Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAY5B0F)

• DOT Name: SLAM family member 5 (CD84)
• Synonyms: Cell surface antigen MAX.3; Hly9-beta; Leukocyte differentiation antigen CD84; Signaling lymphocytic activation molecule 5; CD antigen CD84
• Gene Name: CD84
• Related Disease:
  Advanced cancer
  Arterial disorder
  Autoimmune disease
  Lymphoproliferative syndrome
  Promyelocytic leukaemia
  Psoriasis
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  X-linked lymphoproliferative syndrome
  Rheumatoid arthritis
• UniProt ID: SLAF5_HUMAN
• PDB ID: 2PKD
• Pfam ID: PF13927
• Sequence:
  MAQHHLWILLLCLQTWPEAAGKDSEIFTVNGILGESVTFPVNIQEPRQVKIIAWTSKTSV
  AYVTPGDSETAPVVTVTHRNYYERIHALGPNYNLVISDLRMEDAGDYKADINTQADPYTT
  TKRYNLQIYRRLGKPKITQSLMASVNSTCNVTLTCSVEKEEKNVTYNWSPLGEEGNVLQI
  FQTPEDQELTYTCTAQNPVSNNSDSISARQLCADIAMGFRTHHTGLLSVLAMFFLLVLIL
  SSVFLFRLFKRRQGRIFPEGSCLNTFTKNPYAASKKTIYTYIMASRNTQPAESRIYDEIL
  QSKVLPSKEEPVNTVYSEVQFADKMGKASTQDSKPPGTSSYEIVI
• 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. Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B. Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seem be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A-dependent pathway. May serve as a marker for hematopoietic progenitor cells Required for a prolonged T-cell:B-cell contact, optimal T follicular helper function, and germinal center formation. In germinal centers involved in maintaining B-cell tolerance and in preventing autoimmunity. In mast cells negatively regulates high affinity immunoglobulin epsilon receptor signaling; independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1. In macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB activation and modulates LPS-induced cytokine secretion; involving ITSM 2. Positively regulates macroautophagy in primary dendritic cells via stabilization of IRF8; inhibits TRIM21-mediated proteasomal degradation of IRF8.
• Tissue Specificity: Predominantly expressed in hematopoietic tissues, such as lymph node, spleen and peripheral leukocytes. Expressed in macrophages, B-cells, monocytes, platelets, thymocytes, T-cells and dendritic cells. Highly expressed in memory T-cells. Expressed in mast cells.
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arterial disorder	DISLG4XS	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Lymphoproliferative syndrome	DISMVL8O	Strong	Genetic Variation	[1]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[3]
Psoriasis	DIS59VMN	Strong	Genetic Variation	[4]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[1]
X-linked lymphoproliferative syndrome	DISA7MJ4	Strong	Biomarker	[6]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[1]

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 SLAM family member 5 (CD84).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of SLAM family member 5 (CD84).	[8]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of SLAM family member 5 (CD84).	[9]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of SLAM family member 5 (CD84).	[8]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of SLAM family member 5 (CD84).	[10]
Lindane	DMB8CNL	Approved	Lindane increases the expression of SLAM family member 5 (CD84).	[8]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of SLAM family member 5 (CD84).	[8]
Epanova	DMHEAGL	Approved	Epanova increases the expression of SLAM family member 5 (CD84).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SLAM family member 5 (CD84).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of SLAM family member 5 (CD84).	[14]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of SLAM family member 5 (CD84).	[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 affects the methylation of SLAM family member 5 (CD84).	[12]

References

• [1] CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and autoimmune disorders.Clin Immunol. 2019 Jul;204:43-49. doi: 10.1016/j.clim.2018.10.017. Epub 2018 Oct 26.
• [2] CD84 is markedly up-regulated in Kawasaki disease arteriopathy.Clin Exp Immunol. 2014 Jul;177(1):203-11. doi: 10.1111/cei.12327.
• [3] Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines.Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5434-E5443. doi: 10.1073/pnas.1705759114. Epub 2017 Jun 19.
• [4] Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis. Br J Dermatol. 2017 May;176(5):1288-1296.
• [5] CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia.J Clin Invest. 2018 Dec 3;128(12):5465-5478. doi: 10.1172/JCI96610. Epub 2018 Nov 5.
• [6] Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP.Blood. 2001 Jun 15;97(12):3867-74. doi: 10.1182/blood.v97.12.3867.
• [7] 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.
• [8] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [9] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [10] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [11] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [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.