Molecule Information

General Information of the Molecule (ID: Mol04113)

• Name: Hepatitis B virus X-interacting protein (HBXIP) ,Homo sapiens
• Synonyms: Hepatitis B virus X-interacting protein; Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5
• Molecule Type: Protein
• Gene Name: LAMTOR5
• Gene ID: 10542
• Location: chr1:110401249-110407942[-]
• Sequence:
  MEATLEQHLEDTMKNPSIVGVLCTDSQGLNLGCRGTLSDEHAGVISVLAQQAAKLTSDPT
  DIPVVCLESDNGNIMIQKHDGITVAVHKMAS
• 3D-structure: PDB ID: 6B9X; Classification: Signaling protein; Method: X-ray diffraction; Resolution: 1.42 Å
• Function: As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:22980980, PubMed:29158492, PubMed:30181260). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:22980980, PubMed:28935770, PubMed:29107538, PubMed:29158492, PubMed:30181260). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:22980980, PubMed:29158492, PubMed:30181260). When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway (PubMed:12773388). .
• Uniprot ID: LTOR5_HUMAN
• Ensembl ID: ENSG00000134248
• HGNC ID: HGNC:17955

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

Sorafenib

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: Lipid metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Six-week-old male BALB/c athymic nude mice; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: In this study, we found that HBXIP suppresses ferroptosis by inducing abnormal free FA accumulation and blocks the anti-cancer activity of sorafenib in HCC cells. Mechanistic investigation revealed that HBXIP acts as a coactivator to induce SCD expression via coactivating transcription factor ZNF263, leading to upregulation of FA biosynthesis. Overexpression of HBXIP prevents ferroptosis and reduces the anti-tumor effect of sorafenib in vivo and in vitro.

References

• Ref 1: Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma. Acta Pharmacol Sin. 2023 Mar;44(3):622-634.