Human Gene SLC4A1 (ENST00000262418.12) from GENCODE V44
Description: Homo sapiens solute carrier family 4 member 1 (Diego blood group) (SLC4A1), mRNA. (from RefSeq NM_000342) RefSeq Summary (NM_000342): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because no single transcript was available for the full length of the gene. The extent of this transcript is supported by transcript alignments and published data. Gencode Transcript: ENST00000262418.12 Gencode Gene: ENSG00000004939.16 Transcript (Including UTRs) Position: hg38 chr17:44,248,390-44,268,135 Size: 19,746 Total Exon Count: 20 Strand: - Coding Region Position: hg38 chr17:44,250,458-44,262,866 Size: 12,409 Coding Exon Count: 19
ID:B3AT_HUMAN DESCRIPTION: RecName: Full=Band 3 anion transport protein; AltName: Full=Anion exchange protein 1; Short=AE 1; Short=Anion exchanger 1; AltName: Full=Solute carrier family 4 member 1; AltName: CD_antigen=CD233; FUNCTION: 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. ENZYME REGULATION: Phenyl isothiocyanate inhibits anion transport in vitro. SUBUNIT: A dimer in solution, it spans the membrane asymmetrically and appears to be tetrameric. Interacts (via cytoplasmic N- terminus domain) with ANK1 (via N-terminus ANK repeats). SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Erythrocytes. PTM: Phosphorylated on Tyr-8 and Tyr-21 most likely by SYK. PP1- resistant phosphorylation that precedes Tyr-359 and Tyr-904 phosphorylation. PTM: Phosphorylated on Tyr-359 and Tyr-904 most likely by LYN. PP1-inhibited phosphorylation that follows Tyr-8 and Tyr-21 phosphorylation. POLYMORPHISM: SLC4A1 is responsible for the Diego blood group system. The molecular basis of the Di(a)=Di1/Di(b)/Di2 blood group antigens is a single variation in position 854; Leu-854 corresponds to Di(a) and Pro-854 to Di(b). The molecular basis of the Wr(a)=Di3/Wr(b)/Di4 blood group antigens is a single variation in position 658; Lys-658 corresponds to Wr(a) and Glu-658 to Wr(b). The blood group antigens Wd(a)=Di5 (Waldner-type) has Met- 557; Rb(a)=Di6 has Leu-548 and WARR=Di7 has Ile-552. POLYMORPHISM: SLC4A1 is responsible for the Swann blood group system (SW) [MIM:601550]. Sw(a+) has a Gln or a Trp at position 646 and Sw(a-) has an Arg. POLYMORPHISM: SLC4A1 is responsible for the Froese blood group system (FR) [MIM:601551]. FR(a+) has a Lys at position 480 and FR(a-) has a Glu. POLYMORPHISM: Genetic variations in SLC4A1 are involved in resistance to malaria [MIM:611162]. DISEASE: Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:109270]. 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. DISEASE: Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:612653]; 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. DISEASE: Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA) [MIM:179800]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. DISEASE: Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA) [MIM:611590]. 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. DISEASE: Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC) [MIM:611590]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family. WEB RESOURCE: Name=Wikipedia; Note=Band 3 entry; URL="http://en.wikipedia.org/wiki/Band_3"; WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation database; URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=diego"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC4A1"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/slc4a1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P02730
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
X77737 - H.sapiens mRNA for red cell anion exchanger (EPB3, AE1, Band 3) 3' non-coding region. JD063043 - Sequence 44067 from Patent EP1572962. JD413541 - Sequence 394565 from Patent EP1572962. JD198210 - Sequence 179234 from Patent EP1572962. JD212827 - Sequence 193851 from Patent EP1572962. JD542837 - Sequence 523861 from Patent EP1572962. JD413540 - Sequence 394564 from Patent EP1572962. JD542836 - Sequence 523860 from Patent EP1572962. JD542835 - Sequence 523859 from Patent EP1572962. JD497759 - Sequence 478783 from Patent EP1572962. JD045808 - Sequence 26832 from Patent EP1572962. M27819 - Human anion exchange protein 1 (AE1, band 3) mRNA, complete cds. JD044162 - Sequence 25186 from Patent EP1572962. JD387463 - Sequence 368487 from Patent EP1572962. JD555158 - Sequence 536182 from Patent EP1572962. JD287016 - Sequence 268040 from Patent EP1572962. JD187703 - Sequence 168727 from Patent EP1572962. JD535643 - Sequence 516667 from Patent EP1572962. JD059348 - Sequence 40372 from Patent EP1572962. X12609 - H.sapiens mRNA for red cell anion exchanger (EPB3, AE1, Band3). JD195997 - Sequence 177021 from Patent EP1572962. JD038985 - Sequence 20009 from Patent EP1572962. JD382949 - Sequence 363973 from Patent EP1572962. JD532367 - Sequence 513391 from Patent EP1572962. BC096106 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:116751 IMAGE:40001948), complete cds. BC096107 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:116752 IMAGE:40001951), complete cds. BC099628 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:116750 IMAGE:40001946), complete cds. BC099629 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:116753 IMAGE:40001953), complete cds. GQ981383 - Homo sapiens clone N369AE4 anion exchanger-1 variant mRNA, complete cds, alternatively spliced. GQ981384 - Homo sapiens clone N406AE12 anion exchanger-1 variant mRNA, complete cds, alternatively spliced. GQ981386 - Homo sapiens clone N374AE10 anion exchanger-1 variant mRNA, complete cds, alternatively spliced. GQ981387 - Homo sapiens clone N374AE4 anion exchanger-1 variant mRNA, complete cds, alternatively spliced. GQ981385 - Homo sapiens clone N374AE8 anion exchanger-1 variant mRNA, complete cds, alternatively spliced. JD225213 - Sequence 206237 from Patent EP1572962. JD144834 - Sequence 125858 from Patent EP1572962. JD075675 - Sequence 56699 from Patent EP1572962. JD132049 - Sequence 113073 from Patent EP1572962. JD452028 - Sequence 433052 from Patent EP1572962. JD355949 - Sequence 336973 from Patent EP1572962. DQ419529 - Homo sapiens solute carrier family 4 anion exchanger member 1 variant (SLC4A1) mRNA, complete cds. BC101570 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:126619 IMAGE:8069076), complete cds. BC101574 - Homo sapiens solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group), mRNA (cDNA clone MGC:126623 IMAGE:8069080), complete cds. JD388621 - Sequence 369645 from Patent EP1572962. AB526447 - Homo sapiens SLC4A1 mRNA for solute carrier family 4, anion exchanger, member 1, complete cds. KJ897565 - Synthetic construct Homo sapiens clone ccsbBroadEn_06959 SLC4A1 gene, encodes complete protein. KR711955 - Synthetic construct Homo sapiens clone CCSBHm_00032899 SLC4A1 (SLC4A1) mRNA, encodes complete protein. KR711956 - Synthetic construct Homo sapiens clone CCSBHm_00032912 SLC4A1 (SLC4A1) mRNA, encodes complete protein. KR711957 - Synthetic construct Homo sapiens clone CCSBHm_00032936 SLC4A1 (SLC4A1) mRNA, encodes complete protein. KR711958 - Synthetic construct Homo sapiens clone CCSBHm_00032948 SLC4A1 (SLC4A1) mRNA, encodes complete protein. AB590578 - Synthetic construct DNA, clone: pFN21AE0697, Homo sapiens SLC4A1 gene for solute carrier family 4, anion exchanger, member 1, without stop codon, in Flexi system. AB527862 - Synthetic construct DNA, clone: pF1KB8562, Homo sapiens SLC4A1 gene for solute carrier family 4, anion exchanger, member 1, without stop codon, in Flexi system. AM919470 - Homo sapiens partial mRNA for partial solute carrier family 4, anion exchanger, number 1 (AE1 gene), allele AE1 E522K mutation as band 3 Kaohsiung. LQ980389 - Sequence 35 from Patent WO2013050532. LQ980456 - Sequence 102 from Patent WO2013050532. LQ980431 - Sequence 77 from Patent WO2013050532. S68680 - Homo sapiens anion exchanger 1 (AE1) mRNA, partial cds. JD106465 - Sequence 87489 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04966 - Collecting duct acid secretion
Reactome (by CSHL, EBI, and GO)
Protein P02730 (Reactome details) participates in the following event(s):
R-HSA-1237038 SLC4A1 exchanges cytosolic HCO3- for extracellular Cl- R-HSA-1247665 Band 3 Anion Exchanger (AE1, SLC4A1) exchanges cytosolic chloride for extracellular bicarbonate R-HSA-425482 SLC4A1,2,3 exchanges HCO3- for Cl- R-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen R-HSA-1247673 Erythrocytes take up oxygen and release carbon dioxide R-HSA-425381 Bicarbonate transporters R-HSA-1480926 O2/CO2 exchange in erythrocytes R-HSA-425393 Metabolism of nitrogenous molecules R-HSA-382551 Transport of small molecules R-HSA-425407 SLC-mediated transmembrane transport