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

Written2010-09Guo-Hui Fu
Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai, P R China

(Note : for Links provided by Atlas : click)

Identity

Alias_namesEPB3
AE1
DI
WD
Waldner blood group
erythrocyte membrane protein band 3
Diego blood group
solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group)
solute carrier family 4 (anion exchanger), member 1
solute carrier family 4 (anion exchanger), member 1 (Diego blood group)
Alias_symbol (synonym)RTA1A
CD233
FR
SW
WR
Other aliasBND3
EMPB3
MGC116750
MGC116753
MGC126619
MGC126623
WD1
HGNC (Hugo) SLC4A1
LocusID (NCBI) 6521
Atlas_Id 42325
Location 17q21.31  [Link to chromosome band 17q21]
Location_base_pair Starts at 42325758 and ends at 42345502 bp from pter ( according to hg19-Feb_2009)  [Mapping SLC4A1.png]
Local_order 17q21-q22, chromosome 17: 42325753-42345509.
Fusion genes
(updated 2016)
SLC4A1 (17q21.31) / TCF7L1 (2p11.2)

DNA/RNA

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

Protein

 
  The C-terminal structure of AE1.
Description 911 amino acids; 95 kDa.
 
  A. SDS-PAGE of erythrocyte membrane protein. B. Schematic diagram of membrane skeleton proteins.
Function 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.
 
  The model of erythrocyte Cl-/HCO3- exchange.
Homology Anion exchanger.

Mutations

 
Germinal Point mutations in promoter of AE1 gene were detected in AE1 positive gastric and colon cancer cells.
Somatic These mutations were only detected in cancer, not in normal cells.

Implicated in

Note
  
Entity Gastric and colon cancer
Disease 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.
Prognosis 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.
Cytogenetics 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/Mutated Gene During the process of gastric cancer, AE1 was translated accompanied by the abnormal expression of P16 protein.
 
Oncogenesis 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).
  

To be noted

Most of our information was obtained from National Center for Biotechnology Informationx (NCBI). Tables and diagrams were designed after the databases of Ensembl.

Bibliography

Direct interaction and cooperative role of tumor suppressor p16 with band 3 (AE1).
Fu GH, Wang Y, Xi YH, Shen WW, Pan XY, Shen WZ, Jiang XS, Chen GQ.
FEBS Lett. 2005 Apr 11;579(10):2105-10.
PMID 15811326
 
Expression of cytoplasmic p16 and anion exchanger 1 is associated with the invasion and absence of lymph metastasis in gastric carcinoma.
Liu Q, Song LJ, Xu WQ, Zhao L, Zheng L, Yan ZW, Fu GH.
Molecular Medicine Reports. 2009;2(2):169-74.
 
Expression of anion exchanger 1 sequestrates p16 in the cytoplasm in gastric and colonic adenocarcinoma.
Shen WW, Wu J, Cai L, Liu BY, Gao Y, Chen GQ, Fu GH.
Neoplasia. 2007 Oct;9(10):812-9.
PMID 17971901
 
Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cells.
Tian H, Zhang N, Suo WH, Wang T, Song LJ, Wu J, Liu Q, Shen WW, Fu GH.
Int J Cancer. 2010 Sep 1;127(6):1462-74.
PMID 20020491
 
Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells.
Wu J, Zhang YC, Suo WH, Liu XB, Shen WW, Tian H, Fu GH.
Oncogene. 2010 Apr 1;29(13):1987-96. Epub 2010 Jan 11.
PMID 20062076
 
Expression of anion exchanger 1 is associated with tumor progress in human gastric cancer.
Xu WQ, Song LJ, Liu Q, Zhao L, Zheng L, Yan ZW, Fu GH.
J Cancer Res Clin Oncol. 2009 Oct;135(10):1323-30. Epub 2009 Mar 28.
PMID 19330352
 

Citation

This paper should be referenced as such :
Fu, GH
SLC4A1 (solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):473-476.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SLC4A1ID42325ch17q21.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Head and Neck: Squamous cell carcinoma: an overview


External links

Nomenclature
HGNC (Hugo)SLC4A1   11027
LRG (Locus Reference Genomic)LRG_803
Cards
AtlasSLC4A1ID42325ch17q21
Entrez_Gene (NCBI)SLC4A1  6521  solute carrier family 4 member 1 (Diego blood group)
AliasesAE1; BND3; CD233; CHC; 
DI; EMPB3; EPB3; FR; RTA1A; SAO; SPH4; SW; WD; WD1; WR
GeneCards (Weizmann)SLC4A1
Ensembl hg19 (Hinxton)ENSG00000004939 [Gene_View]  chr17:42325758-42345502 [Contig_View]  SLC4A1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000004939 [Gene_View]  chr17:42325758-42345502 [Contig_View]  SLC4A1 [Vega]
ICGC DataPortalENSG00000004939
TCGA cBioPortalSLC4A1
AceView (NCBI)SLC4A1
Genatlas (Paris)SLC4A1
WikiGenes6521
SOURCE (Princeton)SLC4A1
Genetics Home Reference (NIH)SLC4A1
Genomic and cartography
GoldenPath hg19 (UCSC)SLC4A1  -     chr17:42325758-42345502 -  17q21.31   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SLC4A1  -     17q21.31   [Description]    (hg38-Dec_2013)
EnsemblSLC4A1 - 17q21.31 [CytoView hg19]  SLC4A1 - 17q21.31 [CytoView hg38]
Mapping of homologs : NCBISLC4A1 [Mapview hg19]  SLC4A1 [Mapview hg38]
OMIM109270   110500   112010   112050   179800   601550   601551   611162   611590   612653   
Gene and transcription
Genbank (Entrez)AB526447 AF113686 AM919470 BC096106 BC096107
RefSeq transcript (Entrez)NM_000342
RefSeq genomic (Entrez)NC_000017 NC_018928 NG_007498 NT_010783 NW_004929407
Consensus coding sequences : CCDS (NCBI)SLC4A1
Cluster EST : UnigeneHs.443948 [ NCBI ]
CGAP (NCI)Hs.443948
Alternative Splicing GalleryENSG00000004939
Gene ExpressionSLC4A1 [ NCBI-GEO ]   SLC4A1 [ EBI - ARRAY_EXPRESS ]   SLC4A1 [ SEEK ]   SLC4A1 [ MEM ]
Gene Expression Viewer (FireBrowse)SLC4A1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6521
GTEX Portal (Tissue expression)SLC4A1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP02730   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP02730  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP02730
Splice isoforms : SwissVarP02730
PhosPhoSitePlusP02730
Domaine pattern : Prosite (Expaxy)ANION_EXCHANGER_1 (PS00219)    ANION_EXCHANGER_2 (PS00220)   
Domains : Interpro (EBI)Anion_exchange    Anion_exchange_1    Anion_exchange_CS    Band3_cytoplasmic_dom    HCO3_transpt_C    HCO3_transpt_euk    PTrfase/Anion_transptr   
Domain families : Pfam (Sanger)Band_3_cyto (PF07565)    HCO3_cotransp (PF00955)   
Domain families : Pfam (NCBI)pfam07565    pfam00955   
Conserved Domain (NCBI)SLC4A1
DMDM Disease mutations6521
Blocks (Seattle)SLC4A1
PDB (SRS)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
PDB (PDBSum)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
PDB (IMB)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
PDB (RSDB)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
Structural Biology KnowledgeBase1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
SCOP (Structural Classification of Proteins)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
CATH (Classification of proteins structures)1BH7    1BNX    1BTQ    1BTR    1BTS    1BTT    1BZK    1HYN    2BTA    2BTB    3BTB    4KY9    4YZF   
SuperfamilyP02730
Human Protein AtlasENSG00000004939
Peptide AtlasP02730
HPRD00175
IPIIPI00791534   
Protein Interaction databases
DIP (DOE-UCLA)P02730
IntAct (EBI)P02730
FunCoupENSG00000004939
BioGRIDSLC4A1
STRING (EMBL)SLC4A1
ZODIACSLC4A1
Ontologies - Pathways
QuickGOP02730
Ontology : AmiGOactin binding  inorganic anion exchanger activity  inorganic anion exchanger activity  protein binding  plasma membrane  integral component of plasma membrane  anion transport  chloride transport  cellular ion homeostasis  protein C-terminus binding  anion transmembrane transporter activity  bicarbonate transmembrane transporter activity  chloride transmembrane transporter activity  anion:anion antiporter activity  bicarbonate transport  bicarbonate transport  integral component of membrane  basolateral plasma membrane  enzyme binding  Z disc  ankyrin binding  cortical cytoskeleton  protein homodimerization activity  protein anchor  regulation of intracellular pH  extracellular exosome  blood microparticle  chloride transmembrane transport  
Ontology : EGO-EBIactin binding  inorganic anion exchanger activity  inorganic anion exchanger activity  protein binding  plasma membrane  integral component of plasma membrane  anion transport  chloride transport  cellular ion homeostasis  protein C-terminus binding  anion transmembrane transporter activity  bicarbonate transmembrane transporter activity  chloride transmembrane transporter activity  anion:anion antiporter activity  bicarbonate transport  bicarbonate transport  integral component of membrane  basolateral plasma membrane  enzyme binding  Z disc  ankyrin binding  cortical cytoskeleton  protein homodimerization activity  protein anchor  regulation of intracellular pH  extracellular exosome  blood microparticle  chloride transmembrane transport  
Pathways : KEGGCollecting duct acid secretion   
REACTOMEP02730 [protein]
REACTOME Pathways1237044 [pathway]   1247673 [pathway]   425381 [pathway]   
NDEx NetworkSLC4A1
Atlas of Cancer Signalling NetworkSLC4A1
Wikipedia pathwaysSLC4A1
Orthology - Evolution
OrthoDB6521
GeneTree (enSembl)ENSG00000004939
Phylogenetic Trees/Animal Genes : TreeFamSLC4A1
HOVERGENP02730
HOGENOMP02730
Homologs : HomoloGeneSLC4A1
Homology/Alignments : Family Browser (UCSC)SLC4A1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLC4A1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SLC4A1
dbVarSLC4A1
ClinVarSLC4A1
1000_GenomesSLC4A1 
Exome Variant ServerSLC4A1
ExAC (Exome Aggregation Consortium)SLC4A1 (select the gene name)
Genetic variants : HAPMAP6521
Genomic Variants (DGV)SLC4A1 [DGVbeta]
DECIPHER (Syndromes)17:42325758-42345502  ENSG00000004939
CONAN: Copy Number AnalysisSLC4A1 
Mutations
ICGC Data PortalSLC4A1 
TCGA Data PortalSLC4A1 
Broad Tumor PortalSLC4A1
OASIS PortalSLC4A1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLC4A1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSLC4A1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
BioMutasearch SLC4A1
DgiDB (Drug Gene Interaction Database)SLC4A1
DoCM (Curated mutations)SLC4A1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLC4A1 (select a term)
intoGenSLC4A1
NCG5 (London)SLC4A1
Cancer3DSLC4A1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM109270    110500    112010    112050    179800    601550    601551    611162    611590    612653   
Orphanet3252    3657    22723    12443    12441    13885   
MedgenSLC4A1
Genetic Testing Registry SLC4A1
NextProtP02730 [Medical]
TSGene6521
GENETestsSLC4A1
Huge Navigator SLC4A1 [HugePedia]
snp3D : Map Gene to Disease6521
BioCentury BCIQSLC4A1
ClinGenSLC4A1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6521
Chemical/Pharm GKB GenePA35895
Clinical trialSLC4A1
Miscellaneous
canSAR (ICR)SLC4A1 (select the gene name)
Probes
Litterature
PubMed261 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSLC4A1
EVEXSLC4A1
GoPubMedSLC4A1
iHOPSLC4A1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:39:43 CEST 2017

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