Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT13WAQX)

• DOT Name: Protein-arginine deiminase type-1 (PADI1)
• Synonyms: EC 3.5.3.15; Peptidylarginine deiminase I; Protein-arginine deiminase type I
• Gene Name: PADI1
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Attention deficit hyperactivity disorder
  Behcet disease
  Hermansky-Pudlak syndrome
  High blood pressure
  Myopia
  Neoplasm
  Non-small-cell lung cancer
  Osteogenesis imperfecta
  Osteoporosis
  Peripheral arterial disease
  Peripheral vascular disease
  Schizophrenia
  Triple negative breast cancer
  Visceral leishmaniasis
  Amyotrophic lateral sclerosis
  Bacterial infection
  Hepatocellular carcinoma
  Hypoglycemia
  Plasma cell myeloma
  Type-1/2 diabetes
  Anxiety
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Depression
  Non-insulin dependent diabetes
• UniProt ID: PADI1_HUMAN
• PDB ID: 5HP5
• EC Number: 3.5.3.15
• Pfam ID: PF03068 ; PF08527 ; PF08526
• Sequence:
  MAPKRVVQLSLKMPTHAVCVVGVEAHVDIHSDVPKGANSFRVSGSSGVEVFMVYNRTRVK
  EPIGKARWPLDTDADMVVSVGTASKELKDFKVRVSYFGEQEDQALGRSVLYLTGVDISLE
  VDTGRTGKVKRSQGDKKTWRWGPEGYGAILLVNCDRDNHRSAEPDLTHSWLMSLADLQDM
  SPMLLSCNGPDKLFDSHKLVLNVPFSDSKRVRVFCARGGNSLSDYKQVLGPQCLSYEVER
  QPGEQEIKFYVEGLTFPDADFLGLVSLSVSLVDPGTLPEVTLFTDTVGFRMAPWIMTPNT
  QPPEELYVCRVMDTHGSNEKFLEDMSYLTLKANCKLTICPQVENRNDRWIQDEMEFGYIE
  APHKSFPVVFDSPRNRGLKDFPYKRILGPDFGYVTREIPLPGPSSLDSFGNLDVSPPVTV
  GGTEYPLGRILIGSSFPKSGGRQMARAVRNFLKAQQVQAPVELYSDWLSVGHVDEFLTFV
  PTSDQKGFRLLLASPSACLKLFQEKKEEGYGEAAQFDGLKHQAKRSINEMLADRHLQRDN
  LHAQKCIDWNRNVLKRELGLAESDIVDIPQLFFLKNFYAEAFFPDMVNMVVLGKYLGIPK
  PYGPIINGRCCLEEKVQSLLEPLGLHCIFIDDYLSYHELQGEIHCGTNVRRKPFPFKWWN
  MVP
• Function: Catalyzes the deimination of arginine residues of proteins.
• Tissue Specificity: Detected in epidermal keratinocytes (at protein level). Epidermis, prostate, testis, placenta, spleen and thymus.
• Reactome Pathway: Chromatin modifying enzymes (R-HSA-3247509)
• BioCyc Pathway: MetaCyc:HS06945-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[4]
Behcet disease	DISSYMBS	Strong	Biomarker	[5]
Hermansky-Pudlak syndrome	DISCY0HQ	Strong	Biomarker	[6]
High blood pressure	DISY2OHH	Strong	Biomarker	[3]
Myopia	DISK5S60	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[9]
Osteogenesis imperfecta	DIS7XQSD	Strong	Altered Expression	[10]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[11]
Peripheral arterial disease	DIS78WFB	Strong	Biomarker	[12]
Peripheral vascular disease	DISXSU1Y	Strong	Biomarker	[12]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[13]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[14]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[15]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[16]
Bacterial infection	DIS5QJ9S	moderate	Genetic Variation	[17]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[18]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[20]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[21]
Anxiety	DISIJDBA	Limited	Genetic Variation	[22]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[22]
Breast cancer	DIS7DPX1	Limited	Biomarker	[23]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[23]
Depression	DIS3XJ69	Limited	Genetic Variation	[24]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[25]

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 Protein-arginine deiminase type-1 (PADI1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein-arginine deiminase type-1 (PADI1).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein-arginine deiminase type-1 (PADI1).	[30]

3 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-1 (PADI1).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein-arginine deiminase type-1 (PADI1).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein-arginine deiminase type-1 (PADI1).	[31]

References

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• [17] Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties.Org Biomol Chem. 2017 Dec 6;15(47):10037-10043. doi: 10.1039/c7ob02749d.
• [18] Microvascular Flow Imaging of Residual or Recurrent Hepatocellular Carcinoma after Transarterial Chemoembolization: Comparison with Color/Power Doppler Imaging.Korean J Radiol. 2019 Jul;20(7):1114-1123. doi: 10.3348/kjr.2018.0932.
• [19] Anxiety affects disability and quality of life in patients with painful diabetic neuropathy.Eur J Pain. 2017 Nov;21(10):1632-1641. doi: 10.1002/ejp.1067. Epub 2017 Jun 27.
• [20] Tuning isoform selectivity and bortezomib sensitivity with a new class of alkenyl indene PDI inhibitor.Eur J Med Chem. 2020 Jan 15;186:111906. doi: 10.1016/j.ejmech.2019.111906. Epub 2019 Nov 21.
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• [22] The pain course: a randomised controlled trial comparing a remote-delivered chronic pain management program when provided in online and workbook formats.Pain. 2017 Jul;158(7):1289-1301. doi: 10.1097/j.pain.0000000000000916.
• [23] Delivery of Amonafide from Fructose-Coated Nanodiamonds by Oxime Ligation for the Treatment of Human Breast Cancer.Biomacromolecules. 2018 Feb 12;19(2):481-489. doi: 10.1021/acs.biomac.7b01592. Epub 2018 Jan 23.
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• [25] Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes.PLoS One. 2013 Apr 25;8(4):e62418. doi: 10.1371/journal.pone.0062418. Print 2013.
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• [27] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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• [30] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [31] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.