BBC3_MOUSE
ID BBC3_MOUSE Reviewed; 193 AA.
AC Q99ML1;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Bcl-2-binding component 3;
DE AltName: Full=p53 up-regulated modulator of apoptosis;
GN Name=Bbc3; Synonyms=Puma;
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].
RX PubMed=11463391; DOI=10.1016/s1097-2765(01)00213-1;
RA Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.;
RT "PUMA induces the rapid apoptosis of colorectal cancer cells.";
RL Mol. Cell 7:673-682(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver, and Olfactory epithelium;
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 [3]
RP FUNCTION, AND 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 [4]
RP FUNCTION.
RX PubMed=22761832; DOI=10.1371/journal.pone.0039586;
RA Ghosh A.P., Klocke B.J., Ballestas M.E., Roth K.A.;
RT "CHOP potentially co-operates with FOXO3a in neuronal cells to regulate
RT PUMA and BIM expression in response to ER stress.";
RL PLoS ONE 7:E39586-E39586(2012).
RN [5]
RP STRUCTURE BY NMR OF 130-155 IN COMPLEX WITH MCL1.
RX PubMed=18589438; DOI=10.1016/j.jmb.2008.05.071;
RA Day C.L., Smits C., Fan F.C., Lee E.F., Fairlie W.D., Hinds M.G.;
RT "Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa
RT and Puma in complex with Mcl-1.";
RL J. Mol. Biol. 380:958-971(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 130-155 IN COMPLEX WITH BCL2A1.
RX PubMed=18462686; DOI=10.1016/j.str.2008.02.009;
RA Smits C., Czabotar P.E., Hinds M.G., Day C.L.;
RT "Structural plasticity underpins promiscuous binding of the prosurvival
RT protein A1.";
RL Structure 16:818-829(2008).
CC -!- FUNCTION: Essential mediator of p53/TP53-dependent and p53/TP53-
CC independent apoptosis (By similarity). Promotes partial unfolding of
CC BCL2L1 and dissociation of BCL2L1 from p53/TP53, releasing the bound
CC p53/TP53 to induce apoptosis (By similarity). Regulates ER stress-
CC induced neuronal apoptosis (PubMed:21159964, PubMed:22761832).
CC {ECO:0000250|UniProtKB:Q9BXH1, ECO:0000269|PubMed:21159964,
CC ECO:0000269|PubMed:22761832}.
CC -!- SUBUNIT: Interacts with MCL1 and BCL2A1 (PubMed:18589438,
CC PubMed:18462686). Interacts with BCL2 and BCL2L1/BCL-XL (By
CC similarity). Interacts (via BH3 domain) with NOL3 (via CARD domain);
CC this interaction prevents BBC3 association with BCL2 and results in
CC CASP8 activation (By similarity). {ECO:0000250|UniProtKB:Q80ZG6,
CC ECO:0000250|UniProtKB:Q9BXH1, ECO:0000269|PubMed:18462686,
CC ECO:0000269|PubMed:18589438}.
CC -!- INTERACTION:
CC Q99ML1; Q07440: Bcl2a1; NbExp=2; IntAct=EBI-727801, EBI-707754;
CC Q99ML1; P97287: Mcl1; NbExp=2; IntAct=EBI-727801, EBI-707292;
CC Q99ML1; Q07817-1: BCL2L1; Xeno; NbExp=3; IntAct=EBI-727801, EBI-287195;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Note=Localized to the mitochondria
CC in order to induce cytochrome c release. {ECO:0000250}.
CC -!- INDUCTION: By DNA damage, glucocorticoid treatment, growth factor
CC deprivation and p53 (By similarity). By ER stress in a DDIT3/CHOP-
CC dependent manner. {ECO:0000250, ECO:0000269|PubMed:21159964}.
CC -!- DOMAIN: The BH3 motif is intrinsically disordered in the absence of a
CC binding partner but folds upon binding (PubMed:18589438). Folds when
CC bound to BCL2L1 (By similarity). Also folds when bound to MCL1
CC (PubMed:18589438). {ECO:0000250|UniProtKB:Q9BXH1,
CC ECO:0000269|PubMed:18589438}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; AF332560; AAK31317.1; -; mRNA.
DR EMBL; BC044782; AAH44782.1; -; mRNA.
DR EMBL; BC060370; AAH60370.1; -; mRNA.
DR CCDS; CCDS20847.1; -.
DR RefSeq; NP_573497.1; NM_133234.2.
DR RefSeq; XP_006539640.1; XM_006539577.3.
DR RefSeq; XP_006539641.1; XM_006539578.3.
DR RefSeq; XP_006539642.1; XM_006539579.3.
DR RefSeq; XP_006539643.1; XM_006539580.2.
DR RefSeq; XP_006539644.1; XM_006539581.1.
DR RefSeq; XP_006539645.1; XM_006539582.2.
DR PDB; 2ROC; NMR; -; B=130-155.
DR PDB; 2VOF; X-ray; 1.80 A; B/D=130-155.
DR PDBsum; 2ROC; -.
DR PDBsum; 2VOF; -.
DR AlphaFoldDB; Q99ML1; -.
DR SMR; Q99ML1; -.
DR BioGRID; 228430; 3.
DR ComplexPortal; CPX-2027; PUMA:BCL-2 complex.
DR ComplexPortal; CPX-2029; PUMA:BCL-XL complex.
DR CORUM; Q99ML1; -.
DR DIP; DIP-29805N; -.
DR ELM; Q99ML1; -.
DR IntAct; Q99ML1; 4.
DR STRING; 10090.ENSMUSP00000002152; -.
DR iPTMnet; Q99ML1; -.
DR PhosphoSitePlus; Q99ML1; -.
DR EPD; Q99ML1; -.
DR jPOST; Q99ML1; -.
DR MaxQB; Q99ML1; -.
DR PaxDb; Q99ML1; -.
DR PRIDE; Q99ML1; -.
DR ProteomicsDB; 273545; -.
DR DNASU; 170770; -.
DR Ensembl; ENSMUST00000002152; ENSMUSP00000002152; ENSMUSG00000002083.
DR GeneID; 170770; -.
DR KEGG; mmu:170770; -.
DR UCSC; uc009fho.2; mouse.
DR CTD; 27113; -.
DR MGI; MGI:2181667; Bbc3.
DR VEuPathDB; HostDB:ENSMUSG00000002083; -.
DR eggNOG; ENOG502TECD; Eukaryota.
DR GeneTree; ENSGT00390000002767; -.
DR HOGENOM; CLU_1408355_0_0_1; -.
DR InParanoid; Q99ML1; -.
DR OMA; GPRPDXR; -.
DR OrthoDB; 1534857at2759; -.
DR PhylomeDB; Q99ML1; -.
DR TreeFam; TF338776; -.
DR BioGRID-ORCS; 170770; 3 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q99ML1; -.
DR PRO; PR:Q99ML1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q99ML1; protein.
DR Bgee; ENSMUSG00000002083; Expressed in embryonic brain and 183 other tissues.
DR ExpressionAtlas; Q99ML1; baseline and differential.
DR Genevisible; Q99ML1; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:GOC.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005740; C:mitochondrial envelope; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0097143; C:PUMA-BCL-xl complex; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IGI:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IGI:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:BHF-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0044346; P:fibroblast apoptotic process; IMP:MGI.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISO:MGI.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0070227; P:lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; ISO:MGI.
DR GO; GO:0045926; P:negative regulation of growth; ISS:UniProtKB.
DR GO; GO:2001056; P:positive regulation of cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IMP:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0070230; P:positive regulation of lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0032464; P:positive regulation of protein homooligomerization; ISO:MGI.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; IMP: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:0070245; P:positive regulation of thymocyte apoptotic process; IGI:BHF-UCL.
DR GO; GO:0001844; P:protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0070231; P:T cell apoptotic process; IMP:MGI.
DR GO; GO:1901998; P:toxin transport; IMP:MGI.
DR DisProt; DP01794; -.
DR InterPro; IPR031661; Bbc3.
DR PANTHER; PTHR28639; PTHR28639; 1.
DR Pfam; PF15826; PUMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Mitochondrion; Phosphoprotein; Reference proteome.
FT CHAIN 1..193
FT /note="Bcl-2-binding component 3"
FT /id="PRO_0000143084"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 71..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 137..151
FT /note="BH3"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXH1"
FT HELIX 132..151
FT /evidence="ECO:0007829|PDB:2VOF"
SQ SEQUENCE 193 AA; 20749 MW; 39A98487FA86D226 CRC64;
MARARQEGSS PEPVEGLARD SPRPFPLGRL MPSAVSCSLC EPGLPAAPAA PALLPAAYLC
APTAPPAVTA ALGGPRWPGG HRSRPRGPRP DGPQPSLSPA QQHLESPVPS APEALAGGPT
QAAPGVRVEE EEWAREIGAQ LRRMADDLNA QYERRRQEEQ HRHRPSPWRV MYNLFMGLLP
LPRDPGAPEM EPN
