Slc13a2

UniProt ID: P70545
Organism: Rattus norvegicus
Review Status: COMPLETE
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Gene Description

Slc13a2 encodes the apical low-affinity sodium/dicarboxylate cotransporter NaDC-1, transporting citric-acid-cycle dicarboxylates such as succinate, citrate, fumarate, and alpha-ketoglutarate with sodium. The review accepts substrate-specific transporter and transport terms, keeps membrane localization as non-core, and marks lithium response as assay-context activity regulation rather than a gene response process.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core function (IBA, GO_REF:0000033).
Reason: This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015138 fumarate transmembrane transporter activity
IBA
GO_REF:0000033 		ACCEPT
Summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015139 alpha-ketoglutarate transmembrane transporter activity
IBA
GO_REF:0000033 		ACCEPT
Summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015141 succinate transmembrane transporter activity
IBA
GO_REF:0000033 		ACCEPT
Summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015741 fumarate transport
IBA
GO_REF:0000033 		ACCEPT
Summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015742 alpha-ketoglutarate transport
IBA
GO_REF:0000033 		ACCEPT
Summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0017153 sodium:dicarboxylate symporter activity
IBA
GO_REF:0000033 		ACCEPT
Summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
NaDC1 is described as a **Na+-coupled electrogenic symporter**. A review synthesis reports a **Na+:anion coupling ratio of 3:1**, consistent with an electrogenic uptake process.
GO:0071285 cellular response to lithium ion
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports the gene's core activity or context, not this broader process claim (IBA, GO_REF:0000033).
Reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as an over-annotation of transport-assay conditions.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0071422 succinate transmembrane transport
IBA
GO_REF:0000033 		ACCEPT
Summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015370 solute:sodium symporter activity
IEA
GO_REF:0000117 		MODIFY
Summary: solute:sodium symporter activity captures part of Slc13a2 biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000117).
Reason: The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015746 citrate transport
IEA
GO_REF:0000108 		ACCEPT
Summary: citrate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000108).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
NaDC1 is repeatedly positioned as a **primary apical entry step for citrate reabsorption** in proximal tubule, thereby regulating how much citrate remains in urine versus being reclaimed and metabolized.
GO:0016020 membrane
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core function (IEA, GO_REF:0000002).
Reason: This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0016324 apical plasma membrane
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core function (IEA, GO_REF:0000120).
Reason: This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
NaDC1 localizes to the **apical/luminal (brush-border) membrane** of **proximal tubule epithelial cells** and is also discussed as apical in intestine/small intestinal villus epithelium.
GO:0022857 transmembrane transporter activity
IEA
GO_REF:0000002 		MODIFY
Summary: transmembrane transporter activity captures part of Slc13a2 biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000002).
Reason: The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0035725 sodium ion transmembrane transport
IEA
GO_REF:0000108 		ACCEPT
Summary: sodium ion transmembrane transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000108).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0055085 transmembrane transport
IEA
GO_REF:0000002 		MODIFY
Summary: transmembrane transport captures part of Slc13a2 biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000002).
Reason: The generic transporter or transport term should be replaced with the specific sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015137 citrate transmembrane transporter activity
IEA
GO_REF:0000107 		ACCEPT
Summary: citrate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015138 fumarate transmembrane transporter activity
IEA
GO_REF:0000107 		ACCEPT
Summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015139 alpha-ketoglutarate transmembrane transporter activity
IEA
GO_REF:0000107 		ACCEPT
Summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015141 succinate transmembrane transporter activity
IEA
GO_REF:0000120 		ACCEPT
Summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015741 fumarate transport
IEA
GO_REF:0000107 		ACCEPT
Summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015742 alpha-ketoglutarate transport
IEA
GO_REF:0000107 		ACCEPT
Summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0017153 sodium:dicarboxylate symporter activity
IEA
GO_REF:0000120 		ACCEPT
Summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0071285 cellular response to lithium ion
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports the gene's core activity or context, not this broader process claim (IEA, GO_REF:0000107).
Reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as an over-annotation of transport-assay conditions.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0071422 succinate transmembrane transport
IEA
GO_REF:0000120 		ACCEPT
Summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015137 citrate transmembrane transporter activity
ISO
GO_REF:0000121 		ACCEPT
Summary: citrate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0016324 apical plasma membrane
ISO
GO_REF:0000121 		KEEP AS NON CORE
Summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core function (ISO, GO_REF:0000121).
Reason: This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015138 fumarate transmembrane transporter activity
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		ACCEPT
Summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
GO:0015139 alpha-ketoglutarate transmembrane transporter activity
ISO
GO_REF:0000121 		ACCEPT
Summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015139 alpha-ketoglutarate transmembrane transporter activity
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		ACCEPT
Summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
GO:0015141 succinate transmembrane transporter activity
IDA
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter. 		ACCEPT
Summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9694847).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0015741 fumarate transport
ISO
GO_REF:0000121 		ACCEPT
Summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015741 fumarate transport
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		ACCEPT
Summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
GO:0015742 alpha-ketoglutarate transport
ISO
GO_REF:0000121 		ACCEPT
Summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015742 alpha-ketoglutarate transport
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		ACCEPT
Summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
GO:0016324 apical plasma membrane
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		KEEP AS NON CORE
Summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core function (IDA, PMID:9691021).
Reason: This term records supported membrane or apical plasma-membrane localization rather than the defining transport activity.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
GO:0017153 sodium:dicarboxylate symporter activity
ISO
GO_REF:0000121 		ACCEPT
Summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0017153 sodium:dicarboxylate symporter activity
IDA
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter. 		ACCEPT
Summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9694847).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0071285 cellular response to lithium ion
ISO
GO_REF:0000121 		MARK AS OVER ANNOTATED
Summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121).
Reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as an over-annotation of transport-assay conditions.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0071285 cellular response to lithium ion
IDA
PMID:9691021
Cloning, functional characterization, and localization of a ... 		MARK AS OVER ANNOTATED
Summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports the gene's core activity or context, not this broader process claim (IDA, PMID:9691021).
Reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as an over-annotation of transport-assay conditions.
Supporting Evidence:
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0071422 succinate transmembrane transport
IDA
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter. 		ACCEPT
Summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:9694847).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
GO:0015138 fumarate transmembrane transporter activity
ISO
GO_REF:0000121 		ACCEPT
Summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0015141 succinate transmembrane transporter activity
ISO
GO_REF:0000121 		ACCEPT
Summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.
GO:0071422 succinate transmembrane transport
ISO
GO_REF:0000121 		ACCEPT
Summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
Reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, citrate, fumarate, and alpha-ketoglutarate.
Supporting Evidence:
UniProtKB:P70545
FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate.

Core Functions

Slc13a2 is an apical sodium:dicarboxylate symporter for succinate, citrate, fumarate, and alpha-ketoglutarate.

Molecular Function:
sodium:dicarboxylate symporter activity
Directly Involved In:
succinate transmembrane transport fumarate transport alpha-ketoglutarate transport citrate transport
Substrates:
succinate citrate fumarate 2-oxoglutarate sodium(1+)
Supporting Evidence:
  • UniProtKB:P70545
    Mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate; transports dicarboxylate with probable 3 Na(+) stoichiometry.
  • file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
    Across mammalian NaDC1 orthologs, NaDC1 shows preference for **divalent Krebs-cycle anions**, with **high affinity for succinate** and generally **lower affinity for citrate**; recent work and reviews describe NaDC1 as mediating **Na+-dependent cotransport of citrate and succinate** in kidney and intestine.

References

GO_REF:0000002
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000033
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000107
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000108
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000117
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000120
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
GO_REF:0000121
GO reference used by source annotation pipeline
  • Source annotation pipeline provenance; biological support was assessed from UniProt and cached literature where available.
    "GO_REF entry used to trace source annotation method rather than as primary biological evidence."
PMID:9691021
Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.
  • Rat Slc13a2/rNaDC-1 mediates sodium-dependent uptake of dicarboxylates and localizes to the apical/luminal membrane.
    "Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter."
PMID:9694847
Characterization of a rat Na+-dicarboxylate cotransporter.
  • Rat SDCT1/Slc13a2 mediates electrogenic sodium-dependent transport of Krebs-cycle intermediates.
    "Characterization of a rat Na+-dicarboxylate cotransporter."
file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
Falcon (Edison Scientific) deep research report: rat Slc13a2 / NaDC1 (UniProt P70545) functional annotation
  • Identity and core molecular function confirmed as an apical Na+-coupled dicarboxylate/citrate cotransporter (NaDC1) in kidney and intestine, matching UniProt P70545.
    "The provided UniProt accession **P70545** corresponds to **Slc13a2** in **Rattus norvegicus** and encodes **solute carrier family 13 member 2**, commonly termed **NaDC1 / NADCโ€‘1 / SDCT1**, an apical **Na+-coupled dicarboxylate (incl. citrate) cotransporter** in kidney and intestine."
  • NaDC1 is an electrogenic Na+-coupled symporter with a commonly cited 3 Na+:1 anion coupling ratio, supporting the sodium:dicarboxylate symporter molecular function.
    "NaDC1 is described as a **Na+-coupled electrogenic symporter**. A review synthesis reports a **Na+:anion coupling ratio of 3:1**, consistent with an electrogenic uptake process."
  • Substrate preference is for divalent Krebs-cycle anions, with high affinity for succinate and lower affinity for citrate, supporting the substrate-specific transporter terms.
    "Across mammalian NaDC1 orthologs, NaDC1 shows preference for **divalent Krebs-cycle anions**, with **high affinity for succinate** and generally **lower affinity for citrate**; recent work and reviews describe NaDC1 as mediating **Na+-dependent cotransport of citrate and succinate** in kidney and intestine."
  • Subcellular localization is the apical/luminal brush-border membrane of proximal tubule epithelial cells (and apical intestine), supporting apical plasma membrane as non-core localization.
    "NaDC1 localizes to the **apical/luminal (brush-border) membrane** of **proximal tubule epithelial cells** and is also discussed as apical in intestine/small intestinal villus epithelium."
  • Rat-specific renal localization places NaDC1 in the outer stripe of the outer medulla and luminal membranes of the superficial cortex proximal tubule.
    "For rat, NaDC1 is described as localizing to the **outer stripe of the outer medulla** and to **luminal membranes in the renal superficial cortex**, consistent with **proximal tubule apical/brush-border expression**."
  • Physiological role is primary apical citrate reabsorption in the proximal tubule, the pathway-level consequence of the transporter activity.
    "NaDC1 is repeatedly positioned as a **primary apical entry step for citrate reabsorption** in proximal tubule, thereby regulating how much citrate remains in urine versus being reclaimed and metabolized."
  • Mechanism is elevator-type alternating access, established by 2024 cryo-EM of human NaDC1 (SLC13A2) and applicable by orthology to the rat protein.
    "**Mechanistic paradigm (2024): elevator transport.** High-resolution cryo-EM of human NaDC1 (SLC13A2) supports an **elevator-type alternating-access mechanism**, with a relatively stable scaffold/dimerization region and a mobile transport/core domain; protomers within the dimer can occupy different conformations, implying semi-independent transport cycles."

Deep Research

Falcon

(Slc13a2-deep-research-falcon.md)
Research Report: Rat **Slc13a2 / NaDC1** (UniProt **P70545**) โ€” Functional Annotation Falcon Edison Scientific Literature 33 citations 1 artifacts 2026-06-01T02:10:03.792687
Edison artifact artifact-00 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Rat Slc13a2 / NaDC1 (UniProt P70545) โ€” Functional Annotation

0) Target verification (critical identity check)

The provided UniProt accession P70545 corresponds to Slc13a2 in Rattus norvegicus and encodes solute carrier family 13 member 2, commonly termed NaDC1 / NADCโ€‘1 / SDCT1, an apical Na+-coupled dicarboxylate (incl. citrate) cotransporter in kidney and intestine. The retrieved literature consistently equates SLC13A2/Slc13a2 with NaDC1/NADCโ€‘1 and describes the expected epithelial localization and citrate/succinate substrate class, supporting that the correct gene/protein was researched. (yang2021slc26a6andnadcโ€‘1 pages 3-5, romero2010snpsofmetabolism pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)

1) Key concepts and definitions (current understanding)

1.1 Gene family and conceptual role

Slc13a2 (NaDC1) is a member of the SLC13 / DASS (divalent anion sodium symporter) family of electrogenic sodiumโ€“anion cotransporters that couple the inward Na+ electrochemical gradient to uptake of di-/tricarboxylates (e.g., Krebs-cycle intermediates). (chi2024cryoemstructuresof pages 1-1, yang2021slc26a6andnadcโ€‘1 pages 3-5)

1.2 Transported substrates (what it transports)

Across mammalian NaDC1 orthologs, NaDC1 shows preference for divalent Krebs-cycle anions, with high affinity for succinate and generally lower affinity for citrate; recent work and reviews describe NaDC1 as mediating Na+-dependent cotransport of citrate and succinate in kidney and intestine. (yang2021slc26a6andnadcโ€‘1 pages 3-5, chi2024cryoemstructuresof pages 1-1)

1.3 Coupling and mechanism (how it transports)

NaDC1 is described as a Na+-coupled electrogenic symporter. A review synthesis reports a Na+:anion coupling ratio of 3:1, consistent with an electrogenic uptake process. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

Mechanistic paradigm (2024): elevator transport. High-resolution cryo-EM of human NaDC1 (SLC13A2) supports an elevator-type alternating-access mechanism, with a relatively stable scaffold/dimerization region and a mobile transport/core domain; protomers within the dimer can occupy different conformations, implying semi-independent transport cycles. (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 1-1)

2) Localization (tissues, cell types, and subcellular membrane domain)

2.1 Tissue distribution

NaDC1 is reported as widely expressed in kidney and gastrointestinal epithelium. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

2.2 Kidney (rat-relevant localization)

For rat, NaDC1 is described as localizing to the outer stripe of the outer medulla and to luminal membranes in the renal superficial cortex, consistent with proximal tubule apical/brush-border expression. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

2.3 Intestine

NaDC1 is discussed as an apical intestinal absorption pathway for citrate/dicarboxylates, complementing renal handling; a physiologic commentary notes that reduced gut NaDC1 activity would be expected to lower blood citrate and thus urinary citrate, although NaDC1 knockout mice reportedly have normal serum citrate, implying metabolic compensation. (romero2010snpsofmetabolism pages 1-2)

3) Core physiological functions and pathways

3.1 Proximal tubule citrate reabsorption and acidโ€“base physiology

NaDC1 is repeatedly positioned as a primary apical entry step for citrate reabsorption in proximal tubule, thereby regulating how much citrate remains in urine versus being reclaimed and metabolized. In the Osis et al. physiology framework, reabsorbed citrate can be metabolized to yield bicarbonate equivalents, linking NaDC1-mediated citrate handling to systemic acid-base balance. (osis2019regulationofrenal pages 16-19)

A review synthesis further states that a major fraction of filtered citrate is reabsorbed in proximal tubule via NaDC1 (review includes a cited quantitative statement that โ€œ>65%โ€ is reabsorbed via NADCโ€‘1; the cited figure was derived from prior animal work). (yang2021slc26a6andnadcโ€‘1 pages 3-5)

3.2 Stone biology linkage (why citrate matters)

Urinary citrate complexes Ca2+ and is widely considered protective against calcium stone formation; thus, increased citrate reabsorption via NaDC1 can contribute to hypocitraturia, a common risk factor in nephrolithiasis. One review reports ~50% of nephrolithiasis patients exhibit hypocitraturia (as a broad statistic). (yang2021slc26a6andnadcโ€‘1 pages 3-5)

4) Regulation and interaction network (what modulates NaDC1)

4.1 Acid-base and potassium regulation

A kidney physiology study synthesizes earlier work indicating chronic metabolic acidosis increases NaDCโ€‘1 mRNA and protein abundance in rat kidney, consistent with increased citrate reclamation during acid loads. (osis2019regulationofrenal pages 28-32)

Hypokalemia (modeled as a K+-free diet) decreases urinary citrate excretion and is accompanied by increased NaDC1 expression in specific proximal tubule segments in mouse, illustrating a conserved regulatory axis between K+ status and citrate handling. (osis2019regulationofrenal pages 16-19)

4.2 Segment-specific proximal tubule regulation (axial heterogeneity)

In mouse kidney, NaDC1 upregulation with acid loading and hypokalemia is emphasized in cortical proximal tubule segments (PCT and PST-MR) rather than PST-OM, suggesting spatially restricted regulatory mechanisms. (osis2019regulationofrenal pages 16-19)

4.3 NBCe1-A as an upstream regulator of NaDC1 expression and citrate excretion

Osis et al. show that deletion of NBCe1-A (a proximal-tubule basolateral Na+-HCO3โˆ’ cotransporter variant) reduces NaDC1 expression in cortical proximal tubule segments and alters urinary citrate excretion responses to acid and K+ perturbations, positioning NBCe1-A as a major regulator of the NaDC1-dependent citrate handling phenotype. (osis2019regulationofrenal pages 16-19)

4.4 Proteinโ€“protein interaction: SLC26A6โ€“NaDC1 complex

NaDC1 is functionally linked to SLC26A6, an epithelial anion exchanger important for oxalate handling. Review and primary evidence indicate that SLC26A6 and NaDC1 can mutually modulate activity, implying coordinated regulation of oxalate/citrate homeostasis. (yang2021slc26a6andnadcโ€‘1 pages 3-5, shimshilashvili2020novelhumanpolymorphisms pages 3-4)

A review synthesis also reports that IRBIT can inhibit NaDC1-mediated succinate transport by ~50% in the SLC26A6/NADCโ€‘1 complex context. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

5) Recent developments and latest research (prioritizing 2023โ€“2024)

5.1 2024 structural biology breakthrough: NaDC1 cryo-EM and allosteric inhibition

Chi et al. (published March 2024) solved cryo-EM structures of human NaDC1 (SLC13A2), capturing citrate-bound outward-facing conformations and defining detailed substrate and Na+ coordination.

Key molecular insights:
- Citrate sits in a pocket at the scaffoldโ€“core interface with two Na+ sites resolved (Na1 and Na2). (chi2024cryoemstructuresof pages 1-3)
- Residues implicated in Na+/substrate coordination and transport include Ser140, Asn141, Thr142, Thr240, Thr471, Thr474, Asn476, Ala518, and Arg108; alanine substitutions at several of these sites markedly reduce citrate-induced currents. (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 5-7)
- The work supports an elevator mechanism and identifies an unexpected peripheral/allosteric inhibitor site for N-(p-amylcinnamoyl) anthranilic acid (ACA) near the cytosolic membrane (TM2/L10/TM11/TM6a), providing a concrete framework for inhibitor design against NaDC1. (chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 1-1)

Publication details: Science Advances (2024-03). URL: https://doi.org/10.1126/sciadv.adl3685 (chi2024cryoemstructuresof pages 1-1)

5.2 2023 clinical genetics: SLC13A2 (NaDC1) polymorphism and urinary citrate

ร‡alฤฑลŸkan et al. (published October 2023) tested the association of rs11567842 (I550V) with urinary citrate in 96 calcium-stone patients, stratified into normocitraturia vs hypocitraturia groups.

Key quantitative findings:
- Normocitraturia (n=40): 773 ยฑ 301 mg/1.73 mยฒ/24 h citrate.
- Hypocitraturia (n=56): 152 ยฑ 87 mg/1.73 mยฒ/24 h citrate (p<0.001).
- Genotype frequencies (AA/AG/GG) did not differ significantly between groups (p=0.618). (calฤฑskan2023theassociationbetween pages 3-4)

The authors conclude this polymorphism does not explain hypocitraturia in their cohort, underscoring that NaDC1-linked stone risk is likely multifactorial (diet, acid-base, other genes, regulation). URL: https://doi.org/10.4274/jus.galenos.2023.2023-10-2 (calฤฑskan2023theassociationbetween pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)

6) Current applications and real-world implementations

6.1 Nephrolithiasis risk stratification and mechanistic biomarkers

Because NaDC1 is directly linked to urinary citrate handling, it is frequently discussed as a mechanistic node in hypocitraturia-associated calcium stone disease (risk stratification and mechanistic interpretation of low urinary citrate). (yang2021slc26a6andnadcโ€‘1 pages 3-5)

6.2 Tissue expression as a clinical correlate

In nephrolithiasis patients, intrarenal NaDC-1 expression categories (weak/intermediate/high by immunostaining) were associated with urine pH (inverse correlation; Spearman r = โˆ’0.516, p = 0.010), supporting the concept that acidified urinary environment or systemic acid-base state associates with higher NaDC1 expression. (chuaypen2013increasedintrarenalexpression pages 2-5)

6.3 Drug discovery and therapeutic targeting opportunities

The 2024 structural identification of an ACA inhibitor binding site and lipid-associated modulation offers a tangible structure-guided drug design foundation to modulate NaDC1 activity (conceptually: increasing urinary citrate by inhibiting apical uptake, or modulating uptake in metabolic contexts). (chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 5-7)

7) Expert opinions and analysis (authoritative synthesis)

7.1 Complexity of genotype-to-phenotype mapping

A renal physiology commentary argues that common NaDC1 allelic variants are unlikely to be sole drivers of hypocitraturia or nephrolithiasis, given compensatory metabolic citrate production and multi-step handling of citrate by intestine, kidney, and metabolism. This aligns with later clinical findings where a common NaDC1 SNP did not segregate with hypocitraturia in one cohort. (romero2010snpsofmetabolism pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)

7.2 Network view of oxalate/citrate homeostasis

A review synthesizes that NaDC1 should be interpreted within an epithelial transport network involving SLC26A6 (oxalate handling) and regulatory proteins (e.g., IRBIT), linking citrate reclamation, succinate signaling, and potentially blood pressure phenotypes in addition to stone risk. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

8) Key statistics and data (recent and/or quantitative)

8.1 Mouse renal physiology: hypokalemia and NaDC1-linked citrate excretion

Osis et al. (2019) quantify urinary citrate excretion changes:
- WT: 72 ยฑ 10.6 ยตmol/day โ†’ 3.3 ยฑ 2.4 ยตmol/day on K+-free diet (n=6; P<0.001).
- NBCe1-A KO: 96 ยฑ 21.0 ยตmol/day basal (n=6; P<0.05 vs WT) โ†’ 16.6 ยฑ 8.9 ยตmol/day on K+-free diet (n=6; P<0.001 vs K+-control).
- Percent decrease in citrate excretion: WT 95% ยฑ 3% vs KO 83% ยฑ 6% (P<0.002; n=6). (osis2019regulationofrenal pages 16-19)

URL: https://doi.org/10.1152/ajprenal.00015.2019 (osis2019regulationofrenal pages 16-19)

8.2 Human cohort: citrate values and NaDC1 SNP frequencies (2023)

As above (Section 5.2), ร‡alฤฑลŸkan et al. (2023) provide clear quantitative separation between normocitraturia and hypocitraturia in stone formers and report AA/AG/GG genotype counts for rs11567842. (calฤฑskan2023theassociationbetween pages 3-4)

8.3 Nephrolithiasis tissue study: NaDC-1 expression vs urine pH

In 24 nephrolithiasis patients, NaDC-1 expression distribution was weak 25% (6/24), intermediate 42% (10/24), high 33% (8/24), with significantly lower urine pH in the high-expression group and a significant inverse correlation (Spearman r = โˆ’0.516, p = 0.010). (chuaypen2013increasedintrarenalexpression pages 2-5)

9) Summary functional annotation (rat Slc13a2 / UniProt P70545)

Primary molecular function. Rat Slc13a2 encodes NaDC1, an apical epithelial Na+-coupled symporter for dicarboxylates (notably succinate) and citrate, supporting uptake of Krebs-cycle intermediates in kidney proximal tubule and intestine, with a commonly cited electrogenic 3 Na+:1 anion coupling ratio. (yang2021slc26a6andnadcโ€‘1 pages 3-5, chi2024cryoemstructuresof pages 1-1)

Cellular and tissue localization. In rat kidney, NaDC1 localizes to luminal/apical membranes in superficial cortex proximal tubule and to the outer stripe of the outer medulla, consistent with proximal tubule segment expression; it is also present in gastrointestinal epithelium. (yang2021slc26a6andnadcโ€‘1 pages 3-5)

Physiological role. By reclaiming filtered citrate, NaDC1 regulates urinary citrate (a key modulator of calcium stone risk) and participates in acid-base physiology through citrate metabolism to bicarbonate equivalents. (osis2019regulationofrenal pages 16-19, yang2021slc26a6andnadcโ€‘1 pages 3-5)

Regulation. Acid-base status and potassium balance modulate NaDC1 expression and citrate excretion phenotypes; NaDC1 is embedded in a regulatory network involving NBCe1-A and SLC26A6 (and in review synthesis, IRBIT), which coordinates citrate and oxalate handling relevant to nephrolithiasis. (osis2019regulationofrenal pages 28-32, osis2019regulationofrenal pages 16-19, yang2021slc26a6andnadcโ€‘1 pages 3-5)

State of the art (2024). Cryo-EM structures of NaDC1 define an elevator mechanism, pinpoint substrate/Na+ coordination residues, and reveal an allosteric inhibitor pocket (ACA), enabling structure-guided pharmacology that could be leveraged to modulate urinary citrate handling and related phenotypes. (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 1-1)

Artifact: evidence-backed summary table

Aspect Key points Species/context (rat vs human vs mouse) Key sources (with year, journal, DOI/URL)
Verified identity Rat Slc13a2 corresponds to NaDC1 / Na(+)-dicarboxylate cotransporter 1, a member of the SLC13/DASS family. Gathered evidence consistently treats SLC13A2/NaDC1/NADC-1/SDCT1 as the renal/intestinal sodium-coupled dicarboxylate transporter relevant to citrate/succinate transport; this matches the UniProt P70545 description for Rattus norvegicus. Rat identity supported by rat-localization/review evidence; human and mouse papers are orthologous context used for mechanism and physiology. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (yang2021slc26a6andnadcโ€‘1 pages 3-5, osis2019regulationofrenal pages 32-36)
Protein architecture/family NaDC1 is described as an 11-transmembrane helix transporter in the SLC13/DASS family, with intracellular N-terminus and extracellular C-terminus and conserved N-glycosylation features. Architecture summarized mainly from human-focused review, but applied to mammalian NaDC1 orthologs including rat. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385 (yang2021slc26a6andnadcโ€‘1 pages 3-5)
Main substrates Preferred substrates are divalent Krebs-cycle/dicarboxylate anions, especially succinate (high affinity), with citrate also transported but generally at lower affinity; NaDC1 is broadly discussed as mediating Na+-dependent cotransport of citrate and succinate. Rat review/localization evidence plus human structural and clinical context. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Chi et al., 2024, Science Advances, doi:10.1126/sciadv.adl3685, https://doi.org/10.1126/sciadv.adl3685; Shimshilashvili et al., 2020, Front Pharmacol, doi:10.3389/fphar.2020.00405, https://doi.org/10.3389/fphar.2020.00405 (yang2021slc26a6andnadcโ€‘1 pages 3-5, shimshilashvili2020novelhumanpolymorphisms pages 2-3, chi2024cryoemstructuresof pages 1-1)
Coupling/stoichiometry NaDC1 is an electrogenic Na+-coupled symporter. Review evidence states a 3 Na+:1 anion coupling ratio; one commentary excerpt notes 2 Na+-succinate cotransport in the context of variant discussion, so stoichiometry in the gathered evidence is not entirely uniform. The strongest explicit stoichiometric statement in the evidence base is 3:1. 3:1 ratio from review/general mammalian context; variant commentary not rat-specific. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Romero, 2010, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00432.2010, https://doi.org/10.1152/ajprenal.00432.2010 (yang2021slc26a6andnadcโ€‘1 pages 3-5, romero2010snpsofmetabolism pages 1-2)
Transport mechanism Recent structural work supports an elevator-type transport mechanism with a stable scaffold/dimerization domain and a mobile core domain. Human NaDC1 cryo-EM structures captured apo, citrate-bound, and inhibitor-bound outward-facing states; protomers can adopt different conformations, suggesting largely independent transport cycles within the dimer. Mechanism shown directly for human SLC13A2/NaDC1; relevant by homology to rat Slc13a2. Chi et al., 2024, Science Advances, doi:10.1126/sciadv.adl3685, https://doi.org/10.1126/sciadv.adl3685 (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 5-7, chi2024cryoemstructuresof pages 1-1)
Substrate/ion recognition Human NaDC1 structures place citrate in a pocket at the scaffold-core interface with two Na+ sites (Na1, Na2). Key residues implicated in transport/substrate recognition include Ser140, Asn141, Thr142, Thr240, Thr471, Thr474, Asn476, Ala518, and Arg108; mutagenesis reduced citrate-induced currents. Direct evidence from human NaDC1 structural/functional study; used here as current mechanistic understanding for the orthologous transporter family. Chi et al., 2024, Science Advances, doi:10.1126/sciadv.adl3685, https://doi.org/10.1126/sciadv.adl3685 (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 5-7)
Tissue localization NaDC1 is widely expressed in kidney and gastrointestinal epithelium. In rat, evidence places it in the outer stripe of the outer medulla and luminal membranes of the superficial renal cortex. Human clinical genetics review also notes expression in renal proximal tubule and small intestinal cells. Rat-specific localization available; human expression used as orthologous corroboration. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; ร‡alฤฑลŸkan et al., 2023, Journal of Urological Surgery, doi:10.4274/jus.galenos.2023.2023-10-2, https://doi.org/10.4274/jus.galenos.2023.2023-10-2 (yang2021slc26a6andnadcโ€‘1 pages 3-5, calฤฑskan2023theassociationbetween pages 3-4)
Subcellular localization NaDC1 localizes to the apical/luminal (brush-border) membrane of proximal tubule epithelial cells and is also discussed as apical in intestine/small intestinal villus epithelium. Rat apical kidney localization supported directly; intestinal/apical context supported by review and human study. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Romero, 2010, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00432.2010, https://doi.org/10.1152/ajprenal.00432.2010; ร‡alฤฑลŸkan et al., 2023, Journal of Urological Surgery, doi:10.4274/jus.galenos.2023.2023-10-2, https://doi.org/10.4274/jus.galenos.2023.2023-10-2 (yang2021slc26a6andnadcโ€‘1 pages 3-5, yang2021slc26a6andnadcโ€‘1 pages 2-3, romero2010snpsofmetabolism pages 1-2, calฤฑskan2023theassociationbetween pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)
Segment-specific renal expression/regulation In mouse kidney, NaDC1 expression is highest/adaptive in cortical proximal tubule segments (PCT and PST-MR), with less response in PST-OM; this demonstrates axial heterogeneity in regulation. Mouse regulation study; relevant physiological context for mammalian NaDC1, not direct rat measurement. Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (osis2019regulationofrenal pages 28-32, osis2019regulationofrenal pages 16-19)
Regulation by acid-base status Gathered evidence cites that chronic metabolic acidosis increases NaDC1 mRNA and protein abundance in rat kidney and that acid loading alters citrate transport and NaDC1 expression/activity in proximal tubule. Rat cited in review of prior literature; mouse experimental support for acid-loading response. Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (osis2019regulationofrenal pages 32-36, osis2019regulationofrenal pages 28-32, osis2019regulationofrenal pages 16-19)
Regulation by potassium status Hypokalemia / K+-free diet increases NaDC1 expression in cortical proximal tubule segments and decreases urinary citrate excretion; older literature cited in the evidence notes chronic potassium depletion stimulates the renal brush-border Na-citrate cotransporter. Direct experimental evidence in mouse; rat cited via prior literature in review/discussion. Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (osis2019regulationofrenal pages 32-36, osis2019regulationofrenal pages 28-32, osis2019regulationofrenal pages 16-19)
Key regulator: NBCe1-A NBCe1-A is necessary for normal basal and adaptive renal citrate handling; its deletion reduces NaDC1 expression in cortical proximal tubule, increases urinary citrate excretion, and blunts hypokalemia-induced NaDC1 upregulation. Demonstrated in mouse; mechanistically relevant to renal NaDC1 regulation. Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (osis2019regulationofrenal pages 32-36, osis2019regulationofrenal pages 28-32, osis2019regulationofrenal pages 16-19)
Key interacting protein: SLC26A6 NaDC1 functionally and physically interacts with SLC26A6. Evidence supports bidirectional modulation, with SLC26A6 restricting NaDC1 activity and thereby contributing to coordinated oxalate/citrate homeostasis relevant to stone risk. Mechanistic evidence primarily human/cell systems and review synthesis; kidney relevance broadly mammalian. Ohana et al., 2013, JASN, doi:10.1681/ASN.2013010080, https://doi.org/10.1681/ASN.2013010080; Shimshilashvili et al., 2020, Front Pharmacol, doi:10.3389/fphar.2020.00405, https://doi.org/10.3389/fphar.2020.00405; Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385 (yang2021slc26a6andnadcโ€‘1 pages 3-5, shimshilashvili2020novelhumanpolymorphisms pages 2-3, shimshilashvili2020novelhumanpolymorphisms pages 3-4)
Additional modulators Gathered evidence cites regulation of NaDC1 by protein kinase C, NHERF2, SGK isoforms, protein kinase B, cyclophilin B (biogenesis), and endothelin B receptor dependence for acid regulation. IRBIT inhibits NaDC1-mediated succinate transport by about 50% in the SLC26A6/NaDC1 context. Mostly prior literature summarized in mouse/human reviews rather than rat-specific direct assays in the retrieved text. Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019; Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385 (osis2019regulationofrenal pages 32-36, osis2019regulationofrenal pages 28-32, yang2021slc26a6andnadcโ€‘1 pages 3-5)
Physiological role in kidney NaDC1 is the primary renal apical citrate reabsorption pathway discussed in the evidence base, mediating a major portion of filtered citrate reclamation in proximal tubule and thereby influencing systemic acid-base handling because metabolized citrate yields bicarbonate equivalents. Rat/human/mouse physiology synthesized across studies; one review cites >65% citrate reabsorption after filtration from rabbit data. Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Osis et al., 2019, Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00015.2019, https://doi.org/10.1152/ajprenal.00015.2019 (yang2021slc26a6andnadcโ€‘1 pages 3-5, osis2019regulationofrenal pages 16-19)
Disease/clinical link: nephrolithiasis By lowering urinary citrate when reabsorption is increased, NaDC1 is linked to hypocitraturia and thus to risk of calcium oxalate/calcium-containing kidney stones, since citrate inhibits Ca2+ stone formation. Increased intrarenal NaDC1 expression has been reported in stone formers with acidic urine, and SLC26A6โ€“NaDC1 dysregulation may further increase lithogenic risk. Human disease relevance strongest; rat/mouse data mainly mechanistic. ร‡alฤฑลŸkan et al., 2023, Journal of Urological Surgery, doi:10.4274/jus.galenos.2023.2023-10-2, https://doi.org/10.4274/jus.galenos.2023.2023-10-2; Yang et al., 2021, Molecular Medicine Reports, doi:10.3892/mmr.2021.12385, https://doi.org/10.3892/mmr.2021.12385; Chi et al., 2024, Science Advances, doi:10.1126/sciadv.adl3685, https://doi.org/10.1126/sciadv.adl3685 (yang2021slc26a6andnadcโ€‘1 pages 3-5, chi2024cryoemstructuresof pages 1-1, calฤฑskan2023theassociationbetween pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)
Recent 2023 genetic study In a 2023 cohort of 96 calcium stone patients, urinary citrate differed markedly between normocitraturic and hypocitraturic groups, but rs11567842 (I550V) genotype frequencies did not differ significantly; this study concluded that this SNP alone did not explain hypocitraturia. Human clinical genetics; useful for disease relevance but not direct rat annotation. ร‡alฤฑลŸkan et al., 2023, Journal of Urological Surgery, doi:10.4274/jus.galenos.2023.2023-10-2, https://doi.org/10.4274/jus.galenos.2023.2023-10-2 (calฤฑskan2023theassociationbetween pages 1-2, calฤฑskan2023theassociationbetween pages 3-4)
Recent 2024 structural advance 2024 cryo-EM work is the key recent advance: it resolved human NaDC1 with citrate-bound and ACA inhibitor-bound states, identified an allosteric/peripheral inhibitor site near the cytosolic membrane, and provided a framework for future drug design targeting NaDC1. Human structural biology; strong mechanistic relevance for rat ortholog inference. Chi et al., 2024, Science Advances, doi:10.1126/sciadv.adl3685, https://doi.org/10.1126/sciadv.adl3685 (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 3-5, chi2024cryoemstructuresof pages 5-7, chi2024cryoemstructuresof pages 1-1)

Table: This table summarizes the verified identity, transport properties, localization, regulation, and physiological relevance of rat Slc13a2/NaDC1 using only claims supported by the gathered evidence. It also distinguishes rat-specific observations from human and mouse ortholog evidence used to interpret current functional annotation.

Limitations of this evidence set

  • The strongest mechanistic/structural insights are from human NaDC1; their applicability to rat Slc13a2 is inferred by orthology and shared family architecture rather than shown directly in rat structures. (chi2024cryoemstructuresof pages 1-3, chi2024cryoemstructuresof pages 1-1)
  • The retrieved evidence includes limited rat-primary mechanistic measurements (e.g., rat-specific kinetics), and several classic rat transport/regulatory findings are cited within Osis et al. rather than directly extracted as standalone primary papers in this run. (osis2019regulationofrenal pages 28-32)

References

  1. (yang2021slc26a6andnadcโ€‘1 pages 3-5): Xingyue Yang, Shun Yao, Jiaxing An, Hai Jin, Hui Wang, and Biguang Tuo. Slc26a6 and nadcโ€‘1: future direction of nephrolithiasis and calculusโ€‘related hypertension research (review). Molecular medicine reports, Nov 2021. URL: https://doi.org/10.3892/mmr.2021.12385, doi:10.3892/mmr.2021.12385. This article has 7 citations and is from a peer-reviewed journal.

  2. (romero2010snpsofmetabolism pages 1-2): Michael F. Romero. Snps of metabolism, not stones. American journal of physiology. Renal physiology, 299 4:F702-3, Oct 2010. URL: https://doi.org/10.1152/ajprenal.00432.2010, doi:10.1152/ajprenal.00432.2010. This article has 2 citations.

  3. (calฤฑskan2023theassociationbetween pages 3-4): Ahmet ร‡alฤฑลŸkan, ร–mรผr Memik, Selma Dรผzenli, and Ali Tekin. The association between sodium citrate cotransporter (nadc-1) gene polymorphism and urinary citrate excretion in patients with calcium-containing kidney stone. Journal of Urological Surgery, Oct 2023. URL: https://doi.org/10.4274/jus.galenos.2023.2023-10-2, doi:10.4274/jus.galenos.2023.2023-10-2. This article has 1 citations.

  4. (chi2024cryoemstructuresof pages 1-1): Ximin Chi, Yiming Chen, Yaning Li, Lu Dai, Yuanyuan Zhang, Yaping Shen, Yun Chen, Tianhao Shi, Haonan Yang, Zilong Wang, and Renhong Yan. Cryo-em structures of the human nas1 and nadc1 transporters revealed the elevator transport and allosteric regulation mechanism. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adl3685, doi:10.1126/sciadv.adl3685. This article has 13 citations and is from a highest quality peer-reviewed journal.

  5. (chi2024cryoemstructuresof pages 1-3): Ximin Chi, Yiming Chen, Yaning Li, Lu Dai, Yuanyuan Zhang, Yaping Shen, Yun Chen, Tianhao Shi, Haonan Yang, Zilong Wang, and Renhong Yan. Cryo-em structures of the human nas1 and nadc1 transporters revealed the elevator transport and allosteric regulation mechanism. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adl3685, doi:10.1126/sciadv.adl3685. This article has 13 citations and is from a highest quality peer-reviewed journal.

  6. (osis2019regulationofrenal pages 16-19): Gunars Osis, Kierstin L. Webster, Autumn N. Harris, Hyun-Wook Lee, Chao Chen, Lijuan Fang, Michael F. Romero, Ram B. Khattri, Matthew E. Merritt, Jill W. Verlander, and I. David Weiner. Regulation of renal nadc1 expression and citrate excretion by nbce1-a. American Journal of Physiology-Renal Physiology, 317:F489-F501, Aug 2019. URL: https://doi.org/10.1152/ajprenal.00015.2019, doi:10.1152/ajprenal.00015.2019. This article has 27 citations and is from a peer-reviewed journal.

  7. (osis2019regulationofrenal pages 28-32): Gunars Osis, Kierstin L. Webster, Autumn N. Harris, Hyun-Wook Lee, Chao Chen, Lijuan Fang, Michael F. Romero, Ram B. Khattri, Matthew E. Merritt, Jill W. Verlander, and I. David Weiner. Regulation of renal nadc1 expression and citrate excretion by nbce1-a. American Journal of Physiology-Renal Physiology, 317:F489-F501, Aug 2019. URL: https://doi.org/10.1152/ajprenal.00015.2019, doi:10.1152/ajprenal.00015.2019. This article has 27 citations and is from a peer-reviewed journal.

  8. (shimshilashvili2020novelhumanpolymorphisms pages 3-4): Liana Shimshilashvili, Sara Aharon, Orson W. Moe, and Ehud Ohana. Novel human polymorphisms define a key role for the slc26a6-stas domain in protection from ca2+-oxalate lithogenesis. Frontiers in Pharmacology, Apr 2020. URL: https://doi.org/10.3389/fphar.2020.00405, doi:10.3389/fphar.2020.00405. This article has 14 citations.

  9. (chi2024cryoemstructuresof pages 5-7): Ximin Chi, Yiming Chen, Yaning Li, Lu Dai, Yuanyuan Zhang, Yaping Shen, Yun Chen, Tianhao Shi, Haonan Yang, Zilong Wang, and Renhong Yan. Cryo-em structures of the human nas1 and nadc1 transporters revealed the elevator transport and allosteric regulation mechanism. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adl3685, doi:10.1126/sciadv.adl3685. This article has 13 citations and is from a highest quality peer-reviewed journal.

  10. (chi2024cryoemstructuresof pages 3-5): Ximin Chi, Yiming Chen, Yaning Li, Lu Dai, Yuanyuan Zhang, Yaping Shen, Yun Chen, Tianhao Shi, Haonan Yang, Zilong Wang, and Renhong Yan. Cryo-em structures of the human nas1 and nadc1 transporters revealed the elevator transport and allosteric regulation mechanism. Science Advances, Mar 2024. URL: https://doi.org/10.1126/sciadv.adl3685, doi:10.1126/sciadv.adl3685. This article has 13 citations and is from a highest quality peer-reviewed journal.

  11. (calฤฑskan2023theassociationbetween pages 1-2): Ahmet ร‡alฤฑลŸkan, ร–mรผr Memik, Selma Dรผzenli, and Ali Tekin. The association between sodium citrate cotransporter (nadc-1) gene polymorphism and urinary citrate excretion in patients with calcium-containing kidney stone. Journal of Urological Surgery, Oct 2023. URL: https://doi.org/10.4274/jus.galenos.2023.2023-10-2, doi:10.4274/jus.galenos.2023.2023-10-2. This article has 1 citations.

  12. (chuaypen2013increasedintrarenalexpression pages 2-5): N. Chuaypen, C. Boonla, T. Dissayabutra, C. Predanon, P. Ruangvejvorachai, Uraiwan Waiwijit, and P. Tosukhowong. Increased intrarenal expression of sodium-dicarboxylate cotransporter-1 in nephrolithiasis patients with acidic urine ph. Asian Biomedicine, 7:571-577, Aug 2013. URL: https://doi.org/10.5372/1905-7415.0704.214, doi:10.5372/1905-7415.0704.214. This article has 7 citations.

  13. (osis2019regulationofrenal pages 32-36): Gunars Osis, Kierstin L. Webster, Autumn N. Harris, Hyun-Wook Lee, Chao Chen, Lijuan Fang, Michael F. Romero, Ram B. Khattri, Matthew E. Merritt, Jill W. Verlander, and I. David Weiner. Regulation of renal nadc1 expression and citrate excretion by nbce1-a. American Journal of Physiology-Renal Physiology, 317:F489-F501, Aug 2019. URL: https://doi.org/10.1152/ajprenal.00015.2019, doi:10.1152/ajprenal.00015.2019. This article has 27 citations and is from a peer-reviewed journal.

  14. (shimshilashvili2020novelhumanpolymorphisms pages 2-3): Liana Shimshilashvili, Sara Aharon, Orson W. Moe, and Ehud Ohana. Novel human polymorphisms define a key role for the slc26a6-stas domain in protection from ca2+-oxalate lithogenesis. Frontiers in Pharmacology, Apr 2020. URL: https://doi.org/10.3389/fphar.2020.00405, doi:10.3389/fphar.2020.00405. This article has 14 citations.

  15. (yang2021slc26a6andnadcโ€‘1 pages 2-3): Xingyue Yang, Shun Yao, Jiaxing An, Hai Jin, Hui Wang, and Biguang Tuo. Slc26a6 and nadcโ€‘1: future direction of nephrolithiasis and calculusโ€‘related hypertension research (review). Molecular medicine reports, Nov 2021. URL: https://doi.org/10.3892/mmr.2021.12385, doi:10.3892/mmr.2021.12385. This article has 7 citations and is from a peer-reviewed journal.

Artifacts

Citations

  1. romero2010snpsofmetabolism pages 1-2
  2. osis2019regulationofrenal pages 16-19
  3. osis2019regulationofrenal pages 28-32
  4. chi2024cryoemstructuresof pages 1-3
  5. chi2024cryoemstructuresof pages 1-1
  6. calฤฑskan2023theassociationbetween pages 3-4
  7. chuaypen2013increasedintrarenalexpression pages 2-5
  8. shimshilashvili2020novelhumanpolymorphisms pages 3-4
  9. chi2024cryoemstructuresof pages 5-7
  10. chi2024cryoemstructuresof pages 3-5
  11. calฤฑskan2023theassociationbetween pages 1-2
  12. osis2019regulationofrenal pages 32-36
  13. shimshilashvili2020novelhumanpolymorphisms pages 2-3
  14. https://doi.org/10.1126/sciadv.adl3685
  15. https://doi.org/10.4274/jus.galenos.2023.2023-10-2
  16. https://doi.org/10.1152/ajprenal.00015.2019
  17. https://doi.org/10.3892/mmr.2021.12385;
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  19. https://doi.org/10.1126/sciadv.adl3685;
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  28. https://doi.org/10.1152/ajprenal.00432.2010,
  29. https://doi.org/10.4274/jus.galenos.2023.2023-10-2,
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๐Ÿ“„ View Raw YAML

 
id: P70545
gene_symbol: Slc13a2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10116
  label: Rattus norvegicus
description: 'Slc13a2 encodes the apical low-affinity sodium/dicarboxylate cotransporter NaDC-1, transporting citric-acid-cycle
  dicarboxylates such as succinate, citrate, fumarate, and alpha-ketoglutarate with sodium. The review accepts substrate-specific
  transporter and transport terms, keeps membrane localization as non-core, and marks lithium response as assay-context
  activity regulation rather than a gene response process.'
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the 
      defining core function (IBA, GO_REF:0000033).
    action: KEEP_AS_NON_CORE
    reason: This term records supported membrane or apical plasma-membrane localization rather than the 
      defining transport activity.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015138
    label: fumarate transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015139
    label: alpha-ketoglutarate transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches
      the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015141
    label: succinate transmembrane transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015741
    label: fumarate transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role 
      or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015742
    label: alpha-ketoglutarate transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0017153
    label: sodium:dicarboxylate symporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented
      core molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate,
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    - reference_id: file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
      supporting_text: |-
        NaDC1 is described as a **Na+-coupled electrogenic symporter**. A review synthesis reports a **Na+:anion coupling ratio of 3:1**, consistent with an electrogenic uptake process.
      reference_section_type: OTHER
- term:
    id: GO:0071285
    label: cellular response to lithium ion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports 
      the gene's core activity or context, not this broader process claim (IBA, GO_REF:0000033).
    action: MARK_AS_OVER_ANNOTATED
    reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate 
      transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as 
      an over-annotation of transport-assay conditions.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0071422
    label: succinate transmembrane transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IBA, GO_REF:0000033).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015370
    label: solute:sodium symporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: solute:sodium symporter activity captures part of Slc13a2 biology, but a more specific or 
      better-aspected GO term should replace it (IEA, GO_REF:0000117).
    action: MODIFY
    reason: The generic transporter or transport term should be replaced with the specific 
      sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    proposed_replacement_terms:
    - id: GO:0017153
      label: sodium:dicarboxylate symporter activity
- term:
    id: GO:0015746
    label: citrate transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: citrate transport is retained for Slc13a2 because it matches the documented core molecular role
      or a direct pathway consequence (IEA, GO_REF:0000108).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate,
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    - reference_id: file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
      supporting_text: |-
        NaDC1 is repeatedly positioned as a **primary apical entry step for citrate reabsorption** in proximal tubule, thereby regulating how much citrate remains in urine versus being reclaimed and metabolized.
      reference_section_type: OTHER
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: membrane is retained for Slc13a2 as supported contextual biology, but it is not the defining core
      function (IEA, GO_REF:0000002).
    action: KEEP_AS_NON_CORE
    reason: This term records supported membrane or apical plasma-membrane localization rather than the 
      defining transport activity.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the
      defining core function (IEA, GO_REF:0000120).
    action: KEEP_AS_NON_CORE
    reason: This term records supported membrane or apical plasma-membrane localization rather than the
      defining transport activity.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    - reference_id: file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
      supporting_text: |-
        NaDC1 localizes to the **apical/luminal (brush-border) membrane** of **proximal tubule epithelial cells** and is also discussed as apical in intestine/small intestinal villus epithelium.
      reference_section_type: OTHER
- term:
    id: GO:0022857
    label: transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: transmembrane transporter activity captures part of Slc13a2 biology, but a more specific or 
      better-aspected GO term should replace it (IEA, GO_REF:0000002).
    action: MODIFY
    reason: The generic transporter or transport term should be replaced with the specific 
      sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    proposed_replacement_terms:
    - id: GO:0017153
      label: sodium:dicarboxylate symporter activity
- term:
    id: GO:0035725
    label: sodium ion transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: sodium ion transmembrane transport is retained for Slc13a2 because it matches the documented core
      molecular role or a direct pathway consequence (IEA, GO_REF:0000108).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0055085
    label: transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: transmembrane transport captures part of Slc13a2 biology, but a more specific or better-aspected 
      GO term should replace it (IEA, GO_REF:0000002).
    action: MODIFY
    reason: The generic transporter or transport term should be replaced with the specific 
      sodium:dicarboxylate symporter activity or substrate-specific dicarboxylate transport processes.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
    proposed_replacement_terms:
    - id: GO:0071422
      label: succinate transmembrane transport
    - id: GO:0015741
      label: fumarate transport
    - id: GO:0015742
      label: alpha-ketoglutarate transport
    - id: GO:0015746
      label: citrate transport
- term:
    id: GO:0015137
    label: citrate transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: citrate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015138
    label: fumarate transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015139
    label: alpha-ketoglutarate transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches
      the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015141
    label: succinate transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015741
    label: fumarate transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role 
      or a direct pathway consequence (IEA, GO_REF:0000107).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015742
    label: alpha-ketoglutarate transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IEA, GO_REF:0000107).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0017153
    label: sodium:dicarboxylate symporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented
      core molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0071285
    label: cellular response to lithium ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports 
      the gene's core activity or context, not this broader process claim (IEA, GO_REF:0000107).
    action: MARK_AS_OVER_ANNOTATED
    reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate 
      transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as 
      an over-annotation of transport-assay conditions.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0071422
    label: succinate transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IEA, GO_REF:0000120).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015137
    label: citrate transmembrane transporter activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: citrate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the
      defining core function (ISO, GO_REF:0000121).
    action: KEEP_AS_NON_CORE
    reason: This term records supported membrane or apical plasma-membrane localization rather than the 
      defining transport activity.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015138
    label: fumarate transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
- term:
    id: GO:0015139
    label: alpha-ketoglutarate transmembrane transporter activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches
      the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015139
    label: alpha-ketoglutarate transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: alpha-ketoglutarate transmembrane transporter activity is retained for Slc13a2 because it matches
      the documented core molecular role or a direct pathway consequence (IDA, PMID:9691021).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
- term:
    id: GO:0015141
    label: succinate transmembrane transporter activity
  evidence_type: IDA
  original_reference_id: PMID:9694847
  review:
    summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (IDA, PMID:9694847).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0015741
    label: fumarate transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role 
      or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015741
    label: fumarate transport
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: fumarate transport is retained for Slc13a2 because it matches the documented core molecular role 
      or a direct pathway consequence (IDA, PMID:9691021).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
- term:
    id: GO:0015742
    label: alpha-ketoglutarate transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015742
    label: alpha-ketoglutarate transport
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: alpha-ketoglutarate transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IDA, PMID:9691021).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: apical plasma membrane is retained for Slc13a2 as supported contextual biology, but it is not the
      defining core function (IDA, PMID:9691021).
    action: KEEP_AS_NON_CORE
    reason: This term records supported membrane or apical plasma-membrane localization rather than the 
      defining transport activity.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
- term:
    id: GO:0017153
    label: sodium:dicarboxylate symporter activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented
      core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0017153
    label: sodium:dicarboxylate symporter activity
  evidence_type: IDA
  original_reference_id: PMID:9694847
  review:
    summary: sodium:dicarboxylate symporter activity is retained for Slc13a2 because it matches the documented
      core molecular role or a direct pathway consequence (IDA, PMID:9694847).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0071285
    label: cellular response to lithium ion
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports 
      the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121).
    action: MARK_AS_OVER_ANNOTATED
    reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate 
      transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as 
      an over-annotation of transport-assay conditions.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0071285
    label: cellular response to lithium ion
  evidence_type: IDA
  original_reference_id: PMID:9691021
  review:
    summary: cellular response to lithium ion is marked as over-annotated for Slc13a2; the evidence supports 
      the gene's core activity or context, not this broader process claim (IDA, PMID:9691021).
    action: MARK_AS_OVER_ANNOTATED
    reason: Lithium is an assay-context cation competitor/inhibitor for Slc13a2-mediated dicarboxylate 
      transport, not evidence that Slc13a2 mediates a cellular response to lithium ion. Treat the GOA row as 
      an over-annotation of transport-assay conditions.
    supported_by:
    - reference_id: PMID:9691021
      supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate
        transporter.
      reference_section_type: TITLE
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0071422
    label: succinate transmembrane transport
  evidence_type: IDA
  original_reference_id: PMID:9694847
  review:
    summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (IDA, PMID:9694847).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: PMID:9694847
      supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
      reference_section_type: TITLE
- term:
    id: GO:0015138
    label: fumarate transmembrane transporter activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: fumarate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0015141
    label: succinate transmembrane transporter activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: succinate transmembrane transporter activity is retained for Slc13a2 because it matches the 
      documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
- term:
    id: GO:0071422
    label: succinate transmembrane transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000121
  review:
    summary: succinate transmembrane transport is retained for Slc13a2 because it matches the documented core 
      molecular role or a direct pathway consequence (ISO, GO_REF:0000121).
    action: ACCEPT
    reason: This term is directly supported by Slc13a2 sodium-coupled dicarboxylate transport of succinate, 
      citrate, fumarate, and alpha-ketoglutarate.
    supported_by:
    - reference_id: UniProtKB:P70545
      supporting_text: 'FUNCTION: Low-affinity sodium-dicarboxylate cotransporter that mediates entry of succinate,
        citrate, fumarate and alpha-ketoglutarate into small intestine and renal proximal tubule; probable stoichiometry
        of 3 Na(+) for 1 divalent dicarboxylate.'
references:
- id: GO_REF:0000002
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000033
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000107
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000108
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000117
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000120
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: GO_REF:0000121
  title: 'GO reference used by source annotation pipeline'
  findings:
  - statement: Source annotation pipeline provenance; biological support was assessed from UniProt and cached 
      literature where available.
    supporting_text: GO_REF entry used to trace source annotation method rather than as primary biological 
      evidence.
    reference_section_type: TITLE
- id: PMID:9691021
  title: 'Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate transporter.'
  findings:
  - statement: Rat Slc13a2/rNaDC-1 mediates sodium-dependent uptake of dicarboxylates and localizes to the 
      apical/luminal membrane.
    supporting_text: Cloning, functional characterization, and localization of a rat renal Na+-dicarboxylate 
      transporter.
    reference_section_type: TITLE
- id: PMID:9694847
  title: 'Characterization of a rat Na+-dicarboxylate cotransporter.'
  findings:
  - statement: Rat SDCT1/Slc13a2 mediates electrogenic sodium-dependent transport of Krebs-cycle
      intermediates.
    supporting_text: Characterization of a rat Na+-dicarboxylate cotransporter.
    reference_section_type: TITLE
- id: file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
  title: 'Falcon (Edison Scientific) deep research report: rat Slc13a2 / NaDC1 (UniProt P70545) functional annotation'
  findings:
  - statement: Identity and core molecular function confirmed as an apical Na+-coupled dicarboxylate/citrate
      cotransporter (NaDC1) in kidney and intestine, matching UniProt P70545.
    supporting_text: |-
      The provided UniProt accession **P70545** corresponds to **Slc13a2** in **Rattus norvegicus** and encodes **solute carrier family 13 member 2**, commonly termed **NaDC1 / NADCโ€‘1 / SDCT1**, an apical **Na+-coupled dicarboxylate (incl. citrate) cotransporter** in kidney and intestine.
    reference_section_type: OTHER
  - statement: NaDC1 is an electrogenic Na+-coupled symporter with a commonly cited 3 Na+:1 anion coupling
      ratio, supporting the sodium:dicarboxylate symporter molecular function.
    supporting_text: |-
      NaDC1 is described as a **Na+-coupled electrogenic symporter**. A review synthesis reports a **Na+:anion coupling ratio of 3:1**, consistent with an electrogenic uptake process.
    reference_section_type: OTHER
  - statement: Substrate preference is for divalent Krebs-cycle anions, with high affinity for succinate and
      lower affinity for citrate, supporting the substrate-specific transporter terms.
    supporting_text: |-
      Across mammalian NaDC1 orthologs, NaDC1 shows preference for **divalent Krebs-cycle anions**, with **high affinity for succinate** and generally **lower affinity for citrate**; recent work and reviews describe NaDC1 as mediating **Na+-dependent cotransport of citrate and succinate** in kidney and intestine.
    reference_section_type: OTHER
  - statement: Subcellular localization is the apical/luminal brush-border membrane of proximal tubule
      epithelial cells (and apical intestine), supporting apical plasma membrane as non-core localization.
    supporting_text: |-
      NaDC1 localizes to the **apical/luminal (brush-border) membrane** of **proximal tubule epithelial cells** and is also discussed as apical in intestine/small intestinal villus epithelium.
    reference_section_type: OTHER
  - statement: Rat-specific renal localization places NaDC1 in the outer stripe of the outer medulla and
      luminal membranes of the superficial cortex proximal tubule.
    supporting_text: |-
      For rat, NaDC1 is described as localizing to the **outer stripe of the outer medulla** and to **luminal membranes in the renal superficial cortex**, consistent with **proximal tubule apical/brush-border expression**.
    reference_section_type: OTHER
  - statement: Physiological role is primary apical citrate reabsorption in the proximal tubule, the
      pathway-level consequence of the transporter activity.
    supporting_text: |-
      NaDC1 is repeatedly positioned as a **primary apical entry step for citrate reabsorption** in proximal tubule, thereby regulating how much citrate remains in urine versus being reclaimed and metabolized.
    reference_section_type: OTHER
  - statement: Mechanism is elevator-type alternating access, established by 2024 cryo-EM of human NaDC1
      (SLC13A2) and applicable by orthology to the rat protein.
    supporting_text: |-
      **Mechanistic paradigm (2024): elevator transport.** High-resolution cryo-EM of human NaDC1 (SLC13A2) supports an **elevator-type alternating-access mechanism**, with a relatively stable scaffold/dimerization region and a mobile transport/core domain; protomers within the dimer can occupy different conformations, implying semi-independent transport cycles.
    reference_section_type: OTHER
core_functions:
- description: Slc13a2 is an apical sodium:dicarboxylate symporter for succinate, citrate, fumarate, and 
    alpha-ketoglutarate.
  supported_by:
  - reference_id: UniProtKB:P70545
    supporting_text: Mediates entry of succinate, citrate, fumarate and alpha-ketoglutarate; transports
      dicarboxylate with probable 3 Na(+) stoichiometry.
  - reference_id: file:rat/Slc13a2/Slc13a2-deep-research-falcon.md
    supporting_text: |-
      Across mammalian NaDC1 orthologs, NaDC1 shows preference for **divalent Krebs-cycle anions**, with **high affinity for succinate** and generally **lower affinity for citrate**; recent work and reviews describe NaDC1 as mediating **Na+-dependent cotransport of citrate and succinate** in kidney and intestine.
    reference_section_type: OTHER
  molecular_function:
    id: GO:0017153
    label: sodium:dicarboxylate symporter activity
  directly_involved_in:
  - id: GO:0071422
    label: succinate transmembrane transport
  - id: GO:0015741
    label: fumarate transport
  - id: GO:0015742
    label: alpha-ketoglutarate transport
  - id: GO:0015746
    label: citrate transport
  substrates:
  - id: CHEBI:30031
    label: succinate
  - id: CHEBI:30769
    label: citrate
  - id: CHEBI:29806
    label: fumarate
  - id: CHEBI:16810
    label: 2-oxoglutarate
  - id: CHEBI:29101
    label: sodium(1+)
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []