B2L11_MOUSE
ID B2L11_MOUSE Reviewed; 196 AA.
AC O54918; A2ALQ6; O54919; O54920;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Bcl-2-like protein 11;
DE Short=Bcl2-L-11;
DE AltName: Full=Bcl2-interacting mediator of cell death;
GN Name=Bcl2l11; Synonyms=Bim;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=9430630; DOI=10.1093/emboj/17.2.384;
RA O'Connor L., Strasser A., O'Reilly L.A., Hausmann G., Adams J.M., Cory S.,
RA Huang D.C.S.;
RT "Bim: a novel member of the Bcl-2 family that promotes apoptosis.";
RL EMBO J. 17:384-395(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BIMEL).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH MCL1.
RX PubMed=16543145; DOI=10.1016/j.molcel.2006.02.009;
RA Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.;
RT "Glycogen synthase kinase-3 regulates mitochondrial outer membrane
RT permeabilization and apoptosis by destabilization of MCL-1.";
RL Mol. Cell 21:749-760(2006).
RN [5]
RP INTERACTION WITH GIMAP5.
RX PubMed=16509771; DOI=10.1371/journal.pbio.0040103;
RA Nitta T., Nasreen M., Seike T., Goji A., Ohigashi I., Miyazaki T., Ohta T.,
RA Kanno M., Takahama Y.;
RT "IAN family critically regulates survival and development of T
RT lymphocytes.";
RL PLoS Biol. 4:593-605(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INDUCTION.
RX PubMed=21159964; DOI=10.1523/jneurosci.1598-10.2010;
RA Galehdar Z., Swan P., Fuerth B., Callaghan S.M., Park D.S., Cregan S.P.;
RT "Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by
RT ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA.";
RL J. Neurosci. 30:16938-16948(2010).
RN [8]
RP INTERACTION WITH DYNLL1; TRIM2 AND YWHAZ, UBIQUITINATION, PHOSPHORYLATION
RP AT SER-65, AND MUTAGENESIS OF SER-55; SER-65 AND SER-73.
RX PubMed=21478148; DOI=10.1074/jbc.m110.197707;
RA Thompson S., Pearson A.N., Ashley M.D., Jessick V., Murphy B.M., Gafken P.,
RA Henshall D.C., Morris K.T., Simon R.P., Meller R.;
RT "Identification of a novel Bcl-2-interacting mediator of cell death (Bim)
RT E3 ligase, tripartite motif-containing protein 2 (TRIM2), and its role in
RT rapid ischemic tolerance-induced neuroprotection.";
RL J. Biol. Chem. 286:19331-19339(2011).
RN [9]
RP INTERACTION WITH BCL2L1; MCL1 AND USP27X, PHOSPHORYLATION AT SER-65,
RP UBIQUITINATION, DEUBIQUITINATION BY USP27X, AND MUTAGENESIS OF LEU-150 AND
RP ILE-153.
RX PubMed=27013495; DOI=10.15252/embr.201541392;
RA Weber A., Heinlein M., Dengjel J., Alber C., Singh P.K., Haecker G.;
RT "The deubiquitinase Usp27x stabilizes the BH3-only protein Bim and enhances
RT apoptosis.";
RL EMBO Rep. 17:724-738(2016).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 139-171 IN COMPLEX WITH BCL2L1
RP ISOFORM BCL-XL, IDENTIFICATION IN A COMPLEX WITH DYNLL1 AND BCL-XL, AND
RP INTERACTION WITH BAX.
RX PubMed=14499110; DOI=10.1016/s1074-7613(03)00234-6;
RA Liu X., Dai S., Zhu Y., Marrack P., Kappler J.W.;
RT "The structure of a Bcl-xL/Bim fragment complex: implications for Bim
RT function.";
RL Immunity 19:341-352(2003).
CC -!- FUNCTION: Induces apoptosis and anoikis. The isoforms vary in
CC cytotoxicity with isoform BimS being the most potent and isoform BimEL
CC being the least potent. {ECO:0000269|PubMed:9430630}.
CC -!- SUBUNIT: Forms heterodimers with a number of antiapoptotic Bcl-2
CC proteins, including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1,
CC and BCL2L2/BCLW (PubMed:16543145, PubMed:27013495, PubMed:14499110).
CC Interacts with BAX (in vitro); this interaction may induce the
CC conformationally active form of BAX (PubMed:14499110). Does not
CC heterodimerize with proapoptotic proteins such as BAD, BOK or BAK.
CC Identified in a complex containing BCL2L11, DYNLL1 and BCL2L1 isoform
CC Bcl-X(L); BH3 integrity is required for BCL2L1-binding
CC (PubMed:21478148, PubMed:27013495, PubMed:14499110). Interacts with
CC YWHAZ. When phosphorylated, interacts with TRIM2; this interaction is
CC associated with ubiquitination and degradation (PubMed:21478148).
CC Interacts (via BH3) with MCL1; this interaction may sequester BCL2L11
CC and prevent its pro-apoptotic activity (PubMed:16543145,
CC PubMed:27013495). When phosphorylated, isoform BimEL interacts with
CC USP27X; this interaction leads to BCL2L11 deubiquitination and
CC stabilization (PubMed:27013495). Interacts with GIMAP5
CC (PubMed:16509771). Interacts with BCL2L10/BCL-B (By similarity).
CC {ECO:0000250|UniProtKB:O43521, ECO:0000269|PubMed:14499110,
CC ECO:0000269|PubMed:16509771, ECO:0000269|PubMed:16543145,
CC ECO:0000269|PubMed:21478148, ECO:0000269|PubMed:27013495}.
CC -!- INTERACTION:
CC O54918; P97287: Mcl1; NbExp=5; IntAct=EBI-526067, EBI-707292;
CC O54918; P03182: BHRF1; Xeno; NbExp=3; IntAct=EBI-526067, EBI-1207659;
CC O54918-1; P10417: Bcl2; NbExp=2; IntAct=EBI-526076, EBI-526314;
CC O54918-1; Q9DBC7: Prkar1a; NbExp=2; IntAct=EBI-526076, EBI-645677;
CC O54918-1; P63244: RACK1; Xeno; NbExp=2; IntAct=EBI-526076, EBI-296739;
CC O54918-3; Q07817-1: BCL2L1; Xeno; NbExp=3; IntAct=EBI-526084, EBI-287195;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:9430630}; Peripheral
CC membrane protein {ECO:0000269|PubMed:9430630}. Mitochondrion
CC {ECO:0000250}. Note=Associated with intracytoplasmic membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=BimEL;
CC IsoId=O54918-1; Sequence=Displayed;
CC Name=BimL;
CC IsoId=O54918-2; Sequence=VSP_000536;
CC Name=BimS;
CC IsoId=O54918-3; Sequence=VSP_000537;
CC -!- TISSUE SPECIFICITY: Expressed in a number of B- and T-lymphoid cell
CC lines. {ECO:0000269|PubMed:9430630}.
CC -!- INDUCTION: By ER stress. {ECO:0000269|PubMed:21159964}.
CC -!- DOMAIN: The BH3 motif is required for the interaction with Bcl-2
CC proteins and cytotoxicity. {ECO:0000269|PubMed:14499110,
CC ECO:0000269|PubMed:27013495}.
CC -!- PTM: Phosphorylation at Ser-65 by MAPK1/MAPK3 leads interaction with
CC TRIM2 and ubiquitination, followed by proteasomal degradation
CC (PubMed:21478148). Deubiquitination catalyzed by USP27X stabilizes the
CC protein (PubMed:27013495). {ECO:0000269|PubMed:21478148,
CC ECO:0000269|PubMed:27013495}.
CC -!- PTM: Ubiquitination by TRIM2 following phosphorylation by MAPK1/MAPK3
CC leads to proteasomal degradation. Conversely, deubiquitination
CC catalyzed by USP27X stabilizes the protein.
CC {ECO:0000269|PubMed:21478148, ECO:0000269|PubMed:27013495}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AF032459; AAC40029.1; -; mRNA.
DR EMBL; AF032460; AAC40030.1; -; mRNA.
DR EMBL; AF032461; AAC40031.1; -; mRNA.
DR EMBL; AL805950; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019556; AAH19556.1; -; mRNA.
DR CCDS; CCDS16712.1; -. [O54918-3]
DR CCDS; CCDS16713.1; -. [O54918-1]
DR CCDS; CCDS16714.1; -. [O54918-2]
DR RefSeq; NP_033884.1; NM_009754.3. [O54918-3]
DR RefSeq; NP_997563.1; NM_207680.2. [O54918-1]
DR RefSeq; NP_997564.1; NM_207681.2. [O54918-2]
DR PDB; 1PQ1; X-ray; 1.65 A; B=139-171.
DR PDBsum; 1PQ1; -.
DR AlphaFoldDB; O54918; -.
DR SMR; O54918; -.
DR BioGRID; 198352; 13.
DR ComplexPortal; CPX-2025; BIM:BCL-XL complex.
DR ComplexPortal; CPX-2036; BIM:BCL-2 complex.
DR ComplexPortal; CPX-629; MCL-1-BIM complex.
DR CORUM; O54918; -.
DR DIP; DIP-29214N; -.
DR ELM; O54918; -.
DR IntAct; O54918; 17.
DR MINT; O54918; -.
DR STRING; 10090.ENSMUSP00000105970; -.
DR iPTMnet; O54918; -.
DR PhosphoSitePlus; O54918; -.
DR EPD; O54918; -.
DR jPOST; O54918; -.
DR MaxQB; O54918; -.
DR PaxDb; O54918; -.
DR PeptideAtlas; O54918; -.
DR PRIDE; O54918; -.
DR ProteomicsDB; 277164; -. [O54918-1]
DR ProteomicsDB; 277165; -. [O54918-2]
DR ProteomicsDB; 277166; -. [O54918-3]
DR Antibodypedia; 3621; 1286 antibodies from 45 providers.
DR DNASU; 12125; -.
DR Ensembl; ENSMUST00000019281; ENSMUSP00000019281; ENSMUSG00000027381. [O54918-3]
DR Ensembl; ENSMUST00000103210; ENSMUSP00000099499; ENSMUSG00000027381. [O54918-2]
DR Ensembl; ENSMUST00000103211; ENSMUSP00000099500; ENSMUSG00000027381. [O54918-3]
DR Ensembl; ENSMUST00000110341; ENSMUSP00000105970; ENSMUSG00000027381. [O54918-1]
DR GeneID; 12125; -.
DR KEGG; mmu:12125; -.
DR UCSC; uc008mgh.1; mouse. [O54918-1]
DR UCSC; uc008mgk.1; mouse. [O54918-2]
DR CTD; 10018; -.
DR MGI; MGI:1197519; Bcl2l11.
DR VEuPathDB; HostDB:ENSMUSG00000027381; -.
DR eggNOG; ENOG502S0DF; Eukaryota.
DR GeneTree; ENSGT00390000003178; -.
DR HOGENOM; CLU_104244_1_1_1; -.
DR InParanoid; O54918; -.
DR OMA; EIWIARE; -.
DR OrthoDB; 1460067at2759; -.
DR PhylomeDB; O54918; -.
DR TreeFam; TF335898; -.
DR Reactome; R-MMU-111446; Activation of BIM and translocation to mitochondria.
DR Reactome; R-MMU-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR BioGRID-ORCS; 12125; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Bcl2l11; mouse.
DR EvolutionaryTrace; O54918; -.
DR PRO; PR:O54918; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O54918; protein.
DR Bgee; ENSMUSG00000027381; Expressed in metanephric mesenchyme and 226 other tissues.
DR ExpressionAtlas; O54918; baseline and differential.
DR Genevisible; O54918; MM.
DR GO; GO:0097136; C:Bcl-2 family protein complex; IMP:CAFA.
DR GO; GO:0097141; C:BIM-BCL-2 complex; ISO:MGI.
DR GO; GO:0097140; C:BIM-BCL-xl complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:MGI.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0008017; F:microtubule binding; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:1902263; P:apoptotic process involved in embryonic digit morphogenesis; IGI:MGI.
DR GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:MGI.
DR GO; GO:0048066; P:developmental pigmentation; IGI:MGI.
DR GO; GO:0043583; P:ear development; IGI:MGI.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IGI:MGI.
DR GO; GO:0001822; P:kidney development; IGI:MGI.
DR GO; GO:0001776; P:leukocyte homeostasis; IMP:MGI.
DR GO; GO:0070227; P:lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:0002260; P:lymphocyte homeostasis; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IGI:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:MGI.
DR GO; GO:0007127; P:meiosis I; IBA:GO_Central.
DR GO; GO:0002262; P:myeloid cell homeostasis; IGI:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0060139; P:positive regulation of apoptotic process by virus; IDA:MGI.
DR GO; GO:0034263; P:positive regulation of autophagy in response to ER overload; ISO:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0070230; P:positive regulation of lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:1902110; P:positive regulation of mitochondrial membrane permeability involved in apoptotic process; IGI:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; IMP:MGI.
DR GO; GO:0048563; P:post-embryonic animal organ morphogenesis; IMP:MGI.
DR GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IGI:MGI.
DR GO; GO:0048070; P:regulation of developmental pigmentation; IGI:MGI.
DR GO; GO:0046620; P:regulation of organ growth; IMP:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IGI:MGI.
DR GO; GO:0048536; P:spleen development; IGI:MGI.
DR GO; GO:0070231; P:T cell apoptotic process; IMP:MGI.
DR GO; GO:0043029; P:T cell homeostasis; IMP:MGI.
DR GO; GO:0070242; P:thymocyte apoptotic process; IGI:MGI.
DR GO; GO:0048538; P:thymus development; IGI:MGI.
DR GO; GO:0035148; P:tube formation; IMP:MGI.
DR DisProt; DP00518; -.
DR InterPro; IPR014771; Apoptosis_Bim_N.
DR InterPro; IPR017288; Bcl-2-like_11.
DR InterPro; IPR015040; Bcl-x_interacting_BH3_dom.
DR Pfam; PF08945; Bclx_interact; 1.
DR Pfam; PF06773; Bim_N; 1.
DR PIRSF; PIRSF037827; Bcl-2-like_p11; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Membrane; Mitochondrion;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..196
FT /note="Bcl-2-like protein 11"
FT /id="PRO_0000143110"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 146..160
FT /note="BH3"
FT MOD_RES 65
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000269|PubMed:21478148,
FT ECO:0000269|PubMed:27013495"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88498"
FT MOD_RES 83
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88498"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43521"
FT VAR_SEQ 42..127
FT /note="Missing (in isoform BimS)"
FT /evidence="ECO:0000305"
FT /id="VSP_000537"
FT VAR_SEQ 42..97
FT /note="Missing (in isoform BimL)"
FT /evidence="ECO:0000305"
FT /id="VSP_000536"
FT MUTAGEN 55
FT /note="S->A: Loss of TRIM2-binding; when associated with A-
FT 65 and A-73."
FT /evidence="ECO:0000269|PubMed:21478148"
FT MUTAGEN 65
FT /note="S->A: Loss of TRIM2-binding; when associated with A-
FT 55 and A-73."
FT /evidence="ECO:0000269|PubMed:21478148"
FT MUTAGEN 73
FT /note="S->A: Loss of TRIM2-binding; when associated with A-
FT 55 and A-65."
FT /evidence="ECO:0000269|PubMed:21478148"
FT MUTAGEN 150
FT /note="Missing: Loss of MCL1-binding, strong decrease in
FT BCL2L1-binding, no effect on USP27X-binding; when
FT associated with I-153 del."
FT /evidence="ECO:0000269|PubMed:27013495"
FT MUTAGEN 153
FT /note="Missing: Loss of MCL1-binding, strong decrease in
FT BCL2L1-binding, no effect on USP27X-binding; when
FT associated with L-150 del."
FT /evidence="ECO:0000269|PubMed:27013495"
FT HELIX 142..168
FT /evidence="ECO:0007829|PDB:1PQ1"
SQ SEQUENCE 196 AA; 22067 MW; 531C176E5F1AC9AA CRC64;
MAKQPSDVSS ECDREGGQLQ PAERPPQLRP GAPTSLQTEP QGNPDGEGDR CPHGSPQGPL
APPASPGPFA TRSPLFIFVR RSSLLSRSSS GYFSFDTDRS PAPMSCDKST QTPSPPCQAF
NHYLSAMASI RQSQEEPEDL RPEIRIAQEL RRIGDEFNET YTRRVFANDY REAEDHPQMV
ILQLLRFIFR LVWRRH
