Q9BXH1 (BBC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bcl-2-binding component 3

Alternative name(s):
JFY-1
p53 up-regulated modulator of apoptosis

Gene names

Name:	BBC3
Synonyms:	PUMA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	193 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Apoptosis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.2PubMed 17024184. Source: UniProtKB 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 induction of apoptosis Inferred from direct assay PubMed 16608847. Source: HGNC intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from sequence or structural similarity. Source: BHF-UCL intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of growth Inferred from mutant phenotype Ref.2. 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 reduction of endoplasmic reticulum calcium ion concentration Inferred from direct assay PubMed 17024184. Source: UniProtKB 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
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrial outer membrane Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	5	EBI-519884,EBI-77694
BCL2L1	Q07817-1	7	EBI-519884,EBI-287195
BCL2L2	Q92843	2	EBI-519884,EBI-707714
MCL1	Q07820	3	EBI-519884,EBI-1003422
Mcl1	P97287	3	EBI-519884,EBI-707292	From a different organism.

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 193

193

Bcl-2-binding component 3

PRO_0000143083

Regions

Motif

137 – 151

15

BH3

Natural variations

Alternative sequence

1 – 92

92

MARAR…PRPDG → MKFGMGSAQACPCQVPRAAS TTWVPCQICG in isoform 2.

VSP_012238

Experimental info

Mutagenesis

133

1

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

Secondary structure

1

.

.

.

193

Helix Strand Turn

Details...

Helix

133 – 151

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PUMA alpha) [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 3585527F1858A4FA	FASTA	193	20,532
	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
	Isoform 2 (PUMA beta) [UniParc]. Checksum: 674939670238F4AC	FASTA	131	14,459
	10 20 30 40 50 60 MKFGMGSAQA CPCQVPRAAS TTWVPCQICG PQPSLSLAEQ HLESPVPSAP GALAGGPTQA 70 80 90 100 110 120 APGVRGEEEQ WAREIGAQLR RMADDLNAQY ERRRQEEQQR HRPSPWRVLY NLIMGLLPLP 130 RGHRAPEMEP N
	Isoform 3 (PUMA delta) [UniParc]. See Q96PG8.		–	–
	Isoform 4 (PUMA gamma) [UniParc]. See Q96PG8.		–	–

References

	« Hide 'large scale' referencesShow '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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00004338.
IPI00186516.

RefSeq

NP_001120712.1. NM_001127240.2.
NP_001120713.1. NM_001127241.2.
NP_001120714.1. NM_001127242.2.
NP_055232.1. NM_014417.4.

UniGene

Hs.467020.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2M04	NMR	-	B	130-154	[»]
4HNJ	X-ray	2.90	C	130-154	[»]

ProteinModelPortal

Q9BXH1.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29215N.

IntAct

Q9BXH1. 8 interactions.

MINT

MINT-6629069.

STRING

9606.ENSP00000404503.

PTM databases

PhosphoSite

Q9BXH1.

Polymorphism databases

DMDM

56748610.

Proteomic databases

PaxDb

Q9BXH1.

PRIDE

Q9BXH1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000341983; ENSP00000341155; ENSG00000105327.
ENST00000439096; ENSP00000395862; ENSG00000105327.

GeneID

27113.

KEGG

hsa:27113.

UCSC

uc002pgf.4. human.
uc010eky.3. human.

Organism-specific databases

CTD

27113.

GeneCards

GC19M047724.

HGNC

HGNC:17868. BBC3.

HPA

CAB007752.

MIM

605854. gene.

neXtProt

NX_Q9BXH1.

PharmGKB

PA38471.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG22537.

HOGENOM

HOG000060256.

HOVERGEN

HBG050671.

InParanoid

Q9BXH1.

KO

K10132.

PhylomeDB

Q9BXH1.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q9BXH1.

Bgee

Q9BXH1.

CleanEx

HS_BBC3.

Genevestigator

Q9BXH1.

GermOnline

ENSG00000105327. Homo sapiens.

Family and domain databases

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9BXH1.

ChEMBL

CHEMBL1250409.

ChiTaRS

BBC3. human.

GenomeRNAi

27113.

NextBio

49796.

SOURCE

Search...

Entry information

Entry name

BBC3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 93 of the entry and version 1 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.