Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT40K94)

DOT Name Protein-arginine deiminase type-2 (PADI2)
Synonyms EC 3.5.3.15; PAD-H19; Peptidylarginine deiminase II; Protein-arginine deiminase type II
Gene Name PADI2
Related Disease
Neoplasm ( )
Alzheimer disease ( )
Arthropathy ( )
Autoimmune disease ( )
Breast cancer ( )
Breast neoplasm ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Coronary atherosclerosis ( )
Ductal carcinoma ( )
Estrogen-receptor positive breast cancer ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Lupus ( )
Metastatic malignant neoplasm ( )
Myocardial infarction ( )
Myocardial ischemia ( )
Osteoarthritis ( )
Periodontal disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary disease ( )
Skin cancer ( )
Skin neoplasm ( )
Systemic lupus erythematosus ( )
Ulcerative colitis ( )
Bladder cancer ( )
Breast carcinoma ( )
Gingivitis ( )
Multiple sclerosis ( )
Periodontitis ( )
Peripheral arterial disease ( )
Plasma cell myeloma ( )
Squamous cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Advanced cancer ( )
Arthritis ( )
Glaucoma/ocular hypertension ( )
Nervous system inflammation ( )
OPTN-related open angle glaucoma ( )
UniProt ID
PADI2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
4N20; 4N22; 4N24; 4N25; 4N26; 4N28; 4N2A; 4N2B; 4N2C; 4N2D; 4N2E; 4N2F; 4N2G; 4N2H; 4N2I; 4N2K; 4N2L; 4N2M; 4N2N
EC Number
3.5.3.15
Pfam ID
PF03068 ; PF08527 ; PF08526
Sequence
MLRERTVRLQYGSRVEAVYVLGTYLWTDVYSAAPAGAQTFSLKHSEHVWVEVVRDGEAEE
VATNGKQRWLLSPSTTLRVTMSQASTEASSDKVTVNYYDEEGSIPIDQAGLFLTAIEISL
DVDADRDGVVEKNNPKKASWTWGPEGQGAILLVNCDRETPWLPKEDCRDEKVYSKEDLKD
MSQMILRTKGPDRLPAGYEIVLYISMSDSDKVGVFYVENPFFGQRYIHILGRRKLYHVVK
YTGGSAELLFFVEGLCFPDEGFSGLVSIHVSLLEYMAQDIPLTPIFTDTVIFRIAPWIMT
PNILPPVSVFVCCMKDNYLFLKEVKNLVEKTNCELKVCFQYLNRGDRWIQDEIEFGYIEA
PHKGFPVVLDSPRDGNLKDFPVKELLGPDFGYVTREPLFESVTSLDSFGNLEVSPPVTVN
GKTYPLGRILIGSSFPLSGGRRMTKVVRDFLKAQQVQAPVELYSDWLTVGHVDEFMSFVP
IPGTKKFLLLMASTSACYKLFREKQKDGHGEAIMFKGLGGMSSKRITINKILSNESLVQE
NLYFQRCLDWNRDILKKELGLTEQDIIDLPALFKMDEDHRARAFFPNMVNMIVLDKDLGI
PKPFGPQVEEECCLEMHVRGLLEPLGLECTFIDDISAYHKFLGEVHCGTNVRRKPFTFKW
WHMVP
Function Catalyzes the deimination of arginine residues of proteins.
Tissue Specificity Detected in keratinocytes in epidermis (at protein level).
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Chromatin modifying enzymes (R-HSA-3247509 )
BioCyc Pathway
MetaCyc:HS04094-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Biomarker [1]
Alzheimer disease DISF8S70 Strong Biomarker [2]
Arthropathy DISVEERK Strong Biomarker [3]
Autoimmune disease DISORMTM Strong Altered Expression [4]
Breast cancer DIS7DPX1 Strong Altered Expression [5]
Breast neoplasm DISNGJLM Strong Altered Expression [6]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Altered Expression [7]
Colon cancer DISVC52G Strong Altered Expression [8]
Colon carcinoma DISJYKUO Strong Altered Expression [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Coronary atherosclerosis DISKNDYU Strong Biomarker [10]
Ductal carcinoma DIS15EA5 Strong Altered Expression [7]
Estrogen-receptor positive breast cancer DIS1H502 Strong Biomarker [6]
Liver cancer DISDE4BI Strong Altered Expression [7]
Lung cancer DISCM4YA Strong Biomarker [11]
Lung carcinoma DISTR26C Strong Biomarker [11]
Lupus DISOKJWA Strong Biomarker [12]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [7]
Myocardial infarction DIS655KI Strong Biomarker [10]
Myocardial ischemia DISFTVXF Strong Biomarker [10]
Osteoarthritis DIS05URM Strong Altered Expression [13]
Periodontal disease DISJQHVN Strong Biomarker [14]
Prostate cancer DISF190Y Strong Biomarker [15]
Prostate carcinoma DISMJPLE Strong Biomarker [15]
Pulmonary disease DIS6060I Strong Biomarker [3]
Skin cancer DISTM18U Strong Altered Expression [16]
Skin neoplasm DIS16DDV Strong Altered Expression [16]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [12]
Ulcerative colitis DIS8K27O Strong Altered Expression [17]
Bladder cancer DISUHNM0 moderate Biomarker [1]
Breast carcinoma DIS2UE88 moderate Altered Expression [5]
Gingivitis DISC8RMX moderate Altered Expression [18]
Multiple sclerosis DISB2WZI moderate Biomarker [19]
Periodontitis DISI9JOI moderate Altered Expression [18]
Peripheral arterial disease DIS78WFB moderate Biomarker [20]
Plasma cell myeloma DIS0DFZ0 moderate Altered Expression [21]
Squamous cell carcinoma DISQVIFL moderate Altered Expression [22]
Urinary bladder cancer DISDV4T7 moderate Biomarker [1]
Urinary bladder neoplasm DIS7HACE moderate Biomarker [1]
Advanced cancer DISAT1Z9 Limited Biomarker [23]
Arthritis DIST1YEL Limited Biomarker [24]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [25]
Nervous system inflammation DISB3X5A Limited Biomarker [26]
OPTN-related open angle glaucoma DISDR98A Limited Biomarker [25]
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⏷ Show the Full List of 44 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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-2 (PADI2). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Protein-arginine deiminase type-2 (PADI2). [32]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Protein-arginine deiminase type-2 (PADI2). [28]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein-arginine deiminase type-2 (PADI2). [29]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Protein-arginine deiminase type-2 (PADI2). [30]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of Protein-arginine deiminase type-2 (PADI2). [31]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Protein-arginine deiminase type-2 (PADI2). [33]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Protein-arginine deiminase type-2 (PADI2). [34]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Protein-arginine deiminase type-2 (PADI2). [35]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Protein-arginine deiminase type-2 (PADI2). [36]
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⏷ Show the Full List of 8 Drug(s)

References

1 Peptidyl Arginine Deiminase, Type II (PADI2) Is Involved in Urothelial Bladder Cancer.Pathol Oncol Res. 2020 Apr;26(2):1279-1285. doi: 10.1007/s12253-019-00687-0. Epub 2019 Jul 2.
2 Induction of peptidylarginine deiminase 2 and 3 by dibutyryl cAMP via cAMP-PKA signaling in human astrocytoma U-251MG cells.J Neurosci Res. 2017 Jul;95(7):1503-1512. doi: 10.1002/jnr.23959. Epub 2016 Oct 5.
3 Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis.Front Immunol. 2018 Nov 20;9:2696. doi: 10.3389/fimmu.2018.02696. eCollection 2018.
4 Cutting Edge: Protein Arginine Deiminase 2 and 4 Regulate NLRP3 Inflammasome-Dependent IL-1 Maturation and ASC Speck Formation in Macrophages.J Immunol. 2019 Aug 15;203(4):795-800. doi: 10.4049/jimmunol.1800720. Epub 2019 Jul 10.
5 Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells.J Exp Clin Cancer Res. 2019 Oct 10;38(1):414. doi: 10.1186/s13046-019-1404-8.
6 Targeted H3R26 deimination specifically facilitates estrogen receptor binding by modifying nucleosome structure.PLoS Genet. 2014 Sep 11;10(9):e1004613. doi: 10.1371/journal.pgen.1004613. eCollection 2014 Sep.
7 Investigating the expression, effect and tumorigenic pathway of PADI2 in tumors.Onco Targets Ther. 2017 Mar 8;10:1475-1485. doi: 10.2147/OTT.S92389. eCollection 2017.
8 Protein-arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination.Cancer Sci. 2017 Apr;108(4):713-718. doi: 10.1111/cas.13179. Epub 2017 Apr 12.
9 Integrating proteomics and transcriptomics for the identification of potential targets in early colorectal cancer.Int J Oncol. 2019 Aug;55(2):439-450. doi: 10.3892/ijo.2019.4833. Epub 2019 Jun 27.
10 Peptidylarginine Deiminase 2 Knockout Improves Survival in hemorrhagic shock.Shock. 2020 Oct;54(4):458-463. doi: 10.1097/SHK.0000000000001489.
11 Differential Expression of TOM34, AL1A1, PADI2 and KLRBA in NNK Induced Lung Cancer in Wistar Rats and their Implications.Curr Cancer Drug Targets. 2019;19(11):919-929. doi: 10.2174/1871525717666190717162646.
12 Peptidylarginine deiminases 2 and 4 modulate innate and adaptive immune responses in TLR-7-dependent lupus.JCI Insight. 2018 Dec 6;3(23):e124729. doi: 10.1172/jci.insight.124729.
13 The expression of mRNA for peptidylarginine deiminase type 2 and type 4 in bone marrow CD34+ cells in rheumatoid arthritis.Clin Exp Rheumatol. 2018 Mar-Apr;36(2):248-253. Epub 2017 Nov 14.
14 Gingival crevicular fluid semaphorin 4D and peptidylarginine deiminase-2 levels in periodontal health and disease.J Periodontol. 2019 Sep;90(9):973-981. doi: 10.1002/JPER.18-0608. Epub 2019 May 13.
15 PADI2-Mediated Citrullination Promotes Prostate Cancer Progression.Cancer Res. 2017 Nov 1;77(21):5755-5768. doi: 10.1158/0008-5472.CAN-17-0150. Epub 2017 Aug 17.
16 PAD2 overexpression in transgenic mice augments malignancy and tumor-associated inflammation in chemically initiated skin tumors.Cell Tissue Res. 2017 Nov;370(2):275-283. doi: 10.1007/s00441-017-2669-x. Epub 2017 Aug 2.
17 Downregulation of the Deiminase PADI2 Is an Early Event in Colorectal Carcinogenesis and Indicates Poor Prognosis.Mol Cancer Res. 2016 Sep;14(9):841-8. doi: 10.1158/1541-7786.MCR-16-0034. Epub 2016 Jun 8.
18 Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis.J Transl Med. 2018 Jul 31;16(1):214. doi: 10.1186/s12967-018-1588-2.
19 Development of a Selective Inhibitor of Protein Arginine Deiminase 2.J Med Chem. 2017 Apr 13;60(7):3198-3211. doi: 10.1021/acs.jmedchem.7b00274. Epub 2017 Mar 31.
20 Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial).J Surg Res. 2019 Jun;238:164-174. doi: 10.1016/j.jss.2019.01.038. Epub 2019 Feb 13.
21 Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.Leukemia. 2017 Feb;31(2):373-381. doi: 10.1038/leu.2016.187. Epub 2016 Jul 11.
22 PAD2 overexpression in transgenic mice promotes spontaneous skin neoplasia.Cancer Res. 2014 Nov 1;74(21):6306-17. doi: 10.1158/0008-5472.CAN-14-0749. Epub 2014 Sep 11.
23 Arginine Citrullination at the C-Terminal Domain Controls RNA Polymerase II Transcription.Mol Cell. 2019 Jan 3;73(1):84-96.e7. doi: 10.1016/j.molcel.2018.10.016. Epub 2018 Nov 21.
24 Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation.J Autoimmun. 2017 Jun;80:39-47. doi: 10.1016/j.jaut.2017.01.006. Epub 2017 Feb 7.
25 Proteomics implicates peptidyl arginine deiminase 2 and optic nerve citrullination in glaucoma pathogenesis.Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2508-14. doi: 10.1167/iovs.05-1499.
26 Experimental autoimmune encephalomyelitis induction in peptidylarginine deiminase 2 knockout mice.J Comp Neurol. 2006 Sep 10;498(2):217-26. doi: 10.1002/cne.21055.
27 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.
28 Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
29 Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
30 Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
31 Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
32 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.
33 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
34 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
35 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
36 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.