Molecule Information

General Information of the Molecule (ID: Mol04092)

• Name: Autophagy related 12 (ATG12) ,Homo sapiens
• Synonyms: Autophagy-related protein 12
• Molecule Type: Protein
• Gene Name: ATG12
• Gene ID: 9140
• Location: chr5:115828200-115841837[-]
• Sequence:
  MAEEPQSVLQLPTSIAAGGEGLTDVSPETTTPEPPSSAAVSPGTEEPAGDTKKKIDILLK
  AVGDTPIMKTKKWAVERTRTIQGLIDFIKKFLKLVASEQLFIYVNQSFAPSPDQEVGTLY
  ECFGSDGKLVLHYCKSQAWG
• 3D-structure: PDB ID: 4NAW; Classification: Protein transport/ligase; Method: X-ray diffraction; Resolution: 2.19 Å
• Function: Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. As part of the ATG8 conjugation system with ATG5 and ATG16L1, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity). .; (Microbial infection) May act as a proviral factor. In association with ATG5, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for the initiation of HCV replication, but not required once infection is established (PubMed:19666601). .
• Uniprot ID: ATG12_HUMAN
• Ensembl ID: ENSG00000145782
• HGNC ID: HGNC:588

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: Glutamine metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Resistant Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Hepatocellular carcinoma
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.44E-07; Fold-change: 2.13E-01; Z-score: 5.02E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: NGS and real-time PCR demonstrated the downregulated expression of miR-23b-3p in sorafenib-resistant cells compared to parental cells. In silico analysis showed that miR-23b-3p specifically targeted autophagy through ATG12 and glutaminolysis through GLS1. In transfection assays, mimics of miR-23b-3p demonstrated reduced gene expression for both ATG12 and GLS1, decreased cell viability, and increased cell apoptosis of sorafenib-resistant HepG2 cells, whereas the antimiRs of miR-23b-3p demonstrated contrasting results.

References

• Ref 1: miR-23b-3p Modulating Cytoprotective Autophagy and Glutamine Addiction in Sorafenib Resistant HepG2, a Hepatocellular Carcinoma Cell Line. Genes (Basel). 2022 Aug 1;13(8):1375.