Anti-SLC4A4 (NBC1) (extracellular) Antibody

SLC4 membrane transporter proteins play important roles in kidney acid–base regulation through their transport of bicarbonate (or carbonate), Na‏⁺, Cl^-, and (possibly NH4⁺)¹. These transporters differ in their substrate (Na⁺‏, Cl^-) dependence, charge transport stoichiometry, cell-type and developmental expression, functional regulation, and protein–protein interactions. In mammals, SLC4 proteins are encoded by 10 different genes that share protein sequence homology and are grouped according to their functional properties.

In humans, the electrogenic sodium bicarbonate cotransporter NBCe1 is encoded by the SLC4A4 gene². NBCe1-A has a large N-terminal cytoplasmic region, a lipid embedded transmembrane region, and a C-terminal cytoplasmic tail³. The N-terminal cytoplasmic region is tightly folded and is predicted to form a domain structure, unlike the freely aqueous accessible C-terminal cytoplasmic tail. NBCe1-A is composed of either 10 or 14 transmembrane domains. Based on the 10 transmembrane topology, a large extracellular loop (EL) is present between TM3 and TM4 and contains two glycosylated sites. The oligomeric state of the cotransporter is dimeric and each monomeric subunit has independent transport activity⁴.

Mutations in NBCe1 cause autosomal recessive proximal renal tubular acidosis (pRTA). Patients with NBCe1 mutations have severe pRTA, growth and mental retardation, basal ganglia calcification, cataracts, corneal opacities (band keratopathy), glaucoma, elevated serum amylase and lipase, and defects in the enamel consistent with amelogenesis imperfect³. Mice with loss of NBCe1 have a more severe phenotype with marked volume deletion and decreased survival⁵.