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Symbol BNIP3 contributors: mct/pgu - updated : 15-06-2015
HGNC name BCL2/adenovirus E1B 19kDa interacting protein 3
HGNC id 1084
Location 10q26.3      Physical location : 133.781.203 - 133.795.435
Synonym name BCL-2/E1B 19 kDa interacting protein
Synonym symbol(s) NIP3
TYPE functioning gene
STRUCTURE 14.23 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 1535 - 194 - 2003 1287901
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   moderately
Lymphoid/Immunelymph node   highly
Nervousnervecranial nerve  highly
Reproductivemale systemprostate  highly
Respiratorylung   highly
Urinarykidney   highly
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Connectivebone  highly
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...)
cell lineage
cell lines
  • a BCL-2 homology domain
  • a C terminal putative membrane-spanning hydrophobic domain, transmembrane domain that is essential for homodimerization and proapoptotic function
  • mono polymer homomer , heteromer , dimer
    interspecies homolog to rattus Bnip3 (94.1pc)
  • NIP3 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nuclear envelope
  • coexpression with the E1B/19 kda protein results in a shift in BNIP3 localization pattern to the nuclear envelope
  • is localized to the nucleus in the majority of glioblastoma multiforme (GBM) tumors and fails to induce cell death
  • localized to both mitochondria and the endoplasmic reticulum (ER)
  • localizes to the outer mitochondrial membrane, where it functions in mitophagy and mitochondrial dynamics
  • basic FUNCTION
  • apoptosis inducing protein, even in the presence of BCL2
  • playing a role in hypoxia-induced cell death in epithelial cells that could be circumvented by growth factor signaling
  • mediates mitochondrial dysfunction through activation of BAX or BAK1 which is independent of mitochondrial permeability transition pore opening
  • might play a role in gastric carcinoma development
  • implicated in the pathogenesis of cancer and heart disease
  • involved in the induction of autophagy and required for mitophagy (specialized autophagy that targets mitochondria) , and is clearly a survival mechanism that promotes tumor progression
  • in tumor cells, BNIP3 is regulated by hypoxia and deregulation is associated with tumor growth
  • transcriptional repression function causing reduced apoptosis-inducing factor expression and increased resistance to apoptosis in GBM tumors
  • mediates permeabilization of mitochondria and release of cytochrome c via a novel mechanism
  • BNIP3 and PDK1 are involved in two important pathways, cell death and glycolytic, playing critical roles in these pathways in cardiomyocytes after severe hypoxia
  • might have a dual function in the myocardium, where it regulates both mitochondrial turnover via autophagy and cell death and that these are two separate processes activated by BNIP3
  • contributes to cell death through activation of the mitochondrial pathway of apoptosis
  • caused an increase in mitochondrial protease activity, suggesting that BNIP3 might promote degradation of proteins in the mitochondria
  • BNIP3-mediated impairment of mitochondrial respiration induces mitochondrial turnover by activating mitochondrial autophagy
  • key regulator of cell death/autophagy and can act as an effector of a necrosis-like, atypical death program
  • regulates the apoptotic balance as an autophagy receptor that induces removal of both mitochondria and ER
  • role in limiting mitochondrial mass and maintaining mitochondrial integrity in the liver that has consequences for lipid metabolism and disease
  • BNIP3 and AIFM1 cooperate to induce apoptosis and cavitation during epithelial morphogenesis
  • could play a protective role in tumor cells under hypoxia
  • BNIP3 regulates mitophagy during hypoxia, whereas BNIP3L is required for mitophagy during development of the erythroid lineage
  • temporally regulated role for BNIP3 and BNIP3L in the generation of robust NK cell memory
  • CELLULAR PROCESS cell life, cell death/apoptosis
    a component
    small molecule
  • binding adenovirus E1B, BCL2, bhrf1 of Epstein-Barr virus
  • interacting with BCL2L1 (critically regulates the apoptosis of terminally differentiated chondrocytes)
  • interacting with BNIP3L
  • interacting with FOXO3 (FOXO3 controls the transcription of autophagy-related genes, including MAP1LC3 and BNIP3
  • direct transcriptional target of E2F1 that is necessary and sufficient for E2F1-induced cell death
  • interacts with OPA1, leading to mitochondrial fragmentation and apoptosis
  • under hypoxic conditions VEGFA counteracts and masks the apoptosis promoting affects of BNIP3
  • regulatory target of HRAS
  • induction of autophagy in response to BNIP3 is a protective response activated by the cell that involves DNM1L-mediated mitochondrial fission and recruitment of Parkin
  • BNIP3 and AIFM1 cooperate to induce apoptosis and cavitation during epithelial morphogenesis
  • partners of CLN8 are VAPA, C14orf1/hERG28, STX8, GABARAPL2, BNIP3 and BNIP3L proteins and are associated with biologically relevant processes such as synthesis and transport of lipids, vesicular/membrane trafficking, autophagy/mitophagy and apoptosis
  • different mitophagy effectors, including the mitophagy receptors BNIP3L, BNIP3 and FUNDC1 and the PINK1/Parkin pathway, have been identified to participate in the selective clearance of mitochondria
  • cell & other
    activated by E2F1 (E2F1 activates BNIP3 and the intrinsic death pathway in ventricular myocytes)
    induced by dramatically by hypoxia and by overexpression of HIF1A (role during hypoxia induced cell death)
    nitric oxide that causes cell death in macrophages
    repressed by TYMP
    TP53 (TP53 suppressed BNIP3 expression by directly binding to the TP53-response element motif and recruiting corepressor SIN3A to the BNIP3 promoter)
    Other in heart muscle, regulated by hypoxia and Galphaq-dependent signaling , expression is associated with decreased of myocardial function
    under nonapoptotic conditions, NFKappaB transcriptionally silences BNIP3 gene transcription
    autophagic degradation of BNIP3 was dependent on ATG7 and MAP1LC3
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    by aberrant DNA methylation of the 5' CpG island and histone deacetylation in haematopoietic tumours
    tumoral     --low  
    in chronic pancreatitis and pancreatic cancer with poorer survival
    tumoral     --low  
    downregulated in primary myelofibrosis
    constitutional     --over  
    in heart failure and contributes to loss of myocardial cells during I/R (ischaemia/reperfusion)
    constitutional     --low  
    was protective against hypoxia-induced autophagy and cell death
    Variant & Polymorphism
    Candidate gene
    Therapy target
    . FOXO3 and BNIP3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved
    . FOXO3 and BNIP3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved
    treatment with Torin1, an MTOR inhibitor, decreased the BNIP3 level and enhanced the death of hypoxic tumor cells