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Q92934 (BAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bcl2 antagonist of cell death

Short name=BAD
Alternative name(s):
Bcl-2-binding component 6
Bcl-2-like protein 8
Short name=Bcl2-L-8
Bcl-XL/Bcl-2-associated death promoter
Gene names
Name:BAD
Synonyms:BBC6, BCL2L8
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length168 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 By similarity. The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins By similarity. Interacts with AKT1 and PIM3. Ref.4 Ref.7 Ref.11

Subcellular location

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

Tissue specificity

Expressed in a wide variety of tissues.

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 on one or more of Ser-75, Ser-99, Ser-118 and Ser-134 in response to survival stimuli, which blocks its pro-apoptotic activity. Phosphorylation on Ser-99 or Ser-75 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-118, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-99 is the major site of AKT/PKB phosphorylation, Ser-118 the major site of protein kinase A (CAPK) phosphorylation. Phosphorylation at Ser-99 by PKB/AKT1 is almost completely blocked by the apoptotic C-terminus cleavage product of PKN2 generated by caspases-3 activity during apoptosis. Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the Bcl-2 family.

Sequence caution

The sequence AAB36516.1 differs from that shown. Reason: Frameshift at positions 64 and 91.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityPolymorphism
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete 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 pro-apoptotic gene products

Inferred from mutant phenotype. Source: UniProtKB

cellular response to hypoxia

Inferred from expression pattern. Source: UniProtKB

cellular response to mechanical stimulus

Inferred from expression pattern. Source: UniProtKB

cellular response to nicotine

Inferred from direct assay. Source: UniProtKB

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

induction of apoptosis by extracellular signals

Traceable author statement. Source: Reactome

induction of apoptosis by intracellular signals

Inferred from mutant phenotype. Source: UniProtKB

nerve growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

pore complex assembly

Inferred from direct assay. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of glucokinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mitochondrial membrane potential

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of type B pancreatic cell development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitochondrial membrane permeability

Inferred from mutant phenotype. Source: UniProtKB

type B pancreatic cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentcytosol

Inferred from direct assay. Source: UniProtKB

mitochondrial outer membrane

Inferred from direct assay. Source: UniProtKB

   Molecular functioncysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from direct assay. Source: UniProtKB

phospholipid binding

Inferred from mutant phenotype. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.11. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 168168Bcl2 antagonist of cell death
PRO_0000143103

Regions

Motif110 – 12415BH3

Amino acid modifications

Modified residue251Phosphoserine Ref.14 Ref.15
Modified residue361N6-acetyllysine Ref.16
Modified residue751Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and RAF1 By similarity
Modified residue911Phosphoserine Ref.15
Modified residue991Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ By similarity
Modified residue991Phosphoserine; by PKB/AKT1 Ref.7 Ref.12 Ref.13 Ref.15
Modified residue1181Phosphoserine; by PKA and PKB By similarity
Modified residue1341Phosphoserine By similarity

Natural variations

Natural variant1071A → S.
Corresponds to variant rs3729933 [ dbSNP | Ensembl ].
VAR_015380

Secondary structure

..... 168
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q92934 [UniParc].

Last modified September 26, 2001. Version 3.
Checksum: 69FD8D27DDEE3241

FASTA16818,392
        10         20         30         40         50         60 
MFQIPEFEPS EQEDSSSAER GLGPSPAGDG PSGSGKHHRQ APGLLWDASH QQEQPTSSSH 

        70         80         90        100        110        120 
HGGAGAVEIR SRHSSYPAGT EDDEGMGEEP SPFRGRSRSA PPNLWAAQRY GRELRRMSDE 

       130        140        150        160 
FVDSFKKGLP RPKSAGTATQ MRQSSSWTRV FQSWWDRNLG RGSSAPSQ 

« Hide

References

« Hide 'large scale' references
[1]"A human protein that interacts with Bcl-2 and have homology to mouse BAD."
Yin D.X., Li Z., Huang B., Chen S., Zhou H.
Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Bcl-2 targets the protein kinase Raf-1 to mitochondria."
Wang H.-G., Rapp U.R., Reed J.C.
Cell 87:629-638(1996) [PubMed: 8929532] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION BY RAF-1.
[3]Takayama S., Reed J.C.
Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins."
Ottilie S., Diaz J.-L., Horne W., Chang J., Wang Y., Wilson G., Chang S., Weeks S., Fritz L.C., Oltersdorf T.
J. Biol. Chem. 272:30866-30872(1997) [PubMed: 9388232] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DIMERIZATION.
Tissue: Bone marrow.
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[7]"Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage."
Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.
J. Biol. Chem. 275:34451-34458(2000) [PubMed: 10926925] [Abstract]
Cited for: INTERACTION WITH AKT1, PHOSPHORYLATION AT SER-99.
[8]"The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis."
Gnesutta N., Qu J., Minden A.
J. Biol. Chem. 276:14414-14419(2001) [PubMed: 11278822] [Abstract]
Cited for: PHOSPHORYLATION AT SER-75.
[9]"p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD."
Cotteret S., Jaffer Z.M., Beeser A., Chernoff J.
Mol. Cell. Biol. 23:5526-5539(2003) [PubMed: 12897128] [Abstract]
Cited for: PHOSPHORYLATION AT SER-75.
[10]"Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines."
Li Y.Y., Popivanova B.K., Nagai Y., Ishikura H., Fujii C., Mukaida N.
Cancer Res. 66:6741-6747(2006) [PubMed: 16818649] [Abstract]
Cited for: PHOSPHORYLATION AT SER-75.
[11]"Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis."
Popivanova B.K., Li Y.Y., Zheng H., Omura K., Fujii C., Tsuneyama K., Mukaida N.
Cancer Sci. 98:321-328(2007) [PubMed: 17270021] [Abstract]
Cited for: INTERACTION WITH PIM3.
[12]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-118, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[14]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[15]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25; SER-91; SER-99 AND SER-118, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[16]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed: 19608861] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, MASS SPECTROMETRY.
[17]"Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies."
Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P., Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B., Fesik S.W.
Protein Sci. 9:2528-2534(2000) [PubMed: 11206074] [Abstract]
Cited for: STRUCTURE BY NMR OF 103-127.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U66879 mRNA. Translation: AAB36516.1. Frameshift.
AF021792 mRNA. Translation: AAB72092.1.
AF031523 mRNA. Translation: AAB88124.1.
BT006678 mRNA. Translation: AAP35324.1.
BC001901 mRNA. Translation: AAH01901.1.
IPIIPI00024291.
RefSeqNP_004313.1. NM_004322.3.
NP_116784.1. NM_032989.2.
UniGeneHs.370254.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1G5JNMR-B103-127[»]
ProteinModelPortalQ92934.
SMRQ92934. Positions 100-126.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29184N.
IntActQ92934. 20 interactions.
MINTMINT-216253.
STRINGQ92934.

PTM databases

PhosphoSiteQ92934.

Polymorphism databases

DMDM17371773.

Proteomic databases

PeptideAtlasQ92934.
PRIDEQ92934.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309032; ENSP00000309103; ENSG00000002330.
ENST00000394532; ENSP00000378040; ENSG00000002330.
GeneID572.
KEGGhsa:572.
UCSCuc001nzc.1. human.

Organism-specific databases

CTD572.
GeneCardsGC11M064037.
H-InvDBHIX0009759.
HGNCHGNC:936. BAD.
HPACAB004205.
HPA028185.
MIM603167. gene.
neXtProtNX_Q92934.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19064.
GeneTreeENSGT00390000010740.
HOGENOMHBG125823.
HOVERGENHBG001653.
InParanoidQ92934.
OMASFKGLPR.
OrthoDBEOG42RD8W.
PhylomeDBQ92934.

Enzyme and pathway databases

Pathway_Interaction_DBalphasynuclein_pathway. Alpha-synuclein signaling.
ceramidepathway. Ceramide signaling pathway.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
igf1_pathway. IGF1 pathway.
p75ntrpathway. p75(NTR)-mediated signaling.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
ReactomeREACT_111102. Signal Transduction.
REACT_578. Apoptosis.

Gene expression databases

ArrayExpressQ92934.
BgeeQ92934.
CleanExHS_BAD.
GenevestigatorQ92934.
GermOnlineENSG00000002330. Homo sapiens.

Family and domain databases

InterProIPR018868. Bcl-2_BAD.
[Graphical view]
KOK02158.
PfamPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]
PROSITEPS01259. BH3. False negative.
[Graphical view]
ProtoNetSearch...

Other

NextBio2331.
PMAP-CutDBQ92934.
SOURCESearch...

Entry information

Entry nameBAD_HUMAN
AccessionPrimary (citable) accession number: Q92934
Secondary accession number(s): O14803
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 26, 2001
Last modified: January 25, 2012
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families