The renal Na(+)-dicarboxylate cotransporter reabsorbs Krebs cycle intermediates, such as succinate and citrate, from the glomerular filtrate. The present study describes the cloning and characterization of the human renal Na(+)-dicarboxylate cotransporter, hNaDC-1. The amino acid sequence of hNaDC-1 is 78% identical to the rabbit renal Na(+)-dicarboxylate cotransporter, NaDC-1, and 42% identical to the rat renal Na(+)-sulfate transporter, NaSi-1. The carboxy terminus of hNaDC-1 protein contains two N-glycosylation sites that appear to be utilized. Xenopus oocytes injected with hNaDC-1 cRNA expressed a low-affinity Na(+)-dependent dicarboxylate transporter with Michaelis constant (Km) for succinate around 0.4 mM. The transport of succinate by hNaDC-1 was insensitive to the pH of the medium, whereas the transporter of citrate was stimulated by acidic pH. Northern blot analysis indicates that hNaDC-1 mRNA is found in both kidney and intestine. The gene for hNaDC-1 was localized to chromosome 17. This study provides the first demonstration that the human kidney contains a low-affinity Na(+)-dicarboxylate cotransporter with properties that resemble those of the Na(+)-dicarboxylate cotransporter on the apical membrane of the rabbit renal proximal tubule.

>sp|Q13183|S13A2_HUMAN Solute carrier family 13 member 2 OS=Homo sapiens GN=SLC13A2 PE=2 SV=1
MATCWQALWAYRSYLIVFFVPILLLPLPILVPSKEAYCAYAIILMALFWCTEALPLAVTALFPLILFPMMGIVDASEVAV
EYLKDSNLLFFGGLLVAIAVEHWNLHKRIALRVLLIVGVRPAPLILGFMLVTAFLSMWISNTATSAMMVPIAHAVLDQLH
SSQASSNVEEGSNNPTFELQEPSPQKEVTKLDNGQALPVTSASSEGRAHLSQKHLHLTQCMSLCVCYSASIGGIATLTGT
APNLVLQGQINSLFPQNGNVVNFASWFSFAFPTMVILLLLAWLWLQILFLGFNFRKNFGIGEKMQEQQQAAYCVIQTEHR
LLGPMTFAEKAISILFVILVLLWFTREPGFFLGWGNLAFPNAKGESMVSDGTVAIFIGIIMFIIPSKFPGLTQDPENPGK
LKAPLGLLDWKTVNQKMPWNIVLLLGGGYALAKGSERSGLSEWLGNKLTPLQSVPAPAIAIILSLLVATFTECTSNVATT
TIFLPILASMAQAICLHPLYVMLPCTLATSLAFMLPVATPPNAIVFSFGDLKVLDMARAGFLLNIIGVLIIALAINSWGI
PLFSLHSFPSWAQSNTTAQCLPSLANTTTPSP