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; OMA:BECN1 - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	42,833,350 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	101,193,112 bp
RNA expression pattern
	Top expressed in
	rectum; ; epithelium of colon; ; monocyte; ; Achilles tendon; ; gastric mucosa; ; Skeletal muscle tissue of rectus abdominis; ; gastrocnemius muscle; ; olfactory zone of nasal mucosa; ; muscle layer of sigmoid colon; ; stromal cell of endometrium;
	Top expressed in
	medullary collecting duct; ; Paneth cell; ; blood; ; endothelial cell of lymphatic vessel; ; retinal pigment epithelium; ; endocardial cushion; ; aortic valve; ; ascending aorta; ; hair follicle; ; ciliary body;
	More reference expression data
	; ;
	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; 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
	8678
	56208
	ENSG00000126581
	ENSMUSG00000035086
	Q14457
	O88597
	NM_001313998; NM_001313999; NM_001314000; NM_003766
	NM_019584; NM_001359819; NM_001359820; NM_001359821
	NP_001300927; NP_001300928; NP_001300929; NP_003757
	NP_062530; NP_001346748; NP_001346749; NP_001346750
	Wikidata
View/Edit Human	View/Edit Mouse

Beclin-1 is a protein that in humans is encoded by the BECN1 gene.^[5]^[6] Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode.^[7] 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.^[8] Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.^[9]

Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of those affected, which causes diminished autophagy which in turn results in increased neuronal cell death.^[10]

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.^[14]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000126581 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035086 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al. (November 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". Journal of Virology. 72 (11): 8586–96. doi:10.1128/JVI.72.11.8586-8596.1998. 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, et al. (August 2005). "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans". Current Biology. 15 (16): 1513–7. Bibcode:2005CBio...15.1513T. doi:10.1016/j.cub.2005.07.035. PMID 16111945. S2CID 7404414.
^ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al. (April 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.
^ ^a ^b Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, et al. (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, et al. (February 2015). "Autophagy has a key role in the pathophysiology of schizophrenia". Molecular Psychiatry. 20 (1): 126–32. doi:10.1038/mp.2013.174. PMC 4320293. PMID 24365867.*Lay summary in: Whiteman H (January 1, 2014). "New molecular discovery provides clues to cause of schizophrenia". MediLexicon International Ltd.
^ Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, et al. (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 (August 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. S2CID 10534933.
^ ^a ^b Chang C, Young LN, Morris KL, von Bülow S, Schöneberg J, Yamamoto-Imoto H, et al. (2019-01-17). "Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics". Molecular Cell. 73 (2): 339–353.e6. doi:10.1016/j.molcel.2018.10.035. ISSN 1097-4164. PMC 6450660. PMID 30581147.
^ Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (September 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. S2CID 17641899.

External links

Human BECN1 genome location and BECN1 gene details page in the UCSC Genome Browser.
Overview of all the structural information available in the PDB for UniProt: Q14457 (Beclin-1) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000126581 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000035086 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9765397-5] Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al. (November 1998). "Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein". Journal of Virology. 72 (11): 8586–96. doi:10.1128/JVI.72.11.8586-8596.1998. PMC 110269. PMID 9765397.

[entrez-6] "Entrez Gene: BECN1 beclin 1 (coiled-coil, myosin-like BCL2 interacting protein)".

[pmid16111945-7] Takacs-Vellai K, Vellai T, Puoti A, Passannante M, Wicky C, Streit A, et al. (August 2005). "Inactivation of the autophagy gene bec-1 triggers apoptotic cell death in C. elegans". Current Biology. 15 (16): 1513–7. Bibcode:2005CBio...15.1513T. doi:10.1016/j.cub.2005.07.035. PMID 16111945. S2CID 7404414.

[pmid19270693-8] Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, et al. (April 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.

[Valente_2014-9] Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, et al. (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.

[pmid24365867-10] Merenlender-Wagner A, Malishkevich A, Shemer Z, Udawela M, Gibbons A, Scarr E, et al. (February 2015). "Autophagy has a key role in the pathophysiology of schizophrenia". Molecular Psychiatry. 20 (1): 126–32. doi:10.1038/mp.2013.174. PMC 4320293. PMID 24365867.*Lay summary in: Whiteman H (January 1, 2014). "New molecular discovery provides clues to cause of schizophrenia". MediLexicon International Ltd.

[pmid17643073-11] Erlich S, Mizrachy L, Segev O, Lindenboim L, Zmira O, Adi-Harel S, et al. (2007). "Differential interactions between Beclin 1 and Bcl-2 family members". Autophagy. 3 (6): 561–8. doi:10.4161/auto.4713. PMID 17643073.

[pmid12372286-12] Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N (August 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. S2CID 10534933.

[:0-13] Chang C, Young LN, Morris KL, von Bülow S, Schöneberg J, Yamamoto-Imoto H, et al. (2019-01-17). "Bidirectional Control of Autophagy by BECN1 BARA Domain Dynamics". Molecular Cell. 73 (2): 339–353.e6. doi:10.1016/j.molcel.2018.10.035. ISSN 1097-4164. PMC 6450660. PMID 30581147.

[14] Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H (September 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. S2CID 17641899.

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