Details of Drug Off-Target (DOT)

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

• DOT Name: CMRF35-like molecule 1 (CD300LF)
• Synonyms: CLM-1; CD300 antigen-like family member F; Immune receptor expressed on myeloid cells 1; IREM-1; Immunoglobulin superfamily member 13; IgSF13; NK inhibitory receptor; CD antigen CD300f
• Gene Name: CD300LF
• Related Disease:
  Crohn disease
  Acute myelogenous leukaemia
  Dermatitis
  Hepatitis C virus infection
  Multiple sclerosis
  Coronary heart disease
• UniProt ID: CLM1_HUMAN
• PDB ID: 2NMS
• Pfam ID: PF15330 ; PF07686
• Sequence:
  MPLLTLYLLLFWLSGYSIVTQITGPTTVNGLERGSLTVQCVYRSGWETYLKWWCRGAIWR
  DCKILVKTSGSEQEVKRDRVSIKDNQKNRTFTVTMEDLMKTDADTYWCGIEKTGNDLGVT
  VQVTIDPAPVTQEETSSSPTLTGHHLDNRHKLLKLSVLLPLIFTILLLLLVAASLLAWRM
  MKYQQKAAGMSPEQVLQPLEGDLCYADLTLQLAGTSPQKATTKLSSAQVDQVEVEYVTMA
  SLPKEDISYASLTLGAEDQEPTYCNMGHLSSHLPGRGPEEPTEYSTISRP
• Function: Acts as an inhibitory receptor for myeloid cells and mast cells. Positively regulates the phagocytosis of apoptotic cells (efferocytosis) via phosphatidylserine (PS) recognition; recognizes and binds PS as a ligand which is expressed on the surface of apoptotic cells. Plays an important role in the maintenance of immune homeostasis, by promoting macrophage-mediated efferocytosis and by inhibiting dendritic cell-mediated efferocytosis. Negatively regulates Fc epsilon receptor-dependent mast cell activation and allergic responses via binding to ceramide and sphingomyelin which act as ligands. May act as a coreceptor for interleukin 4 (IL-4). Associates with and regulates IL-4 receptor alpha-mediated responses by augmenting IL-4- and IL-13-induced signaling. Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 and TRIF through activation of PTPN6/SHP-1 and PTPN11/SHP-2. Inhibits osteoclast formation. Induces macrophage cell death upon engagement.
• Tissue Specificity: Highly expressed in spleen, peripheral blood leukocyte and monocyte, and lung. Weakly expressed in thymus, heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, prostate, testis, ovary, small intestine or colon. Expressed selectively in monocytes and monocyte-related cells.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Dermatitis	DISY5SZC	Strong	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[4]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[5]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[6]

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 1 (CD300LF).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CMRF35-like molecule 1 (CD300LF).	[12]

7 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 1 (CD300LF).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CMRF35-like molecule 1 (CD300LF).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of CMRF35-like molecule 1 (CD300LF).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of CMRF35-like molecule 1 (CD300LF).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CMRF35-like molecule 1 (CD300LF).	[13]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of CMRF35-like molecule 1 (CD300LF).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of CMRF35-like molecule 1 (CD300LF).	[14]

References

• [1] Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study.Circ Cardiovasc Genet. 2009 Apr;2(2):134-41. doi: 10.1161/CIRCGENETICS.108.825273. Epub 2009 Feb 12.
• [2] CD300f epitopes are specific targets for acute myeloid leukemia with monocytic differentiation.Mol Oncol. 2019 Oct;13(10):2107-2120. doi: 10.1002/1878-0261.12549. Epub 2019 Aug 20.
• [3] Ceramide-CD300f Binding Inhibits Lipopolysaccharide-induced Skin Inflammation.J Biol Chem. 2017 Feb 17;292(7):2924-2932. doi: 10.1074/jbc.M116.768366. Epub 2017 Jan 10.
• [4] Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome.Mol Immunol. 2008 May;45(9):2429-36. doi: 10.1016/j.molimm.2008.01.002. Epub 2008 Mar 4.
• [5] Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis.Sci Rep. 2017 Oct 19;7(1):13544. doi: 10.1038/s41598-017-12881-8.
• [6] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.