Details of Drug Off-Target (DOT)

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

• DOT Name: DCN1-like protein 5 (DCUN1D5)
• Synonyms: DCNL5; DCUN1 domain-containing protein 5; Defective in cullin neddylation protein 1-like protein 5; Squamous cell carcinoma-related oncogene 5
• Gene Name: DCUN1D5
• Related Disease:
  Cardiovascular disease
  Advanced cancer
  Laryngeal squamous cell carcinoma
• UniProt ID: DCNL5_HUMAN
• Pfam ID: PF03556
• Sequence:
  MPVKKKRKSPGVAAAVAEDGGLKKCKISSYCRSQPPARLISGEEHFSSKKCLAWFYEYAG
  PDEVVGPEGMEKFCEDIGVEPENIIMLVLAWKLEAESMGFFTKEEWLKGMTSLQCDCTEK
  LQNKFDFLRSQLNDISSFKNIYRYAFDFARDKDQRSLDIDTAKSMLALLLGRTWPLFSVF
  YQYLEQSKYRVMNKDQWYNVLEFSRTVHADLSNYDEDGAWPVLLDEFVEWQKVRQTS
• Function: Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs). May play a role in DNA damage response and may participate in cell proliferation and anchorage-independent cell growth.
• Tissue Specificity: Weakly expressed in testis, skin and immune tissues (thymus, spleen and lymph nodes).
• Reactome Pathway: Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Altered Expression	[3]

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 DCN1-like protein 5 (DCUN1D5).	[4]

8 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 DCN1-like protein 5 (DCUN1D5).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DCN1-like protein 5 (DCUN1D5).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DCN1-like protein 5 (DCUN1D5).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DCN1-like protein 5 (DCUN1D5).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DCN1-like protein 5 (DCUN1D5).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DCN1-like protein 5 (DCUN1D5).	[10]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of DCN1-like protein 5 (DCUN1D5).	[11]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of DCN1-like protein 5 (DCUN1D5).	[12]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylation E3 activity and nuclear localization.Clin Cancer Res. 2014 Jan 15;20(2):372-81. doi: 10.1158/1078-0432.CCR-13-1252. Epub 2013 Nov 5.
• [3] In vitro biological characterization of DCUN1D5 in DNA damage response.Asian Pac J Cancer Prev. 2012;13(8):4157-62. doi: 10.7314/apjcp.2012.13.8.4157.
• [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] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model. Arch Toxicol. 2012 Apr;86(4):571-89.
• [12] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.