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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	193 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential mediator of p53-dependent and p53-independent apoptosis. Ref.1
Subunit structure	Interacts with MCL1 and BCL2A1 By similarity. Interacts with BCL2 and BCL2L1/BCL-XL. Ref.1
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/TP53. Ref.2 Ref.3
Sequence similarities	Belongs to the Bcl-2 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Inferred from sequence or structural similarity. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.2. Source: UniProtKB activation of pro-apoptotic gene products Traceable author statement. Source: Reactome cellular response to hypoxia Inferred from expression pattern. Source: UniProtKB determination of adult lifespan Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of growth Inferred from mutant phenotype Ref.2. Source: UniProtKB positive regulation of protein homooligomerization Inferred from direct assay. Source: UniProtKB positive regulation of release of cytochrome c from mitochondria Inferred from direct assay. Source: UniProtKB positive regulation of thymocyte apoptosis Inferred from sequence or structural similarity. Source: BHF-UCL protein insertion into mitochondrial membrane involved in induction of apoptosis Inferred from direct assay. Source: UniProtKB reduction of endoplasmic reticulum calcium ion concentration Inferred from direct assay. 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. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome mitochondrial outer membrane Traceable author statement. Source: Reactome
Molecular function	protein binding Inferred from physical interaction Ref.1Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	4	EBI-519884,EBI-77694
BCL2L1	Q07817-1	6	EBI-519884,EBI-287195
BCL2L2	Q92843	2	EBI-519884,EBI-707714
Mcl1	P97287	3	EBI-519884,EBI-707292	From a different organism.

Alternative products

This entry describes 2 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

Note: No experimental confirmation available.

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

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

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: 11463391] [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: 11463392] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), 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: 11572983] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
+	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_001127240.1. NP_001120713.1. NM_001127241.1. NP_001120714.1. NM_001127242.1. NP_055232.1. NM_014417.3.
UniGene	Hs.467020.
3D structure databases
ProteinModelPortal	Q9BXH1.
SMR	Q9BXH1. Positions 130-155.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29215N.
IntAct	Q9BXH1. 11 interactions.
MINT	MINT-6629069.
STRING	Q9BXH1.
PTM databases
PhosphoSite	Q9BXH1.
Polymorphism databases
DMDM	56748610.
Proteomic databases
PRIDE	Q9BXH1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359924; ENSP00000352999; ENSG00000105327. ENST00000439096; ENSP00000395862; ENSG00000105327.
GeneID	27113.
KEGG	hsa:27113.
UCSC	uc002pgf.2. human. uc010eky.1. human.
Organism-specific databases
CTD	27113.
GeneCards	GC19M047724.
H-InvDB	HIX0027462.
HGNC	HGNC:17868. BBC3.
HPA	CAB007752.
MIM	605854. gene.
neXtProt	NX_Q9BXH1.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG20559.
GeneTree	ENSGT00600000085028.
HOVERGEN	HBG050671.
InParanoid	Q9BXH1.
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
KO	K10132.
PROSITE	PS01259. BH3. False negative. [Graphical view]
ProtoNet	Search...
Other
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:	January 25, 2012
This is version 79 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.