID:10648604 Tim18p, a new subunit of the TIM22 complex that mediates ins...	ACCEPT	Summary: Koehler et al. (PMID:10648604) showed that TIM10 is part of the TIM22 complex that mediates insertion of imported proteins into the yeast mitochondrial inner membrane. Tim18p deletion impaired import and was synthetically lethal with Tim10p temperature-sensitive mutations, establishing TIM10 involvement in the insertion pathway. Reason: TIM10 is an essential component of the carrier protein import and inner membrane insertion pathway. This IDA annotation is well supported by the cited reference and multiple other publications. Supporting Evidence: PMID:10648604 Deletion of Tim18p decreases the growth rate of yeast cells by a factor of two and is synthetically lethal with temperature-sensitive mutations in Tim9p or Tim10p.
GO:0045039 protein insertion into mitochondrial inner membrane	IDA PMID:19037098 Structural and functional requirements for activity of the T...	ACCEPT	Summary: Baker et al. (PMID:19037098) determined the structure of the yeast Tim9-Tim10 hexameric assembly at 2.5 A and performed mutational analysis showing that disruption of the complex causes defective import of precursor substrates. Reason: This IDA annotation from Baker et al. is well supported. The study demonstrated that mutations destabilizing the Tim9-Tim10 complex cause defective import of precursor substrates, directly confirming TIM10 involvement in the process. Supporting Evidence: PMID:19037098 Mutation of these residues destabilizes the complex, causes defective import of precursor substrates, and results in yeast growth defects.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-SCE-9839836	ACCEPT	Summary: This Reactome annotation refers to the reaction "YME1 degrades TIM10", indicating TIM10 is located at the mitochondrial inner membrane where it can be degraded by the i-AAA protease YME1. TIM10 association with the inner membrane is well established. Reason: TIM10 is peripherally associated with the mitochondrial inner membrane as part of the TIM22 complex. The Reactome TAS annotation is consistent with the IDA annotation to the same term. Supporting Evidence: file:yeast/TIM10/TIM10-deep-research-falcon.md misfolded/unassembled small Tims can be cleared by the i-AAA protease Yme1, linking TIM22 import efficiency to stress and proteostasis state.
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	KEEP AS NON CORE	Summary: TIM10 contains a twin CX3C motif that can coordinate zinc ions. However, zinc binding is context-dependent: TIM10 binds zinc in the cytoplasm (in its reduced form before import), but in the mitochondrial IMS the cysteines form disulfide bonds rather than coordinating zinc (PMID:9495346, UniProt). The RCA annotation from a zinc proteome study (PMID:30358795) is acceptable but should be understood in context. Reason: TIM10 does bind zinc via its CX3C motifs, though this occurs in the cytoplasmic reduced state rather than in the functional IMS oxidized state. The annotation is not incorrect -- TIM10 is part of the zinc proteome -- but the zinc binding is transient during biogenesis and is not its core mature activity. Supporting Evidence: PMID:9495346 Both proteins contain a zinc-finger-like motif with four cysteines and bind equimolar amounts of zinc ions. file:yeast/TIM10/TIM10-deep-research-falcon.md Cysteine/disulfide architecture is not merely structural—Baker et al. showed that removing both disulfides is non-viable, and specific cysteine-pair mutants in Tim10 impair carrier import/assembly even when membrane potential is not strongly affected, directly linking oxidative folding to TIM22 pathway function.
GO:0005758 mitochondrial intermembrane space	TAS Reactome:R-SCE-1252259	ACCEPT	Summary: This Reactome annotation references the reaction "TIM9:TIM10 binds hydrophobic proteins" in the IMS. This is consistent with the known function of the TIM9-TIM10 complex as a soluble IMS chaperone. Reason: TIM10 resides in the mitochondrial IMS as part of the soluble TIM9-TIM10 complex. The Reactome TAS annotation is consistent with multiple experimental annotations to the same term. Supporting Evidence: PMID:9889188 Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12.
GO:0005758 mitochondrial intermembrane space	TAS Reactome:R-SCE-1252260	ACCEPT	Summary: This Reactome annotation references the reaction "MIA40:ERV1 oxidizes cysteine residues to cystine disulfide bonds", referring to the Mia40/Erv1 disulfide relay pathway that imports and oxidizes small TIM proteins like TIM10 in the IMS. Reason: TIM10 is a substrate of the Mia40/Erv1 disulfide relay system in the IMS. The annotation correctly places TIM10 in the IMS where it undergoes oxidative folding. Supporting Evidence: file:yeast/TIM10/TIM10-deep-research-falcon.md Small Tim proteins are MIA pathway substrates: they enter mitochondria reduced/unfolded and are oxidatively folded in the IMS through Mia40-catalyzed disulfide exchange, with Erv1/ALR recycling Mia40.
GO:0140318 protein transporter activity	IMP PMID:9430585 Import of mitochondrial carriers mediated by essential prote...	ACCEPT	Summary: Koehler et al. (PMID:9430585) demonstrated that Tim10p is essential for transport of carrier precursors across the outer membrane. Using temperature- sensitive mutants, they showed Tim10p mediates import of multispanning carriers. GO:0140318 (protein transporter activity) is defined as directly binding to a specific protein and delivering it to a specific cellular location. Reason: TIM10 directly binds carrier protein precursors and delivers them from the TOM complex to the TIM22 complex. This is precisely what protein transporter activity describes. The IMP evidence from temperature-sensitive mutant analysis is robust. Supporting Evidence: PMID:9430585 Tim10p readily dissociated from the complex and was required to transport carrier precursors across the outer membrane; Tim12p was firmly bound to Tim22p and mediated the insertion of carriers into the inner membrane. file:yeast/TIM10/TIM10-deep-research-falcon.md binding hydrophobic segments and promoting their release from TOM/GIP intermediates before handoff to the TIM22 insertion complex.
GO:0140318 protein transporter activity	IDA PMID:9495346 Carrier protein import into mitochondria mediated by the int...	ACCEPT	Summary: Sirrenberg et al. (PMID:9495346) showed Tim10 interacts with carrier protein precursors and facilitates their translocation across the outer membrane. Tim10 and Tim12 interact sequentially with precursors and deliver them to Tim22 for insertion. Reason: This IDA annotation is well supported. TIM10 directly binds to and transports carrier protein precursors through the IMS, which is the core definition of protein transporter activity. Supporting Evidence: PMID:9495346 Two related proteins in the intermembrane space, Tim10/Mrs11 and Tim12/Mrs5, interact sequentially with these precursors and facilitate their translocation across the outer membrane, irrespective of the membrane potential.
GO:0005739 mitochondrion	HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph...	ACCEPT	Summary: This HDA annotation from a large-scale quantitative mitochondrial proteomics study (PMID:24769239) confirms TIM10 as a mitochondrial protein. High-throughput direct assay evidence. Reason: TIM10 mitochondrial localization is well established. This HDA annotation from a mitochondrial proteome analysis is consistent with all other localization data.
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	ACCEPT	Summary: This HDA annotation from a yeast mitochondrial proteomics study (PMID:16823961) by Reinders et al. confirms TIM10 as a mitochondrial protein identified by mass spectrometry. Reason: TIM10 mitochondrial localization is well established. This HDA annotation from a mitochondrial proteome analysis provides independent proteomics confirmation.
GO:0045039 protein insertion into mitochondrial inner membrane	IMP PMID:9430585 Import of mitochondrial carriers mediated by essential prote...	ACCEPT	Summary: Koehler et al. (PMID:9430585) used temperature-sensitive Tim10p mutants to show that Tim10p is required for import of multispanning carrier proteins into the inner membrane. Reason: This IMP annotation is well supported by the temperature-sensitive mutant phenotype analysis. Loss of Tim10p function blocks carrier protein insertion into the inner membrane. Supporting Evidence: PMID:9430585 Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane.
GO:0045039 protein insertion into mitochondrial inner membrane	IDA PMID:9495346 Carrier protein import into mitochondria mediated by the int...	ACCEPT	Summary: Sirrenberg et al. (PMID:9495346) demonstrated Tim10 is involved in the pathway for carrier protein insertion into the inner membrane, working with Tim12 and Tim22 to facilitate translocation and insertion. Reason: This IDA annotation is well supported. TIM10 is essential for the carrier protein import and inner membrane insertion pathway. Supporting Evidence: PMID:9495346 Two related proteins in the intermembrane space, Tim10/Mrs11 and Tim12/Mrs5, interact sequentially with these precursors and facilitate their translocation across the outer membrane, irrespective of the membrane potential.
GO:0042719 mitochondrial intermembrane space chaperone complex	IDA PMID:9822593 Tim9p, an essential partner subunit of Tim10p for the import...	ACCEPT	Summary: Koehler et al. (PMID:9822593) showed that Tim9p and Tim10p co-purify in successive chromatographic fractionations and co-immunoprecipitate, forming the soluble 70 kDa IMS chaperone complex. Reason: This is one of the defining experimental demonstrations that TIM10 is a core subunit of the IMS chaperone complex. The IDA evidence is robust. Supporting Evidence: PMID:9822593 Most of Tim9p is associated with Tim10p in a soluble 70 kDa complex. Tim9p and Tim10p co-purify in successive chromatographic fractionations and co-immunoprecipitated with each other.
GO:0042719 mitochondrial intermembrane space chaperone complex	IDA PMID:9889188 Tim9, a new component of the TIM22.54 translocase in mitocho...	ACCEPT	Summary: Adam et al. (PMID:9889188) identified Tim9 as a new component of the TIM22.54 translocase and showed it forms two distinct hetero-oligomeric assemblies with Tim10 and Tim12 in the IMS. Reason: This IDA annotation is well supported. The study demonstrated that TIM10 is organized into the TIM9-TIM10 complex in the IMS. Supporting Evidence: PMID:9889188 Tim9 is located in the mitochondrial intermembrane space and is organized into two distinct hetero-oligomeric assemblies with Tim10 and Tim12.
GO:0051082 unfolded protein binding	IDA PMID:12138093 Assembly of Tim9 and Tim10 into a functional chaperone.	MODIFY	Summary: Vial et al. (PMID:12138093) demonstrated that the reconstituted TIM10 complex binds to the physiological substrate ADP/ATP carrier and displays chaperone activity in refolding model substrate firefly luciferase. While TIM10 does bind unfolded proteins, the term GO:0051082 (unfolded protein binding) fails to capture the critical carrier/escort function of TIM10. TIM10 does not merely bind unfolded proteins -- it actively escorts them across the aqueous IMS from the TOM complex to the TIM22 complex, functioning as a true protein carrier chaperone. Live GO names GO:0140309 "unfolded protein holdase activity" and defines it as binding an unfolded protein, escorting it to an acceptor or location, and preventing its aggregation. This precisely describes TIM10 function. Reason: GO:0051082 (unfolded protein binding) is too generic and misses the essential carrier/escort function of TIM10. The TIM9-TIM10 complex is a quintessential unfolded protein carrier: it binds hydrophobic unfolded precursors in the IMS, prevents their aggregation, and escorts them between two cellular compartments (from the TOM complex at the outer membrane to the TIM22 complex at the inner membrane). GO:0140309 (unfolded protein holdase activity) captures this complete function. The reconstituted complex not only bound substrate but also "facilitated passage of AAC across the outer membrane" and "ensured its accurate membrane insertion" (PMID:11483513), confirming active escort rather than passive binding. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:12138093 the reconstituted TIM10 complex is functional because it bound to the physiological substrate ADP/ATP carrier and displayed chaperone activity in refolding the model substrate firefly luciferase. PMID:11483513 The reconstituted TIM10 complex not only facilitated passage of AAC across the outer membrane but also ensured its accurate membrane insertion. PMID:9430585 Both proteins may function as intermembrane space chaperones for the highly insoluble carrier proteins. file:yeast/TIM10/TIM10-deep-research-falcon.md Tim9 and Tim10 assemble into a functional chaperone that binds AAC in a mitochondrion-free binding assay, supporting direct client engagement.

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