Details of Drug Off-Target (DOT)

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

• DOT Name: Insulinoma-associated protein 2 (INSM2)
• Synonyms: Zinc finger protein IA-6
• Gene Name: INSM2
• Related Disease:
  Autoimmune disease
  Type-1 diabetes
  Adult lymphoma
  Lymphoma
  Pediatric lymphoma
  Type-1/2 diabetes
• UniProt ID: INSM2_HUMAN
• Pfam ID: PF00096
• Sequence:
  MPRGFLVKRTKRTGGLYRVRLAERVFPLLGPQGAPPFLEEAPSASLPGAERATPPTREEP
  GKGLTAEAAREQSGSPCRAAGVSPGTGGREGAEWRAGGREGPGPSPSPSPSPAKPAGAEL
  RRAFLERCLSSPVSAESFPGGAAAVAAFSCSVAPAAAPTPGEQFLLPLRAPFPEPALQPD
  PAPLSAALQSLKRAAGGERRGKAPTDCASGPAAAGIKKPKAMRKLSFADEVTTSPVLGLK
  IKEEEPGAPSRGLGGSRTPLGEFICQLCKEQYADPFALAQHRCSRIVRVEYRCPECDKVF
  SCPANLASHRRWHKPRPAAANAATVSSADGKPPSSSSSSSRDSGAIASFLAEGKENSRIE
  RTADQHPQARDSSGADQHPDSAPRQGLQVLTHPEPPLPQGPYTEGVLGRRVPVPGSTSGG
  RGSEIFVCPYCHKKFRRQAYLRKHLSTHEAGSARALAPGFGSERGAPLAFACPLCGAHFP
  TADIREKHRLWHAVREELLLPALAGAPPETSGPSGPSDGSAQQIFSCKHCPSTFFSSPGL
  TRHINKCHPSESRQVLLLQMPLRPGC
• Function: May function as a growth suppressor or tumor suppressor in liver cells and in certain neurons.
• Tissue Specificity: Expressed in heart, liver, skeletal muscle, kidney and pancreas, and, to a lesser extent, in brain, lung and spleen. In the pancreas, expressed in islet cells, including insulin- and glucagon-producing alpha- and beta-cells, but not in acinar cells (at protein level). Detected in adrenal glands, particularly in the deeper layer of the cortex (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[2]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[3]
Lymphoma	DISN6V4S	Limited	Biomarker	[3]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[3]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Insulinoma-associated protein 2 (INSM2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Insulinoma-associated protein 2 (INSM2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Insulinoma-associated protein 2 (INSM2).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Insulinoma-associated protein 2 (INSM2).	[9]

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 decreases the methylation of Insulinoma-associated protein 2 (INSM2).	[8]

References

• [1] Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes.Diabetologia. 2016 Feb;59(2):334-40. doi: 10.1007/s00125-015-3803-5. Epub 2015 Nov 13.
• [2] Autoantibodies against islet cell antigens in children with type 1 diabetes mellitus.Oncotarget. 2018 Feb 19;9(23):16275-16283. doi: 10.18632/oncotarget.24527. eCollection 2018 Mar 27.
• [3] T(11;18)-bearing pulmonary mucosa-associated lymphoid tissue lymphoma responding to cladribine.Int J Hematol. 2004 Jul;80(1):70-4. doi: 10.1532/ijh97.03170.
• [4] Targeted deletion of Insm2 in mice result in reduced insulin secretion and glucose intolerance.J Transl Med. 2018 Oct 25;16(1):297. doi: 10.1186/s12967-018-1665-6.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] 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.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.