Details of Drug Off-Target (DOT)

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

• DOT Name: Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B)
• Synonyms: Constitutive coactivator of PPAR-gamma; Constitutive coactivator of PPARG; PPARG constitutive coactivator 1; PGCC1; Protein FAM120B
• Gene Name: FAM120B
• Related Disease:
  Fanconi anemia complementation group A
  Fanconi's anemia
  Visceral leishmaniasis
• UniProt ID: F120B_HUMAN
• Sequence:
  MGVRGLQGFVGSTCPHICTVVNFKELAEHHRSKYPGCTPTIVVDAMCCLRYWYTPESWIC
  GGQWREYFSALRDFVKTFTAAGIKLIFFFDGMVEQDKRDEWVKRRLKNNREISRIFHYIK
  SHKEQPGRNMFFIPSGLAVFTRFALKTLGQETLCSLQEADYEVASYGLQHNCLGILGEDT
  DYLIYDTCPYFSISELCLESLDTVMLCREKLCESLGLCVADLPLLACLLGNDIIPEGMFE
  SFRYKCLSSYTSVKENFDKKGNIILAVSDHISKVLYLYQGEKKLEEILPLGPNKALFYKG
  MASYLLPGQKSPWFFQKPKGVITLDKQVISTSSDAESREEVPMCSDAESRQEVPMCTGPE
  SRREVPVYTDSEPRQEVPMCSDPEPRQEVPTCTGPESRREVPMCSDPEPRQEVPMCTGPE
  ARQEVPMYTDSEPRQEVPMYTDSEPRQEVPMYTGSEPRQEVPMYTGPESRQEVPMYTGPE
  SRQEVLIRTDPESRQEIMCTGHESKQEVPICTDPISKQEDSMCTHAEINQKLPVATDFEF
  KLEALMCTNPEIKQEDPTNVGPEVKQQVTMVSDTEILKVARTHHVQAESYLVYNIMSSGE
  IECSNTLEDELDQALPSQAFIYRPIRQRVYSLLLEDCQDVTSTCLAVKEWFVYPGNPLRH
  PDLVRPLQMTIPGGTPSLKILWLNQEPEIQVRRLDTLLACFNLSSSREELQAVESPFQAL
  CCLLIYLFVQVDTLCLEDLHAFIAQALCLQGKSTSQLVNLQPDYINPRAVQLGSLLVRGL
  TTLVLVNSACGFPWKTSDFMPWNVFDGKLFHQKYLQSEKGYAVEVLLEQNRSRLTKFHNL
  KAVVCKACMKENRRITGRAHWGSHHAGRWGRQGSSYHRTGSGYSRSSQGQPWRDQGPGSR
  QYEHDQWRRY
• Function: Functions as a transactivator of PPARG and ESR1. Functions in adipogenesis through PPARG activation.
• Tissue Specificity: Widely expressed.
• Reactome Pathway:
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group A	DIS8PZLI	Strong	Genetic Variation	[1]
Fanconi's anemia	DISGW6Q8	Strong	Genetic Variation	[1]
Visceral leishmaniasis	DISTKEYK	Disputed	Genetic Variation	[2]

2 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 Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[5]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Constitutive coactivator of peroxisome proliferator-activated receptor gamma (FAM120B).	[9]

References

• [1] A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links.Nat Commun. 2018 Jul 3;9(1):2592. doi: 10.1038/s41467-018-05008-8.
• [2] Genetic and functional evaluation of the role of DLL1 in susceptibility to visceral leishmaniasis in India.Infect Genet Evol. 2012 Aug;12(6):1195-201. doi: 10.1016/j.meegid.2012.04.017. Epub 2012 Apr 24.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.