Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NLZ9D)

• DOT Name: Protein phosphatase 1D (PPM1D)
• Synonyms: EC 3.1.3.16; Protein phosphatase 2C isoform delta; PP2C-delta; Protein phosphatase magnesium-dependent 1 delta; p53-induced protein phosphatase 1
• Gene Name: PPM1D
• Related Disease:
  Syndromic intellectual disability
  Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold
  Hereditary breast carcinoma
• UniProt ID: PPM1D_HUMAN
• EC Number: 3.1.3.16
• Pfam ID: PF00481
• Sequence:
  MAGLYSLGVSVFSDQGGRKYMEDVTQIVVEPEPTAEEKPSPRRSLSQPLPPRPSPAALPG
  GEVSGKGPAVAAREARDPLPDAGASPAPSRCCRRRSSVAFFAVCDGHGGREAAQFAREHL
  WGFIKKQKGFTSSEPAKVCAAIRKGFLACHLAMWKKLAEWPKTMTGLPSTSGTTASVVII
  RGMKMYVAHVGDSGVVLGIQDDPKDDFVRAVEVTQDHKPELPKERERIEGLGGSVMNKSG
  VNRVVWKRPRLTHNGPVRRSTVIDQIPFLAVARALGDLWSYDFFSGEFVVSPEPDTSVHT
  LDPQKHKYIILGSDGLWNMIPPQDAISMCQDQEEKKYLMGEHGQSCAKMLVNRALGRWRQ
  RMLRADNTSAIVICISPEVDNQGNFTNEDELYLNLTDSPSYNSQETCVMTPSPCSTPPVK
  SLEEDPWPRVNSKDHIPALVRSNAFSENFLEVSAEIARENVQGVVIPSKDPEPLEENCAK
  ALTLRIHDSLNNSLPIGLVPTNSTNTVMDQKNLKMSTPGQMKAQEIERTPPTNFKRTLEE
  SNSGPLMKKHRRNGLSRSSGAQPASLPTTSQRKNSVKLTMRRRLRGQKKIGNPLLHQHRK
  TVCVC
• Function: Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. Mediates MAPK14 dephosphorylation and inactivation. Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity.
• Tissue Specificity: Expressed in fetal and adult brain. Also detected in fetal liver and skeletal muscle, but not in their adult counterparts.
• KEGG Pathway: p53 sig.ling pathway (hsa04115)
• Reactome Pathway: Transcriptional regulation by RUNX2 (R-HSA-8878166)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal dominant	[1]
Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold	DISHX5R0	Strong	Autosomal dominant	[2]
Hereditary breast carcinoma	DISAEZT5	Disputed	Autosomal dominant	[3]

35 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 Protein phosphatase 1D (PPM1D).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein phosphatase 1D (PPM1D).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein phosphatase 1D (PPM1D).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase 1D (PPM1D).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein phosphatase 1D (PPM1D).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein phosphatase 1D (PPM1D).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein phosphatase 1D (PPM1D).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein phosphatase 1D (PPM1D).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Protein phosphatase 1D (PPM1D).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein phosphatase 1D (PPM1D).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein phosphatase 1D (PPM1D).	[15]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Protein phosphatase 1D (PPM1D).	[13]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Protein phosphatase 1D (PPM1D).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Protein phosphatase 1D (PPM1D).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Protein phosphatase 1D (PPM1D).	[17]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Protein phosphatase 1D (PPM1D).	[18]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Protein phosphatase 1D (PPM1D).	[19]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Protein phosphatase 1D (PPM1D).	[20]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Protein phosphatase 1D (PPM1D).	[21]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Protein phosphatase 1D (PPM1D).	[19]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Protein phosphatase 1D (PPM1D).	[19]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Protein phosphatase 1D (PPM1D).	[22]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Protein phosphatase 1D (PPM1D).	[22]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Protein phosphatase 1D (PPM1D).	[19]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Protein phosphatase 1D (PPM1D).	[22]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Protein phosphatase 1D (PPM1D).	[23]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein phosphatase 1D (PPM1D).	[24]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Protein phosphatase 1D (PPM1D).	[25]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Protein phosphatase 1D (PPM1D).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein phosphatase 1D (PPM1D).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein phosphatase 1D (PPM1D).	[27]
EMODIN	DMAEDQG	Terminated	EMODIN increases the expression of Protein phosphatase 1D (PPM1D).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein phosphatase 1D (PPM1D).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein phosphatase 1D (PPM1D).	[31]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein phosphatase 1D (PPM1D).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein phosphatase 1D (PPM1D).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein phosphatase 1D (PPM1D).	[28]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein phosphatase 1D (PPM1D).	[28]

References

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