Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

BIN1 (Bridging Integrator 1)

Abstract

Abstract The BIN1 gene encodes a set of BAR adapter proteins generated by alternate RNA splicing which function in membrane and actin dynamics, cell polarity and stress signaling. In cancer cells, BIN1 functions as a tumor suppressor gene and it is commonly silenced or misspliced during malignant progression. Genetic investigations in fission yeast, flies, mice and human cells suggest that BIN1 adapter proteins exert a 'moonlighting' function in the nucleus, integrating cell polarity signals generated by actin and vesicle dynamics with central regulators of cell cycle control, apoptosis, and immune surveillance (adapted from Prendergast et al., 2009).

Identity

Other namesAMPH-II
AMPH2
AMPHL
ALP
DKFZp547F068
MGC10367
SH3P9
HGNC (Hugo) BIN1
LocusID (NCBI) 274
Location 2q14.3
Location_base_pair Starts at 127805599 and ends at 127864903 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description The human BIN1 gene is encoded by at least 16 exons spanning at least 59258 bps at chromosome 2q14-2q21 (nucleotides 127522078-127581334). The murine Bin1 gene is similarly sized but localized to a syntenic locus on mouse chromosome 8 (Wechsler-Reya et al., 1997).
Transcription The Bin1 promoter is rich in CpG methylation residues and transcription of the gene produces more than 10 alternative transcripts that are from 2075 to 2637 bp mRNA in size: isoform 1 (2637 bp), isoform 2 (2508 bp), isoform 3 (2376 bp), isoform 4 (2333 bp), isoform 5 (2412 bp), isoform 6 (2289 bp), isoform 7 (2283 bp), isoform 8 (2210) bp, isoform 9 (2165bp), and isoform 10 (2075 bp). Isoforms 9 and 10 are ubiquitous in expression. Isoform 8 is expressed specifically in skeletal muscle. Isoforms 1-7 are expressed predominantly in the central nervous system. An aberrant isoform has been reported to be expressed specifically in tumor cells (Wechsler-Reya et al., 1997).
Pseudogene None reported.

Protein

 
  At least 10 alternate protein isoforms of Bin1 are expressed in different tissues. Isoforms 9 and 10 are ubiquitous. Isoform 8 is muscle-specific. Isoforms 1-7 are expressed predominantly in the central nervous system. Two tumor-specific isoforms include an exon termed 12A that is normally spliced into Bin1 mRNA only with other exons expressed in the central nervous system. These tumor-specific isoforms occur commonly in cancer and they represent loss of function with regard to tumor suppression activity and nuclear localization capability. BAR, BAR domain; SH3, SH3 domain; MBD, Myc binding domain; CLAP, clathrin-associated protein binding region; PI, phosphoinositide binding region. Exons are numbered by reference to Wechsler-Reya et al. (1997).
Description Bin1 contains N-terminal BAR (Bin1/Amphihysin/Rvs) domain with predicted coiled-coil structure and a C-terminal SH3 domain (Sakamuro et al., 1996). Bin1 encodes proteins of 409 to 593 amino acids; isoform 1 (593 aa), isoform 2 (550 aa), isoform 3 (506 aa), isoform 4 (497 aa), isoform 5 (518 aa), isoform 6 (482 aa), isoform 7 (475 aa), isoform 8 (454 aa), isoform 9 (439 aa), and isoform 10 (409 aa). Isoform 10 is the smallest and isoform 1 is the largest in size. Also, Bin1 has predicted molecular weight of 45432 to 64568 Da; isoform 1 (64568 Da), isoform 2 (59806 Da), isoform 3 (55044 Da), isoform 4 (54817 Da), isoform 5 (56368 Da), isoform 6 (52889 Da), isoform 7 (51606 Da), isoform 8 (50054 Da), isoform 9 (48127 Da), and isoform 10 (45432 Da). Isoforms 9 and 10 are ubiquitous in expression. Isoform 8 is expressed specifically in skeletal muscle. Isoforms 1-7 are expressed predominantly in the central nervous system. These 10 different splice isoforms differ widely in subcellular localization, tissue distribution, and ascribed functions, with isoforms 1-7 predominantly cytosolic but isoforms 8-10 found in both the nucleus and/or cytosol of certain cell types (Sakamuro et al., 1996; Muller et al., 2003). Recent studies demonstrated that the coiled-coil BIN1 BAR peptide encodes a novel BIN1 MID domain, through which BIN1 acts as a MYC-independent cancer suppressor (Lundgaard et al., 2011).
Expression Bin1 is widely expressed (Wechsler-Reya et al., 1997; Chapuis et al., 2013). Patterns of isoform expression are noted above in the diagram legend.
Localisation Bin1 is localized both in nuclear and cytosolic in the cerebral cortex and cerebellum of brain. Bin1 is localized mainly in nuclear in bone marrow cells whereas it is localized mainly in cytosolic in peripheral lymphoid cells. Bin1 is nuclear or nucleocytosolic in basal cells of skin, breast, or prostate, whereas it is cytosolic or plasma membrane localized in gastrointestinal cells (DuHadaway et al., 2003). In cardiac muscles Bin1 generate T-tubules and also designates T-tubules as the appropriate site for delivery of L-type calcium channels (Hong et al., 2010).
Function Bin1 encodes members of the BAR (Bin/Amphiphysin/Rvs) adapter family which have been implicated in membrane dynamics, such as vesicle fusion and trafficking, specialized membrane organization, actin organization, cell polarity, stress signaling, transcription, immunomodulation and tumor suppression. BAR adapter proteins are now recognized to be part of a larger superfamily of structurally related proteins that includes the so-called F-BAR and I-BAR adapter proteins (Ren et al., 2006; Prendergast et al., 2009).
Membrane binding and tubulation: The Bin1 BAR domain can mediate binding and tubulation of curved membranes (Lee et al., 2002; Wu et al., 2014). Crystal structures of the BAR domains from human BIN1 and its fruit fly homolog reveal a dimeric banana-shaped 6-alpha-helix bundle that can nestle against the charged head groups on a curved lipid bilayer. Structural studies implicate specific alpha-helices in tubulation activity. Biochemical analyses implicate Bin1 in vesicle fission and fusion processes, with the SH3 domain providing an essential contribution to these processes through the recruitment of dynamins (Ren et al., 2006).
Vesicle trafficking: Bin1 is implicated in endocytosis and intracellular endosome traffic through interactions with Rab5 guanine nucleotide exchange factors (Rab GEFs) and the sorting nexin protein Snx4. Complexes of neuronal Amph-I with neuron-specific isoforms of Bin1 (Amph-II) have been implicated in synaptic vesicle recycling in the brain. Genetic studies of the Bin1 homolog in budding yeast indicate an essential role in endocytosis, however, this role appears to be non-essential for homologs in fission yeast, fruit flies, and mice (Leprince et al., 2003).
Cell polarity: Genetic analyses of the Bin1 homologs in yeast and fruit flies suggest a integrative function in cell polarity, possibly mediated by effects on actin organization and vesicle trafficking. In budding yeast, the Bin1 homolog RVS167 lies at a central nodal point for integrating cell polarity signaling (Balguerie et al., 1999). Genetic ablation of the Bin1 homolog in fruit flies causes mislocalization of the cell polarity complex Dlg/Scr/Lgl, normally localized to the tight junction, that is implicated in epithelial polarity and suppression of tumor-like growths in flies (Humbert et al., 2003).
Transcription: Ubiquitous and muscle-specific isoforms of Bin1 that can localize to the nucleus can bind to c-Myc and suppress its transcriptional transactivation activity (Elliott et al., 1999). Tethering the BAR domain of Bin1 to DNA is sufficient to repress transcription. Genetic studies in fission yeast demonstrate that the functional homolog hob1+ is essential to silence transcription of heterochromatin at telomeric and centromeric chromosomal loci by supporting a Rad6-Set1 pathway of transcriptional repression (Ramalingam and Prendergast, 2007).
Muscle function: Mutations of the human BIN1 gene are associated with centronuclear myopathy, a disorder marked by severe muscle weakness (Nicot et al., 2007; Wu et al., 2014). In skeletal muscle, Bin1 localizes to T tubules where it appears to support ion flux (Lee et al., 2002; Butler et al., 1997). In vitro studies of terminal muscle differentiation implicate Bin1 in myoblast cell cycle arrest and fusion during tubule formation (Wechsler-Reya et al., 1998).
Cardiac function: Mouse genetic studies indicate that Bin1 is required for cardiac development (Hong et al., 2010). Bin1 levels decreases in failing hearts and low level of plasma Bin1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy (Hong et al., 2012).
Cognition and Memory: Bin1 is one of the candidate genes involved in Alzheimer's disease. Bin1 is the most important risk locus for late onset Alzheimer's disease. Bin1 affects AD risk primarily by modulating tau pathology (Tan et al., 2013; Kingwell, 2013; Chapius et al., 2013).
Immunomodulation and Barrier Function: Bin1 is a genetic modifier of experimental colitis that controls the paracellular pathway of transcellular ion transport regulated by cellular tight junctions (Chang et al., 2012).
Apoptosis and Senescence: Bin1 is crucial for the function of default pathways of classical apoptosis or senescence triggered by the Myc or Raf oncogenes in primary cells (Prendergast et al., 2009). In human tumor cells, enforced expression of Bin1 triggers a non-classical program of cell death that is caspase independent and associated with activation of serine proteases (Elliott et al., 2000).
Tumor suppression: Attenuation of Bin1 function by silencing or missplicing is a frequent event in multiple human cancers including breast, prostate, skin, lung, and colon cancers (Sakamuro et al., 1996; Ge et al., 2000b). In breast cancer, attenuated expression of Bin1 is associated with increased metastasis and poor clinical outcome (Chang et al., 2007b). In human tumor cells, ectopic expression of ubiquitous or muscle Bin1 isoforms causes growth arrest or caspase-independent cell death (Prendergast et al., 2009). A Bin1 missplicing event that occurs frequently in human cancers is sufficient to extinguish these activities. In primary rodent cells, Bin1 inhibits oncogenic co-transformation by Myc, adenovirus E1A, or mutant p53 but not SV40 T antigen (Elliott et al., 1999; Elliott et al., 2000). Mouse genetic studies establish that loss of Bin1 causes lung and liver cancers during aging (Chang et al., 2007a). In mice where breast or colon tumors are initiated by carcinogen treatment, Bin1 deletion causes progression to more aggressive malignant states (Chang et al., 2007b). Oncogenically transformed cells lacking Bin1 exhibit reduced susceptibility to apoptosis and increased proliferation, invasion, immune escape, and tumor formation (Muller et al., 2004, Muller et al., 2005). Activation of metalloproteinase MMP9 and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) have been implicated respectively in invasion and immune escape caused by Bin1 loss (Chang et al., 2007b). Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. The oncoprotein c-Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP-ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance (Tanida et al., 2012).
Null phenotype in mouse: Bin1 knockout mice are perinatal lethal owing to myocardial hypertrophy where myofibrils of ventricular cardiomyocytes are severely disorganized (Muller et al., 2003). Genetic mosaic mice display increased susceptibility to inflammation, premalignant lesions in prostate and pancreas, and formation of liver and lung carcinoma. Female mosaic mice exhibit increased fecundity during aging. Tissue-specific gene ablation in skin or breast facilitates carcinogenesis (Chang et al., 2007a).
Homology The longest Bin1 alternate splice variant in human brain exhibits 71% amino acid sequences similarity and 55% amino acid sequence identity with amphiphysin-I (amph-I) (Ren et al., 2006). Bin1 is also closely related to the mammalian amphiphysin-like genes Bin2 and Bin3 (Routhier et al., 2003). Genetic homologs of Bin1 that exist in budding and fission yeast (RVS167 and hob1+) and in fruit flies (amphiphysin) are well-characterized (Ren et al., 2006; Prendergast et al., 2009).

Mutations

Note Epigenetics: Attenuated expression or missplicing occurs in many cases of breast, prostate, lung, skin, brain and colon cancers. Expression analyses have identified Bin1 missplicing as among the most common missplicing events occurring in cancer (Chang et al., 2007).
Germinal Germ-line mutations leading to nonsynonymous alterations in Bin1 have been associated with the familial muscle weakness disorder centronuclear myopathy, a disorder characterized by abnormal centralization of nuclei in muscle fibers. Two missense alterations the BAR domain that have been identified as loss of function mutations for membrane binding are K35N and D151N (Nicot et al., 2007). Another mutation that has been identified, K575X, generates a prematurely terminated Bin1 protein implicated in loss of function (Nicot et al., 2007).
Somatic Loss of heterozygosity of Bin1 in cases of metastatic prostate cancer has been reported in the absence of mutation of the remaining allele. Infrequent instances of gene deletions have been reported in breast tumor cell lines (Chang et al., 2007b; Kuznetsova et al., 2007).

Implicated in

Entity Breast cancer
Oncogenesis Breast cancer is the second leading cause of cancer death in women following lung cancer. Bin1 expression is attenuated significantly in >50% of cases of malignant breast cancer by immunohistochemical or RT-PCR analysis (Ge et al., 2000a). Reduced levels of Bin1 are correlated to increased nodal metastasis and reduced survival in low or middle grade carcinomas. Mouse genetic studies indicate that Bin1 is non-essential for mammary gland development but that it is needed for the rapid kinetics of ductolobular remodeling during pregnancy and weaning. In mammary gland tumors initiated by the ras-activating carcinogen 7,12-dimethylbenzanthracene (DMBA), Bin1 loss strongly accentuates the formation of poorly differentiated tumors characterized by low tubule formation, high mitotic indices, and high degree of nuclear pleomorphism. Bin1 loss facilitates tumor progression at several intrinsic levels, including increased proliferation, survival, and motility of mouse mammary epithelial cells (MMECs) established from DMBA-induced tumors (Chang et al., 2007b).
  
Entity Lung cancer
Oncogenesis Lung cancer is a leading cause of death from cancer. Bin1 expression has been reported to be attenuated significantly in cases of lung adenocarcinoma by immunohistochemical analysis. Mouse genetic studies demonstrate that Bin1 loss is associated with formation of lung adenocarcinoma during aging, indicating that Bin1 attenuation drives disease incidence (Chang et al., 2007a).
  
Entity Colon cancer
Oncogenesis Colorectal cancer is the third most common cancer in the developed world. Bin1 expression has been reported to be attenuated significantly in ~50% of cases of colon cancer by Immunohistochemical analysis. Mouse genetic studies indicate that, in colon tumors initiated by treatment with the carcinogen dimethylhydrazine (DMH), Bin1 loss facilitates progression to more aggressive tumors with a higher multiplicity (Chang et al., 2007a).
  
Entity Skin cancer
Oncogenesis Skin cancer is the most common form of cancer. Basal cell cancer and squamous cell cancer are most common and treatable whereas melanoma is less common and deadlier. Studies of human melanoma revealed that Bin1 is inappropriately expressed as tumor cell-specific isoforms that include exon 12A, which is alternately spliced into isoforms found in the central nervous system but not normally on its own in melanocytes or other non-neuronal cells. This aberrant splicing event abolishes the tumor suppressor functions of Bin1 based on the loss of its anti-oncogenic and programmed cell death inducing activities in oncogenically transformed cells and melanoma cells. Mouse genetic studies indicate that Bin1 loss facilitates skin carcinogenesis (Ge et al., 1999).
  
Entity Prostate cancer
Oncogenesis Prostate cancer is the leading cause of death in men older than 55 years of age. Loss of heterozygosity of the human BIN1 gene has been reported in ~40% of cases of metastatic prostate cancer. Bin1 is expressed in most primary tumors, even at slightly elevated levels relative to benign tissues, but it is frequently grossly attenuated in expression or inactivated by aberrant splicing in metastatic tumors and androgen-independent tumor cell lines. Ectopic expression suppresses the growth of prostate cancer cell lines in vitro. Mouse genetic studies indicate that Bin1 loss is associated with an increased incidence of prostate inflammation, atrophy, hypertrophy, and intraepithelial neoplasia during aging (Ge et al., 2000b).
  
Entity Neuroblastoma
Oncogenesis Neuroblastoma (NB) is the most common solid tumor of childhood and is responsible for 15% of childhood cancer-related deaths. Bin1 expression is grossly reduced in MYCN amplified and metastatic NB compared with MYCN single-copy and localized NB as evaluated by real-time RT-PCR. Enforced expression of Bin1 in MYCN amplified human NB cell lines markedly inhibits colony formation (Hogarty et al., 2000).
  
Entity Cardiomyopathy
Note Dilated cardiomyopathy (DCM) is a leading cause of heart failure with as much as >25% of cases of familial etiology. A whole genome screen performed in a three-generation family with 12 affected individuals with autosomal dominant familial DCM defined linkage to chromosome 2q14-q22 where the human BIN1 gene is located (Jung et al., 1999). While BIN1 was not specifically identified as the germane locus, mouse studies indicate that genetic ablation causes cardiomyopathy during development. Moreover, in mice where Bin1 is ablated after birth in a tissue-specific manner in cardiomyocytes, a progressive cardiomyopathy develops consistent with the possibility that Bin1 loss of function may be a cause of DCM (Muller et al., 2003).
  
Entity Centronuclear myopathy
Note Germ-line mutations of Bin1 are associated with formation of this rare familial disorder characterized by abnormal centralization of nuclei in muscle fibers and severe muscle weakness (Nicot et al., 2007; Smith et al., 2014). In five affected individuals studied from three non-sanguineous families, two mutations extinguishing the membrane binding activity of the BAR domain were identified along one mutation causing a prematurely terminated Bin1 polypeptide (Nicot et al., 2007).
  
Entity Chronic inflammation
Note Mouse genetic studies indicate that Bin1 loss increases the general incidence of chronic inflammation in the heart, pancreas, liver, and prostate.
  
Entity Female fecundity
Note Mouse genetic studies indicate that mosaic loss of Bin1 increases reproductive physiology during aging. Specifically, female mosaic mice exhibit extended fecundity during aging, retaining reproductive capability ~6 months longer than control mice (Chang et al., 2007a).
  
Entity Alzheimer's disease
Note BIN1 transcript levels are increased in AD brains (Tan et al., 2013). Genome-wide association studies (GWAS) have identified the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. Decreased expression of the Drosophila BIN1 suppress Tau-mediated neurotoxicity. Tau and BIN1 has been demonstrated to colocalize and interact in human neuroblastoma cells and in mouse brain (Chapuis et al., 2013; Kingwell, 2013).
  

External links

Nomenclature
HGNC (Hugo)BIN1   1052
Cards
AtlasBIN1ID794ch2q14
Entrez_Gene (NCBI)BIN1  274  bridging integrator 1
GeneCards (Weizmann)BIN1
Ensembl (Hinxton)ENSG00000136717 [Gene_View]  chr2:127805599-127864903 [Contig_View]  BIN1 [Vega]
ICGC DataPortalENSG00000136717
cBioPortalBIN1
AceView (NCBI)BIN1
Genatlas (Paris)BIN1
WikiGenes274
SOURCE (Princeton)NM_004305 NM_139343 NM_139344 NM_139345 NM_139346 NM_139347 NM_139348 NM_139349 NM_139350 NM_139351
Genomic and cartography
GoldenPath (UCSC)BIN1  -  2q14.3   chr2:127805599-127864903 -  2q14   [Description]    (hg19-Feb_2009)
EnsemblBIN1 - 2q14 [CytoView]
Mapping of homologs : NCBIBIN1 [Mapview]
OMIM255200   601248   
Gene and transcription
Genbank (Entrez)AF001383 AF004015 AF043898 AF043899 AF043900
RefSeq transcript (Entrez)NM_004305 NM_139343 NM_139344 NM_139345 NM_139346 NM_139347 NM_139348 NM_139349 NM_139350 NM_139351
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NG_012042 NT_005403 NW_001838849 NW_004929304
Consensus coding sequences : CCDS (NCBI)BIN1
Cluster EST : UnigeneHs.193163 [ NCBI ]
CGAP (NCI)Hs.193163
Alternative Splicing : Fast-db (Paris)GSHG0017968
Alternative Splicing GalleryENSG00000136717
Gene ExpressionBIN1 [ NCBI-GEO ]     BIN1 [ SEEK ]   BIN1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO00499 (Uniprot)
NextProtO00499  [Medical]
With graphics : InterProO00499
Splice isoforms : SwissVarO00499 (Swissvar)
Domaine pattern : Prosite (Expaxy)BAR (PS51021)    SH3 (PS50002)   
Domains : Interpro (EBI)AH/BAR-dom [organisation]   Amphiphysin [organisation]   Amphiphysin_2 [organisation]   BAR_dom [organisation]   SH3_domain [organisation]  
Related proteins : CluSTrO00499
Domain families : Pfam (Sanger)BAR (PF03114)    SH3_9 (PF14604)   
Domain families : Pfam (NCBI)pfam03114    pfam14604   
Domain families : Smart (EMBL)BAR (SM00721)  SH3 (SM00326)  
DMDM Disease mutations274
Blocks (Seattle)O00499
PDB (SRS)1MUZ    1MV0    1MV3    2FIC    2RMY    2RND   
PDB (PDBSum)1MUZ    1MV0    1MV3    2FIC    2RMY    2RND   
PDB (IMB)1MUZ    1MV0    1MV3    2FIC    2RMY    2RND   
PDB (RSDB)1MUZ    1MV0    1MV3    2FIC    2RMY    2RND   
Human Protein AtlasENSG00000136717 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO00499
HPRD03150
IPIIPI00186966   IPI00220586   IPI00220587   IPI00220996   IPI00220997   IPI00329733   IPI00395680   IPI00220998   IPI00220999   IPI00221000   IPI00221001   
Protein Interaction databases
DIP (DOE-UCLA)O00499
IntAct (EBI)O00499
FunCoupENSG00000136717
BioGRIDBIN1
InParanoidO00499
Interologous Interaction database O00499
IntegromeDBBIN1
STRING (EMBL)BIN1
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  cytoplasm  endocytosis  synaptic vesicle  cell proliferation  actin cytoskeleton  viral process  Z disc  T-tubule  axon  I band  protein complex binding  node of Ranvier  muscle cell differentiation  identical protein binding  positive regulation of apoptotic process  axon initial segment  varicosity  positive regulation of GTPase activity  axon terminus  cerebellar mossy fiber  regulation of neuron differentiation  positive regulation of endocytosis  protein heterodimerization activity  tau protein binding  positive regulation of astrocyte differentiation  GTPase binding  lipid tube  lipid tube assembly  regulation of cell cycle arrest  
Ontology : EGO-EBIprotein binding  nucleus  cytoplasm  endocytosis  synaptic vesicle  cell proliferation  actin cytoskeleton  viral process  Z disc  T-tubule  axon  I band  protein complex binding  node of Ranvier  muscle cell differentiation  identical protein binding  positive regulation of apoptotic process  axon initial segment  varicosity  positive regulation of GTPase activity  axon terminus  cerebellar mossy fiber  regulation of neuron differentiation  positive regulation of endocytosis  protein heterodimerization activity  tau protein binding  positive regulation of astrocyte differentiation  GTPase binding  lipid tube  lipid tube assembly  regulation of cell cycle arrest  
Protein Interaction DatabaseBIN1
Wikipedia pathwaysBIN1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BIN1
snp3D : Map Gene to Disease274
SNP (GeneSNP Utah)BIN1
SNP : HGBaseBIN1
Genetic variants : HAPMAPBIN1
Exome VariantBIN1
1000_GenomesBIN1 
ICGC programENSG00000136717 
Somatic Mutations in Cancer : COSMICBIN1 
CONAN: Copy Number AnalysisBIN1 
Mutations and Diseases : HGMDBIN1
Mutations and Diseases : intOGenBIN1
Genomic VariantsBIN1  BIN1 [DGVbeta]
dbVarBIN1
ClinVarBIN1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM255200    601248   
MedgenBIN1
GENETestsBIN1
Disease Genetic AssociationBIN1
Huge Navigator BIN1 [HugePedia]  BIN1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneBIN1
Homology/Alignments : Family Browser (UCSC)BIN1
Phylogenetic Trees/Animal Genes : TreeFamBIN1
Chemical/Protein Interactions : CTD274
Chemical/Pharm GKB GenePA25355
Clinical trialBIN1
Cancer Resource (Charite)ENSG00000136717
Other databases
Probes
Litterature
PubMed120 Pubmed reference(s) in Entrez
CoreMineBIN1
iHOPBIN1
OncoSearchBIN1

Bibliography

BIN1 is a novel MYC-interacting protein with features of a tumour suppressor.
Sakamuro D, Elliott KJ, Wechsler-Reya R, Prendergast GC.
Nat Genet. 1996 Sep;14(1):69-77.
PMID 8782822
 
Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle.
Butler MH, David C, Ochoa GC, Freyberg Z, Daniell L, Grabs D, Cremona O, De Camilli P.
J Cell Biol. 1997 Jun 16;137(6):1355-67.
PMID 9182667
 
Structural analysis of the human BIN1 gene. Evidence for tissue-specific transcriptional regulation and alternate RNA splicing.
Wechsler-Reya R, Sakamuro D, Zhang J, Duhadaway J, Prendergast GC.
J Biol Chem. 1997 Dec 12;272(50):31453-8.
PMID 9395479
 
A role for the putative tumor suppressor Bin1 in muscle cell differentiation.
Wechsler-Reya RJ, Elliott KJ, Prendergast GC.
Mol Cell Biol. 1998 Jan;18(1):566-75.
PMID 9418903
 
Rvs167p, the budding yeast homolog of amphiphysin, colocalizes with actin patches.
Balguerie A, Sivadon P, Bonneu M, Aigle M.
J Cell Sci. 1999 Aug;112 ( Pt 15):2529-37.
PMID 10393809
 
Bin1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms.
Elliott K, Sakamuro D, Basu A, Du W, Wunner W, Staller P, Gaubatz S, Zhang H, Prochownik E, Eilers M, Prendergast GC.
Oncogene. 1999 Jun 17;18(24):3564-73.
PMID 10380878
 
Mechanism for elimination of a tumor suppressor: aberrant splicing of a brain-specific exon causes loss of function of Bin1 in melanoma.
Ge K, DuHadaway J, Du W, Herlyn M, Rodeck U, Prendergast GC.
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9689-94.
PMID 10449755
 
Investigation of a family with autosomal dominant dilated cardiomyopathy defines a novel locus on chromosome 2q14-q22.
Jung M, Poepping I, Perrot A, Ellmer AE, Wienker TF, Dietz R, Reis A, Osterziel KJ.
Am J Hum Genet. 1999 Oct;65(4):1068-77.
PMID 10486326
 
The c-Myc-interacting adaptor protein Bin1 activates a caspase-independent cell death program.
Elliott K, Ge K, Du W, Prendergast GC.
Oncogene. 2000 Sep 28;19(41):4669-84.
PMID 11032017
 
Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity.
Ge K, Duhadaway J, Sakamuro D, Wechsler-Reya R, Reynolds C, Prendergast GC.
Int J Cancer. 2000a Feb 1;85(3):376-83.
PMID 10652430
 
Loss of heterozygosity and tumor suppressor activity of Bin1 in prostate carcinoma.
Ge K, Minhas F, Duhadaway J, Mao NC, Wilson D, Buccafusca R, Sakamuro D, Nelson P, Malkowicz SB, Tomaszewski J, Prendergast GC.
Int J Cancer. 2000b Apr 15;86(2):155-61.
PMID 10738240
 
BIN1 inhibits colony formation and induces apoptosis in neuroblastoma cell lines with MYCN amplification.
Hogarty MD, Liu X, Thompson PM, White PS, Sulman EP, Maris JM, Brodeur GM.
Med Pediatr Oncol. 2000 Dec;35(6):559-62.
PMID 11107117
 
Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle.
Lee E, Marcucci M, Daniell L, Pypaert M, Weisz OA, Ochoa GC, Farsad K, Wenk MR, De Camilli P.
Science. 2002 Aug 16;297(5584):1193-6.
PMID 12183633
 
Transformation-selective apoptotic program triggered by farnesyltransferase inhibitors requires Bin1.
DuHadaway JB, Du W, Donover S, Baker J, Liu AX, Sharp DM, Muller AJ, Prendergast GC.
Oncogene. 2003 Jun 5;22(23):3578-88.
PMID 12789266
 
Immunohistochemical analysis of Bin1/Amphiphysin II in human tissues: diverse sites of nuclear expression and losses in prostate cancer.
DuHadaway JB, Lynch FJ, Brisbay S, Bueso-Ramos C, Troncoso P, McDonnell T, Prendergast GC.
J Cell Biochem. 2003 Feb 15;88(3):635-42.
PMID 12532338
 
Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer.
Humbert P, Russell S, Richardson H.
Bioessays. 2003 Jun;25(6):542-53. (REVIEW)
PMID 12766944
 
Sorting nexin 4 and amphiphysin 2, a new partnership between endocytosis and intracellular trafficking.
Leprince C, Le Scolan E, Meunier B, Fraisier V, Brandon N, De Gunzburg J, Camonis J.
J Cell Sci. 2003 May 15;116(Pt 10):1937-48. Epub 2003 Mar 26.
PMID 12668730
 
Targeted disruption of the murine Bin1/Amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation.
Muller AJ, Baker JF, DuHadaway JB, Ge K, Farmer G, Donover PS, Meade R, Reid C, Grzanna R, Roach AH, Shah N, Soler AP, Prendergast GC.
Mol Cell Biol. 2003 Jun;23(12):4295-306.
PMID 12773571
 
hob1+, the fission yeast homolog of Bin1, is dispensable for endocytosis or actin organization, but required for the response to starvation or genotoxic stress.
Routhier EL, Donover PS, Prendergast GC.
Oncogene. 2003 Feb 6;22(5):637-48.
PMID 12569356
 
Targeted deletion of the suppressor gene bin1/amphiphysin2 accentuates the neoplastic character of transformed mouse fibroblasts.
Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC.
Cancer Biol Ther. 2004 Dec;3(12):1236-42. Epub 2004 Dec 14.
PMID 15611650
 
Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy.
Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC.
Nat Med. 2005 Mar;11(3):312-9. Epub 2005 Feb 13.
PMID 15711557
 
The BAR domain proteins: molding membranes in fission, fusion, and phagy.
Ren G, Vajjhala P, Lee JS, Winsor B, Munn AL.
Microbiol Mol Biol Rev. 2006 Mar;70(1):37-120. (REVIEW)
PMID 16524918
 
Bin1 ablation increases susceptibility to cancer during aging, particularly lung cancer.
Chang MY, Boulden J, Katz JB, Wang L, Meyer TJ, Soler AP, Muller AJ, Prendergast GC.
Cancer Res. 2007a Aug 15;67(16):7605-12.
PMID 17699764
 
Bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression.
Chang MY, Boulden J, Sutanto-Ward E, Duhadaway JB, Soler AP, Muller AJ, Prendergast GC.
Cancer Res. 2007b Jan 1;67(1):100-7.
PMID 17210688
 
Methylation of the BIN1 gene promoter CpG island associated with breast and prostate cancer.
Kuznetsova EB, Kekeeva TV, Larin SS, Zemlyakova VV, Khomyakova AV, Babenko OV, Nemtsova MV, Zaletayev DV, Strelnikov VV.
J Carcinog. 2007 May 4;6:9.
PMID 17477881
 
Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.
Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL, Laporte J.
Nat Genet. 2007 Sep;39(9):1134-9. Epub 2007 Aug 5.
PMID 17676042
 
Bin1 homolog hob1 supports a Rad6-Set1 pathway of transcriptional repression in fission yeast.
Ramalingam A, Prendergast GC.
Cell Cycle. 2007 Jul 1;6(13):1655-62. Epub 2007 May 8.
PMID 17611416
 
BAR the door: cancer suppression by amphiphysin-like genes.
Prendergast GC, Muller AJ, Ramalingam A, Chang MY.
Biochim Biophys Acta. 2009 Jan;1795(1):25-36. doi: 10.1016/j.bbcan.2008.09.001. Epub 2008 Sep 18. (REVIEW)
PMID 18930786
 
BIN1 localizes the L-type calcium channel to cardiac T-tubules.
Hong TT, Smyth JW, Gao D, Chu KY, Vogan JM, Fong TS, Jensen BC, Colecraft HM, Shaw RM.
PLoS Biol. 2010 Feb 16;8(2):e1000312. doi: 10.1371/journal.pbio.1000312.
PMID 20169111
 
Identification of a novel effector domain of BIN1 for cancer suppression.
Lundgaard GL, Daniels NE, Pyndiah S, Cassimere EK, Ahmed KM, Rodrigue A, Kihara D, Post CB, Sakamuro D.
J Cell Biochem. 2011 Oct;112(10):2992-3001. doi: 10.1002/jcb.23222.
PMID 21678469
 
Bin1 attenuation suppresses experimental colitis by enforcing intestinal barrier function.
Chang MY, Boulden J, Valenzano MC, Soler AP, Muller AJ, Mullin JM, Prendergast GC.
Dig Dis Sci. 2012 Jul;57(7):1813-21. doi: 10.1007/s10620-012-2147-y. Epub 2012 Apr 18.
PMID 22526583
 
Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy.
Hong TT, Cogswell R, James CA, Kang G, Pullinger CR, Malloy MJ, Kane JP, Wojciak J, Calkins H, Scheinman MM, Tseng ZH, Ganz P, De Marco T, Judge DP, Shaw RM.
Heart Rhythm. 2012 Jun;9(6):961-7. doi: 10.1016/j.hrthm.2012.01.024. Epub 2012 Jan 31.
PMID 22300662
 
Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment.
Tanida S, Mizoshita T, Ozeki K, Tsukamoto H, Kamiya T, Kataoka H, Sakamuro D, Joh T.
Int J Surg Oncol. 2012;2012:862879. doi: 10.1155/2012/862879. Epub 2012 Jun 12.
PMID 22778941
 
Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology.
Chapuis J, Hansmannel F, Gistelinck M, Mounier A, Van Cauwenberghe C, Kolen KV, Geller F, Sottejeau Y, Harold D, Dourlen P, Grenier-Boley B, Kamatani Y, Delepine B, Demiautte F, Zelenika D, Zommer N, Hamdane M, Bellenguez C, Dartigues JF, Hauw JJ, Letronne F, Ayral AM, Sleegers K, Schellens A, Broeck LV, Engelborghs S, De Deyn PP, Vandenberghe R, O'Donovan M, Owen M, Epelbaum J, Mercken M, Karran E, Bantscheff M, Drewes G, Joberty G, Campion D, Octave JN, Berr C, Lathrop M, Callaerts P, Mann D, Williams J, Buee L, Dewachter I, Van Broeckhoven C, Amouyel P, Moechars D, Dermaut B, Lambert JC; GERAD consortium.
Mol Psychiatry. 2013 Nov;18(11):1225-34. doi: 10.1038/mp.2013.1. Epub 2013 Feb 12.
PMID 23399914
 
Alzheimer disease: BIN1 variant increases risk of Alzheimer disease through tau.
Kingwell K.
Nat Rev Neurol. 2013 Apr;9(4):184. doi: 10.1038/nrneurol.2013.34. Epub 2013 Mar 5.
PMID 23458971
 
Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease.
Tan MS, Yu JT, Tan L.
Trends Mol Med. 2013 Oct;19(10):594-603. doi: 10.1016/j.molmed.2013.06.004. Epub 2013 Jul 17. (REVIEW)
PMID 23871436
 
Bridging integrator 1 (Bin1) deficiency in zebrafish results in centronuclear myopathy.
Smith LL, Gupta VA, Beggs AH.
Hum Mol Genet. 2014 Jul 1;23(13):3566-78. doi: 10.1093/hmg/ddu067. Epub 2014 Feb 18.
PMID 24549043
 
Mutations in BIN1 associated with centronuclear myopathy disrupt membrane remodeling by affecting protein density and oligomerization.
Wu T, Shi Z, Baumgart T.
PLoS One. 2014 Apr 22;9(4):e93060. doi: 10.1371/journal.pone.0093060. eCollection 2014.
PMID 24755653
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written09-2008Mee Young Chang, George C Prendergast
Lankenau Institute for Medical Research, Lankenau Hospital, Wynnewood, Pennsylvania 19096, USA
Updated05-2014Sunil Thomas, Mee Young Chang, George C Prendergast
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA

Citation

This paper should be referenced as such :
Thomas S, Chang MY, Prendergast GC
BIN1 (Bridging Integrator 1);
Atlas Genet Cytogenet Oncol Haematol. May 2014
Free online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. May 2014
URL : http://AtlasGeneticsOncology.org/Genes/BIN1ID794ch2q14.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Sep 23 19:01:10 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.