Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5FL5UI)

DOT Name Protein-arginine deiminase type-3 (PADI3)
Synonyms EC 3.5.3.15; Peptidylarginine deiminase III; Protein-arginine deiminase type III
Gene Name PADI3
Related Disease
Uncombable hair syndrome 1 ( )
Uncombable hair syndrome ( )
UniProt ID
PADI3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6CE1; 7D4Y; 7D56; 7D5R; 7D5V; 7D8N; 7DAN
EC Number
3.5.3.15
Pfam ID
PF03068 ; PF08527 ; PF08526
Sequence
MSLQRIVRVSLEHPTSAVCVAGVETLVDIYGSVPEGTEMFEVYGTPGVDIYISPNMERGR
ERADTRRWRFDATLEIIVVMNSPSNDLNDSHVQISYHSSHEPLPLAYAVLYLTCVDISLD
CDLNCEGRQDRNFVDKRQWVWGPSGYGGILLVNCDRDDPSCDVQDNCDQHVHCLQDLEDM
SVMVLRTQGPAALFDDHKLVLHTSSYDAKRAQVFHICGPEDVCEAYRHVLGQDKVSYEVP
RLHGDEERFFVEGLSFPDAGFTGLISFHVTLLDDSNEDFSASPIFTDTVVFRVAPWIMTP
STLPPLEVYVCRVRNNTCFVDAVAELARKAGCKLTICPQAENRNDRWIQDEMELGYVQAP
HKTLPVVFDSPRNGELQDFPYKRILGPDFGYVTREPRDRSVSGLDSFGNLEVSPPVVANG
KEYPLGRILIGGNLPGSSGRRVTQVVRDFLHAQKVQPPVELFVDWLAVGHVDEFLSFVPA
PDGKGFRMLLASPGACFKLFQEKQKCGHGRALLFQGVVDDEQVKTISINQVLSNKDLINY
NKFVQSCIDWNREVLKRELGLAECDIIDIPQLFKTERKKATAFFPDLVNMLVLGKHLGIP
KPFGPIINGCCCLEEKVRSLLEPLGLHCTFIDDFTPYHMLHGEVHCGTNVCRKPFSFKWW
NMVP
Function Catalyzes the deimination of arginine residues of proteins.
Tissue Specificity Hair follicles, and epidermis at very low levels.
Reactome Pathway
Chromatin modifying enzymes (R-HSA-3247509 )
BioCyc Pathway
MetaCyc:HS06944-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Uncombable hair syndrome 1 DISP96VB Strong Autosomal recessive [1]
Uncombable hair syndrome DISJNMLZ Supportive Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Protein-arginine deiminase type-3 (PADI3). [3]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Protein-arginine deiminase type-3 (PADI3). [4]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein-arginine deiminase type-3 (PADI3). [5]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein-arginine deiminase type-3 (PADI3). [6]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Protein-arginine deiminase type-3 (PADI3). [7]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Protein-arginine deiminase type-3 (PADI3). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Protein-arginine deiminase type-3 (PADI3). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Protein-arginine deiminase type-3 (PADI3). [10]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein-arginine deiminase type-3 (PADI3). [11]
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⏷ Show the Full List of 8 Drug(s)

References

1 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
2 Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome. Am J Hum Genet. 2016 Dec 1;99(6):1292-1304. doi: 10.1016/j.ajhg.2016.10.004. Epub 2016 Nov 17.
3 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.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
6 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
7 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
8 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
9 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
10 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
11 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.