Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBTT3ZQ)

• DOT Name: Signaling lymphocytic activation molecule (SLAMF1)
• Synonyms: CDw150; IPO-3; SLAM family member 1; CD antigen CD150
• Gene Name: SLAMF1
• Related Disease:
  Epstein barr virus infection
  Neoplasm
  Adult glioblastoma
  Advanced cancer
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Central nervous system neoplasm
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Glomerulonephritis
  Hepatocellular carcinoma
  HIV infectious disease
  Leprosy
  Lung cancer
  Lung carcinoma
  Lupus
  Lymphoproliferative syndrome
  Malignant soft tissue neoplasm
  Non-insulin dependent diabetes
  Plasma cell myeloma
  Sarcoma
  Small lymphocytic lymphoma
  Visceral leishmaniasis
  Systemic lupus erythematosus
  Adult lymphoma
  Autoimmune thyroid disease
  Bacterial infection
  Graft-versus-host disease
  Hashimoto thyroiditis
  Lymphoma
  Measles
  Myasthenia gravis
  Nervous system disease
  Pediatric lymphoma
  Psychotic disorder
  Rheumatoid arthritis
  Tuberculosis
  X-linked lymphoproliferative syndrome
• UniProt ID: SLAF1_HUMAN
• PDB ID: 1D4T; 1D4W; 1I3Z; 1KA6; 1KA7; 1M27
• Pfam ID: PF06214
• Sequence:
  MDPKGLLSLTFVLFLSLAFGASYGTGGRMMNCPKILRQLGSKVLLPLTYERINKSMNKSI
  HIVVTMAKSLENSVENKIVSLDPSEAGPPRYLGDRYKFYLENLTLGIRESRKEDEGWYLM
  TLEKNVSVQRFCLQLRLYEQVSTPEIKVLNKTQENGTCTLILGCTVEKGDHVAYSWSEKA
  GTHPLNPANSSHLLSLTLGPQHADNIYICTVSNPISNNSQTFSPWPGCRTDPSETKPWAV
  YAGLLGGVIMILIMVVILQLRRRGKTNHYQTTVEKKSLTIYAQVQKPGPLQKKLDSFPAQ
  DPCTTIYVAATEPVPESVQETNSITVYASVTLPES
• 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. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAMF1 signaling seem to exist: one depending on SH2D1A (and perhaps SH2D1B) and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates. Initially it has been proposed that association with SH2D1A prevents binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2. However, signaling is also regulated by SH2D1A which can simultaneously interact with and recruit FYN which subsequently phosphorylates and activates SLAMF1. Mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production. Downstreaming signaling involves INPP5D, DOK1 and DOK2 leading to inhibited IFN-gamma production in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell activation and Th2 cytokine production. Promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells. Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-cells. Required for IL-4 production by germinal centers T follicular helper (T(Fh))cells. May inhibit CD40-induced signal transduction in monocyte-derived dendritic cells. May play a role in allergic responses and may regulate allergen-induced Th2 cytokine and Th1 cytokine secretion. In conjunction with SLAMF6 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage. Involved in the peripheral differentiation of indifferent natural killer T (iNKT) cells toward a regulatory NKT2 type. In macrophages involved in down-regulation of IL-12, TNF-alpha and nitric oxide in response to lipopolysaccharide (LPS). In B-cells activates the ERK signaling pathway independently of SH2D1A but implicating both, SYK and INPP5D, and activates Akt signaling dependent on SYK and SH2D1A. In B-cells also activates p38 MAPK and JNK1 and JNK2. In conjunction with CD84/SLAMF5 and SLAMF6 may be a negative regulator of the humoral immune response. Involved in innate immune response against Gram-negative bacteria in macrophages; probably recognizes OmpC and/or OmpF on the bacterial surface, regulates phagosome maturation and recruitment of the PI3K complex II (PI3KC3-C2) leading to accumulation of PdtIns(3)P and NOX2 activity in the phagosomes ; (Microbial infection) Acts as a receptor for Measles virus; also including isoform 4.
• Tissue Specificity: Constitutively expressed on peripheral blood memory T-cells, T-cell clones, immature thymocytes and a proportion of B-cells, and is rapidly induced on naive T-cells after activation . Activated B-cells express isoform 1, isoform 3 and a cytoplasmic isoform . Isoform 4 is expressed in B-cells, primary T-cells, dendritic cells and macrophages. Isoform 4 is expressed in tumors of the central nervous system .
• KEGG Pathway: Measles (hsa05162)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epstein barr virus infection	DISOO0WT	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Genetic Variation	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Central nervous system neoplasm	DISFC18W	Strong	Altered Expression	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
HIV infectious disease	DISO97HC	Strong	Altered Expression	[10]
Leprosy	DISAA4UI	Strong	Altered Expression	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[12]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[12]
Lupus	DISOKJWA	Strong	Genetic Variation	[13]
Lymphoproliferative syndrome	DISMVL8O	Strong	Genetic Variation	[14]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[15]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[16]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[17]
Sarcoma	DISZDG3U	Strong	Biomarker	[15]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[18]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[19]
Systemic lupus erythematosus	DISI1SZ7	moderate	Altered Expression	[20]
Adult lymphoma	DISK8IZR	Limited	Altered Expression	[21]
Autoimmune thyroid disease	DISIHC6A	Limited	Biomarker	[22]
Bacterial infection	DIS5QJ9S	Limited	Biomarker	[23]
Graft-versus-host disease	DIS0QADF	Limited	Biomarker	[24]
Hashimoto thyroiditis	DIS77CDF	Limited	Biomarker	[22]
Lymphoma	DISN6V4S	Limited	Altered Expression	[21]
Measles	DISXSUID	Limited	Biomarker	[25]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[26]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[27]
Pediatric lymphoma	DIS51BK2	Limited	Altered Expression	[21]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[28]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[29]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[30]
X-linked lymphoproliferative syndrome	DISA7MJ4	Limited	Biomarker	[31]

10 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 Signaling lymphocytic activation molecule (SLAMF1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[33]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[35]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[34]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[36]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[39]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Signaling lymphocytic activation molecule (SLAMF1).	[36]

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 Signaling lymphocytic activation molecule (SLAMF1).	[38]

References

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