SLC25A10

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Correct core localization. DIC is a multi-pass protein of the mitochondrial inner membrane, consistent with UniProt subcellular location and with the broader SLC25 family. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Mitochondrion inner membrane; Multi-pass membrane
GO:0015116 sulfate transmembrane transporter activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Sulfate is an experimentally supported DIC substrate (sulfate/phosphate and thiosulfate/sulfate exchange are documented). This is a genuine but ancillary substrate specificity relative to the primary dicarboxylate:phosphate exchange, so it is retained as non-core. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt inorganic sulfur-containing anions, and phosphate,
GO:0015117 thiosulfate transmembrane transporter activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Thiosulfate transport (thiosulfate/sulfate antiport) is experimentally documented for DIC. Ancillary substrate specificity, retained as non-core. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Reaction=thiosulfate(in) + sulfate(out) = thiosulfate(out) +
GO:0015141 succinate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Succinate is a core characterized substrate of DIC (malate/succinate and succinate/phosphate exchange). Correct specific transporter MF for the gene. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Reaction=succinate(out) + phosphate(in) = succinate(in) +
GO:0015709 thiosulfate transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Process counterpart of the thiosulfate transporter activity; genuine but ancillary. Retained as non-core.
GO:1902358 sulfate transmembrane transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Process counterpart of sulfate transporter activity; genuine but ancillary substrate. Retained as non-core.
GO:0015140 malate transmembrane transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Malate is the principal characterized substrate of DIC; malate:phosphate exchange is the physiologically dominant activity. Correct and core specific transporter MF. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Reaction=(S)-malate(in) + phosphate(out) = (S)-malate(out) +
GO:0035435 phosphate ion transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Phosphate is the counter-ion for dicarboxylate exchange (malate/succinate:phosphate antiport), so DIC does participate in phosphate ion transmembrane transport. Core to the antiport mechanism. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt inorganic sulfur-containing anions, and phosphate,
GO:0071422 succinate transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Process counterpart of succinate transporter activity; succinate is a core DIC substrate. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Reaction=succinate(out) + phosphate(in) = succinate(in) +
GO:0071423 malate transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Process counterpart of malate transporter activity; malate:phosphate exchange is the central physiological function of DIC. Core. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Reaction=(S)-malate(in) + phosphate(out) = (S)-malate(out) +
GO:0015131 oxaloacetate transmembrane transporter activity	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Oxaloacetate transport is a phylogenetic (IBA) inference and is not among the human-characterized catalytic-activity reactions in UniProt (which list malate, succinate, malonate, sulfate, thiosulfate and phosphate). Plausible for a dicarboxylate carrier but not experimentally established for the human protein; retained as non-core.
GO:0015729 oxaloacetate transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Process counterpart of the IBA oxaloacetate transporter activity; not experimentally established for human DIC. Retained as non-core.
GO:0005310 dicarboxylic acid transmembrane transporter activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Correct at the family level but non-specific. DIC is an antiporter that exchanges dicarboxylates for phosphate; a more precise MF (dicarboxylate:phosphate antiporter activity, GO:0015364) captures both substrate class and mechanism. Retained as a correct generic parent. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt physiologically important metabolites such as dicarboxylates (malonate,
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Correct core localization, mapped from the UniProt subcellular-location vocabulary. Consistent with the IBA and Reactome inner-membrane annotations. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Mitochondrion inner membrane; Multi-pass membrane
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but maximally generic InterPro-derived process term. True of any transporter and uninformative about DIC's specific dicarboxylate:phosphate antiport role; retained as non-core.
GO:1902356 oxaloacetate(2-) transmembrane transport	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Inter-ontology (GO:0015131-derived) inference for oxaloacetate transport; like the parent IBA oxaloacetate annotations, not experimentally established for human DIC. Retained as non-core.
GO:0005515 protein binding	IPI PMID:19060904 An empirical framework for binary interactome mapping.	MARK AS OVER ANNOTATED	Summary: High-throughput binary interactome mapping. Bare 'protein binding' is uninformative about DIC's function, and the reported partners are cytosolic or nuclear proteins that an inner-membrane transporter would not physiologically contact. Over-annotation; not used in core functions.
GO:0005515 protein binding	IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i...	MARK AS OVER ANNOTATED	Summary: High-throughput smart-pooling interactome mapping (MDFI, Q99750). Bare 'protein binding' is uninformative; partner is non-mitochondrial. Likely a high-throughput artifact. Over-annotated.
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: High-throughput next-generation-sequencing interactome dataset. Bare 'protein binding', non-mitochondrial partner; uninformative for an inner-membrane transporter. Over-annotated.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Proteome-scale interactome map (multiple partners: keratins/KRTAPs, MDFI, NOTCH2NLA). Keratins and keratin-associated proteins are classic sticky Y2H or high-throughput false positives; these interactions are non-physiological for an inner-membrane carrier and are uninformative. Over-annotated.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Allelic interactome perturbation study (NOTCH2NLA, Q7Z3S9). Bare 'protein binding', non-mitochondrial partner; high-throughput, uninformative for DIC's function. Over-annotated.
GO:0019418 sulfide oxidation	TAS Reactome:R-HSA-1614517	MARK AS OVER ANNOTATED	Summary: Derived from Reactome pathway participation (DIC provides the dicarboxylate/sulfate antiport step that lets sulfate exit mitochondria in the sulfide-oxidation pathway). DIC does not itself perform sulfide oxidation, which is a pathway-level process carried out by oxidoreductases; this is an over-annotation of the transporter to a downstream pathway.
GO:0055085 transmembrane transport	TAS Reactome:R-HSA-9955298	KEEP AS NON CORE	Summary: Correct but maximally generic Reactome-derived process term (SLC-mediated transport of organic anions). True of any SLC transporter; uninformative about DIC's specific role. Retained as non-core.
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Direct immunofluorescence localization to mitochondria (HPA), consistent with the more precise inner-membrane localization. Correct but less specific than GO:0005743; retained as non-core.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: Detected in the high-confidence human mitochondrial proteome, confirming mitochondrial localization. Correct but less specific than the inner-membrane term; retained as non-core.
GO:0005310 dicarboxylic acid transmembrane transporter activity	EXP PMID:29211846 SLC25A10 biallelic mutations in intractable epileptic enceph...	MODIFY	Summary: Experimentally supported core molecular function: reconstituted transport assays confirmed DIC-mediated dicarboxylate (malate:phosphate) exchange, and its absence in patient cells. The term is correct but general; the more precise MF is dicarboxylate:phosphate antiporter activity (GO:0015364), which captures both substrate class and the antiport mechanism. Proposed replacements: dicarboxylate:phosphate antiporter activity Supporting Evidence: PMID:29211846 SLC25A10 (also known as DIC) transports dicarboxylates and phosphate across the inner mitochondrial membrane
GO:0005310 dicarboxylic acid transmembrane transporter activity	TAS Reactome:R-HSA-1614546	KEEP AS NON CORE	Summary: Reactome-asserted dicarboxylate transporter activity (sulfate exported in exchange for dicarboxylate/malate). Correct at the general level; the specific MF is the dicarboxylate:phosphate antiporter activity captured in core functions.
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: Nuclear localization derives from a human sperm-nucleus proteome dataset. For a multi-pass mitochondrial inner-membrane transporter this is almost certainly a co-purification or contaminant artifact and contradicts the established mitochondrial localization. Over-annotation.
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-1614546	ACCEPT	Summary: Reactome-asserted inner-membrane localization, consistent with the core localization. Correct. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Mitochondrion inner membrane; Multi-pass membrane
GO:0005743 mitochondrial inner membrane	TAS Reactome:R-HSA-372843	ACCEPT	Summary: Reactome-asserted inner-membrane localization (SLC25A10 mediates exchange of malate and phosphate). Consistent with the core localization. Correct. Supporting Evidence: file:human/SLC25A10/SLC25A10-uniprot.txt Mitochondrion inner membrane; Multi-pass membrane
GO:0005310 dicarboxylic acid transmembrane transporter activity	TAS PMID:9733776 The sequence, bacterial expression, and functional reconstit...	MODIFY	Summary: Author statement (Fiermonte et al.) that the reconstituted dicarboxylate carrier transports dicarboxylates, based on functional reconstitution of the rat ortholog. Correct core MF but general; the precise MF is dicarboxylate:phosphate antiporter activity (GO:0015364). Proposed replacements: dicarboxylate:phosphate antiporter activity Supporting Evidence: PMID:9733776 The dicarboxylate carrier (DIC) belongs to a family of transport proteins
GO:0006094 gluconeogenesis	TAS PMID:9733776 The sequence, bacterial expression, and functional reconstit...	KEEP AS NON CORE	Summary: DIC supplies substrates (via malate export from mitochondria) for gluconeogenesis, a well-established downstream physiological role consistent with its high liver/kidney expression. This is a consequence of transport rather than DIC's own molecular activity, so it is kept as a non-core process. Supporting Evidence: PMID:9733776 from the role of the DIC in gluconeogenesis and ureogenesis
GO:0006835 dicarboxylic acid transport	TAS PMID:9733776 The sequence, bacterial expression, and functional reconstit...	ACCEPT	Summary: Core process: DIC mediates transport of dicarboxylic acids (malate, succinate) across the inner membrane. Correct general process term for the gene. Supporting Evidence: PMID:9733776 The dicarboxylate carrier (DIC) belongs to a family of transport proteins

Gene Description

Existing Annotations Review

Core Functions

Dicarboxylate:phosphate antiporter of the mitochondrial inner membrane that catalyzes the electroneutral exchange of dicarboxylates (principally malate and succinate) for inorganic phosphate, operating as a monomer via a ping-pong (single-binding-site) mechanism.

References

📚 Additional Documentation

Notes

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