Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95NRVS)

• DOT Name: Sterile alpha motif domain-containing protein 5 (SAMD5)
• Synonyms: SAM domain-containing protein 5
• Gene Name: SAMD5
• Related Disease:
  Advanced cancer
  Major depressive disorder
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SAMD5_HUMAN
• Pfam ID: PF00536
• Sequence:
  MCTNIVYEWLKALQLPQYAESFVDNGYDDLEVCKQIGDPDLDAIGVLAPAHRRRILEAVR
  RLREQDANAAGLYFTLEPQPAPPGPPADAVPTGRRGEPCGGPAQGTRGDSRGHTTAPRSR
  ELVSYPKLKLKIMIRDKLVRDGIHLSKPPYSRKVPMAGILEYLMNWPKSSQSR
• Tissue Specificity: Detected in biliary epithelial cells on bile ducts at the hepatic hilum (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[9]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Sterile alpha motif domain-containing protein 5 (SAMD5).	[11]

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 increases the methylation of Sterile alpha motif domain-containing protein 5 (SAMD5).	[10]

References

• [1] SAMD5 mRNA was overexpressed in prostate cancer and can predict biochemical recurrence after radical prostatectomy.Int Urol Nephrol. 2019 Mar;51(3):443-451. doi: 10.1007/s11255-019-02096-3. Epub 2019 Feb 9.
• [2] Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.Nat Neurosci. 2019 Mar;22(3):343-352. doi: 10.1038/s41593-018-0326-7. Epub 2019 Feb 4.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [10] 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.
• [11] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.