BECN1

BECN1
Available structures PDB Ortholog search: K7ER46 PDBe K7ER46 RCSB List of PDB id codes 2P1L, 2PON, 3DVU, 4DDP, 4MI8
Identifiers
Aliases	BECN1, ATG6, VPS30, beclin1, beclin 1
External IDs	OMIM: 604378 MGI: 1891828 HomoloGene: 2794 GeneCards: BECN1
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.31 Start 42,810,134 bp End 42,833,350 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 D Start 101,176,778 bp End 101,193,112 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in rectum monocyte Achilles tendon gastric mucosa gastrocnemius muscle stromal cell of endometrium Brodmann area 10 transverse colon islet of Langerhans jejunal mucosa Top expressed in medullary collecting duct Paneth cell blood retinal pigment epithelium endocardial cushion aortic valve ascending aorta hair follicle ciliary body facial motor nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function phosphatidylinositol 3-kinase binding protein binding GTPase binding ubiquitin protein ligase binding protein kinase binding protein homodimerization activity Cellular component endosome membrane cytoplasm mitochondrial membranes trans-Golgi network Golgi apparatus cytosol nucleus autophagosome phagophore assembly site membrane dendrite endoplasmic reticulum phosphatidylinositol 3-kinase complex, class III endoplasmic reticulum membrane phosphatidylinositol 3-kinase complex, class III, type II cytoplasmic vesicle endosome extrinsic component of membrane phosphatidylinositol 3-kinase complex, class III, type I phagocytic vesicle mitochondrion protein-containing complex Biological process negative regulation of cell population proliferation response to hypoxia cellular response to aluminum ion response to vitamin E lysosome organization cell cycle positive regulation of phosphatidylinositol 3-kinase signaling cellular response to glucose starvation cellular defense response cytokinesis cellular response to epidermal growth factor stimulus cell division receptor catabolic process autophagy of nucleus cellular response to nitrogen starvation viral process late endosome to vacuole transport apoptotic process cytoplasm to vacuole transport by the Cvt pathway endocytosis engulfment of apoptotic cell positive regulation of attachment of mitotic spindle microtubules to kinetochore amyloid-beta metabolic process neuron development defense response to virus response to other organism mitotic metaphase plate congression regulation of catalytic activity negative regulation of reactive oxygen species metabolic process regulation of cytokinesis negative regulation of apoptotic process negative regulation of cell death autophagosome assembly macroautophagy human ageing response to iron(II) ion response to lead ion protein deubiquitination response to nutrient levels cellular response to amino acid starvation cellular response to hydrogen peroxide cellular response to copper ion negative regulation of lysosome organization positive regulation of autophagosome assembly autophagy of mitochondrion mitophagy autophagy positive regulation of autophagy response to mitochondrial depolarisation early endosome to late endosome transport negative regulation of autophagy positive regulation of cardiac muscle hypertrophy negative regulation of autophagosome assembly positive regulation of intrinsic apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8678 56208 Ensembl ENSG00000126581 ENSMUSG00000035086 UniProt Q14457 O88597 RefSeq (mRNA) NM_001313998 NM_001313999 NM_001314000 NM_003766 NM_019584 NM_001359819 NM_001359820 NM_001359821 RefSeq (protein) NP_001300927 NP_001300928 NP_001300929 NP_003757 NP_062530 NP_001346748 NP_001346749 NP_001346750 Location (UCSC) Chr 17: 42.81 – 42.83 Mb Chr 11: 101.18 – 101.19 Mb PubMed search
Wikidata
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Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6)  and BEC-1 in the C. elegans nematode. This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.

Role in disease

Beclin-1 plays an important role in tumorigenesis, and neurodegeneration, being implicated in the autophagic programmed cell death. Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.

Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of the affected which causes diminished autophagy which in turn results in increased neuronal cell death.

Interactions

BECN1 has been shown to interact with:

• Bcl-2
• BCL2L2
• GOPC
• MAP1LC3A

Modulators

Trehalose

Trehalose reduces p62/Beclin-1 ratio and increases autophagy in the frontal cortex of ICR mice, possibly by increasing Beclin-1.

Further reading

• Funderburk SF, Wang QJ, Yue Z (Jun 2010). "The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond". Trends in Cell Biology. 20 (6): 355–62. doi:10.1016/j.tcb.2010.03.002. PMID 20356743.
• Rommens JM, Durocher F, McArthur J, Tonin P, LeBlanc JF, Allen T, Samson C, Ferri L, Narod S, Morgan K (Aug 1995). "Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21". Genomics. 28 (3): 530–42. doi:10.1006/geno.1995.1185. PMID 7490091.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Aita VM, Liang XH, Murty VV, Pincus DL, Yu W, Cayanis E, Kalachikov S, Gilliam TC, Levine B (Jul 1999). "Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21". Genomics. 59 (1): 59–65. doi:10.1006/geno.1999.5851. PMID 10395800.
• Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B (Dec 1999). "Induction of autophagy and inhibition of tumorigenesis by beclin 1". Nature. 402 (6762): 672–6. doi:10.1038/45257. PMID 10604474.
• Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (Apr 2001). "Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network". EMBO Reports. 2 (4): 330–5. doi:10.1093/embo-reports/kve061. PMC 1083858. PMID 11306555.
• Liang XH, Yu J, Brown K, Levine B (Apr 2001). "Beclin 1 contains a leucine-rich nuclear export signal that is required for its autophagy and tumor suppressor function". Cancer Research. 61 (8): 3443–9. PMID 11309306.
• Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ (Oct 2001). "Use of chromatin immunoprecipitation to clone novel E2F target promoters". Molecular and Cellular Biology. 21 (20): 6820–32. doi:10.1128/MCB.21.20.6820-6832.2001. PMC 99859. PMID 11564866.
• Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (Aug 2002). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice". Neuron. 35 (5): 921–33. doi:10.1016/S0896-6273(02)00861-9. PMID 12372286.
• Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ (Feb 2004). "Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in human primary hepatocellular carcinoma". World Journal of Gastroenterology. 10 (4): 509–13. doi:10.3748/wjg.v10.i4.509. PMID 14966907.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Scarlatti F, Bauvy C, Ventruti A, Sala G, Cluzeaud F, Vandewalle A, Ghidoni R, Codogno P (Apr 2004). "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". The Journal of Biological Chemistry. 279 (18): 18384–91. doi:10.1074/jbc.M313561200. PMID 14970205.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Furuya D, Tsuji N, Yagihashi A, Watanabe N (Jul 2005). "Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research. 307 (1): 26–40. doi:10.1016/j.yexcr.2005.02.023. PMID 15922724.
• Kruse KB, Brodsky JL, McCracken AA (Jan 2006). "Characterization of an ERAD gene as VPS30/ATG6 reveals two alternative and functionally distinct protein quality control pathways: one for soluble Z variant of human alpha-1 proteinase inhibitor (A1PiZ) and another for aggregates of A1PiZ". Molecular Biology of the Cell. 17 (1): 203–12. doi:10.1091/mbc.E04-09-0779. PMC 1345659. PMID 16267277.
• Zeng X, Overmeyer JH, Maltese WA (Jan 2006). "Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking". Journal of Cell Science. 119 (Pt 2): 259–70. doi:10.1242/jcs.02735. PMID 16390869.
• Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J (May 2006). "Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1". The Journal of Biological Chemistry. 281 (20): 14474–85. doi:10.1074/jbc.M600364200. PMID 16522639.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
• Daniel F, Legrand A, Pessayre D, Vadrot N, Descatoire V, Bernuau D (May 2006). "Partial Beclin 1 silencing aggravates doxorubicin- and Fas-induced apoptosis in HepG2 cells". World Journal of Gastroenterology. 12 (18): 2895–900. PMID 16718815.