Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT812TV7)

• DOT Name: Cbp/p300-interacting transactivator 2 (CITED2)
• Synonyms: MSG-related protein 1; MRG-1; P35srj
• Gene Name: CITED2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Chronic kidney disease
  Liver cancer
  Acute myelogenous leukaemia
  Adrenocortical carcinoma
  Advanced cancer
  Benign neoplasm
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Congenital heart disease
  Estrogen-receptor positive breast cancer
  Metastatic prostate carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Obesity
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Tetralogy of fallot
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Type-1/2 diabetes
  Ulcerative colitis
  Atrial septal defect 8
  Congenital heart defects, multiple types
  Female hypogonadism
  Heart septal defect
  Neurofibromatosis type 1
  Hepatocellular carcinoma
  Intellectual disability
  Neural tube defect
  46,XY sex reversal 2
  Anxiety
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Stomach cancer
  Stroke
  Ventricular septal defect
  Ventricular septal defect 2
• UniProt ID: CITE2_HUMAN
• PDB ID: 1P4Q; 1R8U; 7LVS; 7QGS
• Pfam ID: PF04487
• Sequence:
  MADHMMAMNHGRFPDGTNGLHHHPAHRMGMGQFPSPHHHQQQQPQHAFNALMGEHIHYGA
  GNMNATSGIRHAMGPGTVNGGHPPSALAPAARFNNSQFMGPPVASQGGSLPASMQLQKLN
  NQYFNHHPYPHNHYMPDLHPAAGHQMNGTNQHFRDCNPKHSGGSSTPGGSGGSSTPGGSG
  SSSGGGAGSSNSGGGSGSGNMPASVAHVPAAMLPPNVIDTDFIDEEVLMSLVIEMGLDRI
  KELPELWLGQNEFDFMTDFVCKQQPSRVSC
• Function: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway:
  TFAP2 (AP-2) family regulates transcription of other transcription factors (R-HSA-8866906)
  Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907)
  FOXO-mediated transcription of cell death genes (R-HSA-9614657)
  Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Altered Expression	[1]
Chronic kidney disease	DISW82R7	Definitive	Altered Expression	[2]
Liver cancer	DISDE4BI	Definitive	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Adrenocortical carcinoma	DISZF4HX	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Congenital heart disease	DISQBA23	Strong	Genetic Variation	[9]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[10]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[11]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[12]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Tetralogy of fallot	DISMHFNW	Strong	Genetic Variation	[14]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[15]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[15]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[12]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[16]
Atrial septal defect 8	DIS6T8T5	Moderate	Autosomal dominant	[17]
Congenital heart defects, multiple types	DISWZRYW	Moderate	Autosomal dominant	[18]
Female hypogonadism	DISWASB4	moderate	Genetic Variation	[19]
Heart septal defect	DISQ5C5J	moderate	Genetic Variation	[20]
Neurofibromatosis type 1	DIS53JH9	moderate	Genetic Variation	[21]
Hepatocellular carcinoma	DIS0J828	Disputed	Altered Expression	[22]
Intellectual disability	DISMBNXP	Disputed	Genetic Variation	[23]
Neural tube defect	DIS5J95E	Disputed	Genetic Variation	[24]
46,XY sex reversal 2	DIS0USUN	Limited	Altered Expression	[25]
Anxiety	DISIJDBA	Limited	Biomarker	[26]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[26]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]
Stroke	DISX6UHX	Limited	Biomarker	[27]
Ventricular septal defect	DISICO41	Limited	Biomarker	[28]
Ventricular septal defect 2	DISQ692T	Limited	Unknown	[29]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Cbp/p300-interacting transactivator 2 (CITED2) decreases the response to substance of Doxorubicin.	[6]
Fluorouracil	DMUM7HZ	Approved	Cbp/p300-interacting transactivator 2 (CITED2) affects the response to substance of Fluorouracil.	[62]
Topotecan	DMP6G8T	Approved	Cbp/p300-interacting transactivator 2 (CITED2) affects the response to substance of Topotecan.	[63]

33 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 Cbp/p300-interacting transactivator 2 (CITED2).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[34]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[35]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[38]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[39]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[41]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[39]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[42]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[43]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[44]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[46]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[47]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[48]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[49]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[50]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[51]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[52]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[53]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[56]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[57]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[58]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[59]
eucalyptol	DME5CK3	Investigative	eucalyptol decreases the expression of Cbp/p300-interacting transactivator 2 (CITED2).	[60]

2 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 Cbp/p300-interacting transactivator 2 (CITED2).	[36]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cbp/p300-interacting transactivator 2 (CITED2).	[54]

References

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