Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT864X7M)

DOT Name NACHT, LRR and PYD domains-containing protein 4 (NLRP4)
Synonyms Cancer/testis antigen 58; CT58; PAAD and NACHT-containing protein 2; PAN2; PYRIN and NACHT-containing protein 2; PYRIN-containing APAF1-like protein 4; PYPAF4; Ribonuclease inhibitor 2
Gene Name NLRP4
Related Disease
Asthma ( )
Adenocarcinoma ( )
Advanced cancer ( )
Bladder cancer ( )
Transitional cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Urinary tract disease ( )
Urothelial carcinoma ( )
UniProt ID
NALP4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4EWI
Pfam ID
PF13516 ; PF05729 ; PF17776 ; PF17779 ; PF02758
Sequence
MAASFFSDFGLMWYLEELKKEEFRKFKEHLKQMTLQLELKQIPWTEVKKASREELANLLI
KHYEEQQAWNITLRIFQKMDRKDLCMKVMRERTGYTKTYQAHAKQKFSRLWSSKSVTEIH
LYFEEEVKQEECDHLDRLFAPKEAGKQPRTVIIQGPQGIGKTTLLMKLMMAWSDNKIFRD
RFLYTFYFCCRELRELPPTSLADLISREWPDPAAPITEIVSQPERLLFVIDSFEELQGGL
NEPDSDLCGDLMEKRPVQVLLSSLLRKKMLPEASLLIAIKPVCPKELRDQVTISEIYQPR
GFNESDRLVYFCCFFKDPKRAMEAFNLVRESEQLFSICQIPLLCWILCTSLKQEMQKGKD
LALTCQSTTSVYSSFVFNLFTPEGAEGPTPQTQHQLKALCSLAAEGMWTDTFEFCEDDLR
RNGVVDADIPALLGTKILLKYGERESSYVFLHVCIQEFCAALFYLLKSHLDHPHPAVRCV
QELLVANFEKARRAHWIFLGCFLTGLLNKKEQEKLDAFFGFQLSQEIKQQIHQCLKSLGE
RGNPQGQVDSLAIFYCLFEMQDPAFVKQAVNLLQEANFHIIDNVDLVVSAYCLKYCSSLR
KLCFSVQNVFKKEDEHSSTSDYSLICWHHICSVLTTSGHLRELQVQDSTLSESTFVTWCN
QLRHPSCRLQKLGINNVSFSGQSVLLFEVLFYQPDLKYLSFTLTKLSRDDIRSLCDALNY
PAGNVKELALVNCHLSPIDCEVLAGLLTNNKKLTYLNVSCNQLDTGVPLLCEALCSPDTV
LVYLMLAFCHLSEQCCEYISEMLLRNKSVRYLDLSANVLKDEGLKTLCEALKHPDCCLDS
LCLVKCFITAAGCEDLASALISNQNLKILQIGCNEIGDVGVQLLCRALTHTDCRLEILGL
EECGLTSTCCKDLASVLTCSKTLQQLNLTLNTLDHTGVVVLCEALRHPECALQVLGLRKT
DFDEETQALLTAEEERNPNLTITDDCDTITRVEI
Function
May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways.
KEGG Pathway
Pathogenic Escherichia coli infection (hsa05130 )
Reactome Pathway
Regulation of innate immune responses to cytosolic DNA (R-HSA-3134975 )
IRF3-mediated induction of type I IFN (R-HSA-3270619 )
IRF3 mediated activation of type 1 IFN (R-HSA-1606341 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Asthma DISW9QNS Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Bladder cancer DISUHNM0 Strong Altered Expression [4]
Transitional cell carcinoma DISWVVDR Strong Biomarker [5]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [4]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [4]
Urinary tract disease DIS0HU8N Strong Altered Expression [4]
Urothelial carcinoma DISRTNTN Strong Biomarker [5]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Permethrin DMZ0Q1G Approved Permethrin increases the expression of NACHT, LRR and PYD domains-containing protein 4 (NLRP4). [6]
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References

1 Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.DNA Cell Biol. 2019 Jan;38(1):76-84. doi: 10.1089/dna.2018.4433. Epub 2018 Dec 8.
2 Biologic instability of pancreatic cancer xenografts in the nude mouse.Carcinogenesis. 2000 Jun;21(6):1121-7.
3 Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients.Cancer Res. 1998 Feb 1;58(3):512-8.
4 Evaluation of urinary CA19-9 levels in bladder cancer patients classified according to the combinations of Lewis and Secretor blood group genotypes.Int J Urol. 2007 Sep;14(9):795-9. doi: 10.1111/j.1442-2042.2007.01840.x.
5 Characterization of inflammasome-related genes in urine sediments of patients receiving intravesical BCG therapy.Urol Oncol. 2017 Dec;35(12):674.e19-674.e24. doi: 10.1016/j.urolonc.2017.08.004. Epub 2017 Sep 6.
6 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.