Details of Drug Off-Target (DOT)

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

• DOT Name: Band 4.1-like protein 4A (EPB41L4A)
• Synonyms: Erythrocyte membrane protein band 4.1-like 4A; Protein NBL4
• Gene Name: EPB41L4A
• Related Disease: Thyroid gland carcinoma
• UniProt ID: E41LA_HUMAN
• Pfam ID: PF08736 ; PF09380 ; PF00373 ; PF09379
• Sequence:
  MGCFCAVPEEFYCEVLLLDESKLTLTTQQQGIKKSTKGSVVLDHVFHHVNLVEIDYFGLR
  YCDRSHQTYWLDPAKTLAEHKELINTGPPYTLYFGIKFYAEDPCKLKEEITRYQFFLQVK
  QDVLQGRLPCPVNTAAQLGAYAIQSELGDYDPYKHTAGYVSEYRFVPDQKEELEEAIERI
  HKTLMGQIPSEAELNYLRTAKSLEMYGVDLHPVYGENKSEYFLGLTPVGVVVYKNKKQVG
  KYFWPRITKVHFKETQFELRVLGKDCNETSFFFEARSKTACKHLWKCSVEHHTFFRMPEN
  ESNSLSRKLSKFGSIRYKHRYSGRTALQMSRDLSIQLPRPDQNVTRSRSKTYPKRIAQTQ
  PAESNSISRITANMENGENEGTIKIIAPSPVKSFKKAKNENSPDTQRSKSHAPWEENGPQ
  SGLYNSPSDRTKSPKFPYTRRRNPSCGSDNDSVQPVRRRKAHNSGEDSDLKQRRRSRSRC
  NTSSGSESENSNREYRKKRNRIRQENDMVDSAPQWEAVLRRQKEKNQADPNNRRSRHRSR
  SRSPDIQAKEELWKHIQKELVDPSGLSEEQLKEIPYTKIETQGDPIRIRHSHSPRSYRQY
  RRSQCSDGERSVLSEVNSKTDLVPPLPVTRSSDAQGSGDATVHQRRNGSKDSLMEEKPQT
  STNNLAGKHTAKTIKTIQASRLKTET
• Tissue Specificity: Expressed in many tissues. High levels of expression in brain, liver, thymus and peripheral blood leukocytes and low levels of expression in heart, kidney, testis and colon.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland carcinoma	DISMNGZ0	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Band 4.1-like protein 4A (EPB41L4A).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Band 4.1-like protein 4A (EPB41L4A).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Band 4.1-like protein 4A (EPB41L4A).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Band 4.1-like protein 4A (EPB41L4A).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Band 4.1-like protein 4A (EPB41L4A).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Band 4.1-like protein 4A (EPB41L4A).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Band 4.1-like protein 4A (EPB41L4A).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Band 4.1-like protein 4A (EPB41L4A).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Band 4.1-like protein 4A (EPB41L4A).	[10]

References

• [1] A genome-wide association study yields five novel thyroid cancer risk loci.Nat Commun. 2017 Feb 14;8:14517. doi: 10.1038/ncomms14517.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.