cd06960

DNA-binding domain of heptocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers

CDD entry
Member databaseCDD
CDD typedomain
Short nameNR_DBD_HNF4A
SetNR_DBD_like

Description

DNA-binding domain of hepatocyte nuclear factor 4 (HNF4) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. HNF4 interacts with a DNA site, composed of two direct repeats of AGTTCA with 1 bp spacer, which is upstream of target genes and modulates the rate of transcriptional initiation. HNF4 is a member of the nuclear receptor superfamily. HNF4 plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. 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).
[2, 3, 6, 9, 7, 5, 4, 10, 1, 8]

References

1.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

2.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

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

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

5.Nuclear hormone receptors in C. elegans. Antebi A. WormBook 1-13, (2006). PMID: 18050471

6.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

7.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

8.DNA recognition by nuclear receptors. Claessens F, Gewirth DT. Essays Biochem. 40, 59-72, (2004). PMID: 15242339

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

10.Origins and evolutionary diversification of the nuclear receptor superfamily. Owen GI, Zelent A. Cell. Mol. Life Sci. 57, 809-27, (2000). View articlePMID: 10892345

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