BNIP3 (Bcl-2/adenovirus E1B 19kD-interacting protein 3)

2007-10-01   Sang-Gi Paik  , Hayyoung Lee  

Department of Biology, School of Biosciences, Biotechnology, Chungnam National University, Daejeon 305-764, Korea.

Identity

HGNC
LOCATION
10q26.3
LOCUSID
ALIAS
NIP3
FUSION GENES

DNA/RNA

Atlas Image

Description

14.23 kb on reverse strand; 6 exons

Transcription

mRNA in MCF-7 cells are 1.7kb (major) and 1.5 kb (minor) and 1.3 kb (minor).

Proteins

Atlas Image
Domain map of BNIP3 protein; BH3 domain (Bcl-2 holomogy 3 domain); TM domain (transmembrane domain)

Description

194 amino acids; 1 BH3 domain and 1 TM domain; BH3 only Bcl2 family member. The TM domain and C-terminal tail are essential for mitochondrial membrane localization and proapoptotic function. The predicted molecular weight is 21.5 kDa. BNIP3 migrates as 30 kDa monomeric form and 60 kDa dimeric form on SDS-PAGE.

Expression

BNIP3 is detected in mouse oviduct, uterus, spleen, lung, stomach, brain, seminal, lacrimal, submaxillary, heart, kidney, liver. It can be detected in cell lines such as HeLa, 293T, RAW264.7 and K562 cells. Its expression can be induced in both normal and cancer tissues that experience hypoxia or hypoxia-like conditions. Other stimuli, such as nitric oxide or arsenic trioxide, are also reported to induce BNIP3 expression.

Localisation

Outer mitochondrial membrane

Function

Proapoptotic protein;
BNIP3 leads to opening of the mitochondrial permeability transition pore (PTP) thereby abolishing the proton electrochemical gradient and this is followed by chromatin condensation and DNA fragmentation. BNIP3 leads necrosis-like apoptosis. Unusually to the other Bcl-2 family proteins, the BNIP3-induced cell death depends not on BH3 domain but on C-terminal TM domain. BNIP3-induced cell death is known to be independent the nuclear translocation of AIF. However, whether caspase activation and cytochrome c release are involved in the cell death remains controversial. BNIP3 can induce autophagy. However whether the consequence of the autophagy is the cell death or survival remains to be established.
Since BNIP3 is induced by hypoxia through transcription factor HIF-1, it was postulated to play a role in hypoxia-induced cell death. Hypoxia-induced acidosis augments the proapoptotic function of BNIP3.

Homology

The close homologue: BNIP3L/ BNIP3a/ Nix/ B5 (8q21)
The BH3-only Bcl2 family members: BBC3/PUMA (19q13), BCL2L11/BIM/BOD (2Q13), BID (22q11), BIK/NBK/BBC1 (22q13), BLK (8q23), BMF (15Q14), HRK/DP5/BID3 (12q24), PMAIP1/NOXA (18q21)

Implicated in

Entity name
Pancreatic cancer
Prognosis
Pancreatic adenocarcinoma is highly resistant to chemical and radiation therapy, and has an extremely poor prognosis. Reduced expression of BNIP3 increased resistance to gemcitabine and 5-fluoro-uracil (5-FU) and showed a good correlation with reduced patient survival.
Oncogenesis
In most cases of pancreatic adenocarcinoma, BNIP3 expression was not detected even in response to hypoxia. The promoter of BNIP3 is located within a CpG island and is methylated in most pancreatic cancer cell lines. Restoration of BNIP3 expression by the methyltransferase inhibitor, 5-aza-deoxycytidine, induced death of pancreatic cancer cells in response to hypoxia.
Entity name
Colorectal cancer
Oncogenesis
Methylation of BNIP3 in 66% of primary colorectal cancer

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 664
MIM: 603293
HGNC: 1084
Ensembl: ENSG00000176171

Variants:

dbSNP: 664
ClinVar: 664
TCGA: ENSG00000176171
COSMIC: BNIP3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000176171ENST00000368636Q12983
ENSG00000176171ENST00000540159F6RP06
ENSG00000176171ENST00000633835A0A0J9YW18

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Autophagy - animalKEGGko04140
Autophagy - animalKEGGhsa04140
LegionellosisKEGGko05134
LegionellosisKEGGhsa05134
FoxO signaling pathwayKEGGhsa04068
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
378762792024Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome.0
381428982024BNIP3 and DAPK1 methylation in peripheral blood leucocytes are noninvasive biomarkers for gastric cancer.0
381991162024Autophagy induced by hypoxia in pulpitis is mediated by HIF-1α/BNIP3.1
382116502024CD30 protects EBV-positive diffuse large B-cell lymphoma cells against mitochondrial dysfunction through BNIP3-mediated mitophagy.1
384435982024The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.1
385197712024Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species.1
378762792024Excessive BNIP3- and BNIP3L-dependent mitophagy underlies the pathogenesis of FBXL4-mutated mitochondrial DNA depletion syndrome.0
381428982024BNIP3 and DAPK1 methylation in peripheral blood leucocytes are noninvasive biomarkers for gastric cancer.0
381991162024Autophagy induced by hypoxia in pulpitis is mediated by HIF-1α/BNIP3.1
382116502024CD30 protects EBV-positive diffuse large B-cell lymphoma cells against mitochondrial dysfunction through BNIP3-mediated mitophagy.1
384435982024The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress.1
385197712024Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species.1
366284782023The mitophagy receptor BNIP3 is critical for the regulation of metabolic homeostasis and mitochondrial function in the nucleus pulposus cells of the intervertebral disc.8
367954012023The outer mitochondrial membrane protein TMEM11 demarcates spatially restricted BNIP3/BNIP3L-mediated mitophagy.10
369283442023HIF1α-BNIP3-mediated mitophagy protects against renal fibrosis by decreasing ROS and inhibiting activation of the NLRP3 inflammasome.8

Citation

Sang-Gi Paik ; Hayyoung Lee

BNIP3 (Bcl-2/adenovirus E1B 19kD-interacting protein 3)

Atlas Genet Cytogenet Oncol Haematol. 2007-10-01

Online version: http://atlasgeneticsoncology.org/gene/822/js/favicon/meetings/