Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9Z7EVA)

• DOT Name: Transcription initiation factor TFIID subunit 1-like (TAF1L)
• Synonyms: TAF(II)210; TBP-associated factor 1-like; TBP-associated factor 210 kDa; Transcription initiation factor TFIID 210 kDa subunit
• Gene Name: TAF1L
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Neoplasm
  Prostate cancer
  Prostate neoplasm
  Small-cell lung cancer
• UniProt ID: TAF1L_HUMAN
• PDB ID: 3HMH; 5IGL
• Pfam ID: PF00439 ; PF12157 ; PF09247 ; PF15288
• Sequence:
  MRPGCDLLLRAAATVTAAIMSDSDSEEDSSGGGPFTLAGILFGNISGAGQLEGESVLDDE
  CKKHLAGLGALGLGSLITELTANEELTGTGGALVNDEGWIRSTEDAVDYSDINEVAEDES
  QRHQQTMGSLQPLYHSDYDEDDYDADCEDIDCKLMPPPPPPPGPMKKDKDQDAITCVSES
  GEDIILPSIIAPSFLASEKVDFSSYSDSESEMGPQEATQAESEDGKLTLPLAGIMQHDAT
  KLLPSVTELFPEFRPGKVLRFLHLFGPGKNVPSVWRSARRKRKKHRELIQEEQIQEVECS
  VESEVSQKSLWNYDYAPPPPPEQCLADDEITMMVPVESKFSQSTGDVDKVTDTKPRVAEW
  RYGPARLWYDMLGVSEDGSGFDYGFKLRKTQHEPVIKSRMMEEFRKLEESNGTDLLADEN
  FLMVTQLHWEDSIIWDGEDIKHKGTKPQGASLAGWLPSIKTRNVMAYNVQQGFAPTLDDD
  KPWYSIFPIDNEDLVYGRWEDNIIWDAQAMPRLLEPPVLALDPNDENLILEIPDEKEEAT
  SNSPSKESKKESSLKKSRILLGKTGVIREEPQQNMSQPEVKDPWNLSNDEYYFPKQQGLR
  GTFGGNIIQHSIPAMELWQPFFPTHMGPIKIRQFHRPPLKKYSFGALSQPGPHSVQPLLK
  HIKKKAKMREQERQASGGGELFFMRTPQDLTGKDGDLILAEYSEENGPLMMQVGMATKIK
  NYYKRKPGKDPGAPDCKYGETVYCHTSPFLGSLHPGQLLQALENNLFRAPVYLHKMPETD
  FLIIRTRQGYYIRELVDIFVVGQQCPLFEVPGPNSRRANMHIRDFLQVFIYRLFWKSKDR
  PRRIRMEDIKKAFPSHSESSIRKRLKLCADFKRTGMDSNWWVLKSDFRLPTEEEIRAKVS
  PEQCCAYYSMIAAKQRLKDAGYGEKSFFAPEEENEEDFQMKIDDEVHAAPWNTTRAFIAA
  MKGKCLLEVTGVADPTGCGEGFSYVKIPNKPTQQKDDKEPQAVKKTVTGTDADLRRLSLK
  NAKQLLRKFGVPEEEIKKLSRWEVIDVVRTMSTEQAHSGEGPMSKFARGSRFSVAEHQER
  YKEECQRIFDLQNKVLSSTEVLSTDTDSISAEDSDFEEMGKNIENMLQNKKTSSQLSREW
  EEQERKELRRMLLVAGSAASGNNHRDDVTASMTSLKSSATGHCLKIYRTFRDEEGKEYVR
  CETVRKPAVIDAYVRIRTTKDEKFIQKFALFDEKHREEMRKERRRIQEQLRRLKRNQEKE
  KLKGPPEKKPKKMKERPDLKLKCGACGAIGHMRTNKFCPLYYQTNVPPSKPVAMTEEQEE
  ELEKTVIHNDNEELIKVEGTKIVFGKQLIENVHEVRRKSLVLKFPKQQLPPKKKRRVGTT
  VHCDYLNIPHKSIHRRRTDPMVTLSSILESIINDMRDLPNTHPFHTPVNAKVVKDYYKII
  TRPMDLQTLRENVRKCLYPSREEFREHLELIVKNSATYNGPKHSLTQISQSMLDLCDEKL
  KEKEDKLARLEKAINPLLDDDDQVAFSFILDNIVTQKMMAVPDSWPFHHPVNKKFVPDYY
  KMIVNPVDLETIRKNISKHKYQSRESFLDDVNLILANSVKYNGPESQYTKTAQEIVNICY
  QTITEYDEHLTQLEKDICTAKEAALEEAELESLDPMTPGPYTSQPPDMYDTNTSLSTSRD
  ASVFQDESNLSVLDISTATPEKQMCQGQGRLGEEDSDVDVEGYDDEEEDGKPKPPAPEGG
  DGDLADEEEGTVQQPEASVLYEDLLISEGEDDEEDAGSDEEGDNPFSAIQLSESGSDSDV
  GYGGIRPKQPFMLQHASGEHKDGHGK
• Function: May act as a functional substitute for TAF1/TAFII250 during male meiosis, when sex chromosomes are transcriptionally silenced.
• Tissue Specificity: Testis specific, expressed apparently in germ cells.
• KEGG Pathway: Basal transcription factors (hsa03022)
• Reactome Pathway:
  RNA Polymerase II HIV Promoter Escape (R-HSA-167162)
  Transcription of the HIV genome (R-HSA-167172)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  RNA Polymerase II Promoter Escape (R-HSA-73776)
  RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779)
  RNA Polymerase II Transcription Initiation (R-HSA-75953)
  RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042)
  HIV Transcription Initiation (R-HSA-167161)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Small-cell lung cancer	DISK3LZD	Limited	Genetic Variation	[3]

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 Transcription initiation factor TFIID subunit 1-like (TAF1L).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Transcription initiation factor TFIID subunit 1-like (TAF1L).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription initiation factor TFIID subunit 1-like (TAF1L).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transcription initiation factor TFIID subunit 1-like (TAF1L).	[7]

References

• [1] Frameshift Mutations in the Mononucleotide Repeats of TAF1 and TAF1L Genes in Gastric and Colorectal Cancers with Regional Heterogeneity.Pathol Oncol Res. 2017 Jan;23(1):125-130. doi: 10.1007/s12253-016-0107-0. Epub 2016 Aug 29.
• [2] The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
• [3] Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.Clin Cancer Res. 2018 Apr 1;24(7):1691-1704. doi: 10.1158/1078-0432.CCR-17-0252. Epub 2018 Jan 19.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.