Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDNZDA0)

• DOT Name: NACHT, LRR and PYD domains-containing protein 10 (NLRP10)
• Synonyms: Nucleotide-binding oligomerization domain protein 8
• Gene Name: NLRP10
• Related Disease:
  Atopic dermatitis
  Cutaneous leishmaniasis
  Periodontitis
• UniProt ID: NAL10_HUMAN
• PDB ID: 2M5V
• Pfam ID: PF05729 ; PF17779 ; PF02758
• Sequence:
  MAMAKARKPREALLWALSDLEENDFKKLKFYLRDMTLSEGQPPLARGELEGLIPVDLAEL
  LISKYGEKEAVKVVLKGLKVMNLLELVDQLSHICLHDYREVYREHVRCLEEWQEAGVNGR
  YNQVLLVAKPSSESPESLACPFPEQELESVTVEALFDSGEKPSLAPSLVVLQGSAGTGKT
  TLARKMVLDWATGTLYPGRFDYVFYVSCKEVVLLLESKLEQLLFWCCGDNQAPVTEILRQ
  PERLLFILDGFDELQRPFEEKLKKRGLSPKESLLHLLIRRHTLPTCSLLITTRPLALRNL
  EPLLKQARHVHILGFSEEERARYFSSYFTDEKQADRAFDIVQKNDILYKACQVPGICWVV
  CSWLQGQMERGKVVLETPRNSTDIFMAYVSTFLPPDDDGGCSELSRHRVLRSLCSLAAEG
  IQHQRFLFEEAELRKHNLDGPRLAAFLSSNDYQLGLAIKKFYSFRHISFQDFFHAMSYLV
  KEDQSRLGKESRREVQRLLEVKEQEGNDEMTLTMQFLLDISKKDSFSNLELKFCFRISPC
  LAQDLKHFKEQMESMKHNRTWDLEFSLYEAKIKNLVKGIQMNNVSFKIKHSNEKKSQSQN
  LFSVKSSLSHGPKEEQKCPSVHGQKEGKDNIAGTQKEASTGKGRGTEETPKNTYI
• Function: Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID. Displays anti-inflammatory activity. Required for immunity against C.albicans infection. Involved in the innate immune response by contributing to pro-inflammatory cytokine release in response to invasive bacterial infection. Contributes to T-cell-mediated inflammatory responses in the skin. Plays a role in protection against periodontitis through its involvement in induction of IL1A via ERK activation in oral epithelial cells infected with periodontal pathogens. Exhibits both ATPase and GTPase activities.
• Tissue Specificity: Highly expressed in basal and suprabasal epidermal cell layers with lower levels in dermal fibroblast cells (at protein level) . Widely expressed with highest levels in heart, brain and skeletal muscle . Also expressed in liver, colon, dermis and epidermis . Little expression detected in myeloid cells or peripheral blood mononuclear cells .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[1]
Cutaneous leishmaniasis	DISRK7TS	Strong	Biomarker	[2]
Periodontitis	DISI9JOI	Limited	Biomarker	[3]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of NACHT, LRR and PYD domains-containing protein 10 (NLRP10).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of NACHT, LRR and PYD domains-containing protein 10 (NLRP10).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of NACHT, LRR and PYD domains-containing protein 10 (NLRP10).	[7]

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 NACHT, LRR and PYD domains-containing protein 10 (NLRP10).	[5]

References

• [1] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.Nat Genet. 2012 Nov;44(11):1222-6. doi: 10.1038/ng.2438. Epub 2012 Oct 7.
• [2] An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis.J Immunol. 2017 Oct 15;199(8):2823-2833. doi: 10.4049/jimmunol.1500832. Epub 2017 Sep 20.
• [3] Involvement of NLRP10 in IL-1 induction of oral epithelial cells by periodontal pathogens.Innate Immun. 2017 Oct;23(7):569-577. doi: 10.1177/1753425917722610. Epub 2017 Aug 2.
• [4] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [5] 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.
• [6] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.