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O35147

- BAD_RAT

UniProt

O35147 - BAD_RAT

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Protein

Bcl2-associated agonist of cell death

Gene

Bad

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.By similarity

GO - Molecular functioni

  1. cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
  2. lipid binding Source: UniProtKB
  3. phospholipid binding Source: UniProtKB
  4. protein kinase B binding Source: RGD
  5. protein phosphatase 2B binding Source: RGD

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. ADP metabolic process Source: UniProtKB
  3. ATP metabolic process Source: UniProtKB
  4. cellular process regulating host cell cycle in response to virus Source: Ensembl
  5. cellular response to chromate Source: RGD
  6. cellular response to hypoxia Source: Ensembl
  7. cellular response to lipid Source: Ensembl
  8. cellular response to mechanical stimulus Source: Ensembl
  9. cellular response to nicotine Source: UniProtKB
  10. cytokine-mediated signaling pathway Source: Ensembl
  11. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  12. extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  13. glucose catabolic process Source: Ensembl
  14. glucose homeostasis Source: UniProtKB
  15. intrinsic apoptotic signaling pathway Source: UniProtKB
  16. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
  17. pore complex assembly Source: UniProtKB
  18. positive regulation of apoptotic process by virus Source: Ensembl
  19. positive regulation of B cell differentiation Source: Ensembl
  20. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  21. positive regulation of epithelial cell proliferation Source: UniProtKB
  22. positive regulation of glucokinase activity Source: UniProtKB
  23. positive regulation of insulin secretion Source: UniProtKB
  24. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: Ensembl
  25. positive regulation of mitochondrial membrane potential Source: UniProtKB
  26. positive regulation of neuron death Source: RGD
  27. positive regulation of proteolysis Source: Ensembl
  28. positive regulation of release of cytochrome c from mitochondria Source: Ensembl
  29. positive regulation of T cell differentiation Source: Ensembl
  30. positive regulation of type B pancreatic cell development Source: UniProtKB
  31. regulation of mitochondrial membrane permeability Source: UniProtKB
  32. release of cytochrome c from mitochondria Source: Ensembl
  33. response to amino acid Source: RGD
  34. response to calcium ion Source: RGD
  35. response to drug Source: RGD
  36. response to estradiol Source: RGD
  37. response to ethanol Source: RGD
  38. response to glucocorticoid Source: RGD
  39. response to glucose Source: RGD
  40. response to hormone Source: RGD
  41. response to hydrogen peroxide Source: RGD
  42. response to hypoxia Source: RGD
  43. response to oleic acid Source: RGD
  44. response to organic cyclic compound Source: RGD
  45. response to organic substance Source: RGD
  46. response to progesterone Source: RGD
  47. response to testosterone Source: RGD
  48. suppression by virus of host apoptotic process Source: Ensembl
  49. type B pancreatic cell proliferation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_198729. Constitutive PI3K/AKT Signaling in Cancer.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Bad
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 1

Organism-specific databases

RGDi620103. Bad.

Subcellular locationi

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

GO - Cellular componenti

  1. cytosol Source: RGD
  2. mitochondrial outer membrane Source: UniProtKB
  3. mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi113 – 1131S → A: No effect on heterodimerization with 14-3-3 proteins. 1 Publication
Mutagenesisi137 – 1371S → A: No heterodimerization with 14-3-3 proteins. No effect on heterodimerization with BCL2 nor with protein P11. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 205205Bcl2-associated agonist of cell deathPRO_0000143105Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei113 – 1131Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and RAF1By similarity
Modified residuei129 – 1291PhosphoserineBy similarity
Modified residuei132 – 1321Asymmetric dimethylarginine; by PRMT1By similarity
Modified residuei134 – 1341Asymmetric dimethylarginine; by PRMT1By similarity
Modified residuei137 – 1371Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQBy similarity
Modified residuei156 – 1561Phosphoserine; by PKA and PKBBy similarity
Modified residuei171 – 1711PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiO35147.

PTM databases

PhosphoSiteiO35147.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriO35147.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi249177. 2 interactions.
DIPiDIP-29862N.
MINTiMINT-206504.

Structurei

3D structure databases

ProteinModelPortaliO35147.
SMRiO35147. Positions 138-164.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi148 – 16215BH3Add
BLAST

Domaini

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.

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Phylogenomic databases

eggNOGiNOG43412.
GeneTreeiENSGT00390000010740.
HOGENOMiHOG000095169.
HOVERGENiHBG001653.
InParanoidiO35147.
KOiK02158.
OMAiWVARNAT.
OrthoDBiEOG7MD4RF.
PhylomeDBiO35147.
TreeFamiTF102001.

Family and domain databases

InterProiIPR018868. Bcl-2_BAD.
[Graphical view]
PfamiPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform Alpha (identifier: O35147-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGTPKQPSLA PAHALGLRKS DPGIRSLGSD AGGRRWRPAA QSMFQIPEFE
60 70 80 90 100
PSEQEDASTT DRGLGPSLTE DQPGPYLAPG LLGSIVQQQP GQAANNSHHG
110 120 130 140 150
GAGTMETRSR HSSYPAGTEE DEGMEEELSP FRGRSRSAPP NLWAAQRYGR
160 170 180 190 200
ELRRMSDEFE GSFKGLPRPK SAGTATQMRQ SASWTRIIQS WWDRNLGKGG

STPSQ
Length:205
Mass (Da):22,228
Last modified:September 26, 2001 - v2
Checksum:i7AFA71DAE9CF4A81
GO
Isoform Beta (identifier: O35147-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:220
Mass (Da):24,278
Checksum:iE27BCCD7C969E90F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti29 – 346SDAGGR → ERRGRK in AAC53374. (PubMed:9369453)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei166 – 20540LPRPK…STPSQ → EELTYSVEFLPVRAIAMEGW PLLWSFQSFPHTLPPTPPEV AMFPLRYWTALRRLC in isoform Beta. 1 PublicationVSP_000534Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF003523 mRNA. Translation: AAC53374.1.
AF031227 mRNA. Translation: AAC15100.1.
AF279910 mRNA. Translation: AAF91427.1.
AF279911 mRNA. Translation: AAF91428.1.
RefSeqiNP_073189.1. NM_022698.1. [O35147-1]
XP_006230958.1. XM_006230896.2. [O35147-2]
UniGeneiRn.36696.

Genome annotation databases

EnsembliENSRNOT00000028712; ENSRNOP00000028712; ENSRNOG00000021147. [O35147-1]
ENSRNOT00000067068; ENSRNOP00000061855; ENSRNOG00000021147. [O35147-2]
GeneIDi64639.
KEGGirno:64639.
UCSCiRGD:620103. rat. [O35147-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF003523 mRNA. Translation: AAC53374.1 .
AF031227 mRNA. Translation: AAC15100.1 .
AF279910 mRNA. Translation: AAF91427.1 .
AF279911 mRNA. Translation: AAF91428.1 .
RefSeqi NP_073189.1. NM_022698.1. [O35147-1 ]
XP_006230958.1. XM_006230896.2. [O35147-2 ]
UniGenei Rn.36696.

3D structure databases

ProteinModelPortali O35147.
SMRi O35147. Positions 138-164.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 249177. 2 interactions.
DIPi DIP-29862N.
MINTi MINT-206504.

PTM databases

PhosphoSitei O35147.

Proteomic databases

PaxDbi O35147.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000028712 ; ENSRNOP00000028712 ; ENSRNOG00000021147 . [O35147-1 ]
ENSRNOT00000067068 ; ENSRNOP00000061855 ; ENSRNOG00000021147 . [O35147-2 ]
GeneIDi 64639.
KEGGi rno:64639.
UCSCi RGD:620103. rat. [O35147-1 ]

Organism-specific databases

CTDi 572.
RGDi 620103. Bad.

Phylogenomic databases

eggNOGi NOG43412.
GeneTreei ENSGT00390000010740.
HOGENOMi HOG000095169.
HOVERGENi HBG001653.
InParanoidi O35147.
KOi K02158.
OMAi WVARNAT.
OrthoDBi EOG7MD4RF.
PhylomeDBi O35147.
TreeFami TF102001.

Enzyme and pathway databases

Reactomei REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.

Miscellaneous databases

NextBioi 613624.
PROi O35147.

Gene expression databases

Genevestigatori O35147.

Family and domain databases

InterProi IPR018868. Bcl-2_BAD.
[Graphical view ]
Pfami PF10514. Bcl-2_BAD. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiBAD_RAT
AccessioniPrimary (citable) accession number: O35147
Secondary accession number(s): O70256, Q9JHX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: October 29, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3