BECN1

Beclin 1, autophagy related
PDB rendering based on 2p1l.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2P1L​, 2PON​, 3DVU​, 4DDP​, 4MI8​
Identifiers
Symbols	BECN1 ; ATG6; VPS30; beclin1
External IDs	OMIM: 604378 MGI: 1891828 HomoloGene: 2794 GeneCards: BECN1 Gene
Gene ontology Molecular function • protein binding • ubiquitin protein ligase binding • phosphatidylinositol 3-kinase binding Cellular component • pre-autophagosomal structure • mitochondrion • endosome • autophagosome • endoplasmic reticulum • endoplasmic reticulum membrane • trans-Golgi network • endosome membrane • cytoplasmic membrane-bounded vesicle • extrinsic component of membrane • mitochondrial membrane • phosphatidylinositol 3-kinase complex, class III, type I • phosphatidylinositol 3-kinase complex, class III, type II • phosphatidylinositol 3-kinase complex, class III • phagocytic vesicle Biological process • autophagosome assembly • cytokinesis • autophagy • cellular defense response • cellular response to nitrogen starvation • lysosome organization • mitotic metaphase plate congression • negative regulation of cell proliferation • positive regulation of autophagy • viral process • macroautophagy • CVT pathway • regulation of cytokinesis • receptor catabolic process • cellular response to glucose starvation • negative regulation of apoptotic process • engulfment of apoptotic cell • nucleophagy • late endosome to vacuole transport • neuron development • beta-amyloid metabolic process • regulation of catalytic activity • defense response to virus • activation of mitophagy in response to mitochondrial depolarization • positive regulation of attachment of mitotic spindle microtubules to kinetochore • positive regulation of mitophagy • negative regulation of reactive oxygen species metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8678	56208
Ensembl	ENSG00000126581	ENSMUSG00000035086
UniProt	Q14457	O88597
RefSeq (mRNA)	NM_003766	NM_019584
RefSeq (protein)	NP_003757	NP_062530
Location (UCSC)	Chr 17: 42.81 – 42.83 Mb	Chr 11: 101.29 – 101.3 Mb
PubMed search

Beclin-1 is a protein that in humans is encoded by the BECN1 gene.^[1][2] Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6)  and BEC-1 in the C. elegans nematode.^[3] 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.^[4] Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.^[5]

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.^[6]

Interactions

BECN1 has been shown to interact with:

• Bcl-2^[1]
• BCL2L2^[7]
• GOPC^[8]
• MAP1LC3A^[5]

Modulators

Trehalose

Trehalose reduces p62/Beclin-1 ratio and increases autophagy in the frontal cortex of ICR mice, possibly by increasing Beclin-1.^[9]

References

1. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B (Nov 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". Journal of Virology 72 (11): 8586–96. PMC 110269. PMID 9765397.
2. "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)".
3. Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, Kovacs AL, Müller F (Aug 2005). "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans". Current Biology 15 (16): 1513–7. doi:10.1016/j.cub.2005.07.035. PMID 16111945.
4. Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (Apr 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex". Nature Cell Biology 11 (4): 468–76. doi:10.1038/ncb1854. PMC 2664389. PMID 19270693.
5. Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C (2014). "Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer". BioMed Research International 2014: 462658. doi:10.1155/2014/462658. PMC 4127242. PMID 25136588.
6. Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, Dean B, Levine J, Agam G, Gozes I (Feb 2015). "Autophagy has a key role in the pathophysiology of schizophrenia". Molecular Psychiatry 20 (1): 126–32. doi:10.1038/mp.2013.174. PMID 24365867. Lay summary – MediLexicon International Ltd.
7. Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, Hirsch JA, Stein R, Pinkas-Kramarski R (2007). "Differential interactions between Beclin 1 and Bcl-2 family members". Autophagy 3 (6): 561–8. doi:10.4161/auto.4713. PMID 17643073.
8. 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.
9. Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (Sep 2013). "Trehalose induced antidepressant-like effects and autophagy enhancement in mice". Psychopharmacology 229 (2): 367–75. doi:10.1007/s00213-013-3119-4. PMID 23644913.

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.
• 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.
• 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.
• 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.