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 / NADC‑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."