ID   BECN2_HUMAN             Reviewed;         431 AA.
AC   A8MW95; E9KNW0;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2012, sequence version 2.
DT   28-JAN-2026, entry version 101.
DE   RecName: Full=Beclin-2 {ECO:0000303|PubMed:23954414};
DE   AltName: Full=Beclin-1 autophagy-related pseudogene 1 {ECO:0000312|HGNC:HGNC:38606};
DE   AltName: Full=Beclin-1-like protein 1 {ECO:0000312|MIM:615687};
GN   Name=BECN2 {ECO:0000303|PubMed:23954414, ECO:0000312|HGNC:HGNC:38606};
GN   Synonyms=BECN1L1 {ECO:0000312|MIM:615687}, BECN1P1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ATG14; AMBRA1;
RP   GPRASP1; UVRAG AND PIK3C3, TISSUE SPECIFICITY, AND MUTAGENESIS OF ILE-80.
RX   PubMed=23954414; DOI=10.1016/j.cell.2013.07.035;
RA   He C., Wei Y., Sun K., Li B., Dong X., Zou Z., Liu Y., Kinch L.N., Khan S.,
RA   Sinha S., Xavier R.J., Grishin N.V., Xiao G., Eskelinen E.L., Scherer P.E.,
RA   Whistler J.L., Levine B.;
RT   "Beclin 2 functions in autophagy, degradation of G protein-coupled
RT   receptors, and metabolism.";
RL   Cell 154:1085-1099(2013).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 158-246 OF HOMODIMER OF WILD TYPE
RP   AND MUTANT LEU-187, COILED-COIL DOMAIN, SUBUNIT, INTERACTION WITH ATG14,
RP   AND MUTAGENESIS OF GLU-173; ASN-187; ALA-190; ALA-197; GLU-208; HIS-211;
RP   TYR-215; GLN-222 AND ARG-243.
RX   PubMed=28218432; DOI=10.1002/pro.3140;
RA   Su M., Li Y., Wyborny S., Neau D., Chakravarthy S., Levine B.,
RA   Colbert C.L., Sinha S.C.;
RT   "BECN2 interacts with ATG14 through a metastable coiled-coil to mediate
RT   autophagy.";
RL   Protein Sci. 26:972-984(2017).
CC   -!- FUNCTION: Involved in 2 distinct lysosomal degradation pathways: acts
CC       as a regulator of autophagy and as a regulator of G-protein coupled
CC       receptors turnover. Regulates degradation in lysosomes of a variety of
CC       G-protein coupled receptors via its interaction with GPRASP1/GASP1.
CC       {ECO:0000269|PubMed:23954414}.
CC   -!- SUBUNIT: Homodimer (via coiled-coil domain) (PubMed:28218432).
CC       Interacts (via coiled-coil domain) with ATG14 (via coiled-coil domain);
CC       this interaction is tighter than BECN2 self-association
CC       (PubMed:23954414, PubMed:28218432). Interacts with AMBRA1, UVRAG and
CC       PIK3C3/VPS34; these interactions are not disrupted by starvation
CC       (PubMed:23954414). Does not interact with RUBCN (PubMed:23954414).
CC       Interacts (via N-terminus) with GPRASP1/GASP1; the interaction is
CC       direct (PubMed:23954414). {ECO:0000269|PubMed:23954414,
CC       ECO:0000269|PubMed:28218432}.
CC   -!- INTERACTION:
CC       A8MW95; Q5JY77: GPRASP1; NbExp=4; IntAct=EBI-8839517, EBI-2514717;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Present in fetal and adult brain (at protein
CC       level). {ECO:0000269|PubMed:23954414}.
CC   -!- SIMILARITY: Belongs to the beclin family. {ECO:0000305}.
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DR   EMBL; HM031116; ADM47406.1; -; mRNA.
DR   EMBL; BX571673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS81433.1; -.
DR   RefSeq; NP_001277622.1; NM_001290693.1.
DR   PDB; 5K7B; X-ray; 2.30 A; A/B/C/D=158-250.
DR   PDB; 5K9L; X-ray; 2.52 A; A/B/C/D=158-250.
DR   PDB; 8GT9; X-ray; 2.00 A; A/B/C/D=157-248.
DR   PDB; 8GU7; X-ray; 2.60 A; C/D=157-248.
DR   PDBsum; 5K7B; -.
DR   PDBsum; 5K9L; -.
DR   PDBsum; 8GT9; -.
DR   PDBsum; 8GU7; -.
DR   AlphaFoldDB; A8MW95; -.
DR   SMR; A8MW95; -.
DR   BioGRID; 137882; 10.
DR   FunCoup; A8MW95; 253.
DR   IntAct; A8MW95; 38.
DR   STRING; 9606.ENSP00000488361; -.
DR   GlyGen; A8MW95; 1 site.
DR   iPTMnet; A8MW95; -.
DR   PhosphoSitePlus; A8MW95; -.
DR   BioMuta; BECN2; -.
DR   MassIVE; A8MW95; -.
DR   Antibodypedia; 77840; 293 antibodies from 17 providers.
DR   DNASU; 441925; -.
DR   Ensembl; ENST00000419583.2; ENSP00000488361.1; ENSG00000196289.7.
DR   GeneID; 441925; -.
DR   KEGG; hsa:441925; -.
DR   MANE-Select; ENST00000419583.2; ENSP00000488361.1; NM_001290693.1; NP_001277622.1.
DR   AGR; HGNC:38606; -.
DR   CTD; 441925; -.
DR   DisGeNET; 441925; -.
DR   GeneCards; BECN2; -.
DR   HGNC; HGNC:38606; BECN2.
DR   HPA; ENSG00000196289; Not detected.
DR   MIM; 615687; gene.
DR   OpenTargets; ENSG00000196289; -.
DR   VEuPathDB; HostDB:ENSG00000196289; -.
DR   GeneTree; ENSGT00390000008164; -.
DR   HOGENOM; CLU_024219_4_1_1; -.
DR   InParanoid; A8MW95; -.
DR   OMA; TATFEIW; -.
DR   OrthoDB; 20368at2759; -.
DR   PAN-GO; A8MW95; 6 GO annotations based on evolutionary models.
DR   PathwayCommons; A8MW95; -.
DR   SignaLink; A8MW95; -.
DR   Agora; ENSG00000196289; -.
DR   BioGRID-ORCS; 441925; 3 hits in 127 CRISPR screens.
DR   GenomeRNAi; 441925; -.
DR   Pharos; A8MW95; Tbio.
DR   PRO; PR:A8MW95; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; A8MW95; protein.
DR   GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
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:0043548; F:phosphatidylinositol 3-kinase binding; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR   GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR   GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR   GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR   GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR   GO; GO:1990172; P:G protein-coupled receptor catabolic process; IMP:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR   GO; GO:0045324; P:late endosome to vacuole transport; IBA:GO_Central.
DR   GO; GO:0000423; P:mitophagy; IBA:GO_Central.
DR   FunFam; 1.10.418.40:FF:000001; beclin-1 isoform X1; 1.
DR   Gene3D; 6.10.250.3110; -; 1.
DR   Gene3D; 1.10.418.40; Autophagy protein 6/Beclin 1; 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   PANTHER; PTHR12768; BECLIN 1; 1.
DR   PANTHER; PTHR12768:SF5; BECLIN-2; 1.
DR   Pfam; PF04111; APG6; 1.
DR   Pfam; PF17675; APG6_N; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Autophagy; Coiled coil; Cytoplasm; Reference proteome.
FT   CHAIN           1..431
FT                   /note="Beclin-2"
FT                   /id="PRO_0000332244"
FT   REGION          17..74
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          173..243
FT                   /note="Required for homodimer formation"
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   COILED          125..248
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         80
FT                   /note="I->S: Abolishes interaction with GPRASP1/GASP1 and
FT                   ability to degrade G-protein coupled receptor. Does not
FT                   affect function in autophagy."
FT                   /evidence="ECO:0000269|PubMed:23954414"
FT   MUTAGEN         173
FT                   /note="E->L: Decreases homodimerization. Decreases
FT                   interaction with ATG14."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         187
FT                   /note="N->L: Increases strongly homodimerization. Decreases
FT                   interaction with ATG14."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         190
FT                   /note="A->L: Decreases interaction with ATG14. Increases
FT                   slightly homodimerization; when associated with L-215."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         197
FT                   /note="A->L: Decreases interaction with ATG14. Probably
FT                   strongly increases homodimerization; when associated with
FT                   L-208."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         208
FT                   /note="E->L: Decreases interaction with ATG14. Probably
FT                   strongly increases homodimerization; when associated with
FT                   L-197."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         211
FT                   /note="H->L: Increases homodimerization. Decreases
FT                   interaction with ATG14."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         215
FT                   /note="Y->L: Decreases interaction with ATG14. Increases
FT                   slightly homodimerization; when associated with L-190."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         222
FT                   /note="Q->L: Decreases homodimerization. Decreases
FT                   interaction with ATG14."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   MUTAGEN         243
FT                   /note="R->L: Decreases homodimerization. Decreases
FT                   interaction with ATG14."
FT                   /evidence="ECO:0000269|PubMed:28218432"
FT   HELIX           157..245
FT                   /evidence="ECO:0007829|PDB:8GT9"
SQ   SEQUENCE   431 AA;  48153 MW;  9DB4184BE5C7A574 CRC64;
     MSSIRFLCQR CHQALKLSGS SESRSLPAAP APTSGQAEPG DTREPGVTTR EVTDAEEQQD
     GASSRSPPGD GSVSKGHANI FTLLGELGAM HMLSSIQKAA GDIFDIVSGQ AVVDHPLCEE
     CTDSLLEQLD IQLALTEADS QNYQRCLETG ELATSEDEAA ALRAELRDLE LEEARLVQEL
     EDVDRNNARA AADLQAAQAE AAELDQQERQ HYRDYSALKR QQLELLDQLG NVENQLQYAR
     VQRDRLKEIN CFTATFEIWV EGPLGVINNF RLGRLPTVRV GWNEINTAWG QAALLLLTLA
     NTIGLQFQRY RLIPCGNHSY LKSLTDDRTE LPLFCYGGQD VFLNNKYDRA MVAFLDCMQQ
     FKEEAEKGEL GLSLPYGIQV ETGLMEDVGG RGECYSIRTH LNTQELWTKA LKFMLINFKW
     SLIWVASRYQ K
//