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FLASH GENE

Symbol

BECN1

contributors: mct/ - updated : 10-03-2017

HGNC name	beclin 1, autophagy related
HGNC id	1034

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003766 12 - 2143 NP_003757 51.8 450 - - 10395800

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly   vessel       highly Digestive liver       highly Endocrine neuroendocrine pituitary     highly   parathyroid       highly Lymphoid/Immune spleen       highly Reproductive female system uterus cervix   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective bone       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed tumor

ANIMAL & CELL MODELS