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Q9BXH1 (BBC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bcl-2-binding component 3
Alternative name(s):
JFY-1
p53 up-regulated modulator of apoptosis
Gene names
Name:BBC3
Synonyms:PUMA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length193 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis. Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis. Ref.1 Ref.8

Subunit structure

Interacts with MCL1 and BCL2A1 By similarity. Interacts with BCL2 and BCL2L1/BCL-XL. Ref.1 Ref.8

Subcellular location

Mitochondrion. Note: Localized to the mitochondria in order to induce cytochrome c release. Ref.1 Ref.2 Ref.3

Tissue specificity

Ubiquitously expressed. Ref.1

Induction

By DNA damage, glucocorticoid treatment, growth factor deprivation and p53. By ER stress in a DDIT3/CHOP-dependent manner. Ref.2 Ref.3 Ref.7

Domain

The BH3 motif is intrinsically disordered. Ref.8

Sequence similarities

Belongs to the Bcl-2 family.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.2PubMed 17024184. Source: UniProtKB

apoptotic process

Traceable author statement. Source: Reactome

apoptotic signaling pathway

Inferred from direct assay Ref.2. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to hypoxia

Inferred from expression pattern PubMed 20810912. Source: UniProtKB

determination of adult lifespan

Inferred from sequence or structural similarity. Source: BHF-UCL

execution phase of apoptosis

Inferred from direct assay Ref.1Ref.2. Source: UniProtKB

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of endoplasmic reticulum calcium ion concentration

Inferred from direct assay PubMed 17024184. Source: UniProtKB

negative regulation of growth

Inferred from mutant phenotype Ref.2. Source: UniProtKB

positive regulation of cysteine-type endopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 17289999. Source: UniProtKB

positive regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein homooligomerization

Inferred from direct assay PubMed 17024184. Source: UniProtKB

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Inferred from direct assay PubMed 17024184. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from direct assay PubMed 17024184. Source: UniProtKB

positive regulation of thymocyte apoptotic process

Inferred from sequence or structural similarity. Source: BHF-UCL

release of cytochrome c from mitochondria

Inferred from direct assay Ref.2. Source: UniProtKB

release of sequestered calcium ion into cytosol

Inferred from direct assay PubMed 17024184. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from direct assay Ref.7. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay Ref.1Ref.2. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.1Ref.2. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BXH1-1)

Also known as: PUMA alpha;

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 2 (identifier: Q9BXH1-2)

Also known as: PUMA beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: MARARQEGSS...SRPRGPRPDG → MKFGMGSAQACPCQVPRAASTTWVPCQICG
Isoform 3 (identifier: Q96PG8-1)

Also known as: PUMA delta;

The sequence of this isoform can be found in the external entry Q96PG8.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoform 4 (identifier: Q96PG8-2)

Also known as: PUMA gamma;

The sequence of this isoform can be found in the external entry Q96PG8.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 193193Bcl-2-binding component 3
PRO_0000143083

Regions

Motif137 – 15115BH3

Natural variations

Alternative sequence1 – 9292MARAR…PRPDG → MKFGMGSAQACPCQVPRAAS TTWVPCQICG in isoform 2.
VSP_012238

Experimental info

Mutagenesis1331W → A: Impairs p53/TP53-dependent apoptosis. Ref.8

Secondary structure

..... 193
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PUMA alpha) [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 3585527F1858A4FA

FASTA19320,532
        10         20         30         40         50         60 
MARARQEGSS PEPVEGLARD GPRPFPLGRL VPSAVSCGLC EPGLAAAPAA PTLLPAAYLC 

        70         80         90        100        110        120 
APTAPPAVTA ALGGSRWPGG PRSRPRGPRP DGPQPSLSLA EQHLESPVPS APGALAGGPT 

       130        140        150        160        170        180 
QAAPGVRGEE EQWAREIGAQ LRRMADDLNA QYERRRQEEQ QRHRPSPWRV LYNLIMGLLP 

       190 
LPRGHRAPEM EPN 

« Hide

Isoform 2 (PUMA beta) [UniParc].

Checksum: 674939670238F4AC
Show »

FASTA13114,459
Isoform 3 (PUMA delta) [UniParc].

See Q96PG8.

Isoform 4 (PUMA gamma) [UniParc].

See Q96PG8.

References

« Hide 'large scale' references
[1]"PUMA induces the rapid apoptosis of colorectal cancer cells."
Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.
Mol. Cell 7:673-682(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BCL2 AND BCL2L1, TISSUE SPECIFICITY.
[2]"PUMA, a novel proapoptotic gene, is induced by p53."
Nakano K., Wousden K.H.
Mol. Cell 7:683-694(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), INDUCTION, SUBCELLULAR LOCATION.
[3]"Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals."
Han J.-W., Flemington C., Houghton A.B., Gu Z., Zambetti G.P., Lutz R.J., Zhu L., Chittenden T.
Proc. Natl. Acad. Sci. U.S.A. 98:11318-11323(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress."
Ghosh A.P., Klocke B.J., Ballestas M.E., Roth K.A.
PLoS ONE 7:E39586-E39586(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[8]"PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis."
Follis A.V., Chipuk J.E., Fisher J.C., Yun M.K., Grace C.R., Nourse A., Baran K., Ou L., Min L., White S.W., Green D.R., Kriwacki R.W.
Nat. Chem. Biol. 9:163-168(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 130-154 IN COMPLEX WITH BCL2L1, STRUCTURE BY NMR OF 130-154 IN COMPLEX WITH BCL2L1, FUNCTION, DOMAIN, MUTAGENESIS OF TRP-133, INTERACTION WITH BCL2L1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF332558 mRNA. Translation: AAK31316.1.
AF354654 mRNA. Translation: AAK39542.1.
AF354655 mRNA. Translation: AAK39543.1.
U82987 mRNA. Translation: AAB51243.2.
CH471126 Genomic DNA. Translation: EAW57465.1.
BC136481 mRNA. Translation: AAI36482.1.
CCDSCCDS12697.1. [Q9BXH1-1]
CCDS46130.1. [Q9BXH1-2]
RefSeqNP_001120712.1. NM_001127240.2.
NP_001120713.1. NM_001127241.2. [Q9BXH1-2]
NP_001120714.1. NM_001127242.2.
NP_055232.1. NM_014417.4. [Q9BXH1-1]
XP_005258797.1. XM_005258740.2. [Q9BXH1-1]
XP_006723204.1. XM_006723141.1. [Q9BXH1-1]
UniGeneHs.467020.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2M04NMR-B130-154[»]
4BPIX-ray1.98B136-152[»]
4BPJX-ray1.60D139-153[»]
4BPKX-ray1.76C/D134-152[»]
4HNJX-ray2.90C130-154[»]
ProteinModelPortalQ9BXH1.
SMRQ9BXH1. Positions 130-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118009. 4 interactions.
DIPDIP-29215N.
IntActQ9BXH1. 9 interactions.
MINTMINT-6629069.
STRING9606.ENSP00000404503.

Chemistry

BindingDBQ9BXH1.

PTM databases

PhosphoSiteQ9BXH1.

Polymorphism databases

DMDM56748610.

Proteomic databases

MaxQBQ9BXH1.
PaxDbQ9BXH1.
PRIDEQ9BXH1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341983; ENSP00000341155; ENSG00000105327. [Q9BXH1-2]
ENST00000439096; ENSP00000395862; ENSG00000105327. [Q9BXH1-1]
GeneID27113.
KEGGhsa:27113.
UCSCuc002pgf.4. human. [Q9BXH1-1]
uc010eky.3. human. [Q9BXH1-2]

Organism-specific databases

CTD27113.
GeneCardsGC19M047724.
HGNCHGNC:17868. BBC3.
HPACAB007752.
MIM605854. gene.
neXtProtNX_Q9BXH1.
PharmGKBPA38471.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG22537.
HOGENOMHOG000060256.
HOVERGENHBG050671.
InParanoidQ9BXH1.
KOK10132.
PhylomeDBQ9BXH1.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressQ9BXH1.
BgeeQ9BXH1.
CleanExHS_BBC3.
GenevestigatorQ9BXH1.

Family and domain databases

ProtoNetSearch...

Other

ChiTaRSBBC3. human.
GenomeRNAi27113.
NextBio49796.
PROQ9BXH1.
SOURCESearch...

Entry information

Entry nameBBC3_HUMAN
AccessionPrimary (citable) accession number: Q9BXH1
Secondary accession number(s): B9EGI3, O00171, Q96PG9
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 106 of the entry and version 1 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM