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UniProtKB - Q14457 (BECN1_HUMAN)

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Protein

Beclin-1

Gene

BECN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a central role in autophagy (PubMed:23184933). Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). Protects against infection by a neurovirulent strain of Sindbis virus (PubMed:9765397). May play a role in antiviral host defense.Curated5 Publications
Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors.2 Publications

GO - Molecular functioni

  • GTPase binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • aging Source: Ensembl
  • apoptotic process Source: UniProtKB-KW
  • autophagosome assembly Source: UniProtKB
  • autophagy Source: CAFA
  • beta-amyloid metabolic process Source: Ensembl
  • cellular defense response Source: ProtInc
  • cellular response to aluminum ion Source: Ensembl
  • cellular response to amino acid starvation Source: Ensembl
  • cellular response to copper ion Source: Ensembl
  • cellular response to epidermal growth factor stimulus Source: Ensembl
  • cellular response to glucose starvation Source: UniProtKB
  • cellular response to hydrogen peroxide Source: Ensembl
  • cellular response to nitrogen starvation Source: GO_Central
  • cytokinesis Source: UniProtKB
  • defense response to virus Source: UniProtKB-KW
  • engulfment of apoptotic cell Source: Ensembl
  • late endosome to vacuole transport Source: GO_Central
  • lysosome organization Source: Ensembl
  • macroautophagy Source: UniProtKB
  • macromitophagy Source: ParkinsonsUK-UCL
  • mitophagy Source: ParkinsonsUK-UCL
  • mitotic metaphase plate congression Source: CACAO
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of cell death Source: MGI
  • negative regulation of cell proliferation Source: Ensembl
  • negative regulation of lysosome organization Source: Ensembl
  • negative regulation of reactive oxygen species metabolic process Source: Ensembl
  • neuron development Source: Ensembl
  • nucleophagy Source: GO_Central
  • positive regulation of attachment of mitotic spindle microtubules to kinetochore Source: CACAO
  • positive regulation of autophagosome assembly Source: Ensembl
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: ParkinsonsUK-UCL
  • protein deubiquitination Source: Reactome
  • receptor catabolic process Source: UniProtKB
  • regulation of catalytic activity Source: Ensembl
  • regulation of cytokinesis Source: UniProtKB
  • response to drug Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to iron(II) ion Source: Ensembl
  • response to lead ion Source: Ensembl
  • response to mitochondrial depolarisation Source: BHF-UCL
  • response to vitamin E Source: Ensembl
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywordsi

Biological processAntiviral defense, Apoptosis, Autophagy, Cell cycle, Cell division, Endocytosis, Host-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-5689880. Ub-specific processing proteases.
SIGNORiQ14457.

Names & Taxonomyi

Protein namesi
Recommended name:
Beclin-1
Alternative name(s):
Coiled-coil myosin-like BCL2-interacting protein
Protein GT197
Cleaved into the following 2 chains:
Beclin-1-C 35 kDa1 Publication
Beclin-1-C 37 kDa1 Publication
Gene namesi
Name:BECN1
Synonyms:GT197
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:1034. BECN1.

Subcellular locationi

Beclin-1-C 35 kDa :
Beclin-1-C 37 kDa :
  • Mitochondrion By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90S → A: Complete loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-93. 1 Publication1
Mutagenesisi93S → A: Partial loss of phosphorylation. Complete loss of phosphorylation and defective autophagic function; when associated with Ala-90. 1 Publication1
Mutagenesisi112L → A: Weakly decreases interaction with MUHV-4 M11, greatly decreases interaction with BCL2L1 isoform Bcl-X(L). 2 Publications1
Mutagenesisi116L → A: Decreases interaction with BCL2L1 isoform Bcl-X(L). 3 Publications1
Mutagenesisi117K → A: Weakly decreases interaction with MUHV-4 M11, greatly decreases interaction with BCL2L1 isoform Bcl-X(L). 1 Publication1
Mutagenesisi120 – 121GD → EA: Weakly decreases interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L). 1 Publication2
Mutagenesisi120G → E: Decreases interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L). 1 Publication1
Mutagenesisi121D → A: No effect on interaction with MUHV-4 M11, disrupts interaction with BCL2L1 isoform Bcl-X(L). 1 Publication1
Mutagenesisi123F → A: Weakly decreases interaction with MUHV-4 M11, disrupts interaction with BCL2 and decreases interaction with BCL2L1 isoform Bcl-X(L). 4 Publications1
Mutagenesisi133D → A: Abolishes in vitro cleavage by CASP3 and CASP8; when associated with A-149. 1 Publication1
Mutagenesisi133D → A: Abolishes in vitro cleavage by CASP8; when associated with A-146. 1 Publication1
Mutagenesisi146D → A: Abolishes in vitro cleavage by CASP8; when associated with A-133. 1 Publication1
Mutagenesisi149D → A: Abolishes in vitro cleavage by CASP3 and CASP8; when associated with A-133. 1 Publication1
Mutagenesisi149D → E: Abolishes in vitro cleavage by CASP3. 1 Publication1
Mutagenesisi352Y → A: Significantly reduces ubiquitination. 1 Publication1
Mutagenesisi425W → A: Decrease in membrane-association. 1 Publication1

Organism-specific databases

DisGeNETi8678.
OpenTargetsiENSG00000126581.
PharmGKBiPA25337.

Polymorphism and mutation databases

BioMutaiBECN1.
DMDMi13124704.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002185551 – 450Beclin-1Add BLAST450
ChainiPRO_0000435036134 – 450Beclin-1-C 37 kDa1 PublicationAdd BLAST317
ChainiPRO_0000435037150 – 450Beclin-1-C 35 kDa2 PublicationsAdd BLAST301

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei30PhosphoserineCombined sources1
Modified residuei90Phosphoserine; by AMPK1 Publication1
Modified residuei93Phosphoserine; by AMPK1 Publication1
Modified residuei96Phosphoserine; by AMPKBy similarity1
Modified residuei119Phosphothreonine; by DAPK11 Publication1

Post-translational modificationi

Phosphorylation at Thr-119 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy (PubMed:19180116). In response to autophagic stimuli, phosphorylated at serine residues by AMPK in an ATG14-dependent manner, and this phosphorylation is critical for maximally efficient autophagy (PubMed:23878393).2 Publications
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.2 Publications
Proteolytically processed by caspases including CASP8 and CASP3; the C-terminal fragments lack autophagy-inducing capacity and are proposed to induce apoptosis. Thus the cleavage is proposed to be an determinant to switch from autophagy to apoptosis pathways affecting cellular homeostasis including viral infections and survival of tumor cells.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ14457.
MaxQBiQ14457.
PaxDbiQ14457.
PeptideAtlasiQ14457.
PRIDEiQ14457.

PTM databases

iPTMnetiQ14457.
PhosphoSitePlusiQ14457.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000126581.
CleanExiHS_BECN1.
ExpressionAtlasiQ14457. baseline and differential.
GenevisibleiQ14457. HS.

Organism-specific databases

HPAiCAB010143.
HPA028949.

Interactioni

Subunit structurei

A homodimeric form is proposed to exist; this metastable form readily transits to ATG14- or UVRAG-containing complexes with BECN1:UVRAG being more stable than BECN1:ATG14 (By similarity). Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (PubMed:18843052, PubMed:19050071, PubMed:19270696, PubMed:23878393, PubMed:25490155). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:20643123, PubMed:19270696). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with AMBRA1, GOPC, GRID2 (By similarity). Interacts with BCL2 and BCL2L1 isoform Bcl-X(L); the interaction inhibits BECN1 function in promoting autophagy by interfering with the formation of the PI3K complex (PubMed:9765397, PubMed:16179260, PubMed:17446862, PubMed:17337444, PubMed:17659302). Interacts with cytosolic HMGB1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with USP10, USP13, VMP1, DAPK1, RAB39A (PubMed:19180116, PubMed:17724469, PubMed:17337444, PubMed:21962518, PubMed:24349490). Interacts with SLAMF1 (PubMed:22493499). Interacts with TRIM5; the interaction causes activation of BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057). Interacts with active ULK1 (phosphorylated on 'Ser-317') and MEFV simultaneously (PubMed:26347139). Interacts with human cytomegalovirus/HHV-5 protein TRS1 (PubMed:22205736). Interacts with murine gammaherpesvirus 68 M11 (PubMed:18797192, PubMed:24443581).By similarityCurated22 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • GTPase binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi114226. 84 interactors.
DIPiDIP-44611N.
IntActiQ14457. 97 interactors.
MINTiMINT-2865445.
STRINGi9606.ENSP00000355231.

Structurei

Secondary structure

1450
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi109 – 123Combined sources15
Turni124 – 126Combined sources3
Helixi160 – 169Combined sources10
Helixi176 – 265Combined sources90
Beta strandi276 – 279Combined sources4
Beta strandi282 – 285Combined sources4
Helixi300 – 321Combined sources22
Beta strandi326 – 331Combined sources6
Helixi334 – 336Combined sources3
Beta strandi338 – 343Combined sources6
Beta strandi349 – 351Combined sources3
Helixi358 – 360Combined sources3
Helixi364 – 384Combined sources21
Turni398 – 401Combined sources4
Beta strandi402 – 404Combined sources3
Turni406 – 409Combined sources4
Beta strandi412 – 415Combined sources4
Helixi422 – 446Combined sources25

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5EFMX-ray1.95A141-171[»]
5HHEX-ray1.46A/D175-265[»]
ProteinModelPortaliQ14457.
SMRiQ14457.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14457.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni112 – 159Interaction with BCL2 and BCL2L1 isoform Bcl-X(L)1 PublicationAdd BLAST48
Regioni425 – 450Required for membrane-association1 PublicationAdd BLAST26

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili142 – 270Sequence analysisAdd BLAST129

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi108 – 127BH3Add BLAST20

Domaini

The coiled coil domain can form antiparallel homodimers and mediates dimerization with the coiled coil domains of ATG14 or UVRAG involved in the formation of PI3K complexes.By similarity

Sequence similaritiesi

Belongs to the beclin family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG2751. Eukaryota.
ENOG410XQ85. LUCA.
GeneTreeiENSGT00390000008164.
HOGENOMiHOG000158093.
HOVERGENiHBG003181.
InParanoidiQ14457.
KOiK08334.
OMAiMRYAQMQ.
OrthoDBiEOG091G0COC.
PhylomeDBiQ14457.
TreeFamiTF314282.

Family and domain databases

InterProiView protein in InterPro
IPR007243. Atg6/Beclin.
IPR032913. BECN1.
IPR029318. BH3_dom.
PANTHERiPTHR12768. PTHR12768. 1 hit.
PTHR12768:SF9. PTHR12768:SF9. 1 hit.
PfamiView protein in Pfam
PF04111. APG6. 1 hit.
PF15285. BH3. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q14457-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGSKTSNNS TMQVSFVCQR CSQPLKLDTS FKILDRVTIQ ELTAPLLTTA 
        60         70         80         90        100
QAKPGETQEE ETNSGEEPFI ETPRQDGVSR RFIPPARMMS TESANSFTLI 
       110        120        130        140        150
GEASDGGTME NLSRRLKVTG DLFDIMSGQT DVDHPLCEEC TDTLLDQLDT 
       160        170        180        190        200
QLNVTENECQ NYKRCLEILE QMNEDDSEQL QMELKELALE EERLIQELED 
       210        220        230        240        250
VEKNRKIVAE NLEKVQAEAE RLDQEEAQYQ REYSEFKRQQ LELDDELKSV 
       260        270        280        290        300
ENQMRYAQTQ LDKLKKTNVF NATFHIWHSG QFGTINNFRL GRLPSVPVEW 
       310        320        330        340        350
NEINAAWGQT VLLLHALANK MGLKFQRYRL VPYGNHSYLE SLTDKSKELP 
       360        370        380        390        400
LYCSGGLRFF WDNKFDHAMV AFLDCVQQFK EEVEKGETRF CLPYRMDVEK 
       410        420        430        440        450
GKIEDTGGSG GSYSIKTQFN SEEQWTKALK FMLTNLKWGL AWVSSQFYNK
Length:450
Mass (Da):51,896
Last modified:February 21, 2001 - v2
Checksum:iABF0C2DD7087473C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti150T → A in AAB59573 (PubMed:7490091).Curated1
Sequence conflicti161N → S in BAG35534 (PubMed:14702039).Curated1
Sequence conflicti314L → H in BAG35534 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010384103A → V. 1
Natural variantiVAR_005236403I → T. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS11441.1.
PIRiI54209.
RefSeqiNP_001300927.1. NM_001313998.1.
NP_001300928.1. NM_001313999.1.
NP_001300929.1. NM_001314000.1.
NP_003757.1. NM_003766.4.
UniGeneiHs.716464.

Genome annotation databases

EnsembliENST00000361523; ENSP00000355231; ENSG00000126581.
ENST00000590099; ENSP00000465364; ENSG00000126581.
GeneIDi8678.
KEGGihsa:8678.
UCSCiuc002ibn.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiBECN1_HUMAN
AccessioniPrimary (citable) accession number: Q14457
Secondary accession number(s): B2R6N7, O75595, Q9UNA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: February 21, 2001
Last modified: July 5, 2017
This is version 170 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families