Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT97PWCG)

• DOT Name: RCC1-like G exchanging factor-like protein (RCC1L)
• Synonyms: RCC1-like; Williams-Beuren syndrome chromosomal region 16 protein
• Gene Name: RCC1L
• UniProt ID: RCC1L_HUMAN
• PDB ID: 5XGS
• Pfam ID: PF00415 ; PF13540
• Sequence:
  MALVALVAGARLGRRLSGPGLGRGHWTAAGRSRSRREAAEAEAEVPVVQYVGERAARADR
  VFVWGFSFSGALGVPSFVVPSSGPGPRAGARPRRRIQPVPYRLELDQKISSAACGYGFTL
  LSSKTADVTKVWGMGLNKDSQLGFHRSRKDKTRGYEYVLEPSPVSLPLDRPQETRVLQVS
  CGRAHSLVLTDREGVFSMGNNSYGQCGRKVVENEIYSESHRVHRMQDFDGQVVQVACGQD
  HSLFLTDKGEVYSCGWGADGQTGLGHYNITSSPTKLGGDLAGVNVIQVATYGDCCLAVSA
  DGGLFGWGNSEYLQLASVTDSTQVNVPRCLHFSGVGKVRQAACGGTGCAVLNGEGHVFVW
  GYGILGKGPNLVESAVPEMIPPTLFGLTEFNPEIQVSRIRCGLSHFAALTNKGELFVWGK
  NIRGCLGIGRLEDQYFPWRVTMPGEPVDVACGVDHMVTLAKSFI
• Function: Guanine nucleotide exchange factor (GEF) for mitochondrial dynamin-related GTPase OPA1. Activates OPA1, by exchanging bound GDP for free GTP, and drives OPA1 and MFN1-dependent mitochondrial fusion. Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[1]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[2]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[6]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[7]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of RCC1-like G exchanging factor-like protein (RCC1L).	[8]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [3] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [4] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [5] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [6] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Exposure to dietary fatty acids oleic and palmitic acid alters structure and mechanotransduction of intestinal cells in vitro. Arch Toxicol. 2023 Jun;97(6):1659-1675. doi: 10.1007/s00204-023-03495-3. Epub 2023 Apr 29.
• [8] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.