SLC25A42

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) mitochondrial localization, consistent with the experimentally demonstrated inner-membrane location. Correct but less specific than the IDA mitochondrial inner membrane call (GO:0005743). Reason: Correct compartment inferred from orthologs, but subsumed by the more specific experimental mitochondrial inner membrane annotation.
GO:0015297 antiporter activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Antiport is the correct transport mechanism: SLC25A42 was shown to catalyze only a counter-exchange transport. However, the generic antiporter term does not capture the substrate; the specific coenzyme A transmembrane transporter activity (GO:0015228) is more informative. Reason: Mechanistically correct (strict antiport) but too general; the specific CoA transporter activity is the core molecular function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0005739 mitochondrion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) mitochondrial localization. Correct but redundant with and less specific than the experimental inner-membrane annotation. Reason: Correct compartment but general and machine-generated; superseded by IDA inner-membrane call.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic prediction of mitochondrial inner membrane localization from InterPro mitochondrial carrier signature and UniProt subcellular location, matching the experimental IDA. Correct and specific. Reason: Agrees with the experimentally determined mitochondrial inner-membrane localization of this multi-pass carrier.
GO:0015605 organophosphate ester transmembrane transporter activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Correct-branch parent activity: CoA, dephospho-CoA, ADP/ATP/AMP and PAP are organophosphate esters, so this general transporter term is not wrong, but it is far less informative than the specific coenzyme A transmembrane transporter activity. Reason: General parent of the specific substrate activities; machine-generated and uninformative on its own.
GO:0015932 nucleobase-containing compound transmembrane transporter activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Correct-branch parent activity: the adenine-nucleotide and CoA substrates are nucleobase-containing compounds. Not wrong but too general and machine-generated. Reason: General parent term; the specific CoA and adenine-nucleotide transporter activities are the core function.
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: High-level transmembrane transport process inferred from the InterPro mitochondrial carrier domain. Correct but maximally general; specific CoA transport BP terms apply. Reason: Correct but root-level process term; specific coenzyme A transmembrane transport is preferred.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a high-throughput binary (yeast two-hybrid) interactome, with reported partners KRT31, KRT34, KRTAP10-8 and MTUS2. Keratins and keratin-associated proteins are common non-specific hits in binary interaction screens; these interactions do not inform the molecular function of this inner-membrane CoA carrier. Reason: Uninformative bare protein-binding term from a large-scale interactome; partners (keratins) are typical sticky Y2H hits with no established biological relevance to CoA transport.
GO:0015939 pantothenate metabolic process	TAS Reactome:R-HSA-199220	KEEP AS NON CORE	Summary: Reactome places SLC25A42 in vitamin B5 (pantothenate)/CoA metabolism because CoA is the downstream product of pantothenate. The transporter participates in CoA compartmentalization rather than in pantothenate metabolism per se; retained as a valid pathway-level (non-core) association. Reason: Pathway-level pantothenate/CoA metabolism context; the gene's direct role is CoA transport, not pantothenate conversion.
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Immunofluorescence-based (HPA) mitochondrial localization. Correct but less specific than the mitochondrial inner membrane annotation. Reason: Correct compartment; subsumed by the more specific inner-membrane localization.
GO:0005471 ATP:ADP antiporter activity	EXP PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Experimentally supported: reconstituted SLC25A42 catalyzed ADP(in)/ATP(out) exchange among its counter-exchange reactions (UniProt RHEA:34999). This is a genuine measured exchange activity but represents one of several nucleotide counter-substrates rather than the physiological cargo (CoA import). Reason: Real in-vitro exchange activity, but a secondary/counter-substrate function; the physiological role is CoA import in exchange for adenine nucleotides. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0005743 mitochondrial inner membrane	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	ACCEPT	Summary: Direct experimental evidence for mitochondrial inner-membrane localization: the protein was targeted to mitochondria and functionally reconstituted, and UniProt records inner-membrane, multi-pass localization. This is the correct, specific cellular location and a core feature. Reason: Experimentally supported specific localization of this multi-pass carrier to the mitochondrial inner membrane. Supporting Evidence: file:human/SLC25A42/SLC25A42-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0015228 coenzyme A transmembrane transporter activity	IMP PMID:40925986 Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25...	ACCEPT	Summary: Physiological (IMP) evidence that SLC25A42 mediates mitochondrial CoA import in human cells: A42/A16 are required to build the matrix CoA pool, A42 loss depletes mitochondrial CoASH, and re-expressed wild-type A42 (but not the disease mutant N291D) rescues CoA import. This is the core molecular function. Reason: Core molecular function, confirmed both biochemically (proteoliposomes) and in cellulo (CRISPR KO + rescue + direct import assay). Supporting Evidence: PMID:40925986 SLC25A16 and SLC25A42 are critical for mitochondrial import of free CoASH
GO:1990559 mitochondrial coenzyme A transmembrane transport	IMP PMID:40925986 Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25...	ACCEPT	Summary: Physiological (IMP) evidence that SLC25A42 is required for coenzyme A transport across the mitochondrial inner membrane; loss depletes the mitochondrial CoA pool and impairs CoA-dependent matrix pathways. This is the core biological process. Reason: Core biological process; directly demonstrated by KO/rescue and mitochondrial CoA-uptake assays. Supporting Evidence: PMID:40925986 This CoASH import process supports an enriched mitochondrial CoA pool and CoA-dependent pathways in the matrix, including the high-flux TCA cycle and fatty acid oxidation
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial proteome localization. Consistent with the experimental localization but non-specific relative to the inner-membrane call. Reason: Correct compartment from a proteome-wide dataset; subsumed by the specific inner-membrane annotation.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-9837333	ACCEPT	Summary: Reactome (TAS) inner-membrane localization tied to the annotated reaction in which SLC25A42 exchanges cytosolic CoA-SH for matrix ADP. Correct and specific. Reason: Agrees with experimentally determined mitochondrial inner-membrane localization. Supporting Evidence: Reactome:R-HSA-9837333 SLC25A42 associated with the inner mitochondrial membrane mediates the exchange of cytosolic CoA-SH for mitochondrial ADP
GO:0015228 coenzyme A transmembrane transporter activity	EXP PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	ACCEPT	Summary: Biochemical (EXP, via Reactome) evidence for coenzyme A transmembrane transporter activity from the original proteoliposome reconstitution, which showed high transport affinity for CoA. Core molecular function. Reason: Core molecular function directly demonstrated by reconstitution of purified protein into liposomes. Supporting Evidence: PMID:19429682 SLC25A42 protein is a mitochondrial transporter for CoA and adenosine 3',5'-diphosphate
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: Nuclear localization from a human sperm-nucleus proteomic catalogue (403 proteins identified by LC-MS/MS). This is a high-throughput co-purification, not evidence of a nuclear function for a polytopic mitochondrial inner-membrane CoA carrier; most consistent with residual mitochondrial/sperm-sheath contamination. There is no functional support for a nuclear role. Reason: Isolated high-throughput proteomic detection in sperm nuclei; contradicts the well-established inner-membrane localization and lacks any functional support for nuclear activity. Supporting Evidence: PMID:21630459 403 different proteins have been identified from the isolated sperm nuclei
GO:0005347 ATP transmembrane transporter activity	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Direct in-vitro evidence that reconstituted SLC25A42 transports ATP as part of its counter-exchange repertoire (ADP/ATP exchange, RHEA:34999). A genuine measured substrate but a counter-substrate rather than the physiological CoA cargo. Reason: Experimentally supported secondary substrate of the antiporter; not the core physiological function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0015217 ADP transmembrane transporter activity	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Direct in-vitro evidence that SLC25A42 transports ADP; ADP is a high-affinity counter-substrate (KM ~55 uM) exchanged for CoA. Experimentally sound; represents the intramitochondrial exchange partner for CoA import. Reason: Experimentally supported counter-substrate of CoA import; secondary to the core CoA transporter function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0015228 coenzyme A transmembrane transporter activity	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	ACCEPT	Summary: Direct experimental evidence (proteoliposome reconstitution) that SLC25A42 is a coenzyme A transporter with high affinity for CoA. This is the core molecular function. Reason: Core molecular function established by biochemical reconstitution of the purified protein. Supporting Evidence: PMID:19429682 SLC25A42 protein is a mitochondrial transporter for CoA and adenosine 3',5'-diphosphate
GO:0015866 ADP transport	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Biological-process counterpart of the ADP transmembrane transporter activity; ADP is exchanged out as CoA is imported. Experimentally supported but a counter-substrate process rather than the core CoA-import role. Reason: Experimentally supported process for the antiport counter-substrate; secondary to CoA transport. Supporting Evidence: PMID:19429682 The main physiological role of SLC25A42 is to import CoA into mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3',5'-diphosphate
GO:0015867 ATP transport	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Biological-process counterpart of ATP transmembrane transporter activity, reflecting ATP as an in-vitro counter-exchange substrate. Experimentally supported but secondary. Reason: Experimentally supported secondary substrate process; not the core physiological function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0035349 coenzyme A transmembrane transport	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	ACCEPT	Summary: Direct experimental evidence for coenzyme A transmembrane transport, the core biological process, from proteoliposome reconstitution showing CoA counter-exchange. Reason: Core biological process directly demonstrated biochemically. Supporting Evidence: PMID:19429682 SLC25A42 protein is a mitochondrial transporter for CoA and adenosine 3',5'-diphosphate
GO:0043262 ADP phosphatase activity	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	MARK AS OVER ANNOTATED	Summary: SLC25A42 is a counter-exchange transporter, not a hydrolase. The cited paper assayed transport (including an AMP(in)/ADP(out) exchange, UniProt RHEA:72851), not ADP hydrolysis to AMP + phosphate. This catalytic phosphatase MF is a misclassification of the AMP/ADP exchange transport activity; no phosphatase reaction was measured. Reason: Enzymatic (phosphatase) activity attributed to a solute carrier that performs only counter-exchange transport; derived from misreading the AMP/ADP exchange as hydrolysis. No catalytic assay supports a phosphatase function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0080121 AMP transport	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Biological-process counterpart of AMP transmembrane transporter activity; AMP is an in-vitro counter-exchange substrate (AMP/ADP exchange, RHEA:72851). Experimentally supported but secondary to CoA import. Reason: Experimentally supported secondary substrate process; not the core function. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate
GO:0080122 AMP transmembrane transporter activity	IDA PMID:19429682 A novel member of solute carrier family 25 (SLC25A42) is a t...	KEEP AS NON CORE	Summary: Direct in-vitro evidence that SLC25A42 transports AMP as one of its counter-exchange substrates. Experimentally supported but a secondary substrate rather than the core CoA transporter function. Reason: Experimentally supported secondary substrate; the core molecular function is CoA transport. Supporting Evidence: PMID:19429682 SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate

Gene Description

Existing Annotations Review

Core Functions

Mitochondrial inner-membrane coenzyme A transporter that imports CoA into the matrix by strict counter-exchange (antiport) with intramitochondrial adenine nucleotides (chiefly ADP) and adenosine 3',5'-diphosphate.

Coenzyme A transmembrane transport across the mitochondrial inner membrane, establishing the matrix CoA pool that supports CoA-dependent catabolism (TCA cycle, fatty-acid oxidation), performed by this inner-membrane carrier.

References

📚 Additional Documentation

Notes

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