BECN1

Beclin 1, autophagy related

PDB rendering based on 2p1l.

Available structures

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

RefSeq (mRNA)

RefSeq (protein)

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:

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 2 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.
↑ "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)".
↑ 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.
↑ 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.
1 2 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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.

PDB gallery

2p1l: Structure of the Bcl-XL:Beclin 1 complex

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BECN1

Role in disease

Interactions

Modulators

References

Further reading