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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:44,248,390-44,268,135)mRNA (may differ from genome)Protein (911 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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/";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: SLC4A1
Diseases sorted by gene-association score: renal tubular acidosis, distal, ad* (1671), renal tubular acidosis, distal, ar* (1650), cryohydrocytosis* (1588), spherocytosis, type 4* (1200), ovalocytosis, sa type* (975), slc4a1-related spherocytosis* (500), pseudohyperkalemia, familial, 2, due to red cell leak* (283), hereditary spherocytosis* (228), hemolytic anemia due to band 3 montefiore* (100), renal tubular acidosis, distal (42), renal tubular acidosis (36), nephrocalcinosis (26), blood group incompatibility (21), hereditary elliptocytosis (18), hemolytic anemia (16), vulvar leiomyoma (15), respiratory failure (13), renal tubular acidosis, distal, autosomal recessive (12), malaria (11), kernicterus (11), de quervain disease (11), splenic artery aneurysm (11), vulvar benign neoplasm (11), enterocele (11), prolapse of female genital organ (11), metabolic acidosis (10), rift valley fever (9), chronic laryngitis (8), facial hemiatrophy (7), sleep disorder (6), pyruvate kinase deficiency (6), anemia of prematurity (4), leukocoria (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.85 RPKM in Whole Blood
Total median expression: 34.69 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -54.30150-0.362 Picture PostScript Text
3' UTR -778.602068-0.376 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001717 - Anion_exchange
IPR002977 - Anion_exchange_1
IPR018241 - Anion_exchange_CS
IPR011531 - HCO3_transpt_C
IPR013769 - HCO3_transpt_cyt
IPR003020 - HCO3_transpt_euk
IPR016152 - PTrfase/Anion_transptr

Pfam Domains:
PF07565 - Band 3 cytoplasmic domain
PF00955 - HCO3- transporter family

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1BH7 - NMR MuPIT 1BNX - NMR 1BTQ - NMR 1BTR - NMR MuPIT 1BTS - NMR MuPIT 1BTT - NMR MuPIT 1BZK - NMR 1HYN - X-ray MuPIT 2BTA - NMR MuPIT 2BTB - NMR MuPIT 3BTB - NMR MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologGenome Browser
Gene Details    Gene Details
Gene Sorter    Gene Sorter
MGIRGD   SGD
Protein SequenceProtein Sequence   Protein Sequence
AlignmentAlignment   Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005452 inorganic anion exchanger activity
GO:0005515 protein binding
GO:0008509 anion transmembrane transporter activity
GO:0008510 sodium:bicarbonate symporter activity
GO:0015106 bicarbonate transmembrane transporter activity
GO:0015108 chloride transmembrane transporter activity
GO:0015301 anion:anion antiporter activity
GO:0030506 ankyrin binding
GO:0042803 protein homodimerization activity
GO:0043495 protein anchor

Biological Process:
GO:0006811 ion transport
GO:0006820 anion transport
GO:0006821 chloride transport
GO:0006873 cellular ion homeostasis
GO:0015701 bicarbonate transport
GO:0051453 regulation of intracellular pH
GO:0098656 anion transmembrane transport
GO:1902476 chloride transmembrane transport

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0030018 Z disc
GO:0030863 cortical cytoskeleton
GO:0070062 extracellular exosome
GO:0072562 blood microparticle


-  Descriptions from all associated GenBank mRNAs
  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

-  Other Names for This Gene
  Alternate Gene Symbols: AE1, B3AT_HUMAN, DI, ENST00000262418.1, ENST00000262418.10, ENST00000262418.11, ENST00000262418.2, ENST00000262418.3, ENST00000262418.4, ENST00000262418.5, ENST00000262418.6, ENST00000262418.7, ENST00000262418.8, ENST00000262418.9, EPB3, NM_000342, P02730, P78487, Q1ZZ45, Q4KKW9, Q4VB84, Q9UCY7, Q9UDJ1, uc002igf.1, uc002igf.2, uc002igf.3, uc002igf.4, uc002igf.5, uc002igf.6, uc002igf.7
UCSC ID: ENST00000262418.12
RefSeq Accession: NM_000342
Protein: P02730 (aka B3AT_HUMAN)
CCDS: CCDS11481.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SLC4A1:
hered-drta (Hereditary Distal Renal Tubular Acidosis)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.