SLC4A4
Function
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.
Involvement in disease
Proximal renal tubular acidosis-ocular anomaly syndrome
PRTAO
An extremely rare autosomal recessive syndrome characterized by short stature, profound proximal renal tubular acidosis, intellectual disability, bilateral glaucoma, cataracts and bandkeratopathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).
Post-translational modifications
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 (PubMed:11744745, PubMed:12411514, PubMed:12730338). Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity (By similarity).
N-glycosylated. May not be necessary for the transporter basic functions.
Sequence Similarities
Belongs to the anion exchanger (TC 2.A.31) family.
Tissue Specificity
Isoform 1
Expressed in the corneal endothelium cells (at protein level). Expressed in pancreas and to a lower extent in heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain and spinal chord.
Isoform 2
Specifically expressed in kidney at the level of proximal tubules.
Cellular localization
- Basolateral cell membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
Alternative names
NBC, NBC1, NBCE1, SLC4A4, Electrogenic sodium bicarbonate cotransporter 1, Sodium bicarbonate cotransporter, Na(+)/HCO3(-) cotransporter, Solute carrier family 4 member 4, kNBC1