Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXJ7HNB)

• DOT Name: E3 ubiquitin-protein transferase RMND5A (RMND5A)
• Synonyms: EC 2.3.2.27; P44CTLH; Protein RMD5 homolog A
• Gene Name: RMND5A
• Related Disease: Neoplasm
• UniProt ID: RMD5A_HUMAN
• EC Number: 2.3.2.27
• Pfam ID: PF10607 ; PF13445
• Sequence:
  MDQCVTVERELEKVLHKFSGYGQLCERGLEELIDYTGGLKHEILQSHGQDAELSGTLSLV
  LTQCCKRIKDTVQKLASDHKDIHSSVSRVGKAIDKNFDSDISSVGIDGCWQADSQRLLNE
  VMVEHFFRQGMLDVAEELCQESGLSVDPSQKEPFVELNRILEALKVRVLRPALEWAVSNR
  EMLIAQNSSLEFKLHRLYFISLLMGGTTNQREALQYAKNFQPFALNHQKDIQVLMGSLVY
  LRQGIENSPYVHLLDANQWADICDIFTRDACALLGLSVESPLSVSFSAGCVALPALINIK
  AVIEQRQCTGVWNQKDELPIEVDLGKKCWYHSIFACPILRQQTTDNNPPMKLVCGHIISR
  DALNKMFNGSKLKCPYCPMEQSPGDAKQIFF
• Function: Core component 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. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. Catalytic activity of the complex is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[5]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of E3 ubiquitin-protein transferase RMND5A (RMND5A).	[8]

References

• [1] Regulation of c-Raf Stability through the CTLH Complex.Int J Mol Sci. 2019 Feb 21;20(4):934. doi: 10.3390/ijms20040934.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.