SLC4A1

The protein encoded by this gene is part of the anion exchanger (AE) family and is expressed in the erythrocyte plasma membrane, where it functions as a chloride/bicarbonate exchanger involved in carbon dioxide transport from tissues to lungs. The protein comprises two domains that are structurally and functionally distinct. The N-terminal 40kDa domain is located in the cytoplasm and acts as an attachment site for the red cell skeleton by binding ankyrin. The glycosylated C-terminal membrane-associated domain contains 12-14 membrane spanning segments and carries out the stilbene disulphonate-sensitive exchange transport of anions. The cytoplasmic tail at the extreme C-terminus of the membrane domain binds carbonic anhydrase II. The encoded protein associates with the red cell membrane protein glycophorin A and this association promotes the correct folding and translocation of the exchanger. This protein is predominantly dimeric but forms tetramers in the presence of ankyrin. Many mutations in this gene are known in man, and these mutations can lead to two types of disease: destabilization of red cell membrane leading to hereditary spherocytosis, and defective kidney acid secretion leading to distal renal tubular acidosis. Other mutations that do not give rise to disease result in novel blood group antigens, which form the Diego blood group system. Southeast Asian ovalocytosis (SAO, Melanesian ovalocytosis) results from the heterozygous presence of a deletion in the encoded protein and is common in areas where Plasmodium falciparum malaria is endemic. One null mutation in this gene is known, resulting in very severe anemia and nephrocalcinosis.

solute carrier family 4

Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Major integral membrane glycoprotein of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine.
(Microbial infection) Acts as a receptor for P.falciparum (isolate 3D7) MSP9 and thus, facilitates merozoite invasion of erythrocytes.

Biological Process anion transportManual Assertion Based On ExperimentTAS:ProtInc
Biological Process bicarbonate transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process blood coagulationIEA:Ensembl
Biological Process cellular ion homeostasisManual Assertion Based On ExperimentTAS:ProtInc
Biological Process chloride transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process chloride transportISS:UniProtKB
Biological Process erythrocyte developmentIEA:Ensembl
Biological Process ion homeostasisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of glycolytic process through fructose-6-phosphateIEA:Ensembl
Biological Process negative regulation of oxidoreductase activityIEA:Ensembl
Biological Process negative regulation of urine volumeIEA:Ensembl
Biological Process pH elevationIEA:Ensembl
Biological Process plasma membrane phospholipid scramblingIEA:Ensembl
Biological Process protein localization to plasma membraneIEA:Ensembl
Biological Process regulation of intracellular pHManual Assertion Based On ExperimentIBA:GO_Central
Biological Process transmembrane transportManual Assertion Based On ExperimentIBA:GO_Central

Cell membrane
Basolateral cell membrane
Detected in the erythrocyte cell membrane and on the basolateral membrane of alpha-intercalated cells in the collecting duct in the kidney.

Ovalocytosis, Southeast Asian (SAO):
A hereditary hematologic disorder characterized by ovalocytic erythrocytes that are rigid and exhibit reduced expression of many erythrocyte antigens. Clinical manifestations include mild hemolysis, intermittent jaundice and gallstones. However, the disorder is most often asymptomatic.
Spherocytosis 4 (SPH4):
Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.
Renal tubular acidosis, distal, 1 (DRTA1):
An autosomal dominant disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Renal tubular acidosis, distal, 4, with hemolytic anemia (DRTA4):
An autosomal recessive disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
Renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC):
A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. It is due to functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification.
Cryohydrocytosis (CHC):
An autosomal dominant disorder of red cell membrane permeability characterized by cold-induced changes in cell volume, resulting in cold-sensitive stomatocytosis, and increased erythrocyte osmotic fragility and autohemolysis at 4 degrees Celsius. Patients present with mild to moderate hemolytic anemia, splenomegaly, fatigue, and pseudohyperkalemia due to a potassium leak from the erythrocytes.

Phosphorylated on Tyr-8 and Tyr-21 most likely by SYK. PP1-resistant phosphorylation that precedes Tyr-359 and Tyr-904 phosphorylation.
Phosphorylated on Tyr-359 and Tyr-904 most likely by LYN. PP1-inhibited phosphorylation that follows Tyr-8 and Tyr-21 phosphorylation.
N-glycosylated.