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FLASH GENE
Symbol BECN1 contributors: mct/ - updated : 10-03-2017
HGNC name beclin 1, autophagy related
HGNC id 1034
Location 17q21.31      Physical location : 40.962.149 - 40.976.310
Synonym name
  • autophagic gene 6
  • beclin 1
  • coiled-coil, myosin-like BCL2 interacting protein
  • ATG6 autophagy related 6 homolog (S. cerevisiae)
  • protein GT197
  • Synonym symbol(s) GT197, ATG6, VPS30, beclin1
    DNA
    TYPE functioning gene
    STRUCTURE 14.16 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure conserved NF-KB binding site in the promoter, specifically interacting with RELA (Copetti (2009)
    MAPPING cloned Y linked N status provisional
    Map cen - D17S1320 - TUBG1 - D17S1321 - EZH1 - PSME3 - BECN1 - G6PC - AOC3P - D17S1328 - BRCA1 BRCA1 - qter
    Physical map
    PTRF 17q21.2 polymerase I and transcript release factor ATP6V0A1 17q21.3 ATPase, H+ transporting, lysosomal V0 subunit a isoform 1 NAGLU 17q21.1 N-acetylglucosaminidase, alpha- (Sanfilippo disease IIIB) HSD17BP1 17q11-q21 hydroxysteroid (17-beta) dehydrogenase pseudogene 1 HSD17B1 17q21.1 hydroxysteroid (17-beta) dehydrogenase 1 DPCK 17q12-q21 bifunctional phosphopantetheine adenylyl transferase/dephospho CoA kinase TCFL4 17q21.1 transcription factor-like 4 HUMGT198A 17q12-q21 GT198, complete ORF LOC162427 17q21.31 hypothetical protein LOC162427 TUBG1 17q21 tubulin, gamma 1 LOC342578 17q21.31 similar to high mobility group protein homolog HMG4 TUBG2 17q21 tubulin, gamma 2 FLJ21019 17q21.31 hypothetical protein FLJ21019 GPR2 17q21.1 G protein-coupled receptor 2 CNTNAP1 17q21 contactin associated protein 1 EZH1 17q21 enhancer of zeste homolog 1 (Drosophila) RAMP2 17q12-q21.1 receptor (calcitonin) activity modifying protein 2 MGC10540 17q21.31 hypothetical protein MGC10540 PRKWNK4 17q12 protein kinase, lysine deficient 4 HSPC009 17q21 HSPC009 protein FLJ40137 17q21.31 hypothetical protein FLJ40137 BECN1 17q21 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein) PSME3 17q21 proteasome (prosome, macropain) activator subunit 3 (PA28 gamma; Ki) AOC2 17q21 amine oxidase, copper containing 2 (retina-specific) AOC3 17q21 amine oxidase, copper containing 3 (vascular adhesion protein 1) LOC90586 17q21.31 amine oxidase pseudogene LOC388387 17 hypothetical gene supported by AK055784 G6PC 17q21 glucose-6-phosphatase, catalytic (glycogen storage disease type I, von Gierke disease) MGC2744 17q21.31 hypothetical protein MGC2744 DKFZp761H0421 17q21.31 hypothetical protein DKFZp761H0421 RPL27 17q21 ribosomal protein L27 IFI35 17q21 interferon-induced protein 35 VAT1 17q21 vesicle amine transport protein 1 homolog (T californica) ARHN 17q21 ras homolog gene family, member N BRCA1 17q21 breast cancer 1, early onset RPL21P4 17q21 ribosomal protein L21 pseudogene 4 NBR2 17q21 neighbor of BRCA1 gene 2 LOC387620 17 membrane component, chromosome 17, surface marker 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 2143 51.8 450 - - 10395800
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vessel   highly
    Digestiveliver   highly
    Endocrineneuroendocrinepituitary  highly
     parathyroid   highly
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal BH3 domain
  • a coiled coil domain (CCD) that serves as an interaction platform for assembly of distinct ATG14- and UVRAG-containing complexes to modulate PIK3C3 activity
  • short leucine-rich nuclear export signal (NES) required for autophagy
  • an evolutionarily conserved domain at the C terminus
  • mono polymer complex
    HOMOLOGY
    interspecies homolog to rattus Becn1 (97.8 pc)
    homolog to murine Becn1 (98.4 pc)
    ortholog to yeast Atg6
    Homologene
    FAMILY
  • beclin family
  • CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text
  • golgi apparatus membrane (normally localizes to the trans-Golgi network)
  • peripheral membrane protein
  • with PINK1, localize to the mitochondrial compartment
  • basic FUNCTION
  • potentially involved in antiviral host defense
  • autophagy gene playing an essential role in early embryonic development and in the regulation of tumor development
  • essential to maintain cellular ATP energy production, macromolecular synthesis and cell survival
  • playing a necessary role in non-apoptotic death pathway
  • is required for the clearance of apoptotic cells during embryonic development
  • playing a role in autophagy and in cancer development
  • proautophagic protein, tumor-suppressor factor and interactor of the anti-apoptotic protein BCL2
  • essential regulator of autophagy and plays an active role in programmed cell death
  • phosphatidylinositol 3-kinase class III sub-complex containing PIK3R4, PIK3C3, BECN1, UVRAG and SH3GLB1 regulates cytokinesis and degradative endocytic traffic
  • central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle
  • Beclin 1 dysfunction has been implicated in many disorders, including cancer and neurodegeneration
  • essential autophagic protein, which has a crucial role in the initial stages of autophagy
  • controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities
  • regulates apoptotic cell engulfment in cooperation with RAC1
  • regulator of autophagy that is required for apoptotic cell engulfment
  • coordinates actin dynamics and membrane phospholipid synthesis to promote efficient apoptotic cell engulfment
  • is required for the phagosome maturation to degrade engulfed apoptotic cells
  • is emerging as a central node of autophagy regulation via cross-talk with diverse cellular and viral autophagy stimulatory or inhibitory proteins
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
  • component of the class III phosphatidylinositol 3-kinase (PI3KC3) complex, which also contains a PI3K catalytic subunit and a regulatory subunit (p150)
  • part of the BECN1-PIK3C3 complex that regulate APP processing and play an important role in Alzheimer Disease pathology
  • phosphatidylinositol 3-kinase class III sub-complex containing PIK3R4, PIK3C3, BECN1, UVRAG and SH3GLB1 regulates cytokinesis and degradative endocytic traffic
  • central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle
  • BECN1/PIK3C3 complex plays a crucial role in autophagosome formation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • BCL2-binding disrupt BECN1 autophagy function, by inhibiting the formation of the BECN1/PI3K complex
  • interacting with APG7L for autophagic death (induced by CASP8 inhibition)
  • interacting with GOPC and GRID2
  • physically bind to survivin (BIRC5)
  • can interact with the anti-apoptotic protein BCL2 and this interaction impacts on the activity of both apoptosis and autophagy
  • RELA target gene and present evidence that blockage of RELA signaling leads to a decrease in BECN1 transcription
  • interacts with PINK1 and enhances autophagy
  • interaction between BECN1 and BIRC5 affects the sensitivity of human glioma cells to TNFSF10-induced apoptosis
  • interaction with HRAS (HRAS-induced expression of PMAIP1 and Beclin-1 promotes autophagic cell death)
  • interacting with USP13 and USP10 (BECN1 controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities)
  • TAB2 and TAB3 bind to BECN1 and colocalize in the cytoplasm
  • BECN1 cooperates with RAC1
  • SLAMF1 interacts with the class III PIK3C3 in a complex with BECN1 and UVRAG
  • ATG14 directly interacts with BECN1 through its coiled-coil domain and enhances phosphatidylinositol 3-phosphate kinase class III (PI3KC3) activity to induce autophagosome membrane nucleation
  • actin filaments colocalized with ATG14, BECN1/Beclin1 and PtdIns3P-rich structures, and some of them have a typical omegasome shape stained with the double FYVE domain or ZFYVE1
  • EMC6 interacted with both RAB5A and BECN1/Beclin 1 and colocalized with the omegasome marker ZFYVE1/DFCP1
  • spliced XBP1 translocates into the nucleus and binds as homodimer or heterodimer to the BECN1 gene promoter, leading to BECN1 transcription
  • induces autophagy by disrupting the association between BCL2 and BECN1
  • AMPK directly phosphorylates PIK3C3 and BECN1 to regulate non- and pro-autophagic PIK3C3 complexes, respectively
  • ATG14 is critical in controlling an autophagy-dependent phosphorylation of BECN1
  • WASH1 can suppress BECN1 ubiquitination to inactivate PIK3C3 activity leading to suppression of autophagy
  • EGFR suppression of BECN1 may contribute to tumor progression in lung cancer
  • ligand-dependent EGFR activation leads to the interaction of EGFR and BECN1, which likely occurs primarily in endosomes
  • deubiquitylated RALB promotes the assembly of the RALB-EXOC8-BECN1 complexes driving autophagosome formation
  • PRNP interacts with BECN1 to recruit the PIK3C3 complex into lipid rafts and thus activates autophagy in response to Abeta42, defining a novel role of PRNP in the regulation of autophagy
  • RASD2 robustly binds the autophagy regulator BECN1, decreasing its inhibitory interaction with BCL2 independent of MAPK8 signaling
  • BECN1 interacts with the Parkinson disease-related protein PARK2 (BECN1 interacts with PARK2 and regulates PARK2 translocation to mitochondria as well as PARK2-induced mitophagy prior to autophagosome formation)
  • WASH1 is a new interactor of BECN1 and present in the BECN1-PIK3C3 complex with AMBRA1
  • DACT1 enhances the ATG14-BECN1-PIK3C3 complex formation and PIK3C3 kinase activity
  • NRBF2-BECN1 interaction required the N terminus of NRBF2
  • NRBF2 may interact with the ATG14-containing BECN1-PIK3C3 protein complex to modulate protein-protein interactions within the complex, leading to suppression of PIK3C3 activity, autophagosome biogenesis, and autophagic flux
  • XIAP and BIRC2 induce autophagy by upregulating the transcription of BECN1, an essential autophagy gene
  • SMAD2 is the major transcriptional regulator of autophagy that targets beclin1 (BECN1) gene expression
  • GADD45A inhibits autophagy via impairing the BECN1-PIK3C3 complex formation
  • dual functions of the USP19-BECN1 axis by balancing autophagy and the production of type IIFNs
  • ERBB2 interacts with BECN1 in breast cancer cells and inhibits autophagy
  • RNF216 regulates the migration of GNRH1 neuron by suppressing BECN1 mediated autophagy, suggesting a potential contribution of autophagy to the hypogonadotropic hypogonadism
  • cell & other
    REGULATION
    activated by RELA (Copetti 2009)
    JNK activation (upregulated Beclin-1 expression and induced BCL2 and TP53 phosphorylation)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    frequently monoallelically deleted in breast cancer cell lines, in ovarian and prostate cancer
    constitutional     --low  
    decreases in an age-dependent manner in human brains, leading to a reduction of autophagy with aging, which possibly contributes to the progression of neurodegenerative diseases
    constitutional       loss of function
    may contribute to genome instability and to a defective autophagy that may lead to tumoral cell death in presence of competent apoptosis or senescence pathways
    tumoral     --low  
    loss of beclin 1 and ERBB2 amplification (both on 17q21) in breast cancers )
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target potentially important interaction between BECN1 and BIRC5 having therapeutic implication in human tumor cells
    SystemTypeDisorderPubmed
    tumor  
    ANIMAL & CELL MODELS