Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTKF0XS)

• DTT Name: Estrogen-related receptor-beta (ESRRB)
• Synonyms: Steroid hormone receptor ERR2; Nuclear receptor subfamily 3 group B member 2; NR3B2; Estrogen-related receptor beta; Estrogen receptor-like 2; ESRL2; ERRB2; ERR-beta; ERR beta-2
• Gene Name: ESRRB
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: ERR2_HUMAN
• TTD ID: T42025
• Sequence:
  MSSDDRHLGSSCGSFIKTEPSSPSSGIDALSHHSPSGSSDASGGFGLALGTHANGLDSPP
  MFAGAGLGGTPCRKSYEDCASGIMEDSAIKCEYMLNAIPKRLCLVCGDIASGYHYGVASC
  EACKAFFKRTIQGNIEYSCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRG
  GRQKYKRRLDSESSPYLSLQISPPAKKPLTKIVSYLLVAEPDKLYAMPPPGMPEGDIKAL
  TTLCDLADRELVVIIGWAKHIPGFSSLSLGDQMSLLQSAWMEILILGIVYRSLPYDDKLV
  YAEDYIMDEEHSRLAGLLELYRAILQLVRRYKKLKVEKEEFVTLKALALANSDSMYIEDL
  EAVQKLQDLLHEALQDYELSQRHEEPWRTGKLLLTLPLLRQTAAKAVQHFYSVKLQGKVP
  MHKLFLEMLEAKV
• Function: Isoform 3: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1. Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity. During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity).
• KEGG Pathway: Signaling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DTT

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
biochanin A	DM0HPWY	Discovery agent	N.A.	Investigative	[2]
daidzein	DMRFTJX	Discovery agent	N.A.	Investigative	[2]
DY131	DMFJ3VC	Discovery agent	N.A.	Investigative	[1]

References

• [1] Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma. Bioorg Med Chem Lett. 2005 Mar 1;15(5):1311-3.
• [2] Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res. 2003 Nov;1(13):981-91.