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Q9BXH1

- BBC3_HUMAN

UniProt

Q9BXH1 - BBC3_HUMAN

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Protein

Bcl-2-binding component 3

Gene

BBC3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. apoptotic process Source: Reactome
  3. apoptotic signaling pathway Source: UniProtKB
  4. cellular response to DNA damage stimulus Source: BHF-UCL
  5. cellular response to hypoxia Source: UniProtKB
  6. determination of adult lifespan Source: BHF-UCL
  7. execution phase of apoptosis Source: UniProtKB
  8. intrinsic apoptotic signaling pathway Source: Reactome
  9. intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
  10. negative regulation of endoplasmic reticulum calcium ion concentration Source: UniProtKB
  11. negative regulation of growth Source: UniProtKB
  12. positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
  13. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  14. positive regulation of neuron apoptotic process Source: UniProtKB
  15. positive regulation of protein homooligomerization Source: UniProtKB
  16. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: UniProtKB
  17. positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
  18. positive regulation of thymocyte apoptotic process Source: BHF-UCL
  19. release of cytochrome c from mitochondria Source: UniProtKB
  20. release of sequestered calcium ion into cytosol Source: UniProtKB
  21. response to endoplasmic reticulum stress Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_121. Activation of PUMA and translocation to mitochondria.
REACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.

Names & Taxonomyi

Protein namesi
Recommended name:
Bcl-2-binding component 3
Alternative name(s):
JFY-1
p53 up-regulated modulator of apoptosis
Gene namesi
Name:BBC3
Synonyms:PUMA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:17868. BBC3.

Subcellular locationi

Mitochondrion 3 Publications
Note: Localized to the mitochondria in order to induce cytochrome c release.

GO - Cellular componenti

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

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331W → A: Impairs p53/TP53-dependent apoptosis. 1 Publication

Organism-specific databases

PharmGKBiPA38471.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 193193Bcl-2-binding component 3PRO_0000143083Add
BLAST

Proteomic databases

MaxQBiQ9BXH1.
PaxDbiQ9BXH1.
PRIDEiQ9BXH1.

PTM databases

PhosphoSiteiQ9BXH1.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Inductioni

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

Gene expression databases

BgeeiQ9BXH1.
CleanExiHS_BBC3.
ExpressionAtlasiQ9BXH1. baseline and differential.
GenevestigatoriQ9BXH1.

Organism-specific databases

HPAiCAB007752.

Interactioni

Subunit structurei

Interacts with MCL1 and BCL2A1 (By similarity). Interacts with BCL2 and BCL2L1/BCL-XL.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BCL2P104155EBI-519884,EBI-77694
BCL2L1Q07817-17EBI-519884,EBI-287195
BCL2L2Q928432EBI-519884,EBI-707714
MCL1Q078203EBI-519884,EBI-1003422
Mcl1P972875EBI-519884,EBI-707292From a different organism.

Protein-protein interaction databases

BioGridi118009. 4 interactions.
DIPiDIP-29215N.
IntActiQ9BXH1. 9 interactions.
MINTiMINT-6629069.
STRINGi9606.ENSP00000404503.

Structurei

Secondary structure

1
193
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi138 – 1414
Helixi145 – 1484

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2M04NMR-B130-154[»]
4BPIX-ray1.98B136-152[»]
4BPJX-ray1.60D139-153[»]
4BPKX-ray1.76C/D134-152[»]
4HNJX-ray2.90C130-154[»]
ProteinModelPortaliQ9BXH1.
SMRiQ9BXH1. Positions 130-155.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi137 – 15115BH3Add
BLAST

Domaini

The BH3 motif is intrinsically disordered.1 Publication

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Phylogenomic databases

eggNOGiprNOG22537.
GeneTreeiENSGT00710000107236.
HOGENOMiHOG000060256.
HOVERGENiHBG050671.
KOiK10132.
PhylomeDBiQ9BXH1.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9BXH1-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MARARQEGSS PEPVEGLARD GPRPFPLGRL VPSAVSCGLC EPGLAAAPAA
60 70 80 90 100
PTLLPAAYLC APTAPPAVTA ALGGSRWPGG PRSRPRGPRP DGPQPSLSLA
110 120 130 140 150
EQHLESPVPS APGALAGGPT QAAPGVRGEE EQWAREIGAQ LRRMADDLNA
160 170 180 190
QYERRRQEEQ QRHRPSPWRV LYNLIMGLLP LPRGHRAPEM EPN
Length:193
Mass (Da):20,532
Last modified:June 1, 2001 - v1
Checksum:i3585527F1858A4FA
GO
Isoform 2 (identifier: Q9BXH1-2) [UniParc]FASTAAdd to Basket

Also known as: PUMA beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-92: MARARQEGSS...SRPRGPRPDG → MKFGMGSAQACPCQVPRAASTTWVPCQICG

Show »
Length:131
Mass (Da):14,459
Checksum:i674939670238F4AC
GO
Isoform 3 (identifier: Q96PG8-1) [UniParc]FASTAAdd to Basket

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.
Length:101
Mass (Da):10,326
GO
Isoform 4 (identifier: Q96PG8-2) [UniParc]FASTAAdd to Basket

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.
Length:261
Mass (Da):26,498
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9292MARAR…PRPDG → MKFGMGSAQACPCQVPRAAS TTWVPCQICG in isoform 2. 1 PublicationVSP_012238Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS12697.1. [Q9BXH1-1]
CCDS46130.1. [Q9BXH1-2]
RefSeqiNP_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]
UniGeneiHs.467020.

Genome annotation databases

GeneIDi27113.
KEGGihsa:27113.
UCSCiuc002pgf.4. human. [Q9BXH1-1]
uc010eky.3. human. [Q9BXH1-2]

Polymorphism databases

DMDMi56748610.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS12697.1. [Q9BXH1-1 ]
CCDS46130.1. [Q9BXH1-2 ]
RefSeqi NP_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 ]
UniGenei Hs.467020.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2M04 NMR - B 130-154 [» ]
4BPI X-ray 1.98 B 136-152 [» ]
4BPJ X-ray 1.60 D 139-153 [» ]
4BPK X-ray 1.76 C/D 134-152 [» ]
4HNJ X-ray 2.90 C 130-154 [» ]
ProteinModelPortali Q9BXH1.
SMRi Q9BXH1. Positions 130-155.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 118009. 4 interactions.
DIPi DIP-29215N.
IntActi Q9BXH1. 9 interactions.
MINTi MINT-6629069.
STRINGi 9606.ENSP00000404503.

Chemistry

BindingDBi Q9BXH1.

PTM databases

PhosphoSitei Q9BXH1.

Polymorphism databases

DMDMi 56748610.

Proteomic databases

MaxQBi Q9BXH1.
PaxDbi Q9BXH1.
PRIDEi Q9BXH1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 27113.
KEGGi hsa:27113.
UCSCi uc002pgf.4. human. [Q9BXH1-1 ]
uc010eky.3. human. [Q9BXH1-2 ]

Organism-specific databases

CTDi 27113.
GeneCardsi GC19M047724.
HGNCi HGNC:17868. BBC3.
HPAi CAB007752.
MIMi 605854. gene.
neXtProti NX_Q9BXH1.
PharmGKBi PA38471.
GenAtlasi Search...

Phylogenomic databases

eggNOGi prNOG22537.
GeneTreei ENSGT00710000107236.
HOGENOMi HOG000060256.
HOVERGENi HBG050671.
KOi K10132.
PhylomeDBi Q9BXH1.

Enzyme and pathway databases

Reactomei REACT_121. Activation of PUMA and translocation to mitochondria.
REACT_330. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.

Miscellaneous databases

ChiTaRSi BBC3. human.
GenomeRNAii 27113.
NextBioi 49796.
PROi Q9BXH1.
SOURCEi Search...

Gene expression databases

Bgeei Q9BXH1.
CleanExi HS_BBC3.
ExpressionAtlasi Q9BXH1. baseline and differential.
Genevestigatori Q9BXH1.

Family and domain databases

ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiBBC3_HUMAN
AccessioniPrimary (citable) accession number: Q9BXH1
Secondary accession number(s): B9EGI3, O00171, Q96PG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: June 1, 2001
Last modified: October 29, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3