Q14457 (BECN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beclin-1

Alternative name(s):
Coiled-coil myosin-like BCL2-interacting protein
Protein GT197

Gene names

Name:	BECN1
Synonyms:	GT197

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12
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 upregulates autophagy, while the one containing Rubicon downregulates autophagy By similarity. Interacts with BCL2 and BCL2L1. Interacts with VMP1. Interacts with PIK3CB By similarity. Interacts with DAPK1. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11
Subcellular location	Golgi apparatus › trans-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.8
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylation at Thr-119 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy.
Sequence similarities	Belongs to the beclin family.

Ontologies

Keywords
Biological process	Antiviral defense Autophagy Cell cycle Cell division
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: ProtInc cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cellular defense response Traceable author statement. Source: ProtInc cytokinesis Inferred from mutant phenotype Ref.12. Source: UniProtKB response to virus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Inferred from physical interaction Ref.11. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	3	EBI-949378,EBI-77694
BCL2L1	Q07817-1	4	EBI-949378,EBI-287195
EXOC8	Q8IYI6	4	EBI-949378,EBI-742102
PIK3C3	Q8NEB9	6	EBI-949378,EBI-1056470

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 450

450

Beclin-1

PRO_0000218555

Regions

Coiled coil

142 – 270

129

Potential

Amino acid modifications

Modified residue

29

1

Phosphothreonine Ref.10

Modified residue

30

1

Phosphoserine Ref.10

Modified residue

57

1

Phosphothreonine Ref.5 Ref.10

Modified residue

62

1

Phosphothreonine Ref.10

Modified residue

64

1

Phosphoserine Ref.5 Ref.10

Modified residue

90

1

Phosphoserine Ref.10

Modified residue

93

1

Phosphoserine Ref.10

Modified residue

96

1

Phosphoserine Ref.10

Modified residue

119

1

Phosphothreonine; by DAPK1 Ref.9

Natural variations

Natural variant

103

1

A → V.

VAR_010384

Natural variant

403

1

I → T.

VAR_005236

Experimental info

Sequence conflict

150

1

T → A in AAB59573. Ref.4

Secondary structure

1

.

.

.

450

Helix Strand Turn

Details...

Helix

107 – 125

19

Sequences

	Sequence		Length	Mass (Da)
	Q14457 [UniParc]. Last modified February 21, 2001. Version 2. Checksum: ABF0C2DD7087473C	FASTA	450	51,896
	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

References

	« Hide 'large scale' referencesShow '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: 9765397] [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: 10395800] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cervix.
[4]	"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: 7490091] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 150-450. Tissue: Mammary gland.
[5]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57 AND SER-64, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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: 18843052] [Abstract] Cited for: INTERACTION WITH ATG14; PIK3C3; PIK3R4 AND UVRAG.
[7]	"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: 17724469] [Abstract] Cited for: INTERACTION WITH VMP1.
[8]	"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: 19050071] [Abstract] Cited for: INTERACTION WITH ATG14; PIK3C3 AND UVRAG, SUBCELLULAR LOCATION.
[9]	"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: 19180116] [Abstract] Cited for: PHOSPHORYLATION AT THR-119, INTERACTION WITH DAPK1.
[10]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-29; SER-30; THR-57; THR-62; SER-64; SER-90; SER-93 AND SER-96, MASS SPECTROMETRY.
[11]	"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: 19270696] [Abstract] Cited for: INTERACTION WITH ATG14; KIAA0226; PIK3C3; PIK3R4 AND UVRAG.
[12]	"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: 20208530] [Abstract] Cited for: FUNCTION.
[13]	"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: 17337444] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 107-135 IN COMPLEX WITH BCL2L1.
[14]	"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: 17659302] [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.
BC010276 mRNA. Translation: AAH10276.1.
L38932 mRNA. Translation: AAB59573.1.

IPI

IPI00748342.

PIR

I54209.

RefSeq

NP_003757.1. NM_003766.3.

UniGene

Hs.716464.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P1L	X-ray	2.50	B/D/F/H	107-135	[»]
2PON	NMR	-	A	106-128	[»]
3DVU	X-ray	2.50	C/D	105-130	[»]

ProteinModelPortal

Q14457.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44611N.

IntAct

Q14457. 55 interactions.

MINT

MINT-2865445.

STRING

Q14457.

PTM databases

PhosphoSite

Q14457.

Polymorphism databases

DMDM

13124704.

Proteomic databases

PRIDE

Q14457.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000361523; ENSP00000355231; ENSG00000126581.

GeneID

8678.

KEGG

hsa:8678.

UCSC

uc002ibn.2. human.

Organism-specific databases

CTD

8678.

GeneCards

GC17M040963.

H-InvDB

HIX0018211.

HGNC

HGNC:1034. BECN1.

HPA

CAB010143.

MIM

604378. gene.

neXtProt

NX_Q14457.

PharmGKB

PA25337.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG676980.

HOVERGEN

HBG003181.

InParanoid

Q14457.

OMA

LDTQLNI.

OrthoDB

EOG4320Z3.

PhylomeDB

Q14457.

Gene expression databases

ArrayExpress

Q14457.

Bgee

Q14457.

CleanEx

HS_BECN1.

Genevestigator

Q14457.

GermOnline

ENSG00000126581. Homo sapiens.

Family and domain databases

InterPro

IPR007243. Autophagy-rel_prot_6.
[Graphical view]

KO

K08334.

PANTHER

PTHR12768. APG6. 1 hit.

Pfam

PF04111. APG6. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

32555.

SOURCE

Search...

Entry information

Entry name

BECN1_HUMAN

Accession

Primary (citable) accession number: Q14457
Secondary accession number(s): O75595, Q9UNA8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	February 21, 2001
Last modified:	January 25, 2012
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.