SLC13A3 Membrane Protein Introduction

Introduction of SLC13A3

Solute carrier family 13 member 3 (SLC13A3), also known as sodium-dependent dicarboxylate transporter (NaDC3), is a protein that in humans is encoded by the SLC13A3 gene. Mammalian sodium-dicarboxylate cotransporters transport succinate and other Krebs cycle intermediates. They fall into 2 categories based on their substrate affinity: low affinity and high affinity. Both the low- and high-affinity transporters play an important role in the handling of citrate by the kidneys. The protein encoded by this gene represents the high-affinity form. Spliced transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some has not been characterized yet.

Basic Information of SLC13A3
Protein Name	Solute carrier family 13 member 3
Gene Name	SLC13A3
Aliases	Na(+)/dicarboxylate cotransporter 3(NaDC-3), Sodium-dependent high-affinity dicarboxylate transporter 2
Organism	Homo sapiens (Human)
UniProt ID	Q8WWT9
Transmembrane Times	12
Length (aa)	602
Sequence	MAALAAAAKKVWSARRLLVLLFTPLALLPVVFALPPKEGRCLFVILLMAVYWCTEALPLSVTALLPIVLFPFMGILPSNKVCPQYFLDTNFLFLSGLIMASAIEEWNLHRRIALKILMLVGVQPARLILGMMVTTSFLSMWLSNTASTAMMLPIANAILKSLFGQKEVRKDPSQESEENTAAVRRNGLHTVPTEMQFLASTEAKDHPGETEVPLDLPADSRKEDEYRRNIWKGFLISIPYSASIGGTATLTGTAPNLILLGQLKSFFPQCDVVNFGSWFIFAFPLMLLFLLAGWLWISFLYGGLSFRGWRKNKSEIRTNAEDRARAVIREEYQNLGPIKFAEQAVFILFCMFAILLFTRDPKFIPGWASLFNPGFLSDAVTGVAIVTILFFFPSQRPSLKWWFDFKAPNTETEPLLTWKKAQETVPWNIILLLGGGFAMAKGCEESGLSVWIGGQLHPLENVPPALAVLLITVVIAFFTEFASNTATIIIFLPVLAELAIRLRVHPLYLMIPGTVGCSFAFMLPVSTPPNSIAFASGHLLVKDMVRTGLLMNLMGVLLLSLAMNTWAQTIFQLGTFPDWADMYSVNVTALPPTLANDTFRTL

Function of SLC13A3 Membrane Protein

SLC13A3 is widely found in human. It is a high-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-5 carbon atoms. The stoichiometry is probably 3 Na⁺ for 1 divalent succinate. It functions in many molecular processes, including citrate transmembrane transporter activity, high-affinity sodium (dicarboxylate symporter activity) and succinate transmembrane transporter activity.

Fig.1 Schema for the metabolism of citrate in a proximal tubule cell. (Dogliotti, 2013)

Application of SLC13A3 Membrane Protein in Literature

Strungaru M.H., et al. PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3. Invest Ophthalmol Vis Sci. 2011, 52(10):7625-33. PubMed ID: 21873665

The results indicate that SLC13A3 is a direct downstream target of PITX2 transcriptional regulation and that levels of PITX2 and SLC13A3 modulate responses to oxidative stress in ocular cells.
Hennig M., et al. SLC13A3 as a functional biomarker and determinant of racial discrepancies in renal cell carcinoma. European Urology Supplements. 2018, 17(2):e123.

This article shows that SLC13A3 loss promotes RCC growth, survival and inhibits cellular senescence and its downregulation correlates with metastasis and racial disparity.
Walter M.A., et al. Involvement of Pitx2 in ocular cellular stress response through regulation of SLC13A3. Investigative Ophthalmology & Visual Science. 2011, 52(76).

These results indicate that SLC13A3 is a direct downstream target of PITX2 and suggest for the first time that PITX2, through SLC13A3, is involved in ocular oxidative stress pathway.
Walter M.A., et al. The sodium-dependent dicarboxylate transporter 3 gene (SLC13A3) is a potential downstream target of the axenfeld-rieger PITX2 transcription factor. Investigative Ophthalmology & Visual Science. 2008, 49(13).

This article indicates that SLC13A3 is a potential direct downstream target of PITX2. Interestingly, SLC13A3 is localized on chromosome 20q12, at the same locus as the related transporter SLC4A11, this locus is also a good candidate not only for ARS, but also for glaucoma.
Strungaru M.H., et al. The axenfeld-rieger PITX2 transcription factor directly regulates the expression of solute carrier family 13 sodium-dependent dicarboxylate transporter member 3 (SLC13A3). Investigative Ophthalmology & Visual Science. 2009, 50(13).

These results indicate that SLC13A3 is a direct downstream target of PITX2. Moreover, SLC13A3 is involved in transporting glutathione, a known defense mechanism molecule against reactive oxygen species.

SLC13A3 Preparation Options

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Reference

Dogliotti E, et al. (2013). Nutrition in calcium nephrolithiasis. J Transl Med. 11(1), 1-4.

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