Solute Carrier Family 4, Anion Exchanger, Member 1 (SLC4A1) Antibody – Rabbit Polyclonal

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. [provided by RefSeq, Jul 2008]

SLC4A1: Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4). EL4 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape. Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4); also known as hereditary spherocytosis type 4 (HS4). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA). A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA). A 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. Defects in SLC4A1 are the cause of 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. Belongs to the anion exchanger (TC 2.A.31) family.

Protein type: Transporter; Membrane protein, integral; Membrane protein, multi-pass; Transporter, SLC family

Chromosomal Location of Human Ortholog: 17q21.31

Cellular Component: cortical cytoskeleton; basolateral plasma membrane; integral to plasma membrane; plasma membrane; integral to membrane; Z disc

Molecular Function: protein C-terminus binding; bicarbonate transmembrane transporter activity; protein binding; protein homodimerization activity; protein anchor; chloride transmembrane transporter activity; inorganic anion exchanger activity; anion:anion antiporter activity; anion transmembrane transporter activity; ankyrin binding; actin binding

Biological Process: bicarbonate transport; cellular ion homeostasis; regulation of intracellular pH; chloride transport; ion transport; transmembrane transport; anion transport

Disease: Blood Group--swann System; Blood Group--froese; Renal Tubular Acidosis, Distal, Autosomal Dominant; Blood Group--wright Antigen; Renal Tubular Acidosis, Distal, With Hemolytic Anemia; Spherocytosis, Type 4; Blood Group--diego System; Malaria, Susceptibility To; Blood Group--waldner Type