Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0TOD0M)

• DOT Name: Glucose-induced degradation protein 4 homolog (GID4)
• Synonyms: Vacuolar import and degradation protein 24 homolog
• Gene Name: GID4
• Related Disease: Schizophrenia
• UniProt ID: GID4_HUMAN
• PDB ID: 6CCR; 6CCT; 6CCU; 6CD8; 6CD9; 6CDC; 6CDG; 6WZX; 6WZZ; 7NSC; 7Q4Y; 7Q50; 7SLZ; 7U3E; 7U3F; 7U3G; 7U3H; 7U3I; 7U3J; 7U3K; 7U3L; 8V1P
• Pfam ID: PF09783
• Sequence:
  MCARGQVGRGTQLRTGRPCSQVPGSRWRPERLLRRQRAGGRPSRPHPARARPGLSLPATL
  LGSRAAAAVPLPLPPALAPGDPAMPVRTECPPPAGASAASAASLIPPPPINTQQPGVATS
  LLYSGSKFRGHQKSKGNSYDVEVVLQHVDTGNSYLCGYLKIKGLTEEYPTLTTFFEGEII
  SKKHPFLTRKWDADEDVDRKHWGKFLAFYQYAKSFNSDDFDYEELKNGDYVFMRWKEQFL
  VPDHTIKDISGASFAGFYYICFQKSAASIEGYYYHRSSEWYQSLNLTHVPEHSAPIYEFR
• Function: Substrate-recognition subunit of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (Probable). Binds proteins and peptides with a Pro/N-degron consisting of an unmodified N-terminal Pro followed by a small residue, and has the highest affinity for the peptide Pro-Gly-Leu-Trp. Binds peptides with an N-terminal sequence of the type Pro-[Ala,Gly]-[Leu,Met,Gln,Ser,Tyr]-[Glu,Gly,His,Ser,Val,Trp,Tyr]. Does not bind peptides with an acetylated N-terminal Pro residue.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Glucose-induced degradation protein 4 homolog (GID4).	[2]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glucose-induced degradation protein 4 homolog (GID4).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glucose-induced degradation protein 4 homolog (GID4).	[4]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Glucose-induced degradation protein 4 homolog (GID4).	[5]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Glucose-induced degradation protein 4 homolog (GID4).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glucose-induced degradation protein 4 homolog (GID4).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glucose-induced degradation protein 4 homolog (GID4).	[8]

References

• [1] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.