Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX6RZW1)

• DOT Name: SLAM family member 7 (SLAMF7)
• Synonyms: CD2 subset 1; CD2-like receptor-activating cytotoxic cells; CRACC; Membrane protein FOAP-12; Novel Ly9; Protein 19A; CD antigen CD319
• Gene Name: SLAMF7
• UniProt ID: SLAF7_HUMAN
• Pfam ID: PF07686
• Sequence:
  MAGSPTCLTLIYILWQLTGSAASGPVKELVGSVGGAVTFPLKSKVKQVDSIVWTFNTTPL
  VTIQPEGGTIIVTQNRNRERVDFPDGGYSLKLSKLKKNDSGIYYVGIYSSSLQQPSTQEY
  VLHVYEHLSKPKVTMGLQSNKNGTCVTNLTCCMEHGEEDVIYTWKALGQAANESHNGSIL
  PISWRWGESDMTFICVARNPVSRNFSSPILARKLCEGAADDPDSSMVLLCLLLVPLLLSL
  FVLGLFLWFLKRERQEEYIEEKKRVDICRETPNICPHSGENTEYDTIPHTNRTILKEDPA
  NTVYSTVEIPKKMENPHSLLTMPDTPRLFAYENVI
• Function: Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Isoform 1 mediates NK cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway. Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B. Downstream signaling implicates PLCG1, PLCG2 and PI3K. In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Acts also inhibitory in T-cells. May play a role in lymphocyte adhesion. In LPS-activated monocytes negatively regulates production of pro-inflammatory cytokines ; Isoform 3 does not mediate any NK cell activation.
• Tissue Specificity: Expressed in spleen, lymph node, peripheral blood leukocytes, bone marrow, small intestine, stomach, appendix, lung and trachea. Expression was detected in NK cells, activated B-cells, NK-cell line but not in promyelocytic, B-, or T-cell lines. Expressed in monocytes. Isoform 3 is expressed at much lower level than isoform 1.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

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 SLAM family member 7 (SLAMF7).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SLAM family member 7 (SLAMF7).	[2]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of SLAM family member 7 (SLAMF7).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SLAM family member 7 (SLAMF7).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SLAM family member 7 (SLAMF7).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of SLAM family member 7 (SLAMF7).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SLAM family member 7 (SLAMF7).	[8]

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 SLAM family member 7 (SLAMF7).	[4]

References

• [1] 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.
• [2] 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.
• [3] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [4] 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.
• [5] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [6] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.