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solute carrier family 4 member 4; electrogenic sodium bicarbonate cotransporter 1; sodium bicarbonate cotransporter; Na+/HCO3- cotransporter (SLC4A4, kNBC1, NBC, NBC1, NBCE1)

Electrogenic Na+/HCO3- cotransporter with stoichiometry varying from 1:2 to 1:3. May regulate HCO3- influx/efflux at basolateral membrane of cells & regulate intracellular pH. Defects in SLC4A4 are the cause of renal tubular acidosis 2. Function: - electrogenic Na+/bicarbonate cotransporter with stoichiometry varying from 1:2 to 1:3. - may regulate bicarbonate influx/efflux at basolateral membrane, thus regulate intracellular pH - interaction with carbonic anhydrase 2 & carbonic anhydrase 4 may regulate transporter activity - inhibited by stilbene derivatives - regulated by cyclic AMP - phosphorylation of Ser-1026 by PKA increases the binding of carbonic anhydrase 2 & changes the Na+:HCO3- stoichiometry of the transporter from 3:1 to 2:1 - phosphorylation of Thr-49 regulates isoform 1 conductance Structure: - N-glycosylation is not necessary for transporter basic functions - belongs to the anion exchanger (TC 2.A.31) family Compartment: basolateral cell membrane Alternative splicing: named isoforms=4 Expression: - isoform 1 is expressed in pancreas > heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain & spinal cord - corneal endothelium cells express only isoform 1 (at protein level) - isoform 2 is specifically expressed in proximal tubules of the kidney Pathology: - defects in SLC4A4 are the cause of renal tubular acidosis 2 - loss of interaction & stimulation by carbonic anhydrase 4 is the cause of retinitis pigmentosa 17

Related

renal tubular acidosis (RTA) type II (proximal RTA)

General

glycoprotein human longevity protein phosphoprotein solute carrier family 4 (SLC4, SLC4A) transmembrane 10 protein

Properties

SIZE: MW = 121 kD entity length = 1079 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-468} MOTIF: Tyr phosphorylation site {Y30} Thr phosphorylation site {T49} FOR-PHOSPHORYLATION-BY: protein kinase A Thr phosphorylation site {T254} Ser phosphorylation site {S255} Ser phosphorylation site {S257} Ser phosphorylation site {S262} transmembrane domain {469-488} exoplasmic loop {489-504} transmembrane domain {505-526} cytoplasmic loop {527-554} transmembrane domain {555-580} exoplasmic loop {581-691} MOTIF: N-glycosylation site {N641} N-glycosylation site {N661} transmembrane domain {692-710} cytoplasmic loop {711-725} transmembrane domain {726-748} exoplasmic loop {749-777} MOTIF: binding site SITE: 748-779 FOR-BINDING-OF: carbonic anhydrase-4 transmembrane domain {778-797} cytoplasmic loop {798-822} transmembrane domain {823-847} exoplasmic loop {848-881} transmembrane domain {882-901} cytoplasmic loop {902-949} transmembrane domain {950-967} exoplasmic loop {968-970} transmembrane domain {971-986} cytoplasmic domain {987-1079} MOTIF: binding site SITE: 1002-1004 FOR-BINDING-OF: carbonic anhydrase-2 lysine-rich region {1009-1024} MOTIF: lysine residue (SEVERAL) Ser phosphorylation site {S1026} FOR-PHOSPHORYLATION-BY: protein kinase A binding site SITE: 1030-1033 FOR-BINDING-OF: carbonic anhydrase-2 basolateral targeting. {1057-1059}

Database Correlations

OMIM correlations MORBIDMAP 603345 UniProt Q9Y6R1 PFAM correlations Entrez Gene 8671 Kegg hsa:8671

References

  1. UniProt :accession Q9Y6R1
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC4A4