Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGBQE0Z)

• DOT Name: CMRF35-like molecule 8 (CD300A)
• Synonyms: CLM-8; CD300 antigen-like family member A; CMRF-35-H9; CMRF35-H9; CMRF35-H; IRC1/IRC2; Immunoglobulin superfamily member 12; IgSF12; Inhibitory receptor protein 60; IRp60; NK inhibitory receptor; CD antigen CD300a
• Gene Name: CD300A
• UniProt ID: CLM8_HUMAN
• PDB ID: 2Q87
• Pfam ID: PF15330 ; PF07686
• Sequence:
  MWLPWALLLLWVPGCFALSKCRTVAGPVGGSLSVQCPYEKEHRTLNKYWCRPPQIFLCDK
  IVETKGSAGKRNGRVSIRDSPANLSFTVTLENLTEEDAGTYWCGVDTPWLRDFHDPVVEV
  EVSVFPASTSMTPASITAAKTSTITTAFPPVSSTTLFAVGATHSASIQEETEEVVNSQLP
  LLLSLLALLLLLLVGASLLAWRMFQKWIKAGDHSELSQNPKQAATQSELHYANLELLMWP
  LQEKPAPPREVEVEYSTVASPREELHYASVVFDSNTNRIAAQRPREEEPDSDYSVIRKT
• Function: Inhibitory receptor which may contribute to the down-regulation of cytolytic activity in natural killer (NK) cells, and to the down-regulation of mast cell degranulation. Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 but not TRIF through activation of PTPN6.
• Tissue Specificity: Expressed not only by natural killer (NK) cells but also by T-cell subsets, B-cells, dendritic cells, mast cells, granulocytes and monocytes.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

2 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 CMRF35-like molecule 8 (CD300A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CMRF35-like molecule 8 (CD300A).	[9]

11 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 CMRF35-like molecule 8 (CD300A).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CMRF35-like molecule 8 (CD300A).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of CMRF35-like molecule 8 (CD300A).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of CMRF35-like molecule 8 (CD300A).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of CMRF35-like molecule 8 (CD300A).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of CMRF35-like molecule 8 (CD300A).	[7]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of CMRF35-like molecule 8 (CD300A).	[8]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of CMRF35-like molecule 8 (CD300A).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CMRF35-like molecule 8 (CD300A).	[10]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of CMRF35-like molecule 8 (CD300A).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of CMRF35-like molecule 8 (CD300A).	[11]

References

• [1] 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.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [8] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.