BECN1_PIG
ID BECN1_PIG Reviewed; 448 AA.
AC Q4A1L5;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Beclin-1;
DE Contains:
DE RecName: Full=Beclin-1-C 35 kDa;
DE Contains:
DE RecName: Full=Beclin-1-C 37 kDa;
GN Name=BECN1; Synonyms=ATG6;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Botti J., Djavaheri-Mergny M., Codogno P., Oriol R.;
RT "Phylogeny and biochemistry of the autophagy protein beclin 1.";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INTERACTION WITH ASFV APOPTOSIS REGULATOR BCL-2 HOMOLOG (MICROBIAL
RP INFECTION).
RX PubMed=23228131; DOI=10.2174/156652413804810736;
RA Hernaez B., Cabezas M., Munoz-Moreno R., Galindo I., Cuesta-Geijo M.A.,
RA Alonso C.;
RT "A179L, a new viral Bcl2 homolog targeting Beclin 1 autophagy related
RT protein.";
RL Curr. Mol. Med. 13:305-316(2013).
RN [3] {ECO:0007744|PDB:6TZC}
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 103-128, AND INTERACTION WITH
RP ASFV APOPTOSIS REGULATOR BCL-2 HOMOLOG (MICROBIAL INFECTION).
RX PubMed=31461953; DOI=10.3390/v11090789;
RA Banjara S., Shimmon G.L., Dixon L.K., Netherton C.L., Hinds M.G.,
RA Kvansakul M.;
RT "Crystal Structure of African Swine Fever Virus A179L with the Autophagy
RT Regulator Beclin.";
RL Viruses 11:0-0(2019).
CC -!- FUNCTION: Plays a central role in autophagy. Acts as core subunit of
CC the PI3K complex that mediates formation of phosphatidylinositol 3-
CC phosphate; different complex forms are believed to play a role in
CC multiple membrane trafficking pathways: PI3KC3-C1 is involved in
CC initiation of autophagosomes and PI3KC3-C2 in maturation of
CC autophagosomes and endocytosis. Involved in regulation of degradative
CC endocytic trafficking and required for the abcission step in
CC cytokinesis, probably in the context of PI3KC3-C2. Essential for the
CC formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved
CC in endocytosis. May play a role in antiviral host defense (By
CC similarity). {ECO:0000250|UniProtKB:O88597,
CC ECO:0000250|UniProtKB:Q14457, ECO:0000250|UniProtKB:Q91XJ1}.
CC -!- FUNCTION: Beclin-1-C 35 kDa localized to mitochondria can promote
CC apoptosis; it induces the mitochondrial translocation of BAX and the
CC release of proapoptotic factors. {ECO:0000250|UniProtKB:O88597,
CC ECO:0000250|UniProtKB:Q14457}.
CC -!- SUBUNIT: A homodimeric form is proposed to exist; this metastable form
CC readily transits to ATG14- or UVRAG-containing complexes with
CC BECN1:UVRAG being more stable than BECN1:ATG14 (By similarity).
CC Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol
CC 3-kinase) complex the core of which is composed of the catalytic
CC subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating
CC with additional regulatory/auxilliary subunits to form alternative
CC complex forms. Alternative complex forms containing a forth regulatory
CC subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1)
CC containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG.
CC PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a
CC bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1
CC and PI3KC3-C2, can associate with further regulatory subunits, such as
CC RUBCN, SH3GLB1/Bif-1 and AMBRA1 (By similarity). PI3KC3-C1 probably
CC associates with PIK3CB (By similarity). Interacts with AMBRA1, GOPC,
CC GRID2 (By similarity). Forms a complex with PPP2CA and AMBRA1; AMBRA1
CC and BECN1 components of the complex regulate MYC stability via
CC different pathways. Interacts with BCL2 and BCL2L1 isoform Bcl-X(L);
CC the interaction inhibits BECN1 function in promoting autophagy by
CC interfering with the formation of the PI3K complex. Interacts with
CC cytosolic HMGB1; inhibits the interaction of BECN1 and BCL2 leading to
CC promotion of autophagy. Interacts with USP10, USP13, VMP1, DAPK1,
CC RAB39A. Interacts with the poly-Gln domain of ATXN3; the interaction
CC causes deubiquitination at Lys-400 and stabilizes BECN1. Interacts with
CC SLAMF1. Interacts with TRIM5; the interaction causes activation of
CC BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2.
CC Interacts with active ULK1 (phosphorylated on 'Ser-317') and MEFV
CC simultaneously. Interacts with WDR81 and WDR91; negatively regulates
CC the PI3 kinase/PI3K activity associated with endosomal membranes.
CC Interacts with LAPTM4B; competes with EGFR for LAPTM4B binding;
CC regulates EGFR activity. Interacts with TRIM50. Interacts with TRIM16.
CC Interacts with ATG14; this interaction is increased in the absence of
CC TMEM39A (By similarity). Interacts with WASHC1; preventing interaction
CC with AMBRA1 and the DCX(AMBRA1) complex and subsequent ubiquitination
CC (By similarity). Interacts with TRIM17 (By similarity). Interacts with
CC BCL2L10/BCL-B (via BH1 domain) (By similarity).
CC {ECO:0000250|UniProtKB:O88597, ECO:0000250|UniProtKB:Q14457,
CC ECO:0000250|UniProtKB:Q91XJ1}.
CC -!- SUBUNIT: (Microbial infection) Interacts with African swine fever virus
CC (ASFV) apoptosis regulator Bcl-2 homolog; this interaction allows the
CC virus to inhibit BECN1, and thus autophagy.
CC {ECO:0000269|PubMed:23228131, ECO:0000269|PubMed:31461953}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O88597}. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q14457};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q14457}. Endosome
CC membrane {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:Q14457}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14457}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000305}. Note=Interaction with ATG14 promotes translocation to
CC autophagosomes. Expressed in dendrites and cell bodies of cerebellar
CC Purkinje cells. {ECO:0000250|UniProtKB:O88597,
CC ECO:0000250|UniProtKB:Q14457}.
CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 35 kDa]: Mitochondrion
CC {ECO:0000250|UniProtKB:O88597, ECO:0000250|UniProtKB:Q14457}. Nucleus
CC {ECO:0000250|UniProtKB:Q14457}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q14457}.
CC -!- SUBCELLULAR LOCATION: [Beclin-1-C 37 kDa]: Mitochondrion
CC {ECO:0000250|UniProtKB:O88597}.
CC -!- DOMAIN: The C-terminal evolutionary conserved domain (ECD) contains
CC poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent
CC with structural docking models revealing two highly scored poly-Gln-
CC binding pockets in the ECD (By similarity). As some binding is observed
CC with BECN1 lacking the ECD, other domains of BECN1 may also interact
CC with ATXN3 (By similarity). {ECO:0000250|UniProtKB:Q14457}.
CC -!- PTM: Phosphorylation at Thr-117 by DAPK1 reduces its interaction with
CC BCL2 and BCL2L1 and promotes induction of autophagy. In response to
CC autophagic stimuli, phosphorylated at serine residues by AMPK in an
CC ATG14-dependent manner, and this phosphorylation is critical for
CC maximally efficient autophagy. {ECO:0000250|UniProtKB:O88597,
CC ECO:0000250|UniProtKB:Q14457}.
CC -!- PTM: Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'-
CC linkages (By similarity). 'Lys-11'-linked polyubiquitination leads to
CC degradation and is enhanced when the stabilizing interaction partner
CC VPS34 is depleted (By similarity). Deubiquitinated by USP10 and USP13,
CC leading to stabilize the PIK3C3/VPS34-containing complexes (By
CC similarity). Polyubiquitinated at Lys-400 with 'Lys-48'-linkages (By
CC similarity). 'Lys-48'-linked polyubiquitination of Lys-400 leads to
CC degradation (By similarity). Deubiquitinated by ATXN3, leading to
CC stabilization (By similarity). Ubiquitinated at Lys-435 via 'Lys-63'-
CC linkage by the DCX(AMBRA1) complex, thereby increasing the association
CC between BECN1 and PIK3C3 to promote PIK3C3 activity (By similarity).
CC {ECO:0000250|UniProtKB:Q14457}.
CC -!- PTM: Proteolytically processed by caspases including CASP8 and CASP3;
CC the C-terminal fragments lack autophagy-inducing capacity and are
CC proposed to induce apoptosis. Thus the cleavage is proposed to be an
CC determinant to switch from autophagy to apoptosis pathways affecting
CC cellular homeostasis including viral infections and survival of tumor
CC cells. {ECO:0000250|UniProtKB:O88597, ECO:0000250|UniProtKB:Q14457}.
CC -!- MISCELLANEOUS: Expanded poly-Gln tracts inhibit ATXN3-BECN1
CC interaction, decrease BECN1 levels and impair starvation-induced
CC autophagy (By similarity). {ECO:0000250|UniProtKB:Q14457}.
CC -!- SIMILARITY: Belongs to the beclin family. {ECO:0000305}.
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DR EMBL; AM051354; CAJ19745.1; -; mRNA.
DR RefSeq; NP_001037995.1; NM_001044530.1.
DR PDB; 6TZC; X-ray; 2.41 A; C=103-128.
DR PDBsum; 6TZC; -.
DR AlphaFoldDB; Q4A1L5; -.
DR SMR; Q4A1L5; -.
DR STRING; 9823.ENSSSCP00000018420; -.
DR PaxDb; Q4A1L5; -.
DR PeptideAtlas; Q4A1L5; -.
DR PRIDE; Q4A1L5; -.
DR GeneID; 733576; -.
DR KEGG; ssc:733576; -.
DR CTD; 8678; -.
DR eggNOG; KOG2751; Eukaryota.
DR InParanoid; Q4A1L5; -.
DR OrthoDB; 1085752at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISS:UniProtKB.
DR GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central.
DR GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:InterPro.
DR GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0048583; P:regulation of response to stimulus; IEA:UniProt.
DR Gene3D; 1.10.418.40; -; 1.
DR InterPro; IPR007243; Atg6/Beclin.
DR InterPro; IPR038274; Atg6/Beclin_C_sf.
DR InterPro; IPR041691; Atg6/beclin_CC.
DR InterPro; IPR040455; Atg6_BARA.
DR InterPro; IPR032913; BECN1.
DR InterPro; IPR029318; BH3_dom.
DR PANTHER; PTHR12768; PTHR12768; 1.
DR PANTHER; PTHR12768:SF6; PTHR12768:SF6; 1.
DR Pfam; PF04111; APG6; 1.
DR Pfam; PF17675; APG6_N; 1.
DR Pfam; PF15285; BH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Antiviral defense; Apoptosis; Autophagy;
KW Cell cycle; Cell division; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Endosome; Golgi apparatus; Host-virus interaction;
KW Isopeptide bond; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..448
FT /note="Beclin-1"
FT /id="PRO_0000231036"
FT CHAIN 132..448
FT /note="Beclin-1-C 37 kDa"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT /id="PRO_0000435040"
FT CHAIN 148..448
FT /note="Beclin-1-C 35 kDa"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT /id="PRO_0000435041"
FT REGION 110..157
FT /note="Interaction with BCL2 and BCL2L1"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT REGION 243..448
FT /note="Evolutionary conserved domain (ECD)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT REGION 423..448
FT /note="Required for membrane-association"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT COILED 140..267
FT /evidence="ECO:0000255"
FT MOTIF 106..125
FT /note="BH3"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 88
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 91
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT MOD_RES 94
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:O88597"
FT MOD_RES 117
FT /note="Phosphothreonine; by DAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CROSSLNK 400
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q14457"
FT HELIX 107..123
FT /evidence="ECO:0007829|PDB:6TZC"
SQ SEQUENCE 448 AA; 51759 MW; 48054FC499FE8923 CRC64;
MEGSKTSSST MQVSFVCQRC SQPLKLDTSF KILDRVTIQE LTAPLLATAQ VKPGETQEEE
ANPGEEPFIE TRQDGVSRRF IPPARMMSTE SANSFTLIGE ASDGGTMENL SRRLKVTGDL
FDIMSGQTDV DHPLCEECTD TLLDQLDTQL NVTENECQNY KRCLEILEQM HEDDSEQLRM
ELRELALEEE RLIQELEEVE KNRKIVAENL EKVQAEAERL DQEEAQYQRE YSEFKRQQLE
LDDELKSVEN QMRYAQMQLD KLKKTNVFNA TFHIWHSGQF GTINNFRLGR LPSVPVEWNE
INAAWGQTVL LLHALANKMG LKFQRYRLVP YGNHSYLESL TDKSKELPLY CSGGLRFFWD
NKFDHAMVAF LDCVQQFKEE VEKGETRFCL PYRMDVEKGK IEDTGGSGGS YSIKTQFNSE
EQWTKALKFM LTNLKWGLAW VSSQFYNK
