Details of Drug Off-Target (DOT)

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

• DOT Name: PCNA-associated factor (PCLAF)
• Synonyms: Hepatitis C virus NS5A-transactivated protein 9; HCV NS5A-transactivated protein 9; Overexpressed in anaplastic thyroid carcinoma 1; OEATC-1; PCNA-associated factor of 15 kDa; PAF15; p15PAF; PCNA-clamp-associated factor
• Gene Name: PCLAF
• Related Disease:
  Gastric cancer
  Stomach cancer
  Adult glioblastoma
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Carcinoma of liver and intrahepatic biliary tract
  Cardiovascular disease
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Liver cancer
  Lung cancer
  Lung carcinoma
  Melanoma
  Neoplasm of esophagus
  Neuroblastoma
  Ovarian cancer
  Ovarian neoplasm
  Psoriasis
  Pulmonary fibrosis
  Renal carcinoma
  Renal cell carcinoma
  Schizophrenia
  Thyroid tumor
  Breast cancer
  Breast carcinoma
  leukaemia
  Leukemia
  Rheumatoid arthritis
  Adenocarcinoma
  Atrial fibrillation
  Coronary atherosclerosis
  Coronary heart disease
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
• UniProt ID: PAF15_HUMAN
• PDB ID: 4D2G; 6EHT; 6GWS; 6IIW
• Pfam ID: PF15715
• Sequence:
  MVRTKADSVPGTYRKVVAARAPRKVLGSSTSATNSTSVSSRKAENKYAGGNPVCVRPTPK
  WQKGIGEFFRLSPKDSEKENQIPEEAGSSGLGKAKRKACPLQPDHTNDEKE
• Function: PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number.
• Tissue Specificity: Expressed predominantly in liver, pancreas and placenta. Not detected in heart or brain. Highly expressed in a number of tumors, especially esophageal tumors, in anaplastic thyroid carcinomas, adrenocortical carcinomas, and in non-small-cell lung cancer lines.
• Reactome Pathway: Termination of translesion DNA synthesis (R-HSA-5656169)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Genetic Variation	[8]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Psoriasis	DIS59VMN	Strong	Biomarker	[19]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[20]
Renal carcinoma	DISER9XT	Strong	Altered Expression	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[10]
Schizophrenia	DISSRV2N	Strong	Biomarker	[21]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[22]
Breast cancer	DIS7DPX1	moderate	Biomarker	[23]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[23]
leukaemia	DISS7D1V	moderate	Biomarker	[24]
Leukemia	DISNAKFL	moderate	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	Disputed	Biomarker	[25]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[26]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[27]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[28]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[28]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[26]
Prostate cancer	DISF190Y	Limited	Biomarker	[29]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[29]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of PCNA-associated factor (PCLAF).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PCNA-associated factor (PCLAF).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PCNA-associated factor (PCLAF).	[33]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PCNA-associated factor (PCLAF).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of PCNA-associated factor (PCLAF).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PCNA-associated factor (PCLAF).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PCNA-associated factor (PCLAF).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of PCNA-associated factor (PCLAF).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of PCNA-associated factor (PCLAF).	[38]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of PCNA-associated factor (PCLAF).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of PCNA-associated factor (PCLAF).	[40]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of PCNA-associated factor (PCLAF).	[41]
Marinol	DM70IK5	Approved	Marinol decreases the expression of PCNA-associated factor (PCLAF).	[42]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of PCNA-associated factor (PCLAF).	[43]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of PCNA-associated factor (PCLAF).	[44]
Menadione	DMSJDTY	Approved	Menadione affects the expression of PCNA-associated factor (PCLAF).	[45]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of PCNA-associated factor (PCLAF).	[46]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of PCNA-associated factor (PCLAF).	[47]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of PCNA-associated factor (PCLAF).	[48]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of PCNA-associated factor (PCLAF).	[49]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of PCNA-associated factor (PCLAF).	[50]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of PCNA-associated factor (PCLAF).	[51]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of PCNA-associated factor (PCLAF).	[52]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the expression of PCNA-associated factor (PCLAF).	[53]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of PCNA-associated factor (PCLAF).	[54]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of PCNA-associated factor (PCLAF).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of PCNA-associated factor (PCLAF).	[56]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of PCNA-associated factor (PCLAF).	[57]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of PCNA-associated factor (PCLAF).	[47]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of PCNA-associated factor (PCLAF).	[58]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of PCNA-associated factor (PCLAF).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PCNA-associated factor (PCLAF).	[60]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PCNA-associated factor (PCLAF).	[61]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of PCNA-associated factor (PCLAF).	[63]
NS398	DMINUWH	Terminated	NS398 decreases the expression of PCNA-associated factor (PCLAF).	[64]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PCNA-associated factor (PCLAF).	[65]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of PCNA-associated factor (PCLAF).	[55]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of PCNA-associated factor (PCLAF).	[66]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of PCNA-associated factor (PCLAF).	[67]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of PCNA-associated factor (PCLAF).	[68]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PCNA-associated factor (PCLAF).	[62]

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