Details of Drug Off-Target (DOT)

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

• DOT Name: RAS protein activator like-3 (RASAL3)
• Gene Name: RASAL3
• Related Disease:
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RASL3_HUMAN
• Pfam ID: PF00616
• Sequence:
  MDPPSPSRTSQTQPTATSPLTSYRWHTGGGGEKAAGGFRWGRFAGWGRALSHQEPMVSTQ
  PAPRSIFRRVLSAPPKESRTSRLRLSKALWGRHKNPPPEPDPEPEQEAPELEPEPELEPP
  TPQIPEAPTPNVPVWDIGGFTLLDGKLVLLGGEEEGPRRPRVGSASSEGSIHVAMGNFRD
  PDRMPGKTEPETAGPNQVHNVRGLLKRLKEKKKARLEPRDGPPSALGSRESLATLSELDL
  GAERDVRIWPLHPSLLGEPHCFQVTWTGGSRCFSCRSAAERDRWIEDLRRQFQPTQDNVE
  REETWLSVWVHEAKGLPRAAAGAPGVRAELWLDGALLARTAPRAGPGQLFWAERFHFEAL
  PPARRLSLRLRGLGPGSAVLGRVALALEELDAPRAPAAGLERWFPLLGAPAGAALRARIR
  ARRLRVLPSERYKELAEFLTFHYARLCGALEPALPAQAKEELAAAMVRVLRATGRAQALV
  TDLGTAELARCGGREALLFRENTLATKAIDEYMKLVAQDYLQETLGQVVRRLCASTEDCE
  VDPSKCPASELPEHQARLRNSCEEVFETIIHSYDWFPAELGIVFSSWREACKERGSEVLG
  PRLVCASLFLRLLCPAILAPSLFGLAPDHPAPGPARTLTLIAKVIQNLANRAPFGEKEAY
  MGFMNSFLEEHGPAMQCFLDQVAMVDVDAAPSGYQGSGDLALQLAVLHAQLCTIFAELDQ
  TTRDTLEPLPTILRAIEEGQPVLVSVPMRLPLPPAQVHSSLSAGEKPGFLAPRDLPKHTP
  LISKSQSLRSVRRSESWARPRPDEERPLRRPRPVQRTQSVPVRRPARRRQSAGPWPRPKG
  SLSMGPAPRARPWTRDSASLPRKPSVPWQRQMDQPQDRNQALGTHRPVNKLAELQCEVAA
  LREEQKVLSRLVESLSTQIRALTEQQEQLRGQLQDLDSRLRAGSSEFDSEHNLTSNEGHS
  LKNLEHRLNEMERTQAQLRDAVQSLQLSPRTRGSWSQPQPLKAPCLNGDTT
• Function: Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway.
• Tissue Specificity: Predominantly expressed in cells of hematopoietic lineages.
• KEGG Pathway: Ras sig.ling pathway (hsa04014)
• Reactome Pathway: Regulation of RAS by GAPs (R-HSA-5658442)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RAS protein activator like-3 (RASAL3).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of RAS protein activator like-3 (RASAL3).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RAS protein activator like-3 (RASAL3).	[5]

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 affects the methylation of RAS protein activator like-3 (RASAL3).	[4]

References

• [1] Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming.J Clin Invest. 2018 Oct 1;128(10):4472-4484. doi: 10.1172/JCI99397. Epub 2018 Jul 26.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [4] 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.
• [5] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.