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Q14457 (BECN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beclin-1
Alternative name(s):
Coiled-coil myosin-like BCL2-interacting protein
Protein GT197
Gene names
Name:BECN1
Synonyms:GT197
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length450 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense. Protects against infection by a neurovirulent strain of Sindbis virus. Ref.13

Subunit structure

Interacts with GOPC and GRID2. Interacts with AMBRA1. Forms a complex with PIK3C3 and PIK3R4 and either UVRAG and KIAA0226/Rubicon, or with ATG14. UVRAG and ATG14 form mutually exclusive complexes through direct competition for BECN1-binding. The complex containing ATG14 up-regulates autophagy, while the one containing Rubicon down-regulates autophagy By similarity. Interacts with BCL2 and BCL2L1. Interacts with VMP1. Interacts with PIK3CB By similarity. Interacts with DAPK1. Interacts with human cytomegalovirus/HHV-5 protein TRS1. Ref.1 Ref.6 Ref.8 Ref.9 Ref.10 Ref.12 Ref.14 Ref.16

Subcellular location

Golgi apparatustrans-Golgi network membrane; Peripheral membrane protein. Note: Interaction with ATG14 promotes translocation to autophagosomes. Expressed in dendrites and cell bodies of cerebellar Purkinje cells By similarity. Ref.9

Tissue specificity

Ubiquitous.

Post-translational modification

Phosphorylation at Thr-119 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy.

polyubiquitinated by NEDD4, both with 'Lys11'- and 'Lys63'-linkages. 'Lys'-11-linked poyubiquitination leads to degradation and is enhanced when the stabilizing interaction partner VPS34 is depleted. Deubiquitinated by USP10 and USP13, leading to stabilize the PIK3C3/VPS34-containing complexes.

Sequence similarities

Belongs to the beclin family.

Ontologies

Keywords
   Biological processAntiviral defense
Autophagy
Cell cycle
Cell division
Host-virus interaction
   Cellular componentGolgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processautophagic vacuole assembly

Inferred from electronic annotation. Source: Ensembl

beta-amyloid metabolic process

Inferred from electronic annotation. Source: Ensembl

cellular defense response

Traceable author statement Ref.1. Source: ProtInc

cellular response to aluminum ion

Inferred from electronic annotation. Source: Ensembl

cellular response to epidermal growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cytokinesis

Inferred from mutant phenotype Ref.13. Source: UniProtKB

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

lysosome organization

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Traceable author statement Ref.1. Source: ProtInc

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

neuron development

Inferred from electronic annotation. Source: Ensembl

positive regulation of macroautophagy

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to vitamin E

Inferred from electronic annotation. Source: Ensembl

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 16417406Ref.8Ref.12Ref.14. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 450450Beclin-1
PRO_0000218555

Regions

Coiled coil142 – 270129 Potential
Motif108 – 12720BH3

Amino acid modifications

Modified residue11N-acetylmethionine Ref.17
Modified residue1191Phosphothreonine; by DAPK1 Ref.10

Natural variations

Natural variant1031A → V.
VAR_010384
Natural variant4031I → T.
VAR_005236

Experimental info

Mutagenesis3521Y → A: Significantly reduces ubiquitination. Ref.15
Sequence conflict1501T → A in AAB59573. Ref.5
Sequence conflict1611N → S in BAG35534. Ref.3
Sequence conflict3141L → H in BAG35534. Ref.3

Secondary structure

................................. 450
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14457 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: ABF0C2DD7087473C

FASTA45051,896
        10         20         30         40         50         60 
MEGSKTSNNS TMQVSFVCQR CSQPLKLDTS FKILDRVTIQ ELTAPLLTTA QAKPGETQEE 

        70         80         90        100        110        120 
ETNSGEEPFI ETPRQDGVSR RFIPPARMMS TESANSFTLI GEASDGGTME NLSRRLKVTG 

       130        140        150        160        170        180 
DLFDIMSGQT DVDHPLCEEC TDTLLDQLDT QLNVTENECQ NYKRCLEILE QMNEDDSEQL 

       190        200        210        220        230        240 
QMELKELALE EERLIQELED VEKNRKIVAE NLEKVQAEAE RLDQEEAQYQ REYSEFKRQQ 

       250        260        270        280        290        300 
LELDDELKSV ENQMRYAQTQ LDKLKKTNVF NATFHIWHSG QFGTINNFRL GRLPSVPVEW 

       310        320        330        340        350        360 
NEINAAWGQT VLLLHALANK MGLKFQRYRL VPYGNHSYLE SLTDKSKELP LYCSGGLRFF 

       370        380        390        400        410        420 
WDNKFDHAMV AFLDCVQQFK EEVEKGETRF CLPYRMDVEK GKIEDTGGSG GSYSIKTQFN 

       430        440        450 
SEEQWTKALK FMLTNLKWGL AWVSSQFYNK 

« Hide

References

« Hide 'large scale' references
[1]"Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein."
Liang X.H., Kleeman L.K., Jiang H.H., Gordon G., Goldman J.E., Berry G., Herman B., Levine B.
J. Virol. 72:8586-8596(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH BCL-2.
Tissue: Brain.
[2]"Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21."
Aita V.M., Liang X.H., Murty V.V.V.S., Pincus D.L., Yu W., Cayanis E., Kalachikov S., Gilliam T.C., Levine B.
Genomics 59:59-65(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cervix.
[5]"Generation of a transcription map at the HSD17B locus centromeric to BRCA1 at 17q21."
Rommens J.M., Durocher F., McArthur J., Tonin P., Leblanc J.-F., Allen T., Samson C., Ferri L., Narod S., Morgan K., Simard J.
Genomics 28:530-542(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-450.
Tissue: Mammary gland.
[6]"Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG."
Itakura E., Kishi C., Inoue K., Mizushima N.
Mol. Biol. Cell 19:5360-5372(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG14; PIK3C3; PIK3R4 AND UVRAG.
[7]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells."
Sauermann M., Sahin O., Sultmann H., Hahne F., Blaszkiewicz S., Majety M., Zatloukal K., Fuzesi L., Poustka A., Wiemann S., Arlt D.
Oncogene 27:1320-1326(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VMP1.
[9]"Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase."
Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.
Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG14; PIK3C3 AND UVRAG, SUBCELLULAR LOCATION.
[10]"DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy."
Zalckvar E., Berissi H., Mizrachy L., Idelchuk Y., Koren I., Eisenstein M., Sabanay H., Pinkas-Kramarski R., Kimchi A.
EMBO Rep. 10:285-292(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-119, INTERACTION WITH DAPK1.
[11]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages."
Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N., Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T., Yoshimori T.
Nat. Cell Biol. 11:385-396(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG14; KIAA0226; PIK3C3; PIK3R4 AND UVRAG.
[13]"PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody."
Sagona A.P., Nezis I.P., Pedersen N.M., Liestol K., Poulton J., Rusten T.E., Skotheim R.I., Raiborg C., Stenmark H.
Nat. Cell Biol. 12:362-371(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13."
Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V., Zhang T., Furuya T., Jin M., Zhu Z., Wang H., Yu J., Li Y., Hao Y., Choi A., Ke H., Ma D., Yuan J.
Cell 147:223-234(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH USP10 AND USP13.
[15]"Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1."
Platta H.W., Abrahamsen H., Thoresen S.B., Stenmark H.
Biochem. J. 441:399-406(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY NEDD4, MUTAGENESIS OF TYR-352.
[16]"The human cytomegalovirus protein TRS1 inhibits autophagy via its interaction with Beclin 1."
Chaumorcel M., Lussignol M., Mouna L., Cavignac Y., Fahie K., Cotte-Laffitte J., Geballe A., Brune W., Beau I., Codogno P., Esclatine A.
J. Virol. 86:2571-2584(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HHV-5 PROTEIN TRS1.
[17]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein."
Oberstein A., Jeffrey P.D., Shi Y.
J. Biol. Chem. 282:13123-13132(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 107-135 IN COMPLEX WITH BCL2L1, DOMAIN BH3 MOTIF.
[19]"Molecular basis of Bcl-xL's target recognition versatility revealed by the structure of Bcl-xL in complex with the BH3 domain of beclin-1."
Feng W., Huang S., Wu H., Zhang M.
J. Mol. Biol. 372:223-235(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 106-128 IN COMPLEX WITH BCL2L1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF077301 mRNA. Translation: AAC68653.1.
AF139131 mRNA. Translation: AAD27650.1.
AK312651 mRNA. Translation: BAG35534.1.
BC010276 mRNA. Translation: AAH10276.1.
L38932 mRNA. Translation: AAB59573.1.
CCDSCCDS11441.1.
PIRI54209.
RefSeqNP_003757.1. NM_003766.3.
XP_005257815.1. XM_005257758.1.
UniGeneHs.716464.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2P1LX-ray2.50B/D/F/H107-135[»]
2PONNMR-A106-128[»]
3DVUX-ray2.50C/D105-130[»]
4DDPX-ray1.55A241-450[»]
4MI8X-ray2.10C/D107-130[»]
ProteinModelPortalQ14457.
SMRQ14457. Positions 176-447.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114226. 45 interactions.
DIPDIP-44611N.
IntActQ14457. 73 interactions.
MINTMINT-2865445.
STRING9606.ENSP00000355231.

PTM databases

PhosphoSiteQ14457.

Polymorphism databases

DMDM13124704.

Proteomic databases

MaxQBQ14457.
PaxDbQ14457.
PRIDEQ14457.

Protocols and materials databases

DNASU8678.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361523; ENSP00000355231; ENSG00000126581.
ENST00000590099; ENSP00000465364; ENSG00000126581.
GeneID8678.
KEGGhsa:8678.
UCSCuc002ibn.2. human.

Organism-specific databases

CTD8678.
GeneCardsGC17M040963.
HGNCHGNC:1034. BECN1.
HPACAB010143.
MIM604378. gene.
neXtProtNX_Q14457.
PharmGKBPA25337.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285533.
HOGENOMHOG000158093.
HOVERGENHBG003181.
InParanoidQ14457.
KOK08334.
OMAYIPPARM.
OrthoDBEOG7D2FDG.
PhylomeDBQ14457.
TreeFamTF314282.

Gene expression databases

ArrayExpressQ14457.
BgeeQ14457.
CleanExHS_BECN1.
GenevestigatorQ14457.

Family and domain databases

InterProIPR007243. Atg6/Beclin.
IPR029318. BH3_dom.
[Graphical view]
PANTHERPTHR12768. PTHR12768. 1 hit.
PfamPF04111. APG6. 1 hit.
PF15285. BH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBECN1. human.
EvolutionaryTraceQ14457.
GeneWikiBECN1.
GenomeRNAi8678.
NextBio32555.
PROQ14457.
SOURCESearch...

Entry information

Entry nameBECN1_HUMAN
AccessionPrimary (citable) accession number: Q14457
Secondary accession number(s): B2R6N7, O75595, Q9UNA8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: July 9, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM