D
IPR049635

Hepatocyte nuclear factor 4, ligand-binding domain

InterPro entry
Short nameHNF4_LBD
Overlapping
homologous
superfamilies
 
domain relationships

Description

This entry represents the LBD domain, which is also responsible for recruiting co-activator proteins
[1, 2, 3]
.

HNF4 is a member of the nuclear receptor superfamily and plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is a transcriptional regulator that controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes
[5]
. Additionally, it plays an essential role in circadian rhythm maintenance and period regulation in the liver and colon cells
[4]
. It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD)
[1, 2, 3]
.

References

1.Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids. Wisely GB, Miller AB, Davis RG, Thornquest AD Jr, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, Willson TM, Williams SP. Structure 10, 1225-34, (2002). View articlePMID: 12220494

2.[Hepatocyte nuclear factor 4 (HNF4) in epithelial development and carcinogenesis] Lazarevich NL, Al'pern DV. Mol Biol (Mosk) 42, 786-97, (2008). PMID: 18988528

3.Explosive lineage-specific expansion of the orphan nuclear receptor HNF4 in nematodes. Robinson-Rechavi M, Maina CV, Gissendanner CR, Laudet V, Sluder A. J Mol Evol 60, 577-86, (2005). PMID: 15983867

4.Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks. Qu M, Duffy T, Hirota T, Kay SA. Proc. Natl. Acad. Sci. U.S.A. 115, E12305-E12312, (2018). PMID: 30530698

5.HNF4A Regulates the Formation of Hepatic Progenitor Cells from Human iPSC-Derived Endoderm by Facilitating Efficient Recruitment of RNA Pol II. DeLaForest A, Di Furio F, Jing R, Ludwig-Kubinski A, Twaroski K, Urick A, Pulakanti K, Rao S, Duncan SA. Genes (Basel) 10, E21, (2018). View articlePMID: 30597922

Further reading

6. Expression and function of conserved nuclear receptor genes in Caenorhabditis elegans. Gissendanner CR, Crossgrove K, Kraus KA, Maina CV, Sluder AE. Dev Biol 266, 399-416, (2004). PMID: 14738886

7. Caenorhabditis elegans nuclear receptors: insights into life traits. Magner DB, Antebi A. Trends Endocrinol Metab 19, 153-60, (2008). PMID: 18406164

8. The evolution of the nuclear receptor superfamily. Escriva H, Bertrand S, Laudet V. Essays Biochem. 40, 11-26, (2004). View articlePMID: 15242336

9. Principles for modulation of the nuclear receptor superfamily. Gronemeyer H, Gustafsson JA, Laudet V. Nat Rev Drug Discov 3, 950-64, (2004). View articlePMID: 15520817

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