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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.
Gene References into Functions
Molecular mechanism for the red blood cell senescence clock mediated by the SLC4A1 structural changes has been summarized. (Review) PMID: 29240292
we show that stomatin modulates the transport activity of AE1 through a direct protein-protein interaction. PMID: 28387307
SLC4A1 is the most common defective gene in Korean children with Distal Renal Tubular Acidosis. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA. PMID: 29627839
this study shows functional importance of PDLIM5 for proper kAE1 membrane residency, as a crucial linker between kidney AE1 and actin cytoskeleton-associated proteins in polarized cells PMID: 28045035
The patient was triply homozygous for the loss-of-function mutation, c.2102G>A (p.Gly701Asp) as well as for two benign variations, c.92T>C (p.Met31Thr) and c.166A>C (p.Lys56Glu). PMID: 29573245
The promoter regions of the kidney anion exchanger 1 gene with the minor allele A at rs999716 downstream of the TATA box showed reduced promoter activities compared that with the major allele G. PMID: 27767102
Here, we present the 4.1-A resolution crystal structure of Arabidopsis thaliana Bor1. The structure displays a dimeric architecture in which dimerization is mediated by centralized Gate domains. Comparisons with a structure of Band 3 in an outward-open state reveal that the Core domains of Bor1 have rotated inwards to achieve an occluded state. PMID: 27601653
function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO2/HCO3(-) exchange PMID: 28596233
Results from zero-length chemical crosslinking of erythrocyte membranes, homology modeling, and known domain structures allow to deduce a structure for full-length of SLC4A1. Interaction between AE1 dimers and ankyrin-1 indicate the likely topology for AE1 tetramers and suggest that ankyrin-1 wraps around AE1 tetramers, which may stabilize this oligomer state. PMID: 27989623
The aim of this work was to analyze the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and to assess the clinical phenotype of distal renal tubular acidosis patients that are eventually typical of the different genetic forms of the disease. PMID: 28233610
These results suggested the possible involvement of Band3 in the transport of Sphingosine 1-phosphate, a multi-functional bioactive phospholipid, from erythrocytes. PMID: 28494002
the results of the present study suggest that the diffuse expression of AE1 is related to a worse prognosis in patients with advanced esophageal squamous cell carcinoma, and that it regulates tumor progression by affecting MAPK and Hedgehog signaling pathways. These results provide an insight into the role of AE1 as a mediator of and/or a biomarker for esophageal squamous cell carcinoma. PMID: 28160546
study reports the R589H mutation in SLC4A1 gene in families with hereditary distal renal tubular acidosis for the first time in China PMID: 28407820
Forced FOG1 protein expression in K562 erythroleukemia cells induced the expression of SLC4A1 protein, but repressed that of transcription factor PU.1. PMID: 28216155
Nonsense mutation in exon 12 of SLC4A1 gene is associated with severe hemolytic anemia, dyserythropoiesis and complete distal renal tubular acidosis. PMID: 27718309
While weak interactions between glycophorin and band 3 undoubtedly exist, glycophorin A and band 3 must have separate interactions in the membrane that control their lateral mobility. PMID: 27580023
three merozoite proteins (PvTRAg36, PvATRAg74, and PvTRAg38) of this family interact with Band 3 on human erythrocytes through its three exofacial loops. PMID: 27545606
with exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients, the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates. PMID: 27984639
We propose that, in polarized renal epithelial cells, the apically mistargeted kAE1 R901X mutant is endocytosed faster than kAE1 WT and its recycling to the basolateral membrane is delayed. This resets the equilibrium, such that kAE1 R901X resides predominantly in an endomembrane compartment, thereby likely participating in development of dRTA disease. PMID: 26984737
The conformational dynamics of signal-anchor transmembrane segment 1 of SLC4A1 protein of the Southeast Asian ovalocytosis red blood cells has been reported. PMID: 28068080
Data indicate that the interaction of Zn(2+) ion with His-651 residue of band 3 plays an important role in the Zn(2+)-induced agglutination of erythrocytes. PMID: 26859120
Syk inhibitor suppressed the phosphorylation of band 3 also preventing serine phosphorylation changes and hemolysis. PMID: 27034738
The evolutionary origin of Southeast Asian Ovalocytosis, characterizing DNA sequence variation around the causal mutation in the SLC4A1 gene. PMID: 26047685
This study is considered as a pilot study showing the importance of AE1 mutations in Iranian children with DRTA. PMID: 25957428
The authors demonstrate that the initial vacuolar membrane around internalized Babesia divergens is formed from protein and lipid components of the red blood cells plasma membrane, including band 3, glycophorin A and spectrin. PMID: 25628009
this study reports the crystal structure of the band 3 anion exchanger domain (AE1(CTD)) at 3.5 angstroms. PMID: 26542571
Deficiency in Band 3 is associated with Hereditary Spherocytosis. PMID: 25344524
Results indicate that Tryptophan residues play differential roles in AE1 expression and function depending on their location in the protein and that Trp mutants with low expression are misfolded and retained in the endoplasmic reticulum. PMID: 25257781
Kidney AE1 actually associates with epithelial ankyrin-G and renal ammonium transporter RhBG, which also binds ankyrin-G. PMID: 25616663
Activities of AE1 and the sodium pump are coregulated in kidney. PMID: 25012180
The study reports the refinement for a protein heterodimer complex using limited EPR spectroscopic data and a rigid-body docking algorithm: a three-dimensional model for an ankyrin 1-BND3 complex. PMID: 24758720
Partial pyruvate kinase deficiency aggravates the phenotypic expression of band 3 deficiency in a family with hereditary spherocytosis. PMID: 25388786
kidney AE1 G701D mutant which accumulates predominantly in the Golgi and partially in the endoplasmic reticulum, is prematurely degraded by the lysosome and the proteasome. PMID: 24920676
In 12% of our thalassemia major patients, we found two bands in the agarose gel-electrophoresis of PCR products from band 3 gene with a difference of 65 +/- 10 bp, equivalent to a deletion of 20 to 25 amino acids in band 3 protein. PMID: 24964668
Stopped-flow led to measurement of rapid transport kinetics using the natural substrate for AE1. PMID: 23842529
A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters. PMID: 24121512
SLC4A1 gene was a poor candidate for screening as our patients presented severe metabolic acidosis early in life. PMID: 24252324
analysis of anion exchanger 1 (SLC4A1) transmembrane segments that form the transport site PMID: 23846695
A heterozygous SLC4A1(E508K) mutation (gene encoding erythrocyte membrane protein band 3) was found. PMID: 23878048
Trafficking of intracellularly retained distal renal tubular acidosis kAE1 mutants can be partially restored. PMID: 23460825
Study developed a three-dimensional homology model of the AE1 membrane domain, using the Escherichia coli ClC channel structure as a template and conclude that AE1 has a similar protein fold to ClC chloride channels. PMID: 23583773
description of 15 previously unknown mutations in SLC4A1 in hereditary spherocytosis patients; this genetic association study was conducted in the Netherlands [LETTER] PMID: 23255290
The level of band 3 protein was positively correlated with physical activity and negatively correlated with systolic blood pressure. PMID: 21695904
Deoxygenation of erythrocytes results in displacement of ankyrin from band 3 in the cytoskeleton. PMID: 23013433
Results suggest that mutations in this gene cause morphological changes in erythrocytes and these may afford some protection against malaria PMID: 22919024
Residues 63-73 of cdB3 is also essential for ankyrin binding. PMID: 22861190
1st report of distal renal tubular acidosis patients with compound heterozygous conditions in mainland China. 2 novel SLC4A1 mutations (G494S & D905dup) were identified. PMID: 22609520
There is evidence that Southeast Asian ovalocytosis (SAO) erythrocytes are resistant to multiple Plasmodium species. Here we analyze SLC4A1 in 23 primates and mammals to test for differential selective pressures among different primate lineages. PMID: 22426110