BAD_RAT
ID BAD_RAT Reviewed; 205 AA.
AC O35147; O70256; Q9JHX1;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-SEP-2001, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Bcl2-associated agonist of cell death;
DE Short=BAD;
DE AltName: Full=Bcl-2-binding component 6;
DE AltName: Full=Bcl-xL/Bcl-2-associated death promoter;
DE AltName: Full=Bcl2 antagonist of cell death;
GN Name=Bad;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF SER-113 AND SER-137.
RC TISSUE=Ovary;
RX PubMed=9369453; DOI=10.1210/mend.11.12.0023;
RA Hsu S.Y., Kaipia A., Zhu L., Hsueh A.J.W.;
RT "Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced
RT apoptosis in mammalian cells by 14-3-3 isoforms and P11.";
RL Mol. Endocrinol. 11:1858-1867(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9535132; DOI=10.1016/s0304-3940(98)00116-5;
RA D'Agata V., Magro G., Travali S., Musco S., Cavallaro S.;
RT "Cloning and expression of the programmed cell death regulator BAD in the
RT rat brain.";
RL Neurosci. Lett. 243:137-140(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RC TISSUE=Brain;
RX PubMed=11161472; DOI=10.1006/mcne.2000.0905;
RA Hamner S., Arumae U., Yu L.-Y., Sun Y.-F., Saarma M., Lindholm D.;
RT "Functional characterization of two splice variants of rat BAD and their
RT interaction with Bcl-w in sympathetic neurons.";
RL Mol. Cell. Neurosci. 17:97-106(2001).
RN [4]
RP INTERACTION WITH NOL3.
RX PubMed=17998337; DOI=10.1128/mcb.00738-07;
RA Li Y.Z., Lu D.Y., Tan W.Q., Wang J.X., Li P.F.;
RT "p53 initiates apoptosis by transcriptionally targeting the antiapoptotic
RT protein ARC.";
RL Mol. Cell. Biol. 28:564-574(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113; SER-135 AND SER-156, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Promotes cell death. Successfully competes for the binding to
CC Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of
CC heterodimerization of these proteins with BAX. Can reverse the death
CC repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity).
CC Appears to act as a link between growth factor receptor signaling and
CC the apoptotic pathways. {ECO:0000250}.
CC -!- SUBUNIT: Forms heterodimers with the anti-apoptotic proteins, Bcl-X(L),
CC Bcl-2 and Bcl-W. Also binds protein S100A10. The Ser-113/Ser-137
CC phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3
CC (By similarity). Interacts with HIF3A (via C-terminus domain); the
CC interaction reduces the binding between BAD and BAX (By similarity).
CC Interacts (via BH3 domain) with NOL3 (via CARD domain); preventing the
CC association of BAD with BCL2 (PubMed:17998337). Interacts with
CC GIMAP3/IAN4 and GIMAP5/IAN5 (By similarity).
CC {ECO:0000250|UniProtKB:Q61337, ECO:0000269|PubMed:17998337}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cytoplasm
CC {ECO:0000250|UniProtKB:Q61337}. Note=Colocalizes with HIF3A in the
CC cytoplasm. Upon phosphorylation, locates to the cytoplasm.
CC {ECO:0000250|UniProtKB:Q61337}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=O35147-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=O35147-2; Sequence=VSP_000534;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including brain,
CC liver, spleen and heart. In the brain, restricted to epithelial cells
CC of the choroid plexus. Isoform alpha is the more abundant form.
CC -!- DOMAIN: Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for
CC their pro-apoptotic activity and for their interaction with anti-
CC apoptotic members of the Bcl-2 family.
CC -!- PTM: Phosphorylated at one or more of Ser-113, Ser-137, Ser-156 and
CC Ser-171 in response to survival stimuli, which blocks its pro-apoptotic
CC activity. Phosphorylation on Ser-137 or Ser-113 promotes
CC heterodimerization with 14-3-3 proteins. This interaction then
CC facilitates the phosphorylation at Ser-156, a site within the BH3
CC motif, leading to the release of Bcl-X(L) and the promotion of cell
CC survival. Ser-137 is the major site of AKT/PKB phosphorylation, Ser-156
CC the major site of protein kinase A (CAPK) phosphorylation.
CC -!- PTM: Methylation at Arg-132 and Arg-134 by PRMT1 inhibits Akt-mediated
CC phosphorylation at Ser-137. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
CC -!- CAUTION: The protein name 'Bcl2 antagonist of cell death' may be
CC misleading. The protein antagonises Bcl2-mediated repression of cell
CC death, hence it promotes apoptosis. {ECO:0000305}.
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DR EMBL; AF003523; AAC53374.1; -; mRNA.
DR EMBL; AF031227; AAC15100.1; -; mRNA.
DR EMBL; AF279910; AAF91427.1; -; mRNA.
DR EMBL; AF279911; AAF91428.1; -; mRNA.
DR RefSeq; NP_073189.1; NM_022698.1. [O35147-1]
DR RefSeq; XP_006230958.1; XM_006230896.3. [O35147-2]
DR AlphaFoldDB; O35147; -.
DR SMR; O35147; -.
DR BioGRID; 249177; 3.
DR ComplexPortal; CPX-2020; BAD:BCL-2 complex.
DR ComplexPortal; CPX-2022; BAD:BCL-XL complex.
DR DIP; DIP-29862N; -.
DR ELM; O35147; -.
DR IntAct; O35147; 1.
DR STRING; 10116.ENSRNOP00000061855; -.
DR iPTMnet; O35147; -.
DR PhosphoSitePlus; O35147; -.
DR PaxDb; O35147; -.
DR PRIDE; O35147; -.
DR GeneID; 64639; -.
DR KEGG; rno:64639; -.
DR UCSC; RGD:620103; rat. [O35147-1]
DR CTD; 572; -.
DR RGD; 620103; Bad.
DR VEuPathDB; HostDB:ENSRNOG00000021147; -.
DR eggNOG; ENOG502S71H; Eukaryota.
DR HOGENOM; CLU_129052_0_0_1; -.
DR InParanoid; O35147; -.
DR OMA; SSWTRIF; -.
DR OrthoDB; 1454876at2759; -.
DR PhylomeDB; O35147; -.
DR TreeFam; TF102001; -.
DR Reactome; R-RNO-111447; Activation of BAD and translocation to mitochondria.
DR Reactome; R-RNO-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR PRO; PR:O35147; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000021147; Expressed in stomach and 20 other tissues.
DR Genevisible; O35147; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:RGD.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:0043422; F:protein kinase B binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0030346; F:protein phosphatase 2B binding; IPI:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0046031; P:ADP metabolic process; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071247; P:cellular response to chromate; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
DR GO; GO:0071396; P:cellular response to lipid; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0071316; P:cellular response to nicotine; ISS:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0006007; P:glucose catabolic process; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
DR GO; GO:0046931; P:pore complex assembly; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; ISS:UniProtKB.
DR GO; GO:1904710; P:positive regulation of granulosa cell apoptotic process; IDA:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:1902220; P:positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; ISO:RGD.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISS:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IDA:RGD.
DR GO; GO:0045862; P:positive regulation of proteolysis; ISO:RGD.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:RGD.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:RGD.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:1901423; P:response to benzene; IEP:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0034201; P:response to oleic acid; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; ISO:RGD.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
DR InterPro; IPR018868; BAD.
DR PANTHER; PTHR28540; PTHR28540; 1.
DR Pfam; PF10514; Bcl-2_BAD; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasm; Membrane; Methylation;
KW Mitochondrion; Mitochondrion outer membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..205
FT /note="Bcl2-associated agonist of cell death"
FT /id="PRO_0000143105"
FT REGION 1..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 148..162
FT /note="BH3"
FT COMPBIAS 85..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92934"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92934"
FT MOD_RES 132
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q92934"
FT MOD_RES 134
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q92934"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 137
FT /note="Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1
FT and PKC/PRKCQ"
FT /evidence="ECO:0000250|UniProtKB:Q61337"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92934"
FT VAR_SEQ 166..205
FT /note="LPRPKSAGTATQMRQSASWTRIIQSWWDRNLGKGGSTPSQ -> EELTYSVE
FT FLPVRAIAMEGWPLLWSFQSFPHTLPPTPPEVAMFPLRYWTALRRLC (in isoform
FT Beta)"
FT /evidence="ECO:0000303|PubMed:11161472"
FT /id="VSP_000534"
FT MUTAGEN 113
FT /note="S->A: No effect on heterodimerization with 14-3-3
FT proteins."
FT /evidence="ECO:0000269|PubMed:9369453"
FT MUTAGEN 137
FT /note="S->A: No heterodimerization with 14-3-3 proteins. No
FT effect on heterodimerization with BCL2 nor with protein
FT P11."
FT /evidence="ECO:0000269|PubMed:9369453"
FT CONFLICT 29..34
FT /note="SDAGGR -> ERRGRK (in Ref. 1; AAC53374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 205 AA; 22228 MW; 7AFA71DAE9CF4A81 CRC64;
MGTPKQPSLA PAHALGLRKS DPGIRSLGSD AGGRRWRPAA QSMFQIPEFE PSEQEDASTT
DRGLGPSLTE DQPGPYLAPG LLGSIVQQQP GQAANNSHHG GAGTMETRSR HSSYPAGTEE
DEGMEEELSP FRGRSRSAPP NLWAAQRYGR ELRRMSDEFE GSFKGLPRPK SAGTATQMRQ
SASWTRIIQS WWDRNLGKGG STPSQ
