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Protein

Bcl-2-binding component 3

Gene

BBC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

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 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:17868. BBC3.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • endoplasmic reticulum Source: GOC
  • mitochondrial outer membrane Source: Reactome
  • 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.

Polymorphism and mutation databases

BioMutaiC10orf118.
DMDMi56748610.

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.
GenevisibleiQ9BXH1. HS.

Organism-specific databases

HPAiCAB007752.

Interactioni

Subunit structurei

Interacts with MCL1 and BCL2A1 (By similarity). Interacts with BCL2 and BCL2L1/BCL-XL. Interacts (via BH3 domain) with NOL3 (via CARD domain); preventing the association of BBC3 with BCL2 and resulting in activation of CASP8 (By similarity).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. 6 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 – 1414Combined sources
Helixi145 – 1484Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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. AlignAdd to basket

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:
EMBLi
GenBanki
DDBJi
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_006723204.1. XM_006723141.2. [Q9BXH1-1]
UniGeneiHs.467020.

Genome annotation databases

EnsembliENST00000341983; ENSP00000341155; ENSG00000105327. [Q9BXH1-2]
ENST00000439096; ENSP00000395862; ENSG00000105327. [Q9BXH1-1]
GeneIDi27113.
KEGGihsa:27113.
UCSCiuc002pgf.4. human. [Q9BXH1-1]
uc010eky.3. human. [Q9BXH1-2]

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:
EMBLi
GenBanki
DDBJi
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_006723204.1. XM_006723141.2. [Q9BXH1-1]
UniGeneiHs.467020.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

BioGridi118009. 6 interactions.
DIPiDIP-29215N.
IntActiQ9BXH1. 9 interactions.
MINTiMINT-6629069.
STRINGi9606.ENSP00000404503.

Chemistry

BindingDBiQ9BXH1.

PTM databases

PhosphoSiteiQ9BXH1.

Polymorphism and mutation databases

BioMutaiC10orf118.
DMDMi56748610.

Proteomic databases

MaxQBiQ9BXH1.
PaxDbiQ9BXH1.
PRIDEiQ9BXH1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341983; ENSP00000341155; ENSG00000105327. [Q9BXH1-2]
ENST00000439096; ENSP00000395862; ENSG00000105327. [Q9BXH1-1]
GeneIDi27113.
KEGGihsa:27113.
UCSCiuc002pgf.4. human. [Q9BXH1-1]
uc010eky.3. human. [Q9BXH1-2]

Organism-specific databases

CTDi27113.
GeneCardsiGC19M047724.
HGNCiHGNC:17868. BBC3.
HPAiCAB007752.
MIMi605854. gene.
neXtProtiNX_Q9BXH1.
PharmGKBiPA38471.
GenAtlasiSearch...

Phylogenomic databases

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

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.

Miscellaneous databases

ChiTaRSiBBC3. human.
GenomeRNAii27113.
NextBioi49796.
SOURCEiSearch...

Gene expression databases

BgeeiQ9BXH1.
CleanExiHS_BBC3.
ExpressionAtlasiQ9BXH1. baseline and differential.
GenevisibleiQ9BXH1. HS.

Family and domain databases

ProtoNetiSearch...

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: June 24, 2015
This is version 115 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.