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MGP003645

UniProt Annotations

Entry Information
Gene Namesolute carrier family 4 (sodium bicarbonate cotransporter), member 4
Protein EntryS4A4_HUMAN
UniProt IDQ9Y6R1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Name=1; Synonyms=hcNBC, hhNBC, hNBC1, pNBC, pNCB1, pNBC-1, NBC1b; IsoId=Q9Y6R1-1; Sequence=Displayed; Name=2; Synonyms=hkNBC, hkNBCe1, kNBC, kNBC1, kNBC-1, NBC1a; IsoId=Q9Y6R1-2; Sequence=VSP_016704, VSP_016705; Name=3; IsoId=Q9Y6R1-3; Sequence=VSP_016704, VSP_016705, VSP_016706, VSP_016707; Name=4; IsoId=Q9Y6R1-4; Sequence=VSP_016708; Name=5; IsoId=Q9Y6R1-5; Sequence=VSP_041003;
DiseaseNote=Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).
DiseaseRenal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA) [MIM:604278]: An extremely rare autosomal recessive syndrome characterized by short stature, profound proximal renal tubular acidosis, mental retardation, bilateral glaucoma, cataracts and bandkeratopathy. pRTA is due to a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. {ECO:0000269|PubMed:10545938, ECO:0000269|PubMed:15471865, ECO:0000269|PubMed:15713912, ECO:0000269|PubMed:15930088, ECO:0000269|PubMed:16636648, ECO:0000269|PubMed:17661077}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationInhibited by stilbene derivatives and regulated by cyclic AMP.
FunctionElectrogenic 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. {ECO:0000269|PubMed:10069984, ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:16636648, ECO:0000269|PubMed:17661077, ECO:0000269|PubMed:9235899, ECO:0000269|PubMed:9651366}.
InteractionP48283:CA4 (xeno); NbExp=2; IntAct=EBI-6859278, EBI-6859264;
PtmN-glycosylation is not necessary for the transporter basic functions. {ECO:0000269|PubMed:12604466}.
PtmPhosphorylation 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. {ECO:0000269|PubMed:11744745, ECO:0000269|PubMed:12730338}.
SimilarityBelongs to the anion exchanger (TC 2.A.31) family. {ECO:0000305}.
Subcellular LocationBasolateral cell membrane {ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:15273250, ECO:0000269|PubMed:16636648, ECO:0000269|PubMed:17661077}; Multi- pass membrane protein {ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:15273250}.
SubunitInteracts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. {ECO:0000269|PubMed:12411514, ECO:0000269|PubMed:14567693, ECO:0000269|PubMed:15218065, ECO:0000269|PubMed:15563508}.
Tissue SpecificityIsoform 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. {ECO:0000269|PubMed:10069984, ECO:0000269|PubMed:11743927, ECO:0000269|PubMed:12907161, ECO:0000269|PubMed:14559244, ECO:0000269|PubMed:15329059, ECO:0000269|PubMed:9235899, ECO:0000269|PubMed:9651366}.
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