Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD1RZAD)

• DOT Name: Nucleosome-remodeling factor subunit BPTF (BPTF)
• Synonyms: Bromodomain and PHD finger-containing transcription factor; Fetal Alz-50 clone 1 protein; Fetal Alzheimer antigen
• Gene Name: BPTF
• Related Disease:
  Lung adenocarcinoma
  Syndromic intellectual disability
  Acute megakaryoblastic leukemia
  Alzheimer disease
  Bladder cancer
  Breast neoplasm
  Cataract
  Childhood acute megakaryoblastic leukemia
  Chronic diarrhoea
  Colorectal carcinoma
  Constipation
  Cystic fibrosis
  Esophageal squamous cell carcinoma
  Exocrine pancreatic insufficiency
  Glioma
  Hepatocellular carcinoma
  Intellectual disability
  Lung cancer
  Microcephaly
  Myopia
  Neoplasm
  Neurodevelopmental disorder
  Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies
  Non-small-cell lung cancer
  Patent ductus arteriosus
  Telecanthus
  Urinary bladder cancer
  Urinary bladder neoplasm
  Endometrial carcinoma
  Isolated congenital microcephaly
  Neuroblastoma
  Advanced cancer
  Kennedy disease
  Melanoma
  Psoriasis
• UniProt ID: BPTF_HUMAN
• PDB ID: 2F6J ; 2F6N ; 2FSA ; 2FUI ; 2FUU ; 2RI7 ; 3QZS ; 3QZT ; 3QZV ; 3UV2 ; 5H6Y ; 5R4G ; 5R4H ; 5R4I ; 5R4J ; 5R4K ; 5R4L ; 5R4M ; 5R4N ; 5R4O ; 6AZE ; 6LU5 ; 6LU6 ; 7DMY ; 7DN4 ; 7F5D ; 7F5E ; 7JT4 ; 7K6R ; 7K6S ; 7KDW ; 7KDZ ; 7LP0 ; 7LPK ; 7LRK ; 7LRO ; 7M2E ; 7RWN ; 7RWO ; 7RWP ; 7RWQ ; 7VD4 ; 8AG2
• Pfam ID: PF00439 ; PF02791 ; PF00628 ; PF15613
• Sequence:
  MRGRRGRPPKQPAAPAAERCAPAPPPPPPPPTSGPIGGLRSRHRGSSRGRWAAAQAEVAP
  KTRLSSPRGGSSSRRKPPPPPPAPPSTSAPGRGGRGGGGGRTGGGGGGGHLARTTAARRA
  VNKVVYDDHESEEEEEEEDMVSEEEEEEDGDAEETQDSEDDEEDEMEEDDDDSDYPEEME
  DDDDDASYCTESSFRSHSTYSSTPGRRKPRVHRPRSPILEEKDIPPLEFPKSSEDLMVPN
  EHIMNVIAIYEVLRNFGTVLRLSPFRFEDFCAALVSQEQCTLMAEMHVVLLKAVLREEDT
  SNTTFGPADLKDSVNSTLYFIDGMTWPEVLRVYCESDKEYHHVLPYQEAEDYPYGPVENK
  IKVLQFLVDQFLTTNIAREELMSEGVIQYDDHCRVCHKLGDLLCCETCSAVYHLECVKPP
  LEEVPEDEWQCEVCVAHKVPGVTDCVAEIQKNKPYIRHEPIGYDRSRRKYWFLNRRLIIE
  EDTENENEKKIWYYSTKVQLAELIDCLDKDYWEAELCKILEEMREEIHRHMDITEDLTNK
  ARGSNKSFLAAANEEILESIRAKKGDIDNVKSPEETEKDKNETENDSKDAEKNREEFEDQ
  SLEKDSDDKTPDDDPEQGKSEEPTEVGDKGNSVSANLGDNTTNATSEETSPSEGRSPVGC
  LSETPDSSNMAEKKVASELPQDVPEEPNKTCESSNTSATTTSIQPNLENSNSSSELNSSQ
  SESAKAADDPENGERESHTPVSIQEEIVGDFKSEKSNGELSESPGAGKGASGSTRIITRL
  RNPDSKLSQLKSQQVAAAAHEANKLFKEGKEVLVVNSQGEISRLSTKKEVIMKGNINNYF
  KLGQEGKYRVYHNQYSTNSFALNKHQHREDHDKRRHLAHKFCLTPAGEFKWNGSVHGSKV
  LTISTLRLTITQLENNIPSSFLHPNWASHRANWIKAVQMCSKPREFALALAILECAVKPV
  VMLPIWRESLGHTRLHRMTSIEREEKEKVKKKEKKQEEEETMQQATWVKYTFPVKHQVWK
  QKGEEYRVTGYGGWSWISKTHVYRFVPKLPGNTNVNYRKSLEGTKNNMDENMDESDKRKC
  SRSPKKIKIEPDSEKDEVKGSDAAKGADQNEMDISKITEKKDQDVKELLDSDSDKPCKEE
  PMEVDDDMKTESHVNCQESSQVDVVNVSEGFHLRTSYKKKTKSSKLDGLLERRIKQFTLE
  EKQRLEKIKLEGGIKGIGKTSTNSSKNLSESPVITKAKEGCQSDSMRQEQSPNANNDQPE
  DLIQGCSESDSSVLRMSDPSHTTNKLYPKDRVLDDVSIRSPETKCPKQNSIENDIEEKVS
  DLASRGQEPSKSKTKGNDFFIDDSKLASADDIGTLICKNKKPLIQEESDTIVSSSKSALH
  SSVPKSTNDRDATPLSRAMDFEGKLGCDSESNSTLENSSDTVSIQDSSEEDMIVQNSNES
  ISEQFRTREQDVEVLEPLKCELVSGESTGNCEDRLPVKGTEANGKKPSQQKKLEERPVNK
  CSDQIKLKNTTDKKNNENRESEKKGQRTSTFQINGKDNKPKIYLKGECLKEISESRVVSG
  NVEPKVNNINKIIPENDIKSLTVKESAIRPFINGDVIMEDFNERNSSETKSHLLSSSDAE
  GNYRDSLETLPSTKESDSTQTTTPSASCPESNSVNQVEDMEIETSEVKKVTSSPITSEEE
  SNLSNDFIDENGLPINKNENVNGESKRKTVITEVTTMTSTVATESKTVIKVEKGDKQTVV
  SSTENCAKSTVTTTTTTVTKLSTPSTGGSVDIISVKEQSKTVVTTTVTDSLTTTGGTLVT
  SMTVSKEYSTRDKVKLMKFSRPKKTRSGTALPSYRKFVTKSSKKSIFVLPNDDLKKLARK
  GGIREVPYFNYNAKPALDIWPYPSPRPTFGITWRYRLQTVKSLAGVSLMLRLLWASLRWD
  DMAAKAPPGGGTTRTETSETEITTTEIIKRRDVGPYGIRSEYCIRKIICPIGVPETPKET
  PTPQRKGLRSSALRPKRPETPKQTGPVIIETWVAEEELELWEIRAFAERVEKEKAQAVEQ
  QAKKRLEQQKPTVIATSTTSPTSSTTSTISPAQKVMVAPISGSVTTGTKMVLTTKVGSPA
  TVTFQQNKNFHQTFATWVKQGQSNSGVVQVQQKVLGIIPSSTGTSQQTFTSFQPRTATVT
  IRPNTSGSGGTTSNSQVITGPQIRPGMTVIRTPLQQSTLGKAIIRTPVMVQPGAPQQVMT
  QIIRGQPVSTAVSAPNTVSSTPGQKSLTSATSTSNIQSSASQPPRPQQGQVKLTMAQLTQ
  LTQGHGGNQGLTVVIQGQGQTTGQLQLIPQGVTVLPGPGQQLMQAAMPNGTVQRFLFTPL
  ATTATTASTTTTTVSTTAAGTGEQRQSKLSPQMQVHQDKTLPPAQSSSVGPAEAQPQTAQ
  PSAQPQPQTQPQSPAQPEVQTQPEVQTQTTVSSHVPSEAQPTHAQSSKPQVAAQSQPQSN
  VQGQSPVRVQSPSQTRIRPSTPSQLSPGQQSQVQTTTSQPIPIQPHTSLQIPSQGQPQSQ
  PQVQSSTQTLSSGQTLNQVTVSSPSRPQLQIQQPQPQVIAVPQLQQQVQVLSQIQSQVVA
  QIQAQQSGVPQQIKLQLPIQIQQSSAVQTHQIQNVVTVQAASVQEQLQRVQQLRDQQQKK
  KQQQIEIKREHTLQASNQSEIIQKQVVMKHNAVIEHLKQKKSMTPAEREENQRMIVCNQV
  MKYILDKIDKEEKQAAKKRKREESVEQKRSKQNATKLSALLFKHKEQLRAEILKKRALLD
  KDLQIEVQEELKRDLKIKKEKDLMQLAQATAVAAPCPPVTPAPPAPPAPPPSPPPPPAVQ
  HTGLLSTPTLPAASQKRKREEEKDSSSKSKKKKMISTTSKETKKDTKLYCICKTPYDESK
  FYIGCDRCQNWYHGRCVGILQSEAELIDEYVCPQCQSTEDAMTVLTPLTEKDYEGLKRVL
  RSLQAHKMAWPFLEPVDPNDAPDYYGVIKEPMDLATMEERVQRRYYEKLTEFVADMTKIF
  DNCRYYNPSDSPFYQCAEVLESFFVQKLKGFKASRSHNNKLQSTAS
• Function: Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex. Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development. Histone-binding protein which binds to H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of active genes. Binds to histone H3 tails dimethylated on 'Lys-4' (H3K4Me2) to a lesser extent. May also regulate transcription through direct binding to DNA or transcription factors.
• Tissue Specificity: Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level).
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Syndromic intellectual disability	DISH7SDF	Definitive	Autosomal dominant	[2]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cataract	DISUD7SL	Strong	CausalMutation	[7]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Biomarker	[3]
Chronic diarrhoea	DISH3PX3	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Constipation	DISRQXWI	Strong	CausalMutation	[7]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[10]
Exocrine pancreatic insufficiency	DISCZYU2	Strong	Genetic Variation	[7]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Intellectual disability	DISMBNXP	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Microcephaly	DIS2GRD8	Strong	Genetic Variation	[7]
Myopia	DISK5S60	Strong	CausalMutation	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[14]
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies	DIS3U21R	Strong	Autosomal dominant	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Patent ductus arteriosus	DIS9P8YS	Strong	CausalMutation	[7]
Telecanthus	DISKPIOJ	Strong	CausalMutation	[7]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Endometrial carcinoma	DISXR5CY	moderate	Genetic Variation	[17]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[7]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[18]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[19]
Kennedy disease	DISXZVM1	Limited	Biomarker	[20]
Melanoma	DIS1RRCY	Limited	Altered Expression	[21]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[22]

17 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 Nucleosome-remodeling factor subunit BPTF (BPTF).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[29]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[30]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[31]
Marinol	DM70IK5	Approved	Marinol increases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[32]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[33]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[34]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[35]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[33]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[38]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[40]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Nucleosome-remodeling factor subunit BPTF (BPTF).	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Nucleosome-remodeling factor subunit BPTF (BPTF).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nucleosome-remodeling factor subunit BPTF (BPTF).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Nucleosome-remodeling factor subunit BPTF (BPTF).	[39]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Nucleosome-remodeling factor subunit BPTF (BPTF).	[37]

References

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• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
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• [4] Fetal Alz-50 clone 1 (FAC1) protein interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity.Biochemistry. 2000 Mar 28;39(12):3206-15. doi: 10.1021/bi992211q.
• [5] Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31-5p/RAB27A axis.Aging (Albany NY). 2018 Aug 9;10(8):1964-1976. doi: 10.18632/aging.101520.
• [6] Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes.Nat Commun. 2019 Jul 5;10(1):2983. doi: 10.1038/s41467-019-11020-3.
• [7] Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. Am J Hum Genet. 2017 Oct 5;101(4):503-515. doi: 10.1016/j.ajhg.2017.08.014. Epub 2017 Sep 21.
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• [11] Bromodomain PHDfinger transcription factor promotes glioma progression and indicates poor prognosis.Oncol Rep. 2019 Jan;41(1):246-256. doi: 10.3892/or.2018.6832. Epub 2018 Oct 30.
• [12] BPTF promotes hepatocellular carcinoma growth by modulating hTERT signaling and cancer stem cell traits.Redox Biol. 2019 Jan;20:427-441. doi: 10.1016/j.redox.2018.10.018. Epub 2018 Oct 25.
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• [17] Identification of nine new susceptibility loci for endometrial cancer.Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7.
• [18] DNA binding activity of the fetal Alz-50 clone 1 (FAC1) protein is enhanced by phosphorylation.Biochem Biophys Res Commun. 1999 Jul 14;260(3):785-9. doi: 10.1006/bbrc.1999.0986.
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• [37] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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