BNIP3 (Mus musculus)

Description [+]

Synonyms: BNIP3, BNIP3, BCL2/ADENOVIRUS E1B INTERACTING PROTEIN 3
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Rodentia; Mus musculus
Short gene description: BCL2/adenovirus E1B interacting protein 3 Gene [Source:MGI (curated);Acc:Bnip3-001]
Family: Bcl-2 family : BH3-only
Process: cell death (other), apoptosis,
Pathways: intrinsic pathway,
Criteria: manually curated
Curator comment:
Human ortholog(s): BNIP3
WIKI: BNIP3-M_musculus

References [+]

BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions.
Chinnadurai G, Vijayalingam S, Gibson SB
The BNIP3 subfamily of BH3-only proteins consists of BNIP3 and BNIP3-like (BNIP3L) proteins. These proteins form stable homodimerization complexes that localize to the outer membrane of the mitochondria after cellular stress. This promotes either apoptotic or non-apoptotic cell death such as autophagic cell death. Although the mammalian cells contain both members of this subfamily, the genome of Caenorhabditis elegans codes for a single BNIP3 ortholog, ceBNIP3, which shares homology in the transmembrane (TM) domain and in a conserved region close to the BH3 domain of mammalian BNIP3 protein. The cell death activities of BNIP3 and BNIP3L are determined by either the BH3 domain or the C-terminal TM domain. The TM domain of BNIP3 is unique, as it is capable of autonomous stable dimerization and contributes to mitochondrial localization of BNIP3. In knockout mouse models, BNIP3L was shown to be essential for normal erythrocyte differentiation and hematopoietic homeostasis, whereas BNIP3 plays a role in cellular responses to ischemia/reperfusion injury in the heart. Both BNIP3 and BNIP3L play a role in cellular responses to stress. Under hypoxia, both BNIP3 and BNIP3L expression levels are elevated and contribute to hypoxia-induced cell death. In addition, these proteins play critical roles in disease states. In heart disease, both BNIP3 and BNIP3L play a critical role in cardiomyocyte cell death following ischemic and non-ischemic injuries. In cancer, expression of BNIP3 and BNIP3L is downregulated by promoter hypermethylation or by homozygous deletion of the gene locus in certain cancers, whereas their expression was increased in other cancers. In addition, BNIP3 expression has been correlated with poor prognosis in some cancers. The results reviewed here suggest that BNIP3 and BNIP3L may be novel therapeutic targets for intervention because of their pathological roles in regulating cell death in disease states. Oncogene. 2008 Dec;27 Suppl 1:S114-27.

Adenovirus E1B-19K/BCL-2 interacting protein BNIP3 contains a BH3 domain and a mitochondrial targeting sequence.
Yasuda M, Theodorakis P, Subramanian T, Chinnadurai G
Adenovirus E1B-19K and BCL-2 anti-apoptosis proteins interact with certain BCL-2 family pro-apoptotic proteins. A conserved domain, BH3, present in these proteins is essential for their pro-apoptotic activity and for heterodimerization with anti-apoptosis proteins. Cellular protein BNIP3 (previously NIP3) interacts with E1B-19K, BCL-2, BCL-xL, and EBV-BHRF1. BNIP3 contains a motif similar to the BH3 domain. Deletion of the BH3-like motif in BNIP3 abrogates its ability to heterodimerize with E1B-19K and BCL-xL. Substitution of the BH3 domain of BNIP3 for the corresponding sequences of BAX functionally restores the pro-apoptotic and protein heterodimerization activities of BAX. BNIP3 exhibits a delayed cell death activity that is partially relieved by deletion of the BH3 domain. BNIP3 suppresses the anti-apoptosis activity of BCL-xL in a BH3-dependent manner. BNIP3 contains a C-terminal trans-membrane (TM) domain similar to other BCL-2 family proteins and BNIP1 (previously NIP1). The TM domains of BNIP3 and BNIP1 can functionally substitute for the TM domain of a BCL-2 family member EBV-BHRF1. The BNIP3 TM domain exclusively targets the heterologous green fluorescent protein (GFP) to mitochondria. These results suggest that BNIP3 is a member of the BH3-contaning BCL-2 family of pro-apoptotic proteins and functions in mitochondria. J Biol Chem. 1998 May 15;273(20):12415-21.

References from Human ortholog(s):

Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins.
Chen G, Cizeau J, Vande Velde C, Park JH, Bozek G, Bolton J, Shi L, Dubik D, Greenberg A
We have identified Nix, a homolog of the E1B 19K/Bcl-2 binding and pro-apoptotic protein Nip3. Human and murine Nix have a 56 and 53% amino acid identity to human and murine Nip3, respectively. The carboxyl terminus of Nix, including a transmembrane domain, is highly homologous to Nip3 but it bears a longer and distinct asparagine/proline-rich N terminus. Human Nip3 maps to chromosome 14q11.2-q12, whereas Nix/BNip3L was found on 8q21. Nix encodes a 23. 8-kDa protein but it is expressed as a 48-kDa protein, suggesting that it homodimerizes similarly to Nip3. Following transfection, Nix protein undergoes progressive proteolysis to an 11-kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin. Nix colocalizes with the mitochondrial matrix protein HSP60, and removal of the putative transmembrane domain (TM) results in general cytoplasmic and nuclear expression. When transiently expressed, Nix and Nip3 but not TM deletion mutants rapidly activate apoptosis. Nix can overcome the suppressers Bcl-2 and Bcl-XL, although high levels of Bcl-XL expression will inhibit apoptosis. We propose that Nix and Nip3 form a new subfamily of pro-apoptotic mitochondrial proteins. J Biol Chem. 1999 Jan 1;274(1):7-10.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	BNIP3	1	187

Evolution [+]

Name	Relationship	Species
A_aegypti_AAEL006711-PA	orthology	Aedes
A_gambiae_AGAP001411-PA	orthology	Anopheles
BNIP3	orthology	Chicken
BNIP3	orthology	Chimpanzee
BNIP3_BOVIN	orthology	Cow
Q005W6_CANFA	orthology	Dog
BNIP3	orthology	Fugu
BNIP3	orthology	Gasterosteus
BNIP3	orthology	Gorilla
BNIP3	orthology	Horse
BNIP3	orthology	Human
BNIP3	orthology	Lyzard
BNIP3	orthology	Macaca
BNIP3	orthology	Medaka
BNIP3	orthology	Monodelphis
BNIP3	orthology	Orangutan
BNIP3	orthology	Ornithorhynchus
BNIP3	orthology	Rabbit
R_norvegicus_ENSRNOP00000016874	orthology	Rat
Bnip3	orthology	Rat
BNIP3	orthology	Tetraodon
Q5EAM0_XENTR	orthology	Xenopus
BNIP3	orthology	Zebra finch
wu:fj49c01	orthology	Zebrafish
NP_001026056.1	paralogy	Chicken
BNIP3L	paralogy	Chimpanzee
BNI3L_BOVIN	paralogy	Cow
BNIP3L	paralogy	Dog
BNIP3L (1 of 2)	paralogy	Fugu
BNIP3L (2 of 2)	paralogy	Fugu
T_rubripes_ENSTRUP00000046089	paralogy	Fugu
BNIP3L (2 of 2)	paralogy	Gasterosteus
BNIP3L (1 of 2)	paralogy	Gasterosteus
G_aculeatus_ENSGACP00000021335	paralogy	Gasterosteus
BNIP3L	paralogy	Horse
BNIP3L	paralogy	Human
BNIP3L	paralogy	Lyzard
NP_001032361.1	paralogy	Macaca
BNIP3L (1 of 2)	paralogy	Medaka
BNIP3L (2 of 2)	paralogy	Medaka
O_latipes_ENSORLP00000006124	paralogy	Medaka
BNIP3L	paralogy	Monodelphis
Bnip3l	paralogy	Mouse
CT030242.6	paralogy	Mouse
BNIP3L	paralogy	Orangutan
BNIP3L	paralogy	Ornithorhynchus
BNIP3L	paralogy	Rabbit
Bnip3l	paralogy	Rat
R_norvegicus_ENSRNOP00000049965	paralogy	Rat
R_norvegicus_ENSRNOP00000041876	paralogy	Rat
R_norvegicus_ENSRNOP00000055295	paralogy	Rat
BNIP3L	paralogy	Tetraodon
T_nigroviridis_ENSTNIP00000017287	paralogy	Tetraodon
BNIP3L	paralogy	Xenopus
BNIP3L	paralogy	Zebra finch
zgc:123120	paralogy	Zebrafish
bnip3l	paralogy	Zebrafish
zgc:73226	paralogy	Zebrafish
bnip3l2	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0043065	positive regulation of apoptosis	biological_proccess	IEA
GO:0001666	response to hypoxia	biological_proccess	ISS
GO:0006309	DNA fragmentation during apoptosis	biological_proccess	ISS
GO:0006338	chromatin remodeling	biological_proccess	ISS
GO:0006800	oxygen and reactive oxygen species metabolic process	biological_proccess	ISS
GO:0006917	induction of apoptosis	biological_proccess	ISS
GO:0008219	cell death	biological_proccess	ISS
GO:0008634	negative regulation of survival gene product expression	biological_proccess	ISS
GO:0045837	negative regulation of membrane potential	biological_proccess	ISS
GO:0046902	regulation of mitochondrial membrane permeability	biological_proccess	ISS
GO:0050873	brown fat cell differentiation	biological_proccess	IDA
GO:0051402	neuron apoptosis	biological_proccess	ISS
GO:0051607	defense response to virus	biological_proccess	ISS
GO:0006915	apoptosis	biological_proccess	RCA
GO:0042981	regulation of apoptosis	biological_proccess	RCA
GO:0001666	response to hypoxia	biological_proccess	IEA
GO:0008219	cell death	biological_proccess	IEA
GO:0051402	neuron apoptosis	biological_proccess	IEA
GO:0006309	DNA fragmentation during apoptosis	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IEA
GO:0006800	oxygen and reactive oxygen species metabolic process	biological_proccess	IEA
GO:0006338	chromatin remodeling	biological_proccess	IEA
GO:0051607	defense response to virus	biological_proccess	IEA
GO:0008634	negative regulation of survival gene product expression	biological_proccess	IEA
GO:0046902	regulation of mitochondrial membrane permeability	biological_proccess	IEA
GO:0045837	negative regulation of membrane potential	biological_proccess	IEA
GO:0042803	protein homodimerization activity	mollecular_function	IEA
GO:0046982	protein heterodimerization activity	mollecular_function	IEA
GO:0005740	mitochondrial envelope	cell_component	IEA
GO:0016021	integral to membrane	cell_component	IEA
GO:0005634	nucleus	cell_component	ISS
GO:0005635	nuclear envelope	cell_component	ISS
GO:0005654	nucleoplasm	cell_component	ISS
GO:0005737	cytoplasm	cell_component	ISS
GO:0005739	mitochondrion	cell_component	ISS
GO:0016020	membrane	cell_component	IEA
GO:0030425	dendrite	cell_component	ISS
GO:0031307	integral to mitochondrial outer membrane	cell_component	ISS
GO:0031966	mitochondrial membrane	cell_component	IDA
GO:0005634	nucleus	cell_component	IEA
GO:0005737	cytoplasm	cell_component	IEA
GO:0030425	dendrite	cell_component	IEA
GO:0005654	nucleoplasm	cell_component	IEA
GO:0005635	nuclear envelope	cell_component	IEA
GO:0031307	integral to mitochondrial outer membrane	cell_component	IEA
GO:0031966	mitochondrial membrane	cell_component	IEA

Check GO Evidence Codes here

Curated Isoforms [+]

Transcript	Translation
OTTMUST00000055539 *	OTTMUSP00000026604 *
OTTMUST00000055540
OTTMUST00000055541
OTTMUST00000055542
OTTMUST00000055543

Information from other databases [+]

Gene related links:

Gene info from MGI [?] MGI:109326
Ensembl genome browser [?] : ENSMUSG00000078566
Expression info from Arrayexpress [?] : ENSMUSG00000078566
Protein expression from Protein Atlas: [?] ENSMUSG00000078566
Community gene edition from Wikigenes: [?] 100042570

Protein related links:

Uniprot protein info: O55003
PIR protein info: O55003
Protein interactions from IntAct: O55003

Other links

entrezgene: 12176
entrezgene: 624862
entrezgene: 100042570
refseq_dna: NM_009760
refseq_peptide: NP_033890

Click on [?] for more information.