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O35147 (BAD_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bcl2-associated agonist of cell death

Short name=BAD
Alternative name(s):
Bcl-2-binding component 6
Bcl-xL/Bcl-2-associated death promoter
Bcl2 antagonist of cell death
Gene names
Name:Bad
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length205 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 By similarity. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.

Subunit structure

Forms heterodimers with the anti-apoptotic proteins, Bcl-X(L), Bcl-2 and Bcl-W. Also binds protein S100A10. The Ser-113/Ser-137 phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3 By similarity.

Subcellular location

Mitochondrion outer membrane By similarity. Cytoplasm By similarity. Note: Upon phosphorylation, locates to the cytoplasm By similarity.

Tissue specificity

Expressed in all tissues tested, including brain, liver, spleen and heart. In the brain, restricted to epithelial cells of the choroid plexus. Isoform alphais the more abundant form.

Domain

Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.

Post-translational modification

Phosphorylated at one or more of Ser-113, Ser-137, Ser-156 and Ser-171 in response to survival stimuli, which blocks its pro-apoptotic activity. Phosphorylation on Ser-137 or Ser-113 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-156, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-137 is the major site of AKT/PKB phosphorylation, Ser-156 the major site of protein kinase A (CAPK) phosphorylation.

Methylation at Arg-132 and Arg-134 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-137 By similarity.

Sequence similarities

Belongs to the Bcl-2 family.

Caution

The protein name 'Bcl2 antagonist of cell death' may be misleading. The protein antagonises Bcl2-mediated repression of cell death, hence it promotes apoptosis.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative splicing
   PTMMethylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processADP metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

ATP metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular process regulating host cell cycle in response to virus

Inferred from electronic annotation. Source: Ensembl

cellular response to chromate

Inferred from expression pattern PubMed 21262251. Source: RGD

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to lipid

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to nicotine

Inferred from sequence or structural similarity. Source: UniProtKB

cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

glucose catabolic process

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from electronic annotation. Source: Ensembl

pore complex assembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of B cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process by virus

Inferred from electronic annotation. Source: Ensembl

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucokinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of insulin secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitochondrial membrane potential

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron death

Inferred from direct assay Ref.3. Source: RGD

positive regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

positive regulation of release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

positive regulation of type B pancreatic cell development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitochondrial membrane permeability

Inferred from sequence or structural similarity. Source: UniProtKB

release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

response to amino acid

Inferred from expression pattern PubMed 17967733. Source: RGD

response to calcium ion

Inferred from expression pattern PubMed 17663748. Source: RGD

response to drug

Inferred from expression pattern PubMed 12099715. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 17196335. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 17283395. Source: RGD

response to glucocorticoid

Inferred from expression pattern PubMed 15845918. Source: RGD

response to glucose

Inferred from expression pattern PubMed 15596134. Source: RGD

response to hormone

Inferred from expression pattern PubMed 18078455. Source: RGD

response to hydrogen peroxide

Inferred from expression pattern PubMed 17978575. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 16005992. Source: RGD

response to oleic acid

Inferred from expression pattern PubMed 15627513. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 15625305. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 17293559. Source: RGD

response to progesterone

Inferred from expression pattern PubMed 15941375. Source: RGD

response to testosterone

Inferred from expression pattern PubMed 16011741. Source: RGD

suppression by virus of host apoptotic process

Inferred from electronic annotation. Source: Ensembl

type B pancreatic cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay PubMed 15120593. Source: RGD

mitochondrial outer membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 15120593. Source: RGD

   Molecular_functioncysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.3PubMed 12871587PubMed 15120593. Source: RGD

protein kinase B binding

Inferred from physical interaction PubMed 15120593. Source: RGD

protein phosphatase 2B binding

Inferred from physical interaction PubMed 15120593. Source: RGD

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha (identifier: O35147-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Beta (identifier: O35147-2)

The sequence of this isoform differs from the canonical sequence as follows:
     166-205: LPRPKSAGTA...LGKGGSTPSQ → EELTYSVEFL...RYWTALRRLC

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 205205Bcl2-associated agonist of cell death
PRO_0000143105

Regions

Motif148 – 16215BH3

Amino acid modifications

Modified residue1131Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and RAF1 By similarity
Modified residue1291Phosphoserine By similarity
Modified residue1321Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue1341Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue1371Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ By similarity
Modified residue1561Phosphoserine; by PKA and PKB By similarity
Modified residue1711Phosphoserine By similarity

Natural variations

Alternative sequence166 – 20540LPRPK…STPSQ → EELTYSVEFLPVRAIAMEGW PLLWSFQSFPHTLPPTPPEV AMFPLRYWTALRRLC in isoform Beta.
VSP_000534

Experimental info

Mutagenesis1131S → A: No effect on heterodimerization with 14-3-3 proteins. Ref.1
Mutagenesis1371S → A: No heterodimerization with 14-3-3 proteins. No effect on heterodimerization with BCL2 nor with protein P11. Ref.1
Sequence conflict29 – 346SDAGGR → ERRGRK in AAC53374. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified September 26, 2001. Version 2.
Checksum: 7AFA71DAE9CF4A81

FASTA20522,228
        10         20         30         40         50         60 
MGTPKQPSLA PAHALGLRKS DPGIRSLGSD AGGRRWRPAA QSMFQIPEFE PSEQEDASTT 

        70         80         90        100        110        120 
DRGLGPSLTE DQPGPYLAPG LLGSIVQQQP GQAANNSHHG GAGTMETRSR HSSYPAGTEE 

       130        140        150        160        170        180 
DEGMEEELSP FRGRSRSAPP NLWAAQRYGR ELRRMSDEFE GSFKGLPRPK SAGTATQMRQ 

       190        200 
SASWTRIIQS WWDRNLGKGG STPSQ 

« Hide

Isoform Beta [UniParc].

Checksum: E27BCCD7C969E90F
Show »

FASTA22024,278

References

[1]"Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11."
Hsu S.Y., Kaipia A., Zhu L., Hsueh A.J.W.
Mol. Endocrinol. 11:1858-1867(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF SER-113 AND SER-137.
Tissue: Ovary.
[2]"Cloning and expression of the programmed cell death regulator BAD in the rat brain."
D'Agata V., Magro G., Travali S., Musco S., Cavallaro S.
Neurosci. Lett. 243:137-140(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Functional characterization of two splice variants of rat BAD and their interaction with Bcl-w in sympathetic neurons."
Hamner S., Arumae U., Yu L.-Y., Sun Y.-F., Saarma M., Lindholm D.
Mol. Cell. Neurosci. 17:97-106(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF003523 mRNA. Translation: AAC53374.1.
AF031227 mRNA. Translation: AAC15100.1.
AF279910 mRNA. Translation: AAF91427.1.
AF279911 mRNA. Translation: AAF91428.1.
RefSeqNP_073189.1. NM_022698.1. [O35147-1]
XP_006230958.1. XM_006230896.1. [O35147-2]
UniGeneRn.36696.

3D structure databases

ProteinModelPortalO35147.
SMRO35147. Positions 138-164.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249177. 2 interactions.
DIPDIP-29862N.
MINTMINT-206504.

PTM databases

PhosphoSiteO35147.

Proteomic databases

PaxDbO35147.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000028712; ENSRNOP00000028712; ENSRNOG00000021147. [O35147-1]
ENSRNOT00000067068; ENSRNOP00000061855; ENSRNOG00000021147. [O35147-2]
GeneID64639.
KEGGrno:64639.
UCSCRGD:620103. rat. [O35147-1]

Organism-specific databases

CTD572.
RGD620103. Bad.

Phylogenomic databases

eggNOGNOG43412.
GeneTreeENSGT00390000010740.
HOGENOMHOG000095169.
HOVERGENHBG001653.
InParanoidO35147.
KOK02158.
OMAWVARNAT.
OrthoDBEOG7MD4RF.
PhylomeDBO35147.
TreeFamTF102001.

Gene expression databases

GenevestigatorO35147.

Family and domain databases

InterProIPR018868. Bcl-2_BAD.
[Graphical view]
PfamPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio613624.
PROO35147.

Entry information

Entry nameBAD_RAT
AccessionPrimary (citable) accession number: O35147
Secondary accession number(s): O70256, Q9JHX1
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: July 9, 2014
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families