BECN2_HUMAN
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 03-AUG-2022, entry version 86.
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 PDBsum; 5K7B; -.
DR PDBsum; 5K9L; -.
DR AlphaFoldDB; A8MW95; -.
DR SMR; A8MW95; -.
DR BioGRID; 137882; 9.
DR IntAct; A8MW95; 6.
DR iPTMnet; A8MW95; -.
DR PhosphoSitePlus; A8MW95; -.
DR BioMuta; BECN2; -.
DR PRIDE; A8MW95; -.
DR Antibodypedia; 77840; 347 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 CTD; 441925; -.
DR DisGeNET; 441925; -.
DR GeneCards; BECN2; -.
DR HGNC; HGNC:38606; BECN2.
DR HPA; ENSG00000196289; Not detected.
DR MIM; 615687; gene.
DR neXtProt; NX_A8MW95; -.
DR OpenTargets; ENSG00000196289; -.
DR VEuPathDB; HostDB:ENSG00000196289; -.
DR GeneTree; ENSGT00390000008164; -.
DR HOGENOM; CLU_024219_4_1_1; -.
DR InParanoid; A8MW95; -.
DR OMA; VGWNEIN; -.
DR OrthoDB; 1085752at2759; -.
DR PathwayCommons; A8MW95; -.
DR SignaLink; A8MW95; -.
DR BioGRID-ORCS; 441925; 2 hits in 88 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:0044877; F:protein-containing complex binding; IEA:Ensembl.
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 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; IPR032912; BECN2.
DR PANTHER; PTHR12768; PTHR12768; 1.
DR PANTHER; PTHR12768:SF5; PTHR12768:SF5; 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 COMPBIAS 44..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 161..244
FT /evidence="ECO:0007829|PDB:5K7B"
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
