Q92934 (BAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	168 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Polymorphism
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	ADP 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 component	cytosol Inferred from direct assay. Source: UniProtKB mitochondrial outer membrane Inferred from direct assay. Source: UniProtKB
Molecular function	cysteine-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

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	5	EBI-700771,EBI-77694
BCL2L1	Q07817-1	6	EBI-700771,EBI-287195
BNIP3L	O60238	2	EBI-700771,EBI-849893

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 168

168

Bcl2 antagonist of cell death

PRO_0000143103

Regions

Motif

110 – 124

15

BH3

Amino acid modifications

Modified residue

25

1

Phosphoserine Ref.14 Ref.15

Modified residue

36

1

N6-acetyllysine Ref.16

Modified residue

75

1

Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and RAF1 By similarity

Modified residue

91

1

Phosphoserine Ref.15

Modified residue

99

1

Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ By similarity

Modified residue

99

1

Phosphoserine; by PKB/AKT1 Ref.7 Ref.12 Ref.13 Ref.15

Modified residue

118

1

Phosphoserine; by PKA and PKB By similarity

Modified residue

134

1

Phosphoserine By similarity

Natural variations

Natural variant

107

1

A → S.
Corresponds to variant rs3729933 [ dbSNP | Ensembl ].

VAR_015380

Secondary structure

1

.

.

.

.

.

168

Helix Strand Turn

Details...

Helix

106 – 121

16

Beta strand

123 – 125

3

Sequences

	Sequence		Length	Mass (Da)
	Q92934 [UniParc]. Last modified September 26, 2001. Version 3. Checksum: 69FD8D27DDEE3241	FASTA	168	18,392
	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

References

	« Hide 'large scale' referencesShow '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

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Wikipedia

Bcl 2-associated death promoter entry

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.

IPI

IPI00024291.

RefSeq

NP_004313.1. NM_004322.3.
NP_116784.1. NM_032989.2.

UniGene

Hs.370254.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G5J	NMR	-	B	103-127	[»]

ProteinModelPortal

Q92934.

SMR

Q92934. Positions 100-126.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29184N.

IntAct

Q92934. 20 interactions.

MINT

MINT-216253.

STRING

Q92934.

PTM databases

PhosphoSite

Q92934.

Polymorphism databases

DMDM

17371773.

Proteomic databases

PeptideAtlas

Q92934.

PRIDE

Q92934.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309032; ENSP00000309103; ENSG00000002330.
ENST00000394532; ENSP00000378040; ENSG00000002330.

GeneID

572.

KEGG

hsa:572.

UCSC

uc001nzc.1. human.

Organism-specific databases

CTD

572.

GeneCards

GC11M064037.

H-InvDB

HIX0009759.

HGNC

HGNC:936. BAD.

HPA

CAB004205.
HPA028185.

MIM

603167. gene.

neXtProt

NX_Q92934.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19064.

GeneTree

ENSGT00390000010740.

HOGENOM

HBG125823.

HOVERGEN

HBG001653.

InParanoid

Q92934.

OMA

SFKGLPR.

OrthoDB

EOG42RD8W.

PhylomeDB

Q92934.

Enzyme and pathway databases

Pathway_Interaction_DB

alphasynuclein_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.

Reactome

REACT_111102. Signal Transduction.
REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q92934.

Bgee

Q92934.

CleanEx

HS_BAD.

Genevestigator

Q92934.

GermOnline

ENSG00000002330. Homo sapiens.

Family and domain databases

InterPro

IPR018868. Bcl-2_BAD.
[Graphical view]

KO

K02158.

Pfam

PF10514. Bcl-2_BAD. 1 hit.
[Graphical view]

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

2331.

PMAP-CutDB

Q92934.

SOURCE

Search...

Entry information

Entry name

BAD_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.