Details of Drug Off-Target (DOT)

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

• DOT Name: Rhomboid-related protein 1 (RHBDL1)
• Synonyms: RRP; EC 3.4.21.105; Rhomboid-like protein 1
• Gene Name: RHBDL1
• Related Disease:
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Respiratory papillomatosis
  Human papillomavirus infection
• UniProt ID: RHBL1_HUMAN
• EC Number: 3.4.21.105
• Pfam ID: PF01694
• Sequence:
  MGRVEDGGTTEELEDWDPGTSALPAPGIKQGPREQTGTGPLSQKCWEPEPDAPSQPGPAL
  WSRGRARTQALAGGSSLQQLDPENTGFIGADTFTGLVHSHELPLDPAKLDMLVALAQSNE
  QGQVCYQELVDLISSKRSSSFKRAIANGQRALPRDGPLDEPGLGVYKRFVRYVAYEILPC
  EVDRRWYFYRHRSCPPPVFMASVTLAQIIVFLCYGARLNKWVLQTYHPEYMKSPLVYHPG
  HRARAWRFLTYMFMHVGLEQLGFNALLQLMIGVPLEMVHGLLRISLLYLAGVLAGSLTVS
  ITDMRAPVVGGSGGVYALCSAHLANVVMNWAGMRCPYKLLRMVLALVCMSSEVGRAVWLR
  FSPPLPASGPQPSFMAHLAGAVVGVSMGLTILRSYEERLRDQCGWWVVLLAYGTFLLFAV
  FWNVFAYDLLGAHIPPPP
• Function: May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors.
• Tissue Specificity: Detected in heart, brain, skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Respiratory papillomatosis	DISXL96I	Strong	Biomarker	[1]
Human papillomavirus infection	DISX61LX	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Rhomboid-related protein 1 (RHBDL1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rhomboid-related protein 1 (RHBDL1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rhomboid-related protein 1 (RHBDL1).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Rhomboid-related protein 1 (RHBDL1).	[7]

References

• [1] Model of human recurrent respiratory papilloma on chicken embryo chorioallantoic membrane for tumor angiogenesis research.Histol Histopathol. 2017 Jul;32(7):699-710. doi: 10.14670/HH-11-831. Epub 2016 Oct 10.
• [2] Predictive factors for prolonged hospital stay after retropubic radical prostatectomy in a high-volume teaching center.Int Braz J Urol. 2018 Nov-Dec;44(6):1089-1105. doi: 10.1590/S1677-5538.IBJU.2017.0339.
• [3] HPV genotyping and HLA II analysis in a pedigree study of pediatric RRP: preliminary results.Int J Pediatr Otorhinolaryngol. 2006 Nov;70(11):1935-9. doi: 10.1016/j.ijporl.2006.07.003. Epub 2006 Aug 21.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.