Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS42I3K)

• DOT Name: Protein-arginine deiminase type-6 (PADI6)
• Synonyms: EC 3.5.3.15; Peptidyl arginine deiminase-like protein; Peptidylarginine deiminase VI; hPADVI; Protein-arginine deiminase type VI
• Gene Name: PADI6
• Related Disease:
  Arthritis
  Breast carcinoma
  Hydatidiform mole
  Nasopharyngeal carcinoma
  Obsolete preimplantation embryonic lethality 2
  Osteoarthritis
  Rheumatoid arthritis
  Basal cell carcinoma
  Basal cell neoplasm
• UniProt ID: PADI6_HUMAN
• PDB ID: 4DAT; 4DAU
• EC Number: 3.5.3.15
• Pfam ID: PF03068 ; PF08527 ; PF08526
• Sequence:
  MVSVEGRAMSFQSIIHLSLDSPVHAVCVLGTEICLDLSGCAPQKCQCFTIHGSGRVLIDV
  ANTVISEKEDATIWWPLSDPTYATVKMTSPSPSVDADKVSVTYYGPNEDAPVGTAVLYLT
  GIEVSLEVDIYRNGQVEMSSDKQAKKKWIWGPSGWGAILLVNCNPADVGQQLEDKKTKKV
  IFSEEITNLSQMTLNVQGPSCILKKYRLVLHTSKEESKKARVYWPQKDNSSTFELVLGPD
  QHAYTLALLGNHLKETFYVEAIAFPSAEFSGLISYSVSLVEESQDPSIPETVLYKDTVVF
  RVAPCVFIPCTQVPLEVYLCRELQLQGFVDTVTKLSEKSNSQVASVYEDPNRLGRWLQDE
  MAFCYTQAPHKTTSLILDTPQAADLDEFPMKYSLSPGIGYMIQDTEDHKVASMDSIGNLM
  VSPPVKVQGKEYPLGRVLIGSSFYPSAEGRAMSKTLRDFLYAQQVQAPVELYSDWLMTGH
  VDEFMCFIPTDDKNEGKKGFLLLLASPSACYKLFREKQKEGYGDALLFDELRADQLLSNG
  REAKTIDQLLADESLKKQNEYVEKCIHLNRDILKTELGLVEQDIIEIPQLFCLEKLTNIP
  SDQQPKRSFARPYFPDLLRMIVMGKNLGIPKPFGPQIKGTCCLEEKICCLLEPLGFKCTF
  INDFDCYLTEVGDICACANIRRVPFAFKWWKMVP
• Function: Catalyzes the deimination of arginine residues of proteins. May be involved in cytoskeletal reorganization in the egg and early embryo ; Catalyzes the deimination of arginine residues of proteins. In oocytes, is released during cortical reaction and plays a role in preimplantation cleavage and early embryonic development. May be involved in cytoskeletal reorganization in the egg and early embryo.
• Tissue Specificity: Highly expressed in oocytes and weakly expressed in other somatic tissues.
• Reactome Pathway: Chromatin modifying enzymes (R-HSA-3247509)
• BioCyc Pathway: MetaCyc:G66-31585-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Hydatidiform mole	DISKNP7O	Strong	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[4]
Obsolete preimplantation embryonic lethality 2	DISCCEBT	Strong	Autosomal recessive	[5]
Osteoarthritis	DIS05URM	Strong	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[1]
Basal cell carcinoma	DIS7PYN3	Limited	Genetic Variation	[6]
Basal cell neoplasm	DIS37IXW	Limited	Genetic Variation	[6]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein-arginine deiminase type-6 (PADI6).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein-arginine deiminase type-6 (PADI6).	[8]

References

• [1] Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation.Arthritis Rheum. 2007 Nov;56(11):3541-53. doi: 10.1002/art.22983.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] Biallelic PADI6 variants linking infertility, miscarriages, and hydatidiform moles.Eur J Hum Genet. 2018 Jul;26(7):1007-1013. doi: 10.1038/s41431-018-0141-3. Epub 2018 Apr 25.
• [4] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [5] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [6] New basal cell carcinoma susceptibility loci.Nat Commun. 2015 Apr 9;6:6825. doi: 10.1038/ncomms7825.
• [7] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [8] 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.