BNIP3 (Homo sapiens)
Description [+]
- Synonyms: BNIP3, NIP3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 [Source:UniProtKB/Swiss-Prot;Acc:Q12983]
- Family: Bcl-2 family : BH3-only
- Process: apoptosis,
- Pathways: intrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Bnip3
- WIKI: BNIP3-H_sapiens
References [+]
- 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.
- References from Mouse ortholog(s):
- 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.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | BNIP3 | 1 | 194 |
Protein sequence [+]
BNIP3 | Homo sapiens | 9606 | length:194
MSQNGAPGMQEESLQGSWVELHFSNNGNGGSVPASVSIYNGDMEKILLDAQHESGRSSSK
SSHCDSPPRSQTPQDTNRASETDTHSIGEKNSSQSEEDDIERRKEVESILKKNSDWIWDW
SSRPENIPPKEFLFKHPKRTATLSMRNTSVMKKGGIFSAEFLKVFLPSLLLSHLLAIGLG
IYIGRRLTTSTSTF
SSHCDSPPRSQTPQDTNRASETDTHSIGEKNSSQSEEDDIERRKEVESILKKNSDWIWDW
SSRPENIPPKEFLFKHPKRTATLSMRNTSVMKKGGIFSAEFLKVFLPSLLLSHLLAIGLG
IYIGRRLTTSTSTF
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| 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 | Lyzard |
| BNIP3 | orthology | Macaca |
| BNIP3 | orthology | Medaka |
| BNIP3 | orthology | Monodelphis |
| Bnip3 | orthology | Mouse |
| 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 (2 of 2) | paralogy | Fugu |
| BNIP3L (1 of 2) | paralogy | Fugu |
| T_rubripes_ENSTRUP00000046089 | paralogy | Fugu |
| BNIP3L (2 of 2) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000021335 | paralogy | Gasterosteus |
| BNIP3L (1 of 2) | paralogy | Gasterosteus |
| BNIP3L | paralogy | Horse |
| BNIP3L | paralogy | Human |
| BNIP3L | paralogy | Lyzard |
| NP_001032361.1 | paralogy | Macaca |
| O_latipes_ENSORLP00000006124 | paralogy | Medaka |
| BNIP3L (1 of 2) | paralogy | Medaka |
| BNIP3L (2 of 2) | paralogy | Medaka |
| BNIP3L | paralogy | Monodelphis |
| Bnip3l | paralogy | Mouse |
| CT030242.6 | paralogy | Mouse |
| BNIP3L | paralogy | Orangutan |
| BNIP3L | paralogy | Ornithorhynchus |
| BNIP3L | paralogy | Rabbit |
| R_norvegicus_ENSRNOP00000049965 | paralogy | Rat |
| R_norvegicus_ENSRNOP00000055295 | paralogy | Rat |
| Bnip3l | paralogy | Rat |
| R_norvegicus_ENSRNOP00000041876 | paralogy | Rat |
| BNIP3L | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000017287 | paralogy | Tetraodon |
| BNIP3L | paralogy | Xenopus |
| BNIP3L | paralogy | Zebra finch |
| zgc:123120 | paralogy | Zebrafish |
| bnip3l2 | paralogy | Zebrafish |
| zgc:73226 | paralogy | Zebrafish |
| bnip3l | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0050873 | brown fat cell differentiation | biological_proccess | IEA |
| GO:0044419 | interspecies interaction between organisms | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | IDA |
| GO:0051607 | defense response to virus | biological_proccess | IDA |
| GO:0008634 | negative regulation of survival gene product expression | biological_proccess | IDA |
| GO:0001666 | response to hypoxia | biological_proccess | ISS |
| GO:0008219 | cell death | biological_proccess | ISS |
| GO:0051402 | neuron apoptosis | biological_proccess | ISS |
| GO:0046902 | regulation of mitochondrial membrane permeability | biological_proccess | IDA |
| GO:0006309 | DNA fragmentation during apoptosis | biological_proccess | IDA |
| GO:0006338 | chromatin remodeling | biological_proccess | IDA |
| GO:0006800 | oxygen and reactive oxygen species metabolic process | biological_proccess | IDA |
| GO:0045837 | negative regulation of membrane potential | biological_proccess | IDA |
| GO:0006916 | anti-apoptosis | biological_proccess | TAS |
| GO:0043065 | positive regulation of apoptosis | biological_proccess | IEA |
| GO:0001666 | response to hypoxia | biological_proccess | IEA |
| GO:0008219 | cell death | biological_proccess | IEA |
| GO:0051402 | neuron apoptosis | biological_proccess | IEA |
| GO:0042803 | protein homodimerization activity | mollecular_function | IDA |
| GO:0046982 | protein heterodimerization activity | mollecular_function | IDA |
| GO:0016021 | integral to membrane | cell_component | IEA |
| GO:0016020 | membrane | cell_component | IEA |
| GO:0005739 | mitochondrion | cell_component | TAS |
| GO:0031966 | mitochondrial membrane | cell_component | IMP |
| GO:0005634 | nucleus | cell_component | ISS |
| GO:0005737 | cytoplasm | cell_component | ISS |
| GO:0031307 | integral to mitochondrial outer membrane | cell_component | IDA |
| GO:0005635 | nuclear envelope | cell_component | IDA |
| GO:0005654 | nucleoplasm | cell_component | ISS |
| GO:0030425 | dendrite | cell_component | ISS |
| GO:0005740 | mitochondrial envelope | cell_component | IEA |
| 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:0031966 | mitochondrial membrane | cell_component | IEA |
Check GO Evidence Codes here
Curated Isoforms [+]
| Transcript | Translation |
|---|---|
| OTTHUMT00000051039 * | OTTHUMP00000020752 * |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1084
- Gene related info from GeneCards [?] : BNIP3
- Ensembl genome browser [?] : ENSG00000176171
- Expression info from Arrayexpress [?] : ENSG00000176171
- Protein expression from Protein Atlas: [?] ENSG00000176171
- Community gene edition from Wikigenes: [?] 664
- OMIM gene information: 603293
- OMIM disease information:
Click on [?] for more information.
