UniProtKB - Q9BXH1 (BBC3_HUMAN)
Protein
Bcl-2-binding component 3, isoforms 1/2
Gene
BBC3
Organism
Homo sapiens (Human)
Status
Functioni
Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (PubMed:11463391). Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis (PubMed:23340338).2 Publications
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- apoptotic signaling pathway Source: UniProtKB
- cellular response to DNA damage stimulus Source: BHF-UCL
- cellular response to hypoxia Source: UniProtKB
- determination of adult lifespan Source: BHF-UCL
- execution phase of apoptosis Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
- negative regulation of endoplasmic reticulum calcium ion concentration Source: UniProtKB
- negative regulation of growth Source: UniProtKB
- positive regulation of cysteine-type endopeptidase activity Source: UniProtKB
- positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of IRE1-mediated unfolded protein response Source: ParkinsonsUK-UCL
- positive regulation of neuron apoptotic process Source: UniProtKB
- positive regulation of protein-containing complex assembly Source: UniProtKB
- positive regulation of protein homooligomerization Source: UniProtKB
- positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: UniProtKB
- positive regulation of release of cytochrome c from mitochondria Source: BHF-UCL
- positive regulation of thymocyte apoptotic process Source: BHF-UCL
- protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
- regulation of apoptotic process Source: Reactome
- release of cytochrome c from mitochondria Source: UniProtKB
- release of sequestered calcium ion into cytosol Source: UniProtKB
- response to endoplasmic reticulum stress Source: UniProtKB
Keywordsi
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | Q9BXH1 |
Reactomei | R-HSA-111453, BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members R-HSA-139915, Activation of PUMA and translocation to mitochondria R-HSA-6803204, TP53 Regulates Transcription of Genes Involved in Cytochrome C Release R-HSA-9614657, FOXO-mediated transcription of cell death genes |
SIGNORi | Q9BXH1 |
Names & Taxonomyi
Protein namesi | Recommended name: Bcl-2-binding component 3, isoforms 1/2Alternative name(s): JFY-1 p53 up-regulated modulator of apoptosis |
Gene namesi | Name:BBC3 Synonyms:PUMA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17868, BBC3 |
MIMi | 605854, gene |
neXtProti | NX_Q9BXH1 |
VEuPathDBi | HostDB:ENSG00000105327.15 |
Subcellular locationi
Mitochondrion
- Mitochondrion 3 Publications
Note: Localized to the mitochondria in order to induce cytochrome c release.
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- endoplasmic reticulum Source: GOC
Mitochondrion
- mitochondrial outer membrane Source: Reactome
- mitochondrion Source: UniProtKB
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 133 | W → A: Impairs p53/TP53-dependent apoptosis. 1 Publication | 1 | |
Mutagenesisi | 141 – 143 | Missing : Abolishes BLC2-binding. Impairs growth inhibitory activity. No effect on mitochondrial subcellular location. 1 Publication | 3 |
Organism-specific databases
DisGeNETi | 27113 |
OpenTargetsi | ENSG00000105327 |
PharmGKBi | PA38471 |
Miscellaneous databases
Pharosi | Q9BXH1, Tbio |
Genetic variation databases
BioMutai | BBC3 |
DMDMi | 56748610 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000143083 | 1 – 193 | Bcl-2-binding component 3, isoforms 1/2Add BLAST | 193 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 10 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9BXH1 |
jPOSTi | Q9BXH1 |
MassIVEi | Q9BXH1 |
MaxQBi | Q9BXH1 |
PeptideAtlasi | Q9BXH1 |
PRIDEi | Q9BXH1 |
ProteomicsDBi | 79423 [Q9BXH1-1] 79424 [Q9BXH1-2] |
PTM databases
iPTMneti | Q9BXH1 |
PhosphoSitePlusi | Q9BXH1 |
Expressioni
Tissue specificityi
Ubiquitously expressed.1 Publication
Inductioni
Up-regulated by TP53 (PubMed:11463392). Up-regulated by DNA damage, glucocorticoid treatment, growth factor deprivation and TP53 (PubMed:11572983). Up-regulated by ER stress in a DDIT3/CHOP-dependent manner (PubMed:22761832).3 Publications
Gene expression databases
Bgeei | ENSG00000105327, Expressed in dorsal plus ventral thalamus and 231 other tissues |
ExpressionAtlasi | Q9BXH1, baseline and differential |
Genevisiblei | Q9BXH1, HS |
Organism-specific databases
HPAi | ENSG00000105327, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with MCL1 and BCL2A1 (By similarity).
Interacts (via BH3 domain) with BCL2 (PubMed:11463391).
Interacts with BCL2L1/BCL-XL (PubMed:23340338).
Interacts (via BH3 domain) with NOL3/ARC (via CARD domain); this interaction prevents BBC3 association with BCL2 and results in CASP8 activation (By similarity).
By similarity2 PublicationsBinary interactionsi
Hide detailsQ9BXH1
Isoform 2 [Q9BXH1-2]
With | #Exp. | IntAct |
---|---|---|
MCL1 [Q07820] | 2 | EBI-519896,EBI-1003422 |
Protein-protein interaction databases
BioGRIDi | 118009, 28 interactors |
ComplexPortali | CPX-1986, PUMA:BCL-2 complex CPX-1987, PUMA:BCL-XL complex |
DIPi | DIP-29215N |
IntActi | Q9BXH1, 10 interactors |
MINTi | Q9BXH1 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9BXH1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 137 – 151 | BH3Add BLAST | 15 |
Domaini
The BH3 motif is intrinsically disordered.1 Publication
Sequence similaritiesi
Belongs to the Bcl-2 family.Curated
Phylogenomic databases
GeneTreei | ENSGT00710000107236 |
HOGENOMi | CLU_158732_0_0_1 |
OrthoDBi | 1536383at2759 |
PhylomeDBi | Q9BXH1 |
Family and domain databases
DisProti | DP01307 |
InterProi | View protein in InterPro IPR031661, Bbc3 |
PANTHERi | PTHR28639, PTHR28639, 1 hit |
Pfami | View protein in Pfam PF15826, PUMA, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q9BXH1-1) [UniParc]FASTAAdd to basket
Also known as: PUMA alpha
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_012238 | 1 – 92 | MARAR…PRPDG → MKFGMGSAQACPCQVPRAAS TTWVPCQICG in isoform 2. 1 PublicationAdd BLAST | 92 |
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 |
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_006723204.1, XM_006723141.3 [Q9BXH1-1] |
Genome annotation databases
Ensembli | ENST00000341983; ENSP00000341155; ENSG00000105327 [Q9BXH1-2] ENST00000439096; ENSP00000395862; ENSG00000105327 [Q9BXH1-1] |
GeneIDi | 27113 |
KEGGi | hsa:27113 |
UCSCi | uc002pgf.5, human [Q9BXH1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
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_006723204.1, XM_006723141.3 [Q9BXH1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
5UUL | X-ray | 1.33 | B | 132-154 | [»] | |
6QFM | X-ray | 2.00 | B | 127-149 | [»] | |
6QG8 | X-ray | 1.90 | B | 127-149 | [»] | |
6TQP | X-ray | 1.85 | B | 130-155 | [»] | |
SMRi | Q9BXH1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118009, 28 interactors |
ComplexPortali | CPX-1986, PUMA:BCL-2 complex CPX-1987, PUMA:BCL-XL complex |
DIPi | DIP-29215N |
IntActi | Q9BXH1, 10 interactors |
MINTi | Q9BXH1 |
PTM databases
iPTMneti | Q9BXH1 |
PhosphoSitePlusi | Q9BXH1 |
Genetic variation databases
BioMutai | BBC3 |
DMDMi | 56748610 |
Proteomic databases
EPDi | Q9BXH1 |
jPOSTi | Q9BXH1 |
MassIVEi | Q9BXH1 |
MaxQBi | Q9BXH1 |
PeptideAtlasi | Q9BXH1 |
PRIDEi | Q9BXH1 |
ProteomicsDBi | 79423 [Q9BXH1-1] 79424 [Q9BXH1-2] |
Protocols and materials databases
Antibodypediai | 3572, 790 antibodies |
Genome annotation databases
Ensembli | ENST00000341983; ENSP00000341155; ENSG00000105327 [Q9BXH1-2] ENST00000439096; ENSP00000395862; ENSG00000105327 [Q9BXH1-1] |
GeneIDi | 27113 |
KEGGi | hsa:27113 |
UCSCi | uc002pgf.5, human [Q9BXH1-1] |
Organism-specific databases
CTDi | 27113 |
DisGeNETi | 27113 |
GeneCardsi | BBC3 |
HGNCi | HGNC:17868, BBC3 |
HPAi | ENSG00000105327, Low tissue specificity |
MIMi | 605854, gene |
neXtProti | NX_Q9BXH1 |
OpenTargetsi | ENSG00000105327 |
PharmGKBi | PA38471 |
VEuPathDBi | HostDB:ENSG00000105327.15 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00710000107236 |
HOGENOMi | CLU_158732_0_0_1 |
OrthoDBi | 1536383at2759 |
PhylomeDBi | Q9BXH1 |
Enzyme and pathway databases
PathwayCommonsi | Q9BXH1 |
Reactomei | R-HSA-111453, BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members R-HSA-139915, Activation of PUMA and translocation to mitochondria R-HSA-6803204, TP53 Regulates Transcription of Genes Involved in Cytochrome C Release R-HSA-9614657, FOXO-mediated transcription of cell death genes |
SIGNORi | Q9BXH1 |
Miscellaneous databases
BioGRID-ORCSi | 27113, 13 hits in 994 CRISPR screens |
ChiTaRSi | BBC3, human |
GenomeRNAii | 27113 |
Pharosi | Q9BXH1, Tbio |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105327, Expressed in dorsal plus ventral thalamus and 231 other tissues |
ExpressionAtlasi | Q9BXH1, baseline and differential |
Genevisiblei | Q9BXH1, HS |
Family and domain databases
DisProti | DP01307 |
InterProi | View protein in InterPro IPR031661, Bbc3 |
PANTHERi | PTHR28639, PTHR28639, 1 hit |
Pfami | View protein in Pfam PF15826, PUMA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | BBC3_HUMAN | |
Accessioni | Q9BXH1Primary (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: | April 7, 2021 | |
This is version 156 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - 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