BNIP3L (Homo sapiens)
- Synonyms: BNIP3L, NIX, BNIP3A
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (NIP3-like protein X)(NIP3L)(BCL2/adenovirus E1B 19 kDa protein-interacting protein 3A)(Adenovirus E1B19K-binding protein B5) [Source:UniProtKB/Swiss-Prot;Acc:O60238]
- Family: Bcl-2 family : BH3-only
- Process: cell death (other), apoptosis,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Bnip3l CT030242.6
- WIKI: BNIP3L-H_sapiens
- 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.
- The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death.
- Burton TR, Gibson SB
- Bcl-2 nineteen-kilodalton interacting protein (BNIP3) is a BH-3-only Bcl-2 family member whose expression levels increase during stress such as hypoxia through hypoxia-inducing factor-1-dependent or -independent mechanisms. When BNIP3 expression is induced, it localizes to the mitochondria and triggers a loss of membrane potential, and an increase in the reactive oxygen species production, which often leads to cell death. Cells under normal growth conditions suppress BNIP3 expression through transcriptional repression. There is considerable debate in the literature regarding what type of cell death is induced by BNIP3. It has been observed that BNIP3 could induce necrosis, autophagy and/or apoptosis. In contrast, other studies indicate that BNIP3 could promote cell survival. Besides its cell death regulation, BNIP3 plays a key role in the pathogenicity of many diseases. In cardiac infarction, loss of BNIP3 expression has been shown to reduce the number of damaged cardiomyocytes after ischemia and reperfusion. BNIP3 expression also plays an important role in the deregulation of cell death in many cancers. In this review, we will discuss the different and often contradictory mechanisms of BNIP3 regulation of cell death and the role that BNIP3 may play in diseases. Cell Death Differ. 2009 Apr;16(4):515-23. Epub 2009 Jan 9.
- References from Mouse ortholog(s):
- The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis.
- Chen G, Ray R, Dubik D, Shi L, Cizeau J, Bleackley RC, Saxena S, Gietz RD, Greenberg AH
- Nip3 (nineteen kD interacting protein-3) is an E1B 19K and Bcl-2 binding protein of unknown function. Nip3 is detected as both a 60- and 30-kD protein in vivo and in vitro and exhibits strong homologous interaction in a yeast two-hybrid system indicating that it can homodimerize. Nip3 is expressed in mitochondria and a mutant (Nip3(163)) lacking the putative transmembrane domain and COOH terminus does not dimerize or localize to mitochondria. Transient transfection of epitope-tagged Nip3 in Rat-1 fibroblasts and MCF-7 breast carcinoma induces apoptosis within 12 h while cells transfected with the Nip3(163) mutant have a normal phenotype, suggesting that mitochondrial localization is necessary for induction of cell death. Nip3 overexpression increases the sensitivity to apoptosis induced by granzyme B and topoisomerase I and II inhibitors. After transfection, both Nip3 and Nip3(163) protein levels decrease steadily over 48 h indicating that the protein is rapidly degraded and this occurs in the absence of cell death. Bcl-2 overexpression initially delays the onset of apoptosis induced by Nip3 but the resistance is completely overcome in longer periods of incubation. Nip3 protein levels are much higher and persist longer in Bcl-2 expressing cells. In conclusion, Nip3 is an apoptosis-inducing dimeric mitochondrial protein that can overcome Bcl-2 suppression. J Exp Med. 1997 Dec 15;186(12):1975-83.
Structure & Sequence [+]
Pfam domains: (Pfam is a large collection of protein families.)
Protein sequence [+]
BNIP3L | Homo sapiens | 9606 | length:219
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Homologs list [+]
|BNIP3L (2 of 2)||orthology||Fugu|
|BNIP3L (1 of 2)||orthology||Fugu|
|BNIP3L (1 of 2)||orthology||Gasterosteus|
|BNIP3L (2 of 2)||orthology||Gasterosteus|
|BNIP3L (2 of 2)||orthology||Medaka|
|BNIP3L (1 of 2)||orthology||Medaka|
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Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0043065||positive regulation of apoptosis||biological_proccess||IEA|
|GO:0044419||interspecies interaction between organisms||biological_proccess||IEA|
|GO:0043066||negative regulation of apoptosis||biological_proccess||IDA|
|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:0042803||protein homodimerization activity||mollecular_function||IDA|
|GO:0046982||protein heterodimerization activity||mollecular_function||IDA|
|GO:0016021||integral to membrane||cell_component||IEA|
Check GO Evidence Codes here
Curated Isoforms [+]
Information from other databases [+]
- OMIM gene information: 605368
- OMIM disease information:
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