Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4JMFPH)

DOT Name NACHT domain- and WD repeat-containing protein 1 (NWD1)
Gene Name NWD1
Related Disease
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Temporal lobe epilepsy ( )
UniProt ID
NWD1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF12894 ; PF05729 ; PF00400
Sequence
MQRGKPCRALPTLKCQTFCQRHGLMFEVVDLRWGIRNIEATDHLTTELCLEEVDRCWKTS
IGPAFVALIGDQYGPCLIPSRIDEKEWEVLRDHLTARPSDLELVARYFQRDENAFPPTYV
LQAPGTGEACEPEEATLTSVLRSGAQEARRLGLITQEQWQHYHRSVIEWEIERSLLSSED
REQGATVFLREIQDLHKHILEDCALRMVDRLADGCLDADAQNLLSSLKSHITDMHPGVLK
THRLPWSRDLVNPKNKTHACYLKELGEQFVVRANHQVLTRLRELDTAGQELAWLYQEIRH
HLWQSSEVIQTFCGRQELLARLGQQLRHDDSKQHTPLVLFGPPGIGKTALMCKLAEQMPR
LLGHKTVTVLRLLGTSQMSSDARGLLKSICFQVCLAYGLPLPPAQVLDAHTRVVQFFHTL
LHTVSCRNFESLVLLLDAMDDLDSVRHARRVPWLPLNCPPRVHLILSACSGALGVLDTLQ
RVLLDPEAYWEVKPLSGNQGQQMIQLLLAAARRTLSPVHTDLLWASLPECGNPGRLRLAF
EEARKWASFTVPVPLATTAEEATHQLCTRLEQTHGQLLVAHVLGYIVSSRHGLSEAELKD
VLSLDDEVLQDVYRDWTPPSKELLRFPPLLWVRLRRDLGYYLARRPVDGFTLLAIAHRQL
VEVVRERYLSGSERAKRHGVLADFFSGTWSQGTKKLITLPLVGKPLNLDRKVAPQPLWFS
HTVANLRKLKELPYHLLHSGRLEELKQEVLGSMSWISCRGISGGIEDLLDDFDLCAPHLD
SPEVGLVREALQLCRPAVELRGMERSLLYTELLARLHFFATSHPALVGQLCQQAQSWFQL
CAHPVLVPLGGFLQPPGGPLRATLSGCHKGITAMAWGVEEKLLVIGTQDGIMAVWDMEEQ
HVIHMLTGHTGEVRCVKIFAKGTLANSASKDYTLHLWNLLSGQEKFTIWDGGSKNPAEPQ
IWNLHVDEAHKVVYSASGSKINAWNLETAEPVFHILGDASDPWMCMAVLASQATLLTVSR
DGVVSLWSSATGKLQGKQHMSSIKEETPTCAVSVQKQGKLVTGFSNGSISLVSSKGDRLL
EKLPDAVRFLVVSEDESLLAAGFGRSVRIFLADSRGFRRFMAMDLEHEDMVETAVFGTEN
NLIITGSLDALIQVWSLSEQGTLLDILEGVGAPVSLLARGGALVASASPQSSSFKVWDLS
DAHRSRVPAPFLDRTGLTAVSHNGSYVYFPKIGDKNKVTIWDLAEGEEQDSLDTSSEIRC
LEVAEQRKLLFTGLVSGVVLVFPLNSRQDVICIPPPEARKAINCMSLSKCEDRLAIAYDN
IVLVLDITSGDPCPVIDGPRYTFYTQLPETLSSVAILTDYRVVYSMTNGDLFLYECATSK
AFPLETHRSRVACVEVSHKEQLVVSGSEDALLCLWDLQARKWKFEMSYTSSYCRGVQCAC
FSKDDKYVYVGLKDRSILVWSVLDGTLLTVQFVHAVVNRIIPTTSGFIAPTRHGYLIREN
FQCLSAKASPQDPLKNFKKAMWMVKSRQREELVAAAGAPQDLESESAQGNETKSNKCSQV
CLIV
Function May play a role in the control of androgen receptor (AR) protein steady-state levels.
Tissue Specificity
Expressed at highest levels in prostate, followed by testis, retina, trachea and optic nerve. Also detected in brain, epididymis, lung, vagina and pituitary. In the prostate, tends to be up-regulated during malignant progression compared to normal epithelium (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Colon cancer DISVC52G moderate Genetic Variation [3]
Colon carcinoma DISJYKUO moderate Genetic Variation [3]
Prostate cancer DISF190Y Limited Altered Expression [4]
Prostate carcinoma DISMJPLE Limited Altered Expression [4]
Temporal lobe epilepsy DISNOPXX Limited Altered Expression [5]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of NACHT domain- and WD repeat-containing protein 1 (NWD1). [6]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of NACHT domain- and WD repeat-containing protein 1 (NWD1). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of NACHT domain- and WD repeat-containing protein 1 (NWD1). [8]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Milchsaure DM462BT Investigative Milchsaure decreases the expression of NACHT domain- and WD repeat-containing protein 1 (NWD1). [9]
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References

1 A genome-wide analysis of the response to inhaled 2-agonists in chronic obstructive pulmonary disease.Pharmacogenomics J. 2016 Aug;16(4):326-35. doi: 10.1038/tpj.2015.65. Epub 2015 Oct 27.
2 The nutritional environment determines which and how intestinal stem cells contribute to homeostasis and tumorigenesis.Carcinogenesis. 2019 Aug 22;40(8):937-946. doi: 10.1093/carcin/bgz106.
3 Vitamin D and the nutritional environment in functions of intestinal stem cells: Implications for tumorigenesis and prevention.J Steroid Biochem Mol Biol. 2020 Apr;198:105556. doi: 10.1016/j.jsbmb.2019.105556. Epub 2019 Nov 26.
4 The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.Oncotarget. 2014 Mar 30;5(6):1666-82. doi: 10.18632/oncotarget.1850.
5 Inhibition of Nwd1 activity attenuates neuronal hyperexcitability and GluN2B phosphorylation in the hippocampus.EBioMedicine. 2019 Sep;47:470-483. doi: 10.1016/j.ebiom.2019.08.050. Epub 2019 Aug 29.
6 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
7 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
8 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.
9 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.