Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ40GRN)

• DOT Name: Proteoglycan 3 (PRG3)
• Synonyms: Eosinophil major basic protein homolog; Prepro-major basic protein homolog; Prepro-MBPH
• Gene Name: PRG3
• Related Disease:
  Stroke
  Advanced cancer
  Brain neoplasm
• UniProt ID: PRG3_HUMAN
• Pfam ID: PF00059
• Sequence:
  MQCLLLLPFLLLGTVSALHLENDAPHLESLETQADLGQDLDSSKEQERDLALTEEVIQAE
  GEEVKASACQDNFEDEEAMESDPAALDKDFQCPREEDIVEVQGSPRCKICRYLLVRTPKT
  FAEAQNVCSRCYGGNLVSIHDFNFNYRIQCCTSTVNQAQVWIGGNLRGWFLWKRFCWTDG
  SHWNFAYWSPGQPGNGQGSCVALCTKGGYWRRAQCDKQLPFVCSF
• Function: Possesses similar cytotoxic and cytostimulatory activities to PRG2/MBP. In vitro, stimulates neutrophil superoxide production and IL8 release, and histamine and leukotriene C4 release from basophils.
• Tissue Specificity: Expressed in bone marrow. Not detected in placenta.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Stroke	DISX6UHX	moderate	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Brain neoplasm	DISY3EKS	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Proteoglycan 3 (PRG3).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Proteoglycan 3 (PRG3).	[4]

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 Proteoglycan 3 (PRG3).	[5]

References

• [1] Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia.Blood. 2013 Apr 18;121(16):3237-45. doi: 10.1182/blood-2012-10-464156. Epub 2013 Feb 19.
• [2] PRG3 induces Ras-dependent oncogenic cooperation in gliomas.Oncotarget. 2016 May 3;7(18):26692-708. doi: 10.18632/oncotarget.8592.
• [3] 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.
• [4] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [5] 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.