ID   BECN1_HUMAN             Reviewed;         450 AA.
AC   Q14457; O75595; Q9UNA8;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   21-FEB-2001, sequence version 2.
DT   25-JAN-2012, entry version 110.
DE   RecName: Full=Beclin-1;
DE   AltName: Full=Coiled-coil myosin-like BCL2-interacting protein;
DE   AltName: Full=Protein GT197;
GN   Name=BECN1; Synonyms=GT197;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH BCL-2.
RC   TISSUE=Brain;
RX   MEDLINE=98440516; PubMed=9765397;
RA   Liang X.H., Kleeman L.K., Jiang H.H., Gordon G., Goldman J.E.,
RA   Berry G., Herman B., Levine B.;
RT   "Protection against fatal Sindbis virus encephalitis by beclin, a
RT   novel Bcl-2-interacting protein.";
RL   J. Virol. 72:8586-8596(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=99326523; PubMed=10395800; DOI=10.1006/geno.1999.5851;
RA   Aita V.M., Liang X.H., Murty V.V.V.S., Pincus D.L., Yu W., Cayanis E.,
RA   Kalachikov S., Gilliam T.C., Levine B.;
RT   "Cloning and genomic organization of beclin 1, a candidate tumor
RT   suppressor gene on chromosome 17q21.";
RL   Genomics 59:59-65(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cervix;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 150-450.
RC   TISSUE=Mammary gland;
RX   MEDLINE=96039267; PubMed=7490091; DOI=10.1006/geno.1995.1185;
RA   Rommens J.M., Durocher F., McArthur J., Tonin P., Leblanc J.-F.,
RA   Allen T., Samson C., Ferri L., Narod S., Morgan K., Simard J.;
RT   "Generation of a transcription map at the HSD17B locus centromeric to
RT   BRCA1 at 17q21.";
RL   Genomics 28:530-542(1995).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57 AND SER-64, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [6]
RP   INTERACTION WITH ATG14; PIK3C3; PIK3R4 AND UVRAG.
RX   PubMed=18843052; DOI=10.1091/mbc.E08-01-0080;
RA   Itakura E., Kishi C., Inoue K., Mizushima N.;
RT   "Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes
RT   with mammalian Atg14 and UVRAG.";
RL   Mol. Biol. Cell 19:5360-5372(2008).
RN   [7]
RP   INTERACTION WITH VMP1.
RX   PubMed=17724469; DOI=10.1038/sj.onc.1210743;
RA   Sauermann M., Sahin O., Sultmann H., Hahne F., Blaszkiewicz S.,
RA   Majety M., Zatloukal K., Fuzesi L., Poustka A., Wiemann S., Arlt D.;
RT   "Reduced expression of vacuole membrane protein 1 affects the invasion
RT   capacity of tumor cells.";
RL   Oncogene 27:1320-1326(2008).
RN   [8]
RP   INTERACTION WITH ATG14; PIK3C3 AND UVRAG, AND SUBCELLULAR LOCATION.
RX   PubMed=19050071; DOI=10.1073/pnas.0810452105;
RA   Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.;
RT   "Identification of Barkor as a mammalian autophagy-specific factor for
RT   Beclin 1 and class III phosphatidylinositol 3-kinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008).
RN   [9]
RP   PHOSPHORYLATION AT THR-119, AND INTERACTION WITH DAPK1.
RX   PubMed=19180116; DOI=10.1038/embor.2008.246;
RA   Zalckvar E., Berissi H., Mizrachy L., Idelchuk Y., Koren I.,
RA   Eisenstein M., Sabanay H., Pinkas-Kramarski R., Kimchi A.;
RT   "DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1
RT   promotes dissociation of beclin 1 from Bcl-XL and induction of
RT   autophagy.";
RL   EMBO Rep. 10:285-292(2009).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-29; SER-30; THR-57;
RP   THR-62; SER-64; SER-90; SER-93 AND SER-96, AND MASS SPECTROMETRY.
RX   PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [11]
RP   INTERACTION WITH ATG14; KIAA0226; PIK3C3; PIK3R4 AND UVRAG.
RX   PubMed=19270696; DOI=10.1038/ncb1846;
RA   Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N.,
RA   Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S.,
RA   Noda T., Yoshimori T.;
RT   "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally
RT   regulate autophagy at different stages.";
RL   Nat. Cell Biol. 11:385-396(2009).
RN   [12]
RP   FUNCTION.
RX   PubMed=20208530; DOI=10.1038/ncb2036;
RA   Sagona A.P., Nezis I.P., Pedersen N.M., Liestol K., Poulton J.,
RA   Rusten T.E., Skotheim R.I., Raiborg C., Stenmark H.;
RT   "PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment
RT   of FYVE-CENT to the midbody.";
RL   Nat. Cell Biol. 12:362-371(2010).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 107-135 IN COMPLEX WITH
RP   BCL2L1.
RX   PubMed=17337444; DOI=10.1074/jbc.M700492200;
RA   Oberstein A., Jeffrey P.D., Shi Y.;
RT   "Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is
RT   a novel BH3-only protein.";
RL   J. Biol. Chem. 282:13123-13132(2007).
RN   [14]
RP   STRUCTURE BY NMR OF 106-128 IN COMPLEX WITH BCL2L1.
RX   PubMed=17659302; DOI=10.1016/j.jmb.2007.06.069;
RA   Feng W., Huang S., Wu H., Zhang M.;
RT   "Molecular basis of Bcl-xL's target recognition versatility revealed
RT   by the structure of Bcl-xL in complex with the BH3 domain of beclin-
RT   1.";
RL   J. Mol. Biol. 372:223-235(2007).
CC   -!- FUNCTION: Plays a central role in autophagy. Required for the
CC       abcission step in cytokinesis. May play a role in antiviral host
CC       defense. Protects against infection by a neurovirulent strain of
CC       Sindbis virus.
CC   -!- SUBUNIT: Interacts with GOPC and GRID2. Interacts with AMBRA1.
CC       Forms a complex with PIK3C3 and PIK3R4 and either UVRAG and
CC       KIAA0226/Rubicon, or with ATG14. UVRAG and ATG14 form mutually
CC       exclusive complexes through direct competition for BECN1-binding.
CC       The complex containing ATG14 upregulates autophagy, while the one
CC       containing Rubicon downregulates autophagy (By similarity).
CC       Interacts with BCL2 and BCL2L1. Interacts with VMP1. Interacts
CC       with PIK3CB (By similarity). Interacts with DAPK1.
CC   -!- INTERACTION:
CC       P10415:BCL2; NbExp=3; IntAct=EBI-949378, EBI-77694;
CC       Q07817-1:BCL2L1; NbExp=4; IntAct=EBI-949378, EBI-287195;
CC       Q8IYI6:EXOC8; NbExp=4; IntAct=EBI-949378, EBI-742102;
CC       Q8NEB9:PIK3C3; NbExp=6; IntAct=EBI-949378, EBI-1056470;
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC       membrane; Peripheral membrane protein. Note=Interaction with ATG14
CC       promotes translocation to autophagosomes. Expressed in dendrites
CC       and cell bodies of cerebellar Purkinje cells (By similarity).
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- PTM: Phosphorylation at Thr-119 by DAPK1 reduces its interaction
CC       with BCL2 and BCL2L1 and promotes induction of autophagy.
CC   -!- SIMILARITY: Belongs to the beclin family.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; AF077301; AAC68653.1; -; mRNA.
DR   EMBL; AF139131; AAD27650.1; -; mRNA.
DR   EMBL; BC010276; AAH10276.1; -; mRNA.
DR   EMBL; L38932; AAB59573.1; -; mRNA.
DR   IPI; IPI00748342; -.
DR   PIR; I54209; I54209.
DR   RefSeq; NP_003757.1; NM_003766.3.
DR   UniGene; Hs.716464; -.
DR   PDB; 2P1L; X-ray; 2.50 A; B/D/F/H=107-135.
DR   PDB; 2PON; NMR; -; A=106-128.
DR   PDB; 3DVU; X-ray; 2.50 A; C/D=105-130.
DR   PDBsum; 2P1L; -.
DR   PDBsum; 2PON; -.
DR   PDBsum; 3DVU; -.
DR   ProteinModelPortal; Q14457; -.
DR   DIP; DIP-44611N; -.
DR   IntAct; Q14457; 55.
DR   MINT; MINT-2865445; -.
DR   STRING; Q14457; -.
DR   PhosphoSite; Q14457; -.
DR   DMDM; 13124704; -.
DR   PRIDE; Q14457; -.
DR   Ensembl; ENST00000361523; ENSP00000355231; ENSG00000126581.
DR   GeneID; 8678; -.
DR   KEGG; hsa:8678; -.
DR   UCSC; uc002ibn.2; human.
DR   CTD; 8678; -.
DR   GeneCards; GC17M040963; -.
DR   H-InvDB; HIX0018211; -.
DR   HGNC; HGNC:1034; BECN1.
DR   HPA; CAB010143; -.
DR   MIM; 604378; gene.
DR   neXtProt; NX_Q14457; -.
DR   PharmGKB; PA25337; -.
DR   HOGENOM; HBG676980; -.
DR   HOVERGEN; HBG003181; -.
DR   InParanoid; Q14457; -.
DR   OMA; LDTQLNI; -.
DR   OrthoDB; EOG4320Z3; -.
DR   PhylomeDB; Q14457; -.
DR   NextBio; 32555; -.
DR   ArrayExpress; Q14457; -.
DR   Bgee; Q14457; -.
DR   CleanEx; HS_BECN1; -.
DR   Genevestigator; Q14457; -.
DR   GermOnline; ENSG00000126581; Homo sapiens.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0006916; P:anti-apoptosis; TAS:ProtInc.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR   GO; GO:0000910; P:cytokinesis; IMP:UniProtKB.
DR   GO; GO:0009615; P:response to virus; IEA:UniProtKB-KW.
DR   InterPro; IPR007243; Autophagy-rel_prot_6.
DR   KO; K08334; -.
DR   PANTHER; PTHR12768; APG6; 1.
DR   Pfam; PF04111; APG6; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antiviral defense; Autophagy; Cell cycle; Cell division;
KW   Coiled coil; Complete proteome; Golgi apparatus; Membrane;
KW   Phosphoprotein; Polymorphism; Reference proteome.
FT   CHAIN         1    450       Beclin-1.
FT                                /FTId=PRO_0000218555.
FT   COILED      142    270       Potential.
FT   MOD_RES      29     29       Phosphothreonine.
FT   MOD_RES      30     30       Phosphoserine.
FT   MOD_RES      57     57       Phosphothreonine.
FT   MOD_RES      62     62       Phosphothreonine.
FT   MOD_RES      64     64       Phosphoserine.
FT   MOD_RES      90     90       Phosphoserine.
FT   MOD_RES      93     93       Phosphoserine.
FT   MOD_RES      96     96       Phosphoserine.
FT   MOD_RES     119    119       Phosphothreonine; by DAPK1.
FT   VARIANT     103    103       A -> V.
FT                                /FTId=VAR_010384.
FT   VARIANT     403    403       I -> T.
FT                                /FTId=VAR_005236.
FT   CONFLICT    150    150       T -> A (in Ref. 4; AAB59573).
FT   HELIX       107    125
SQ   SEQUENCE   450 AA;  51896 MW;  ABF0C2DD7087473C CRC64;
     MEGSKTSNNS TMQVSFVCQR CSQPLKLDTS FKILDRVTIQ ELTAPLLTTA QAKPGETQEE
     ETNSGEEPFI ETPRQDGVSR RFIPPARMMS TESANSFTLI GEASDGGTME NLSRRLKVTG
     DLFDIMSGQT DVDHPLCEEC TDTLLDQLDT QLNVTENECQ NYKRCLEILE QMNEDDSEQL
     QMELKELALE EERLIQELED VEKNRKIVAE NLEKVQAEAE RLDQEEAQYQ REYSEFKRQQ
     LELDDELKSV ENQMRYAQTQ LDKLKKTNVF NATFHIWHSG QFGTINNFRL GRLPSVPVEW
     NEINAAWGQT VLLLHALANK MGLKFQRYRL VPYGNHSYLE SLTDKSKELP LYCSGGLRFF
     WDNKFDHAMV AFLDCVQQFK EEVEKGETRF CLPYRMDVEK GKIEDTGGSG GSYSIKTQFN
     SEEQWTKALK FMLTNLKWGL AWVSSQFYNK
//