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EPB41L3 (erythrocyte membrane protein band 4.1-like 3)

Written2008-05Sunny Y Wong
Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)4.1B
HGNC (Hugo) EPB41L3
HGNC Alias symbDAL1
LocusID (NCBI) 23136
Atlas_Id 40458
Location 18p11.31  [Link to chromosome band 18p11]
Location_base_pair Starts at 5392276 and ends at 5543997 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping EPB41L3.png]
Local_order Located between ZFP161 (Zinc Finger Protein 161 homolog; 5279018-5286039) and L(3)MBT-Like 4 (5944712-6404910).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EPB41L3 (18p11.31)::FYB1 (5p13.1)EPB41L3 (18p11.31)::LAMA1 (18p11.31)EPB41L3 (18p11.31)::LRRC34 (3q26.2)
EPB41L3 (18p11.31)::MAPRE3 (2p23.3)


Description The gene consists of 23 exons, with exons 1 and 23 being non-coding. The total gene length is 4,446 bases.
Transcription The coding sequence (87-3350) generates an approximatively 3.3 kb mRNA transcript.


Description Protein 4.1B is a member of the Protein 4.1 superfamily of proteins, which is characterized by the presence of a conserved N-terminal 4.1/ezrin/radixin/moesin (FERM) domain. The full-length protein consists of the following domains (N- to C-termini): U1-FERM-U2-SABD-U3-CTD ("U" = unique domains, SABD = spectrin/actin binding domain, CTD = C-terminal domain).
This protein consists of 1,088 amino acids and has been detected at sizes between 125-145 kDa by Western blot. A truncated variant of Protein 4.1B (named DAL-1) has also been found to be generated by translational initiation at Met110 and termination at Ser542, relative to full-length 4.1B. DAL-1 lacks the 4.1B N-terminal U1 domain and the entire CTD, and also has internal deletions in portions of the U2 and U3 subdomains. DAL-1 is believed to possess the full tumor suppressive capabilities exhibited by full-length Protein 4.1B.
Expression Highly expressed in the brain and neurons, as well as in adipose tissue, adrenal gland, testis, placenta and kidney. Moderate expression in lungs and intestines. Lower expression across many other organs.
Localisation As with other members of the Protein 4.1 superfamily, Protein 4.1B likely functions to link cellular receptors with the cytoskeleton, and thus localizes to the plasma membrane. By immunofluorescence, 4.1B has been reported to display a "honeycomb" pattern, with enrichment at points of cell-cell contact. 4.1B has also been localized to the cytoplasm and, at least in one report, to the nucleus.
Function The tumor suppressive function of 4.1B has been reported in several studies, both in vitro and in vivo. Overexpression of 4.1B can suppress growth and, in some cases, induce apoptosis in human breast cancer, non-small cell lung cancer and meningioma cells. Although the mechanism by which 4.1B induces apoptosis remains unclear, one report has observed that overexpression of 4.1B increases caspase-8 activity in MCF-7 cells, and that inhibitors of caspase-8 can block 4.1B-mediated apoptosis. Others have reported that overexpression of 4.1B induces Rac1-dependent JNK signaling, which leads to growth suppression of meningioma cells. Truncation studies have also suggested that the U2 region of 4.1B contains the minimal growth suppressive domain when tethered to the membrane by FERM domain-mediated protein-protein interactions. Finally, downregulation of 4.1B by shRNAs has been reported to increase metastatic capability in human prostate cancer cells. However, the growth inhibitory effects of 4.1B are not general and may be cell-type-specific. For instance, overexpression of 4.1B inhibits the growth of some subclones of MCF-7 breast cancer cells, but not others, and 4.1B has been reported not to affect the growth of schwannomas.
4.1B knock-out animals are largely normal and fertile, and do not display any detectable predisposition to spontaneous tumor formation above background levels. However, in the TRAMP tumorigenesis model of prostate cancer, 4.1B null mice have been reported to display increased susceptibility for developing primary tumors and metastases. The only non-tumor phenotype observed in mutant animals is that mammary glands from 4.1B-/- female mice displayed a 60% increase in Ki67-positive epithelial cells during pregnancy, but not during the lactating or involution stages. The precise function of 4.1B remains unclear.
Homology The FERM domain of Protein 4.1B is 73% homologous with the FERM domain of Protein 4.1R, the founding member of the Protein 4.1 superfamily of proteins. 4.1B is most similar to other members of the Protein 4.1 sub-group (e.g. 4.1R, 4.1G, 4.1N), which is one branch of the Protein 4.1 superfamily.


Note To date, no mutations have been linked to human developmental abnormalities or to cancer. However, the chromosomal region containing 4.1B, 18p11.3, is frequently lost during tumorigenesis for a variety of tumor types (see below).

Implicated in

Entity Various cancers
Disease 4.1B was originally identified as a protein whose expression was reduced in human non-small cell lung carcinomas. Subsequent studies have shown that 4.1B levels are downregulated in many different types of tumors. The location of the gene encoding Protein 4.1B, 18p11.3, is a region that has been reported to be lost in 38% of human lung, brain and breast tumors. Others have reported that loss of 18p11.3 is detected in 55% of ductal carcinomas in situ, and in 67% of invasive breast cancers. In addition, 4.1B expression has been reported to be reduced in up to 70% of meningiomas, and is significantly downregulated in several studies of human clinical prostate cancer, particularly in metastatic prostate cancer.


Note None.


ERM proteins and merlin: integrators at the cell cortex.
Bretscher A, Edwards K, Fehon RG.
Nat Rev Mol Cell Biol. 2002 Aug;3(8):586-99.
PMID 12154370
Suppression of growth and increased cellular attachment after expression of DAL-1 in MCF-7 breast cancer cells.
Charboneau AL, Singh V, Yu T, Newsham IF.
Int J Cancer. 2002 Jul 10;100(2):181-8.
PMID 12115567
Protein 4.1B/differentially expressed in adenocarcinoma of the lung-1 functions as a growth suppressor in meningioma cells by activating Rac1-dependent c-Jun-NH2-kinase signaling.
Gerber MA, Bahr SM, Gutmann DH.
Cancer Res. 2006 May 15;66(10):5295-303.
PMID 16707455
The protein 4.1 tumor suppressor, DAL-1, impairs cell motility, but regulates proliferation in a cell-type-specific fashion.
Gutmann DH, Hirbe AC, Huang ZY, Haipek CA.
Neurobiol Dis. 2001 Apr;8(2):266-78.
PMID 11300722
The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells.
Jiang W, Newsham IF.
Mol Cancer. 2006 Jan 18;5:4.
PMID 16420693
Allelic loss on chromosome band 18p11.3 occurs early and reveals heterogeneity in breast cancer progression.
Kittiniyom K, Gorse KM, Dalbegue F, Lichy JH, Taubenberger JK, Newsham IF.
Breast Cancer Res. 2001;3(3):192-8. Epub 2001 Feb 12.
PMID 11305954
An interaction between alpha(v)beta(8) integrin and Band 4.1B via a highly conserved region of the Band 4.1 C-terminal domain.
McCarty JH, Cook AA, Hynes RO.
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13479-83. Epub 2005 Sep 12.
PMID 16157875
Immunolocalization of protein 4.1B/DAL-1 during neoplastic transformation of mouse and human intestinal epithelium.
Ohno N, Terada N, Murata S, Yamakawa H, Newsham IF, Katoh R, Ohara O, Ohno S.
Histochem Cell Biol. 2004 Dec;122(6):579-86. Epub 2004 Oct 29.
PMID 15517334
ONCOMINE: a cancer microarray database and integrated data-mining platform.
Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM.
Neoplasia. 2004 Jan-Feb;6(1):1-6.
PMID 15068665
Membrane localization of the U2 domain of protein 4.1B is necessary and sufficient for meningioma growth suppression.
Robb VA, Gerber MA, Hart-Mahon EK, Gutmann DH.
Oncogene. 2005 Mar 10;24(11):1946-57.
PMID 15688033
Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation.
Sun CX, Robb VA, Gutmann DH.
J Cell Sci. 2002 Nov 1;115(Pt 21):3991-4000.
PMID 12356905
Protein 4.1B in mouse islets of Langerhans and beta-cell tumorigenesis.
Terada N, Ohno N, Yamakawa H, Baba T, Fujii Y, Christofori G, Ohara O, Ohno S.
Histochem Cell Biol. 2003 Oct;120(4):277-83. Epub 2003 Sep 9.
PMID 14574582
A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer.
Tran YK., Bogler O, Gorse KM, Wieland I, Green MR, Newsham IF.
Cancer Res. 1999 Jan 1;59(1):35-43.
PMID 9892180
Protein 4.1B suppresses prostate cancer progression and metastasis.
Wong SY, Haack H, Kissil JL, Barry M, Bronson RT, Shen S, Whittaker CA, Crowley D, Hynes RO.
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12784-9. Epub 2007 Jul 18.
PMID 17640904
Loss of the putative tumor suppressor Band 4.1B/Dal1 gene is dispensible for normal development and does not predispose to cancer.
Yi C, McCarty JH, Troutman SA, Eckman MS, Bronson RT, Kissil JL.
Mol Cell Biol. 2005 Nov;25(22):10052-9.
PMID 16260618


This paper should be referenced as such :
Wong, SY
EPB41L3 (erythrocyte membrane protein band 4.1-like 3)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(4):265-267.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]

External links


HGNC (Hugo)EPB41L3   3380
Entrez_Gene (NCBI)EPB41L3    erythrocyte membrane protein band 4.1 like 3
Aliases4.1B; DAL-1; DAL1
GeneCards (Weizmann)EPB41L3
Ensembl hg19 (Hinxton)ENSG00000082397 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000082397 [Gene_View]  ENSG00000082397 [Sequence]  chr18:5392276-5543997 [Contig_View]  EPB41L3 [Vega]
ICGC DataPortalENSG00000082397
TCGA cBioPortalEPB41L3
AceView (NCBI)EPB41L3
Genatlas (Paris)EPB41L3
SOURCE (Princeton)EPB41L3
Genetics Home Reference (NIH)EPB41L3
Genomic and cartography
GoldenPath hg38 (UCSC)EPB41L3  -     chr18:5392276-5543997 -  18p11.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)EPB41L3  -     18p11.31   [Description]    (hg19-Feb_2009)
GoldenPathEPB41L3 - 18p11.31 [CytoView hg19]  EPB41L3 - 18p11.31 [CytoView hg38]
Genome Data Viewer NCBIEPB41L3 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB023204 AF069072 AF515797 AK090875 AK094952
RefSeq transcript (Entrez)NM_001281533 NM_001281534 NM_001281535 NM_001330557 NM_001384682 NM_001384683 NM_001384684 NM_001384685 NM_001384686 NM_001384687 NM_001384688 NM_001384689 NM_001384690 NM_001384691 NM_001384692 NM_001384693 NM_001384694 NM_001384695 NM_001384696 NM_001384697 NM_001384698 NM_001384699 NM_001384700 NM_001384701 NM_001384702 NM_001384703 NM_001384704 NM_001384705 NM_001384706 NM_012307
Consensus coding sequences : CCDS (NCBI)EPB41L3
Gene ExpressionEPB41L3 [ NCBI-GEO ]   EPB41L3 [ EBI - ARRAY_EXPRESS ]   EPB41L3 [ SEEK ]   EPB41L3 [ MEM ]
Gene Expression Viewer (FireBrowse)EPB41L3 [ Firebrowse - Broad ]
GenevisibleExpression of EPB41L3 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23136
GTEX Portal (Tissue expression)EPB41L3
Human Protein AtlasENSG00000082397-EPB41L3 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y2J2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y2J2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y2J2
Domaine pattern : Prosite (Expaxy)FERM_1 (PS00660)    FERM_2 (PS00661)    FERM_3 (PS50057)   
Domains : Interpro (EBI)Band4.1-L3    Band_4.1_C    Band_41_domain    Ez/rad/moesin-like    FERM-adjacent    FERM/acyl-CoA-bd_prot_sf    FERM_2    FERM_central    FERM_CS    FERM_domain    FERM_N    FERM_PH-like_C    PH-like_dom_sf    SAB_dom    Ubiquitin-like_domsf   
Domain families : Pfam (Sanger)4_1_CTD (PF05902)    FA (PF08736)    FERM_C (PF09380)    FERM_M (PF00373)    FERM_N (PF09379)    SAB (PF04382)   
Domain families : Pfam (NCBI)pfam05902    pfam08736    pfam09380    pfam00373    pfam09379    pfam04382   
Domain families : Smart (EMBL)B41 (SM00295)  FA (SM01195)  FERM_C (SM01196)  
Conserved Domain (NCBI)EPB41L3
PDB (RSDB)2HE7    3BIN    6IBE   
PDB Europe2HE7    3BIN    6IBE   
PDB (PDBSum)2HE7    3BIN    6IBE   
PDB (IMB)2HE7    3BIN    6IBE   
Structural Biology KnowledgeBase2HE7    3BIN    6IBE   
SCOP (Structural Classification of Proteins)2HE7    3BIN    6IBE   
CATH (Classification of proteins structures)2HE7    3BIN    6IBE   
AlphaFold pdb e-kbQ9Y2J2   
Human Protein Atlas [tissue]ENSG00000082397-EPB41L3 [tissue]
Protein Interaction databases
IntAct (EBI)Q9Y2J2
Ontologies - Pathways
Ontology : AmiGOregulation of cell growth  protein localization to paranode region of axon  actin binding  structural constituent of cytoskeleton  protein binding  cytosol  cytoskeleton  plasma membrane  plasma membrane  plasma membrane  cell-cell junction  apoptotic process  biological_process  regulation of cell shape  cell junction  axolemma  cortical cytoskeleton organization  cortical actin cytoskeleton organization  paranodal junction assembly  actomyosin structure organization  paranode region of axon  myelin maintenance  juxtaparanode region of axon  neuron projection morphogenesis  protein localization to juxtaparanode region of axon  protein localization to plasma membrane  cytoskeletal protein-membrane anchor activity  
Ontology : EGO-EBIregulation of cell growth  protein localization to paranode region of axon  actin binding  structural constituent of cytoskeleton  protein binding  cytosol  cytoskeleton  plasma membrane  plasma membrane  plasma membrane  cell-cell junction  apoptotic process  biological_process  regulation of cell shape  cell junction  axolemma  cortical cytoskeleton organization  cortical actin cytoskeleton organization  paranodal junction assembly  actomyosin structure organization  paranode region of axon  myelin maintenance  juxtaparanode region of axon  neuron projection morphogenesis  protein localization to juxtaparanode region of axon  protein localization to plasma membrane  cytoskeletal protein-membrane anchor activity  
Pathways : KEGGTight junction   
REACTOMEQ9Y2J2 [protein]
REACTOME PathwaysR-HSA-6794361 [pathway]   
NDEx NetworkEPB41L3
Atlas of Cancer Signalling NetworkEPB41L3
Wikipedia pathwaysEPB41L3
Orthology - Evolution
GeneTree (enSembl)ENSG00000082397
Phylogenetic Trees/Animal Genes : TreeFamEPB41L3
Homologs : HomoloGeneEPB41L3
Homology/Alignments : Family Browser (UCSC)EPB41L3
Gene fusions - Rearrangements
Fusion : MitelmanEPB41L3::LAMA1 [18p11.31/18p11.31]  
Fusion : MitelmanEPB41L3::LRRC34 [18p11.31/3q26.2]  
Fusion : QuiverEPB41L3
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerEPB41L3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EPB41L3
Exome Variant ServerEPB41L3
GNOMAD BrowserENSG00000082397
Varsome BrowserEPB41L3
ACMGEPB41L3 variants
Genomic Variants (DGV)EPB41L3 [DGVbeta]
DECIPHEREPB41L3 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisEPB41L3 
ICGC Data PortalEPB41L3 
TCGA Data PortalEPB41L3 
Broad Tumor PortalEPB41L3
OASIS PortalEPB41L3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICEPB41L3  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DEPB41L3
Mutations and Diseases : HGMDEPB41L3
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)EPB41L3
DoCM (Curated mutations)EPB41L3
CIViC (Clinical Interpretations of Variants in Cancer)EPB41L3
NCG (London)EPB41L3
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry EPB41L3
NextProtQ9Y2J2 [Medical]
Target ValidationEPB41L3
Huge Navigator EPB41L3 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDEPB41L3
Pharm GKB GenePA27813
Clinical trialEPB41L3
DataMed IndexEPB41L3
PubMed126 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:17:11 CEST 2021

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