Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTM4WDO)

• DOT Name: Periplakin (PPL)
• Synonyms: 190 kDa paraneoplastic pemphigus antigen; 195 kDa cornified envelope precursor protein
• Gene Name: PPL
• Related Disease:
  Autism
  Metabolic disorder
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Carcinoma
  Carcinoma of esophagus
  Cholangiocarcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glycogen storage disease V
  High blood pressure
  Neoplasm
  Neoplasm of esophagus
  Prostate carcinoma
  Prostate neoplasm
  Squamous cell carcinoma
  Thyroid gland carcinoma
  Transitional cell carcinoma
  Triple negative breast cancer
  Urothelial carcinoma
  Autoimmune disease
  Acute myelogenous leukaemia
  Prostate cancer
  Pulmonary fibrosis
  Venous thromboembolism
• UniProt ID: PEPL_HUMAN
• PDB ID: 4Q28
• Pfam ID: PF17902
• Sequence:
  MNSLFRKRNKGKYSPTVQTRSISNKELSELIEQLQKNADQVEKNIVDTEAKMQSDLARLQ
  EGRQPEHRDVTLQKVLDSEKLLYVLEADAAIAKHMKHPQGDMIAEDIRQLKERVTNLRGK
  HKQIYRLAVKEVDPQVNWAALVEEKLDKLNNQSFGTDLPLVDHQVEEHNIFHNEVKAIGP
  HLAKDGDKEQNSELRAKYQKLLAASQARQQHLSSLQDYMQRCTNELYWLDQQAKGRMQYD
  WSDRNLDYPSRRRQYENFINRNLEAKEERINKLHSEGDQLLAAEHPGRNSIEAHMEAVHA
  DWKEYLNLLICEESHLKYMEDYHQFHEDVKDAQELLRKVDSDLNQKYGPDFKDRYQIELL
  LRELDDQEKVLDKYEDVVQGLQKRGQQVVPLKYRRETPLKPIPVEALCDFEGEQGLISRG
  YSYTLQKNNGESWELMDSAGNKLIAPAVCFVIPPTDPEALALADSLGSQYRSVRQKAAGS
  KRTLQQRYEVLKTENPGDASDLQGRQLLAGLDKVASDLDRQEKAITGILRPPLEQGRAVQ
  DSAERAKDLKNITNELLRIEPEKTRSTAEGEAFIQALPGSGTTPLLRTRVEDTNRKYEHL
  LQLLDLAQEKVDVANRLEKSLQQSWELLATHENHLNQDDTVPESSRVLDSKGQELAAMAC
  ELQAQKSLLGEVEQNLQAAKQCSSTLASRFQEHCPDLERQEAEVHKLGQRFNNLRQQVER
  RAQSLQSAKAAYEHFHRGHDHVLQFLVSIPSYEPQETDSLSQMETKLKNQKNLLDEIASR
  EQEVQKICANSQQYQQAVKDYELEAEKLRSLLDLENGRRSHVSKRARLQSPATKVKEEEA
  ALAAKFTEVYAINRQRLQNLEFALNLLRQQPEVEVTHETLQRNRPDSGVEEAWKIRKELD
  EETERRRQLENEVKSTQEEIWTLRNQGPQESVVRKEVLKKVPDPVLEESFQQLQRTLAEE
  QHKNQLLQEELEALQLQLRALEQETRDGGQEYVVKEVLRIEPDRAQADEVLQLREELEAL
  RRQKGAREAEVLLLQQRVAALAEEKSRAQEKVTEKEVVKLQNDPQLEAEYQQLQEDHQRQ
  DQLREKQEEELSFLQDKLKRLEKERAMAEGKITVKEVLKVEKDAATEREVSDLTRQYEDE
  AAKARASQREKTELLRKIWALEEENAKVVVQEKVREIVRPDPKAESEVANLRLELVEQER
  KYRGAEEQLRSYQSELEALRRRGPQVEVKEVTKEVIKYKTDPEMEKELQRLREEIVDKTR
  LIERCDLEIYQLKKEIQALKDTKPQVQTKEVVQEILQFQEDPQTKEEVASLRAKLSEEQK
  KQVDLERERASQEEQIARKEEELSRVKERVVQQEVVRYEEEPGLRAEASAFAESIDVELR
  QIDKLRAELRRLQRRRTELERQLEELERERQARREAEREVQRLQQRLAALEQEEAEAREK
  VTHTQKVVLQQDPQQAREHALLRLQLEEEQHRRQLLEGELETLRRKLAALEKAEVKEKVV
  LSESVQVEKGDTEQEIQRLKSSLEEESRSKRELDVEVSRLEARLSELEFHNSKSSKELDF
  LREENHKLQLERQNLQLETRRLQSEINMAATETRDLRNMTVADSGTNHDSRLWSLERELD
  DLKRLSKDKDLEIDELQKRLGSVAVKREQRENHLRRSIVVIHPDTGRELSPEEAHRAGLI
  DWNMFVKLRSQECDWEEISVKGPNGESSVIHDRKSGKKFSIEEALQSGRLTPAQYDRYVN
  KDMSIQELAVLVSGQK
• Function: Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling.
• Tissue Specificity: Expressed in stratified squamous epithelia and in some other epithelia.
• Reactome Pathway:
  Butyrophilin (BTN) family interactions (R-HSA-8851680)
  Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Metabolic disorder	DIS71G5H	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Glycogen storage disease V	DISJNC0O	Strong	Genetic Variation	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[12]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[13]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[8]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[6]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[14]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[6]
Autoimmune disease	DISORMTM	moderate	Altered Expression	[15]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[16]
Prostate cancer	DISF190Y	Limited	Biomarker	[11]
Pulmonary fibrosis	DISQKVLA	Limited	Genetic Variation	[15]
Venous thromboembolism	DISUR7CR	Limited	Biomarker	[17]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Periplakin (PPL).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Periplakin (PPL).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Periplakin (PPL).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Periplakin (PPL).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Periplakin (PPL).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Periplakin (PPL).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Periplakin (PPL).	[24]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Periplakin (PPL).	[25]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Periplakin (PPL).	[26]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Periplakin (PPL).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Periplakin (PPL).	[28]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Periplakin (PPL).	[29]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Periplakin (PPL).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Periplakin (PPL).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Periplakin (PPL).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Periplakin (PPL).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Periplakin (PPL).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Periplakin (PPL).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Periplakin (PPL).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Periplakin (PPL).	[39]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Periplakin (PPL).	[40]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Periplakin (PPL).	[32]

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 decreases the methylation of Periplakin (PPL).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Periplakin (PPL).	[35]

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