Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG3BT3M)

• DOT Name: Histone-binding protein RBBP4 (RBBP4)
• Synonyms: Chromatin assembly factor 1 subunit C; CAF-1 subunit C; Chromatin assembly factor I p48 subunit; CAF-I 48 kDa subunit; CAF-I p48; Nucleosome-remodeling factor subunit RBAP48; Retinoblastoma-binding protein 4; RBBP-4; Retinoblastoma-binding protein p48
• Gene Name: RBBP4
• Related Disease:
  Advanced cancer
  Brain cancer
  Brain neoplasm
  Breast neoplasm
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Gastric cancer
  Hepatocellular carcinoma
  HIV infectious disease
  Neoplasm
  Postmenopausal osteoporosis
  Premature aging syndrome
  Retinoblastoma
  Sjogren syndrome
  Stomach cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Adult glioblastoma
  Colon carcinoma
  Glioblastoma multiforme
  Tuberous sclerosis
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Chronic renal failure
  Colon cancer
  End-stage renal disease
  Neuroblastoma
• UniProt ID: RBBP4_HUMAN
• PDB ID: 2XU7 ; 3GFC ; 4PBY ; 4PBZ ; 4PC0 ; 4R7A ; 5FXY ; 5VTB ; 5WAI ; 5WAK ; 5XWR ; 5XXQ ; 5Y1U ; 6BW3 ; 6BW4 ; 6C23 ; 6C24 ; 6G16 ; 6NQ3 ; 6WKR ; 6ZRC ; 6ZRD ; 7AOA ; 7KSO ; 7KSR ; 7KTP ; 7M40 ; 7N40 ; 7R1D ; 7Y5K ; 7Y5L ; 7Y5O ; 7Y5U ; 7Y5V ; 8FYH ; 8IQF ; 8IQG
• Pfam ID: PF12265 ; PF00400
• Sequence:
  MADKEAAFDDAVEERVINEEYKIWKKNTPFLYDLVMTHALEWPSLTAQWLPDVTRPEGKD
  FSIHRLVLGTHTSDEQNHLVIASVQLPNDDAQFDASHYDSEKGEFGGFGSVSGKIEIEIK
  INHEGEVNRARYMPQNPCIIATKTPSSDVLVFDYTKHPSKPDPSGECNPDLRLRGHQKEG
  YGLSWNPNLSGHLLSASDDHTICLWDISAVPKEGKVVDAKTIFTGHTAVVEDVSWHLLHE
  SLFGSVADDQKLMIWDTRSNNTSKPSHSVDAHTAEVNCLSFNPYSEFILATGSADKTVAL
  WDLRNLKLKLHSFESHKDEIFQVQWSPHNETILASSGTDRRLNVWDLSKIGEEQSPEDAE
  DGPPELLFIHGGHTAKISDFSWNPNEPWVICSVSEDNIMQVWQMAENIYNDEDPEGSVDP
  EGQGS
• Function: Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.
• Tissue Specificity: Expressed in neuroblastoma cells.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Polycomb repressive complex (hsa03083)
  Cellular senescence (hsa04218)
• Reactome Pathway:
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  G0 and Early G1 (R-HSA-1538133)
  Polo-like kinase mediated events (R-HSA-156711)
  PRC2 methylates histones and DNA (R-HSA-212300)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  HDACs deacetylate histones (R-HSA-3214815)
  PKMTs methylate histone lysines (R-HSA-3214841)
  ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression (R-HSA-427389)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)
  Regulation of TP53 Activity through Acetylation (R-HSA-6804758)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A (R-HSA-69656)
  RNA Polymerase I Transcription Initiation (R-HSA-73762)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  HCMV Early Events (R-HSA-9609690)
  Potential therapeutics for SARS (R-HSA-9679191)
  Defective pyroptosis (R-HSA-9710421)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Brain cancer	DISBKFB7	Strong	Biomarker	[2]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[6]
Gastric cancer	DISXGOUK	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
HIV infectious disease	DISO97HC	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[11]
Premature aging syndrome	DIS51AGT	Strong	Biomarker	[12]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[5]
Sjogren syndrome	DISUBX7H	Strong	Altered Expression	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[7]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[4]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[4]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[4]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[14]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[15]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[14]
Tuberous sclerosis	DISEMUGZ	moderate	Altered Expression	[16]
Acute lymphocytic leukaemia	DISPX75S	Limited	Biomarker	[17]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[17]
Chronic renal failure	DISGG7K6	Limited	Altered Expression	[18]
Colon cancer	DISVC52G	Limited	Altered Expression	[15]
End-stage renal disease	DISXA7GG	Limited	Altered Expression	[18]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Sulforaphane	DMQY3L0	Investigative	Histone-binding protein RBBP4 (RBBP4) affects the binding of Sulforaphane.	[40]

2 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 Histone-binding protein RBBP4 (RBBP4).	[20]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Histone-binding protein RBBP4 (RBBP4).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone-binding protein RBBP4 (RBBP4).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Histone-binding protein RBBP4 (RBBP4).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone-binding protein RBBP4 (RBBP4).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[26]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Histone-binding protein RBBP4 (RBBP4).	[29]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[30]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Histone-binding protein RBBP4 (RBBP4).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[32]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[33]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[34]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Histone-binding protein RBBP4 (RBBP4).	[22]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Histone-binding protein RBBP4 (RBBP4).	[35]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Histone-binding protein RBBP4 (RBBP4).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[38]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Histone-binding protein RBBP4 (RBBP4).	[25]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Histone-binding protein RBBP4 (RBBP4).	[39]

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