SLC4A1 (solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group))

2010-09-01   Guo-Hui Fu 

Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai, P R China




Atlas Image
A. SLC4A1 chromosome 17: bp 42325753-42345509, strand+ (UCSC). B. SLC4A1 genomic DNA (20 exons). C. Transcripts.


SLC4A1 is a gene that spans 19.757 kb of genomic DNA on the long arm of chromosome 17, in the telomere-to-centromere orientation. The gene consists of twenty exons of which the first exon is non-coding. The start codon is located at the beginning of exon 2 and the stop codon in the beginning of exon 20.


The SLC4A1 mRNA is 4.953 kb long. In the Ensembl database, its mRNA is 4.965 kb long. Compared with NCBI database, the beginning additional bases are GCTGTCA; the stop bases are GTGGC. However the coding sequences of them are the same. There are also five other transcripts: 419 bp, 1922 bp and 460 bp, that encode no protein, and 393 bp 462 bp, that encode other proteins.


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The C-terminal structure of AE1.


911 amino acids; 95 kDa.
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A. SDS-PAGE of erythrocyte membrane protein. B. Schematic diagram of membrane skeleton proteins.


Anion exchanger protein 1 (AE1), is a classical cell membrane transporter, also called band 3, that participates in the regulation of intracellular pH and ion homeostasis in vivo by transmembrane Cl-/HCO3- exchange. The C-terminal region of AE1 directly interacts with tumor suppressor p16, and then, it sequestrates p16 protein in the cytoplasm and causes gastric cancer. The transmembrane of AE2 interfered with AE1. They can form heterodimers. AE2 was degradated through ubiquitination by APC in the cytoplasm. Clinical data analysis showed that abnormal expression of AE1 with p16 is correlated with occurrence and development of gastric cancer.
Atlas Image
The model of erythrocyte Cl-/HCO3- exchange.


Anion exchanger.


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Point mutations in promoter of AE1 gene were detected in AE1 positive gastric and colon cancer cells.


These mutations were only detected in cancer, not in normal cells.

Implicated in

Entity name
Gastric and colon cancer
Gastric cancer is the most common gastrointestinal cancer; it has a high incidence area in China. In China, multiple gastric cancers patients were more than 40 years old; during all of the gastric cancers, two-third of the patients were 40-60 years old, and the ratio of male to female is 3.6:1.
In China, 5-year survival rate of gastric cancer: I a was 99%~100%; I b was 81%~89%; II was 65%~73%; III a was 43%~50%; III b was 25%; V was 13%. With the increase of the staging of the trend rate of 5-year survival gradually decreased. The 5-year survival rate was closely negatively related to the expression of SLC4A1.
AE1 immunoreactivity was negative in normal gastric tissue. Positive immunostaining of AE1 was detected in gastric carcinoma regardless of the location. AE1 was most frequently expressed in the gastric antrum carcinoma compared with gastric body cancer (P=0.034). Expression of AE1 was significantly associated with bigger tumor size, deeper invasion, shorter survival period, and non-lymph metastasis. In para-cancer tissues of intestinal type gastric cancer, the expression frequency of AE1 was higher than that in diffuse-type (P=0.011) (Xu et al., 2009; Liu et al., 2009).
Hybrid gene
During the process of gastric cancer, AE1 was translated accompanied by the abnormal expression of P16 protein.
Atlas Image
p16INK4A (p16) binds to cyclin-dependent kinase 4/cyclin-dependent kinase 6 and negatively regulates cell growth. During the process of gastric and colon cancer and in gastric and colon cancer cell lines, forced expression of AE1 in the cytoplasm interacted with p16, and sequestrated the protein in the cytoplasm (Fu et al., 2005). So, AE1 plays a crucial role in the pathogenesis of gastric and colon adenocarcinoma (Shen et al., 2007; Wu et al., 2010).


Pubmed IDLast YearTitleAuthors
158113262005Direct interaction and cooperative role of tumor suppressor p16 with band 3 (AE1).Fu GH et al
179719012007Expression of anion exchanger 1 sequestrates p16 in the cytoplasm in gastric and colonic adenocarcinoma.Shen WW et al
200204912010Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cells.Tian H et al
200620762010Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells.Wu J et al
193303522009Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer.Xu WQ et al

Other Information

Locus ID:

NCBI: 6521
MIM: 109270
HGNC: 11027
Ensembl: ENSG00000004939


dbSNP: 6521
ClinVar: 6521
TCGA: ENSG00000004939


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Collecting duct acid secretionKEGGko04966
Collecting duct acid secretionKEGGhsa04966
Transmembrane transport of small moleculesREACTOMER-HSA-382551
SLC-mediated transmembrane transportREACTOMER-HSA-425407
Transport of inorganic cations/anions and amino acids/oligopeptidesREACTOMER-HSA-425393
Bicarbonate transportersREACTOMER-HSA-425381
O2/CO2 exchange in erythrocytesREACTOMER-HSA-1480926
Erythrocytes take up carbon dioxide and release oxygenREACTOMER-HSA-1237044
Erythrocytes take up oxygen and release carbon dioxideREACTOMER-HSA-1247673

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
265425712015Crystal structure of the anion exchanger domain of human erythrocyte band 3.53
119942992002The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV.46
176524302007Interactions of transmembrane carbonic anhydrase, CAIX, with bicarbonate transporters.42
124467372003Novel topology in C-terminal region of the human plasma membrane anion exchanger, AE1.41
198467812009Role of band 3 in regulating metabolic flux of red blood cells.37
189452142009Oxidized and poorly glycosylated band 3 is selectively phosphorylated by Syk kinase to form large membrane clusters in normal and G6PD-deficient red blood cells.33
203467152010Band 3 multiprotein complexes in the red cell membrane; of mice and men.32
124828692003Identification of a critical ankyrin-binding loop on the cytoplasmic domain of erythrocyte membrane band 3 by crystal structure analysis and site-directed mutagenesis.31
158476542005A flexible array format for large-scale, rapid blood group DNA typing.30


Guo-Hui Fu

SLC4A1 (solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group))

Atlas Genet Cytogenet Oncol Haematol. 2010-09-01

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