Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZUDJ6Q)

• DOT Name: Receptor-transporting protein 3 (RTP3)
• Synonyms: 3CxxC-type zinc finger protein 3; Transmembrane protein 7
• Gene Name: RTP3
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
  Liver cancer
• UniProt ID: RTP3_HUMAN
• Pfam ID: PF13695
• Sequence:
  MAGDTEVWKQMFQELMREVKPWHRWTLRPDKGLLPNVLKPGWMQYQQWTFARFQCSSCSR
  NWASAQVLVLFHMNWSEEKSRGQVKMRVFTQRCKKCPQPLFEDPEFTQENISRILKNLVF
  RILKKCYRGRFQLIEEVPMIKDISLEGPHNSDNCEACLQGFCAGPIQVTSLPPSQTPRVH
  SIYKVEEVVKPWASGENVYSYACQNHICRNLSIFCCCVILIVIVVIVVKTAI
• Function: Promotes functional cell surface expression of the bitter taste receptors TAS2R16 and TAS2R43.
• Tissue Specificity: Expressed predominantly in adult liver . Expressed in testis . Also expressed in kidney, lung and fetal liver . Low levels in heart, thyroid, adrenal gland, pancreas, ovary, prostate, skin, plasma leukocytes, bone marrow and fetal brain . Not detected in brain, spleen, colon, small intestine, skeletal muscle, stomach, placenta, salivary gland and uterus .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Liver cancer	DISDE4BI	Limited	Biomarker	[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 Receptor-transporting protein 3 (RTP3).	[2]

4 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 Receptor-transporting protein 3 (RTP3).	[3]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Receptor-transporting protein 3 (RTP3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Receptor-transporting protein 3 (RTP3).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Receptor-transporting protein 3 (RTP3).	[6]

References

• [1] The interferon-alpha responsive gene TMEM7 suppresses cell proliferation and is downregulated in human hepatocellular carcinoma.Cancer Genet Cytogenet. 2007 Aug;177(1):6-15. doi: 10.1016/j.cancergencyto.2007.04.007.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [5] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.