Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFKRP2H)

• DOT Name: Dendritic cell-specific transmembrane protein (DCSTAMP)
• Synonyms: DC-STAMP; hDC-STAMP; Dendrocyte-expressed seven transmembrane protein; IL-four-induced protein; FIND; Transmembrane 7 superfamily member 4
• Gene Name: DCSTAMP
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Juvenile Paget disease
  Osteoarthritis
  Paget's disease
  Endometriosis
  Periodontitis
  Thyroid gland papillary carcinoma
• UniProt ID: DCSTP_HUMAN
• Pfam ID: PF07782
• Sequence:
  MGIWTSGTDIFLSLWEIYVSPRSPGWMDFIQHLGVCCLVALISVGLLSVAACWFLPSIIA
  AAASWIITCVLLCCSKHARCFILLVFLSCGLREGRNALIAAGTGIVILGHVENIFHNFKG
  LLDGMTCNLRAKSFSIHFPLLKKYIEAIQWIYGLATPLSVFDDLVSWNQTLAVSLFSPSH
  VLEAQLNDSKGEVLSVLYQMATTTEVLSSLGQKLLAFAGLSLVLLGTGLFMKRFLGPCGW
  KYENIYITRQFVQFDERERHQQRPCVLPLNKEERRKYVIIPTFWPTPKERKNLGLFFLPI
  LIHLCIWVLFAAVDYLLYRLIFSVSKQFQSLPGFEVHLKLHGEKQGTQDIIHDSSFNISV
  FEPNCIPKPKFLLSETWVPLSVILLILVMLGLLSSILMQLKILVSASFYPSVERKRIQYL
  HAKLLKKRSKQPLGEVKRRLSLYLTKIHFWLPVLKMIRKKQMDMASADKS
• Function: Probable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis. Plays a role in TNFSF11-mediated osteoclastogenesis. Cooperates with OCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Participates in osteoclast bone resorption. Involved in inducing the expression of tartrate-resistant acid phosphatase in osteoclast precursors. Plays a role in haematopoietic stem cell differentiation of bone marrow cells toward the myeloid lineage. Inhibits the development of neutrophilic granulocytes. Plays also a role in the regulation of dendritic cell (DC) antigen presentation activity by controlling phagocytic activity. Involved in the maintenance of immune self-tolerance and avoidance of autoimmune reactions.
• Tissue Specificity: Preferentially expressed by dendritic cells (DCs). Detected in both immature and mature DCs. Highly expressed in lymph nodes, lung, kidney and liver. Expressed at lower levels in pancreas, bone marrow, spleen, leukocytes, in freshly isolated peripheral blood mononuclear cells (PBMC) and B-cells. Not expressed in freshly isolated monocytes.
• Reactome Pathway: CREB3 factors activate genes (R-HSA-8874211)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Juvenile Paget disease	DISNVDB2	Strong	Genetic Variation	[2]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[3]
Paget's disease	DISO3MC0	moderate	Genetic Variation	[4]
Endometriosis	DISX1AG8	Disputed	Biomarker	[5]
Periodontitis	DISI9JOI	Limited	Biomarker	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methamphetamine	DMPM4SK	Approved	Dendritic cell-specific transmembrane protein (DCSTAMP) affects the response to substance of Methamphetamine.	[14]

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 Dendritic cell-specific transmembrane protein (DCSTAMP).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[9]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[10]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[13]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Dendritic cell-specific transmembrane protein (DCSTAMP).	[9]

References

• [1] Downregulation of TM7SF4 inhibits cell proliferation and metastasis of A549 cells through regulating the PI3K/AKT/mTOR signaling pathway.Mol Med Rep. 2017 Nov;16(5):6122-6127. doi: 10.3892/mmr.2017.7324. Epub 2017 Aug 22.
• [2] Polymorphisms of CSF1 and TM7SF4 genes in a case of mild juvenile Paget's disease found using next-generation sequencing.Croat Med J. 2015 Apr;56(2):145-51. doi: 10.3325/cmj.2015.56.145.
• [3] Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis.J Orthop Res. 2008 Jan;26(1):106-16. doi: 10.1002/jor.20486.
• [4] Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.Nat Genet. 2011 May 29;43(7):685-9. doi: 10.1038/ng.845.
• [5] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [6] DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption.J Dent Res. 2017 Jun;96(6):685-693. doi: 10.1177/0022034517690490. Epub 2017 Feb 15.
• [7] Identification of differentially expressed genes in papillary thyroid cancers.Yonsei Med J. 2009 Feb 28;50(1):60-7. doi: 10.3349/ymj.2009.50.1.60. Epub 2009 Feb 24.
• [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] 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.
• [10] 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.
• [11] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. J Biol Chem. 2015 Oct 16;290(42):25322-32. doi: 10.1074/jbc.M115.645234. Epub 2015 Aug 20.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.