Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJM5S74)

• DOT Name: SID1 transmembrane family member 1 (SIDT1)
• Gene Name: SIDT1
• Related Disease:
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
  Adenocarcinoma
• UniProt ID: SIDT1_HUMAN
• PDB ID: 8JUL; 8JUN
• Pfam ID: PF13965
• Sequence:
  MRGCLRLALLCALPWLLLAASPGHPAKSPRQPPAPRRDPFDAARGADFDHVYSGVVNLST
  ENIYSFNYTSQPDQVTAVRVYVNSSSENLNYPVLVVVRQQKEVLSWQVPLLFQGLYQRSY
  NYQEVSRTLCPSEATNETGPLQQLIFVDVASMAPLGAQYKLLVTKLKHFQLRTNVAFHFT
  ASPSQPQYFLYKFPKDVDSVIIKVVSEMAYPCSVVSVQNIMCPVYDLDHNVEFNGVYQSM
  TKKAAITLQKKDFPGEQFFVVFVIKPEDYACGGSFFIQEKENQTWNLQRKKNLEVTIVPS
  IKESVYVKSSLFSVFIFLSFYLGCLLVGFVHYLRFQRKSIDGSFGSNDGSGNMVASHPIA
  ASTPEGSNYGTIDESSSSPGRQMSSSDGGPPGQSDTDSSVEESDFDTMPDIESDKNIIRT
  KMFLYLSDLSRKDRRIVSKKYKIYFWNIITIAVFYALPVIQLVITYQTVVNVTGNQDICY
  YNFLCAHPLGVLSAFNNILSNLGHVLLGFLFLLIVLRRDILHRRALEAKDIFAVEYGIPK
  HFGLFYAMGIALMMEGVLSACYHVCPNYSNFQFDTSFMYMIAGLCMLKLYQTRHPDINAS
  AYSAYASFAVVIMVTVLGVVFGKNDVWFWVIFSAIHVLASLALSTQIYYMGRFKIDLGIF
  RRAAMVFYTDCIQQCSRPLYMDRMVLLVVGNLVNWSFALFGLIYRPRDFASYMLGIFICN
  LLLYLAFYIIMKLRSSEKVLPVPLFCIVATAVMWAAALYFFFQNLSSWEGTPAESREKNR
  ECILLDFFDDHDIWHFLSATALFFSFLVLLTLDDDLDVVRRDQIPVF
• Function: In vitro binds long double-stranded RNA (dsRNA) (500 and 700 base pairs), but not dsRNA shorter than 300 bp. Not involved in RNA autophagy, a process in which RNA is directly imported into lysosomes in an ATP-dependent manner, and degraded.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SID1 transmembrane family member 1 (SIDT1).	[6]

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 SID1 transmembrane family member 1 (SIDT1).	[7]

References

• [1] Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity.Gene. 1998 Feb 27;208(2):331-6. doi: 10.1016/s0378-1119(98)00030-4.
• [2] Integrated Bioinformatics Data Analysis Reveals Prognostic Significance Of SIDT1 In Triple-Negative Breast Cancer.Onco Targets Ther. 2019 Oct 11;12:8401-8410. doi: 10.2147/OTT.S215898. eCollection 2019.
• [3] Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.Nat Genet. 2013 Apr;45(4):385-91, 391e1-2. doi: 10.1038/ng.2560.
• [4] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [5] Homo sapiens systemic RNA interference-defective-1 transmembrane family member 1 (SIDT1) protein mediates contact-dependent small RNA transfer and microRNA-21-driven chemoresistance.J Biol Chem. 2012 Feb 17;287(8):5267-77. doi: 10.1074/jbc.M111.318865. Epub 2011 Dec 15.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.