Molecule Information

General Information of the Molecule (ID: Mol04096)

• Name: BCL2 interacting protein 3 (BNIP3) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: BNIP3
• Gene ID: 664
• Location: chr10:131967684-131981967[-]
• Sequence:
  MSQNGAPGMQEESLQGSWVELHFSNNGNGGSVPASVSIYNGDMEKILLDAQHESGRSSSK
  SSHCDSPPRSQTPQDTNRASETDTHSIGEKNSSQSEEDDIERRKEVESILKKNSDWIWDW
  SSRPENIPPKEFLFKHPKRTATLSMRNTSVMKKGGIFSAEFLKVFLPSLLLSHLLAIGLG
  IYIGRRLTTSTSTF
• 3D-structure: PDB ID: 2J5D; Classification: Membrane protein; Method: Solution nmr; Resolution: No Resolution Dat Å
• Function: Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway. .
• Uniprot ID: BNIP3_HUMAN
• Ensembl ID: ENSG00000176171
• HGNC ID: HGNC:1084

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Lenvatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• Experiment for Molecule Alteration: Mitochondrial morphology assay; Mitophagy colocalization assay; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Of note, our transcriptome analyses showed that, in HCC cell competition scenario, lenvatinib-resistant cells captured the increased glycolysis activity but the attenuated oxidative phosphorylation level as well as decreased mitochondria mass; however, lenvatinib-sensitive cells obtain opposite metabolic features.

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.02] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Six-week-old female BALB/c nude mice, Huh7R/PLC-PRF-5R; Mice
• Experiment for Molecule Alteration: Mitochondrial morphology assay; Mitophagy colocalization assay; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Of note, our transcriptome analyses showed that, in HCC cell competition scenario, lenvatinib-resistant cells captured the increased glycolysis activity but the attenuated oxidative phosphorylation level as well as decreased mitochondria mass; however, lenvatinib-sensitive cells obtain opposite metabolic features.

References

• Ref 1: BNIP3-mediated mitophagy boosts the competitive growth of Lenvatinib-resistant cells via energy metabolism reprogramming in HCC. Cell Death Dis. 2024 Jul 5;15(7):484.