Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6P54HC)

• DOT Name: GTPase IMAP family member 8 (GIMAP8)
• Synonyms: Immune-associated nucleotide-binding protein 9; IAN-9; Protein IanT
• Gene Name: GIMAP8
• Related Disease: Neoplasm
• UniProt ID: GIMA8_HUMAN
• Pfam ID: PF04548
• Sequence:
  MSEQSCQMSELRLLLLGKCRSGKSATGNAILGKHVFKSKFSDQTVIKMCQRESWVLRERK
  VVVIDTPDLFSSIACAEDKQRNIQHCLELSAPSLHALLLVIAIGHFTREDEETAKGIQQV
  FGAEARRHIIIVFTRKDDLGDDLLQDFIEKNKPLKQLVQDYEGRYCIFNNKTNSKDEQIT
  QVLELLRKVESLVNTNGGPYHVNFKTEGSRFQDCVNEAASQEGDKPQGPRERQLQSTGPE
  QNPGTSELTVLLVGKRGAGKSAAGNSILGRQAFQTGFSEQSVTQSFLSESRSWRKKKVSI
  IDAPDISSLKNIDSEVRKHICTGPHAFLLVTPLGFYTKNDEAVLSTIQNNFGEKFFEYMI
  ILLTRKEDLGDQDLDTFLRNSNKALYGLIQKCKNRYSAFNYRATGEEEQRQADELLEKIE
  SMVHQNGNKHCVFREKETLNIVLVGRSGTGKSATGNSILGSLVFTSRLRAQPVTKTSQSG
  RRTWDGQEVVVVDTPSFNQMLDVEKDPSRLEEEVKRCLSCCEKGDTFFVLVFQLGRFTEE
  DKTAVAKLEAIFGADFTKYAIMLFTRKEDLGAGNLEDFMKNSDNKALRRIFKKCGRRVCA
  FNNKETGQAQETQVKALLTKVNDLRKESGWSGYPHTQENVSKLIKNVQEMSQAEKLLKNL
  IGILQ
• Function: Exerts an anti-apoptotic effect in the immune system and is involved in responses to infections.
• Tissue Specificity: Expressed in the spleen, intestine, liver, and colon, as well as in lung, placenta, kidney, muscle, and heart. Extremely low expression, if any, in brain, in thymus, bone marrow, and blood leukocytes . Detected in T-cells .

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Disputed	Altered Expression	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of GTPase IMAP family member 8 (GIMAP8).	[2]

5 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 GTPase IMAP family member 8 (GIMAP8).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GTPase IMAP family member 8 (GIMAP8).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of GTPase IMAP family member 8 (GIMAP8).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of GTPase IMAP family member 8 (GIMAP8).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of GTPase IMAP family member 8 (GIMAP8).	[7]

References

• [1] Dysregulation of GIMAP genes in non-small cell lung cancer.Lung Cancer. 2008 Dec;62(3):287-94. doi: 10.1016/j.lungcan.2008.03.021. Epub 2008 May 6.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.