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Protein BNIP3 PDB 2j5d.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesBNIP3, NIP3, BCL2/adenovirus E1B 19kDa interacting protein 3, BCL2 interacting protein 3
External IDsMGI: 109326 HomoloGene: 2990 GeneCards: BNIP3
Gene location (Human)
Chromosome 10 (human)
Chr.Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for BNIP3
Genomic location for BNIP3
Band10q26.3Start131,966,455 bp[1]
End131,982,013 bp[1]
RNA expression pattern
PBB GE BNIP3 201849 at fs.png

PBB GE BNIP3 201848 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 10: 131.97 – 131.98 MbChr 7: 138.89 – 138.91 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene.[5]

BNIP3 is a member of the apoptotic Bcl-2 protein family that is involved an atypical programmed cell death pathway resembling both necrosis and apoptosis. Many Bcl-2 family proteins modulate the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers. However, sequence similarity with Bcl-2 family members was not detected. Humans and other animals (Drosophila, Caenorhabditis), as well as lower eukaryotes (Dictyostelium, Trypanosoma, Cryptosporidium, Paramecium) encode several BNIP3 paralogues including the human NIP3L, which induces apoptosis by interacting with viral and cellular anti-apoptosis proteins.


The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNIP3 transmembrane domain into an artificial lipid bilayer resulted in a pH-dependent conductivity increase. Necrosis-like cell death induced by BNIP3 may be related to this activity.[6]


BNIP3 interacts with the E1B 19 kDa protein which is responsible for the protection of virally induced cell death, as well as E1B 19 kDa-like sequences of BCL2, also an apoptotic protector. This gene contains a BH3 domain and a transmembrane domain, which have been associated with pro-apoptotic function. The dimeric mitochondrial protein encoded by this gene is known to induce apoptosis, even in the presence of BCL2.[7] Change of BNIP3 expression along other members of the Bcl-2 family measured by qPCR captures important characteristics of malignant transformation, and are defined as markers of resistance toward cell death, a key Cancer Hallmark.[8]

Transport reaction[edit]

The reaction catalyzed by BNIP3 is:

small molecules (out) ⇌ small molecules (in)


BNIP3 has been shown to interact with CD47,[9] BCL2-like 1[10] and Bcl-2.[5][10]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000176171 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000078566 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b Boyd JM, Malstrom S, Subramanian T, Venkatesh LK, Schaeper U, Elangovan B, D'Sa-Eipper C, Chinnadurai G (Oct 1994). "Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins". Cell. 79 (2): 341–51. doi:10.1016/0092-8674(94)90202-X. PMID 7954800.
  6. ^ Bocharov EV, Pustovalova YE, Pavlov KV, Volynsky PE, Goncharuk MV, Ermolyuk YS, Karpunin DV, Schulga AA, Kirpichnikov MP, Efremov RG, Maslennikov IV, Arseniev AS (June 2007). "Unique dimeric structure of BNip3 transmembrane domain suggests membrane permeabilization as a cell death trigger". The Journal of Biological Chemistry. 282 (22): 16256–66. doi:10.1074/jbc.M701745200. PMID 17412696.
  7. ^ "Entrez Gene: BNIP3 BCL2/adenovirus E1B 19kDa interacting protein 3".
  8. ^ Menyhárt O, Harami-Papp H, Sukumar S, Schäfer R, Magnani L, de Barrios O, Győrffy B (December 2016). "Guidelines for the selection of functional assays to evaluate the hallmarks of cancer". Biochimica et Biophysica Acta. 1866 (2): 300–319. doi:10.1016/j.bbcan.2016.10.002. PMID 27742530.
  9. ^ Lamy L, Ticchioni M, Rouquette-Jazdanian AK, Samson M, Deckert M, Greenberg AH, Bernard A (Jun 2003). "CD47 and the 19 kDa interacting protein-3 (BNIP3) in T cell apoptosis". The Journal of Biological Chemistry. 278 (26): 23915–21. doi:10.1074/jbc.M301869200. PMID 12690108.
  10. ^ a b Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, Gietz RD, Greenberg AH (Jan 2000). "BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites". The Journal of Biological Chemistry. 275 (2): 1439–48. doi:10.1074/jbc.275.2.1439. PMID 10625696.

Further reading[edit]

External links[edit]

As of this edit, this article uses content from "1.A.20 The BCL2/Adenovirus E1B-interacting Protein 3 (BNip3) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.