Details of Drug Off-Target (DOT)

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

• DOT Name: Protein SET (SET)
• Synonyms: HLA-DR-associated protein II; Inhibitor of granzyme A-activated DNase; IGAAD; PHAPII; Phosphatase 2A inhibitor I2PP2A; I-2PP2A; Template-activating factor I; TAF-I
• Gene Name: SET
• Related Disease:
  Acute lymphocytic leukaemia
  Intellectual disability
  Advanced cancer
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Intellectual disability, autosomal dominant 58
  leukaemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Lymphoma
  Osteoarthritis
  Plasma cell myeloma
  Polycystic ovarian syndrome
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Schizophrenia
  Small lymphocytic lymphoma
  Small-cell lung cancer
  Systemic lupus erythematosus
  T-cell acute lymphoblastic leukaemia
  Triple negative breast cancer
  Wolf-Hirschhorn syndrome
  Carcinoma
  Leukemia
  Melanoma
  Neuroblastoma
  Transitional cell carcinoma
  Autosomal dominant non-syndromic intellectual disability
  Alzheimer disease
  Gastric cancer
  Hepatitis C virus infection
  Neoplasm
  Non-small-cell lung cancer
  Pancreatic cancer
  Squamous cell carcinoma
  Stomach cancer
• UniProt ID: SET_HUMAN
• PDB ID: 2E50; 7MTO
• Pfam ID: PF00956
• Sequence:
  MAPKRQSPLPPQKKKPRPPPALGPEETSASAGLPKKGEKEQQEAIEHIDEVQNEIDRLNE
  QASEEILKVEQKYNKLRQPFFQKRSELIAKIPNFWVTTFVNHPQVSALLGEEDEEALHYL
  TRVEVTEFEDIKSGYRIDFYFDENPYFENKVLSKEFHLNESGDPSSKSTEIKWKSGKDLT
  KRSSQTQNKASRKRQHEEPESFFTWFTDHSDAGADELGEVIKDDIWPNPLQYYLVPDMDD
  EEGEGEEDDDDDEEEEGLEDIDEEGDEDEGEEDEDDDEGEEGEEDEGEDD
• Function: Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher.
• Tissue Specificity: Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.
• Reactome Pathway:
  HuR (ELAVL1) binds and stabilizes mRNA (R-HSA-450520)
  Condensation of Prophase Chromosomes (R-HSA-2299718)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Altered Expression	[1]
Intellectual disability	DISMBNXP	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Intellectual disability, autosomal dominant 58	DISK02XR	Strong	Autosomal dominant	[11]
leukaemia	DISS7D1V	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[15]
Lymphoma	DISN6V4S	Strong	Altered Expression	[16]
Osteoarthritis	DIS05URM	Strong	Posttranslational Modification	[17]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[18]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[19]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[4]
Schizophrenia	DISSRV2N	Strong	Biomarker	[23]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[24]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[26]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	FusionGene	[27]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[28]
Wolf-Hirschhorn syndrome	DISE4WMQ	Strong	Biomarker	[29]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[30]
Leukemia	DISNAKFL	moderate	Biomarker	[12]
Melanoma	DIS1RRCY	moderate	Altered Expression	[31]
Neuroblastoma	DISVZBI4	moderate	Genetic Variation	[32]
Transitional cell carcinoma	DISWVVDR	moderate	Biomarker	[33]
Autosomal dominant non-syndromic intellectual disability	DISD6L06	Supportive	Autosomal dominant	[34]
Alzheimer disease	DISF8S70	Limited	Biomarker	[35]
Gastric cancer	DISXGOUK	Limited	Biomarker	[36]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[37]
Neoplasm	DISZKGEW	Limited	Altered Expression	[38]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[13]
Pancreatic cancer	DISJC981	Limited	Biomarker	[39]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[40]
Stomach cancer	DISKIJSX	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Protein SET (SET) increases the response to substance of Cisplatin.	[62]

22 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 Protein SET (SET).	[41]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SET (SET).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein SET (SET).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Protein SET (SET).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein SET (SET).	[46]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Protein SET (SET).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein SET (SET).	[48]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein SET (SET).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein SET (SET).	[50]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Protein SET (SET).	[51]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Protein SET (SET).	[52]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of Protein SET (SET).	[53]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Protein SET (SET).	[53]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein SET (SET).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Protein SET (SET).	[55]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Protein SET (SET).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein SET (SET).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein SET (SET).	[51]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Protein SET (SET).	[58]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Protein SET (SET).	[59]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Protein SET (SET).	[60]
9-hydroxyoctadecadienoic acid	DM0FWNJ	Investigative	9-hydroxyoctadecadienoic acid decreases the expression of Protein SET (SET).	[61]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the localization of Protein SET (SET).	[45]
Afatinib	DMTKD7Q	Approved	Afatinib affects the localization of Protein SET (SET).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde affects the localization of Protein SET (SET).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein SET (SET).	[57]

References

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