Solute carrier family 4 sodium bicarbonate cotransporter member 4
Solute carrier family 4 sodium bicarbonate cotransporter member 5
Solute carrier family 4, sodium bicarbonate cotransporter, member 4, brain type
Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.
Isoform 1 is expressed in pancreas and to a lower extent in heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain and spinal chord. Corneal endothelium cells express only isoform 1 (at protein level). Isoform 2 is specifically expressed in kidney at the level of proximal tubules.
Involvement in disease
Defects in SLC4A4 are the cause of proximal renal tubular acidosis with ocular abnormalities (pRTA-OA) [MIM:604278]; also known as renal tubular acidosis II. Caused by an impairment of bicarbonate absorption in the proximal tubule, proximal renal tubular acidosis (pRTA) is characterized by a decreased renal HCO3(-) threshold. pRTA-OA is an extremely rare autosomal recessive syndrome characterized by short stature, profound pRTA, mental retardation, bilateral glaucoma, cataracts and bandkeratopathy. Note=Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).
Belongs to the anion exchanger (TC 2.A.31) family.
Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1. Phosphorylation of Thr-49 regulates isoform 1 conductance. N-glycosylation is not necessary for the transporter basic functions.