Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4XVRRF)

• DOT Name: E3 SUMO-protein ligase CBX4 (CBX4)
• Synonyms: EC 2.3.2.-; Chromobox protein homolog 4; Polycomb 2 homolog; Pc2; hPc2
• Gene Name: CBX4
• Related Disease:
  Hepatocellular carcinoma
  Benign prostatic hyperplasia
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Familial prostate carcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Pheochromocytoma
  Pure red-cell aplasia
  Small-cell lung cancer
  Benign neoplasm
  Cervical carcinoma
  Gastric cancer
  Stomach cancer
  Autosomal dominant polycystic kidney disease
  Hereditary chronic pancreatitis
  Metastatic malignant neoplasm
  Osteoarthritis
• UniProt ID: CBX4_HUMAN
• PDB ID: 2K28; 3I8Z; 5EPL
• EC Number: 2.3.2.-
• Pfam ID: PF17218 ; PF00385
• Sequence:
  MELPAVGEHVFAVESIEKKRIRKGRVEYLVKWRGWSPKYNTWEPEENILDPRLLIAFQNR
  ERQEQLMGYRKRGPKPKPLVVQVPTFARRSNVLTGLQDSSTDNRAKLDLGAQGKGQGHQY
  ELNSKKHHQYQPHSKERAGKPPPPGKSGKYYYQLNSKKHHPYQPDPKMYDLQYQGGHKEA
  PSPTCPDLGAKSHPPDKWAQGAGAKGYLGAVKPLAGAAGAPGKGSEKGPPNGMMPAPKEA
  VTGNGIGGKMKIVKNKNKNGRIVIVMSKYMENGMQAVKIKSGEVAEGEARSPSHKKRAAD
  ERHPPADRTFKKAAGAEEKKVEAPPKRREEEVSGVSDPQPQDAGSRKLSPTKEAFGEQPL
  QLTTKPDLLAWDPARNTHPPSHHPHPHPHHHHHHHHHHHHAVGLNLSHVRKRCLSETHGE
  REPCKKRLTARSISTPTCLGGSPAAERPADLPPAAALPQPEVILLDSDLDEPIDLRCVKT
  RSEAGEPPSSLQVKPETPASAAVAVAAAAAPTTTAEKPPAEAQDEPAESLSEFKPFFGNI
  IITDVTANCLTVTFKEYVTV
• Function: E3 SUMO-protein ligase which facilitates SUMO1 conjugation by UBE2I. Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression. Monosumoylates ZNF131 ; Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3). Plays a role in the lineage differentiation of the germ layers in embryonic development.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway:
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA methylation proteins (R-HSA-4655427)
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[2]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Familial prostate carcinoma	DISL9KNO	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[3]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[9]
Pure red-cell aplasia	DIST91OT	Strong	Genetic Variation	[10]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[8]
Benign neoplasm	DISDUXAD	moderate	Genetic Variation	[2]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[11]
Gastric cancer	DISXGOUK	moderate	Genetic Variation	[12]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[12]
Autosomal dominant polycystic kidney disease	DISBHWUI	Limited	Biomarker	[13]
Hereditary chronic pancreatitis	DISF0J1Q	Limited	Genetic Variation	[10]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[14]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of E3 SUMO-protein ligase CBX4 (CBX4).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of E3 SUMO-protein ligase CBX4 (CBX4).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the sumoylation of E3 SUMO-protein ligase CBX4 (CBX4).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of E3 SUMO-protein ligase CBX4 (CBX4).	[28]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of E3 SUMO-protein ligase CBX4 (CBX4).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[24]
Menthol	DMG2KW7	Approved	Menthol increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[25]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[27]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[34]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[35]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of E3 SUMO-protein ligase CBX4 (CBX4).	[36]

References

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