Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLU1YML)

• DOT Name: NACHT, LRR and PYD domains-containing protein 5 (NLRP5)
• Synonyms: Mater protein homolog; Maternal Antigen that Embryos Require
• Gene Name: NLRP5
• Related Disease:
  Infertility
  Autoimmune disease
  Autoimmune polyendocrine syndrome type 1
  Colon cancer
  Colon carcinoma
  Endometritis
  Female hypogonadism
  Hypoparathyroidism
  Multiple sclerosis
  Oocyte/zygote/embryo maturation arrest 19
• UniProt ID: NALP5_HUMAN
• Pfam ID: PF13516 ; PF05729 ; PF17776 ; PF17779 ; PF02758
• Sequence:
  MKVAGGLELGAAALLSASPRALVTLSTGPTCSILPKNPLFPQNLSSQPCIKMEGDKSLTF
  SSYGLQWCLYELDKEEFQTFKELLKKKSSESTTCSIPQFEIENANVECLALLLHEYYGAS
  LAWATSISIFENMNLRTLSEKARDDMKRHSPEDPEATMTDQGPSKEKVPGISQAVQQDSA
  TAAETKEQEISQAMEQEGATAAETEEQEISQAMEQEGATAAETEEQGHGGDTWDYKSHVM
  TKFAEEEDVRRSFENTAADWPEMQTLAGAFDSDRWGFRPRTVVLHGKSGIGKSALARRIV
  LCWAQGGLYQGMFSYVFFLPVREMQRKKESSVTEFISREWPDSQAPVTEIMSRPERLLFI
  IDGFDDLGSVLNNDTKLCKDWAEKQPPFTLIRSLLRKVLLPESFLIVTVRDVGTEKLKSE
  VVSPRYLLVRGISGEQRIHLLLERGIGEHQKTQGLRAIMNNRELLDQCQVPAVGSLICVA
  LQLQDVVGESVAPFNQTLTGLHAAFVFHQLTPRGVVRRCLNLEERVVLKRFCRMAVEGVW
  NRKSVFDGDDLMVQGLGESELRALFHMNILLPDSHCEEYYTFFHLSLQDFCAALYYVLEG
  LEIEPALCPLYVEKTKRSMELKQAGFHIHSLWMKRFLFGLVSEDVRRPLEVLLGCPVPLG
  VKQKLLHWVSLLGQQPNATTPGDTLDAFHCLFETQDKEFVRLALNSFQEVWLPINQNLDL
  IASSFCLQHCPYLRKIRVDVKGIFPRDESAEACPVVPLWMRDKTLIEEQWEDFCSMLGTH
  PHLRQLDLGSSILTERAMKTLCAKLRHPTCKIQTLMFRNAQITPGVQHLWRIVMANRNLR
  SLNLGGTHLKEEDVRMACEALKHPKCLLESLRLDCCGLTHACYLKISQILTTSPSLKSLS
  LAGNKVTDQGVMPLSDALRVSQCALQKLILEDCGITATGCQSLASALVSNRSLTHLCLSN
  NSLGNEGVNLLCRSMRLPHCSLQRLMLNQCHLDTAGCGFLALALMGNSWLTHLSLSMNPV
  EDNGVKLLCEVMREPSCHLQDLELVKCHLTAACCESLSCVISRSRHLKSLDLTDNALGDG
  GVAALCEGLKQKNSVLARLGLKACGLTSDCCEALSLALSCNRHLTSLNLVQNNFSPKGMM
  KLCSAFACPTSNLQIIGLWKWQYPVQIRKLLEEVQLLKPRVVIDGSWHSFDEDDRYWWKN
• Function: As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics. Required for the formation of F-actin cytoplasmic lattices (CPL) in oocytes, which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning. Required for the localization of cortical granules to the cortex of oocytes, via association with the cortical actin scaffold. Required for cortical actin clearance prior to oocyte exocytosis. Involved in regulating post-fertilization Ca(2+) release and endoplasmic reticulum (ER) storage via regulation of ER localization. May be involved in the localization of mitochondria to the cytoplasm and perinuclear region in oocytes and early stage embryos, independent of its role in CPL formation.
• Tissue Specificity: Expressed in cumulus cells (at protein level) . Highly abundant in oocytes and early embryos, however poorly expressed in somatic tissues such as the liver and spinal cord .

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infertility	DISAMOWP	Definitive	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[2]
Autoimmune polyendocrine syndrome type 1	DISWJP8J	Strong	Genetic Variation	[2]
Colon cancer	DISVC52G	Strong	Altered Expression	[3]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[3]
Endometritis	DISHGJ6G	Strong	Biomarker	[4]
Female hypogonadism	DISWASB4	Strong	Biomarker	[2]
Hypoparathyroidism	DISICS0V	Strong	Biomarker	[5]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[6]
Oocyte/zygote/embryo maturation arrest 19	DISIC6CY	Strong	Autosomal recessive	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of NACHT, LRR and PYD domains-containing protein 5 (NLRP5).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of NACHT, LRR and PYD domains-containing protein 5 (NLRP5).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of NACHT, LRR and PYD domains-containing protein 5 (NLRP5).	[9]

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 decreases the methylation of NACHT, LRR and PYD domains-containing protein 5 (NLRP5).	[10]

References

• [1] A human homologue of mouse Mater, a maternal effect gene essential for early embryonic development.Hum Reprod. 2002 Apr;17(4):903-11. doi: 10.1093/humrep/17.4.903.
• [2] Autoimmune oophoritis with multiple molecular targets mitigated by transgenic expression of mater.Endocrinology. 2011 Jun;152(6):2465-73. doi: 10.1210/en.2011-0022. Epub 2011 Mar 29.
• [3] Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer.PLoS One. 2018 Jun 21;13(6):e0199350. doi: 10.1371/journal.pone.0199350. eCollection 2018.
• [4] The "RESEAU MATER": An efficient infection control for endometritis, but not for urinary tract infection after vaginal delivery.J Infect Public Health. 2017 Jul-Aug;10(4):457-469. doi: 10.1016/j.jiph.2016.08.002. Epub 2016 Sep 1.
• [5] Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen.N Engl J Med. 2008 Mar 6;358(10):1018-28. doi: 10.1056/NEJMoa0706487.
• [6] Genetic modifiers of multiple sclerosis progression, severity and onset.Clin Immunol. 2017 Jul;180:100-105. doi: 10.1016/j.clim.2017.05.009. Epub 2017 May 10.
• [7] Mater, a maternal effect gene required for early embryonic development in mice. Nat Genet. 2000 Nov;26(3):267-8. doi: 10.1038/81547.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] 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.