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Structural highlights

Disease

[HNF4A_HUMAN] Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:125850]; also symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.^{[1] [2] [3]}

Function

[HNF4A_HUMAN] Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine. [PA2G4_HUMAN] May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site) (By similarity).^{[4] [5] [6] [7]}

References

1. ↑ Furuta H, Iwasaki N, Oda N, Hinokio Y, Horikawa Y, Yamagata K, Yano N, Sugahiro J, Ogata M, Ohgawara H, Omori Y, Iwamoto Y, Bell GI. Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. Diabetes. 1997 Oct;46(10):1652-7. PMID:9313765
2. ↑ Bulman MP, Dronsfield MJ, Frayling T, Appleton M, Bain SC, Ellard S, Hattersley AT. A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young. Diabetologia. 1997 Jul;40(7):859-62. PMID:9243109
3. ↑ Hani EH, Suaud L, Boutin P, Chevre JC, Durand E, Philippi A, Demenais F, Vionnet N, Furuta H, Velho G, Bell GI, Laine B, Froguel P. A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus. J Clin Invest. 1998 Feb 1;101(3):521-6. PMID:9449683 doi:10.1172/JCI1403
4. ↑ Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW. Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation. J Cell Physiol. 2001 May;187(2):209-17. PMID:11268000 doi:http://dx.doi.org/10.1002/jcp.1075
5. ↑ Zhang Y, Woodford N, Xia X, Hamburger AW. Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases. Nucleic Acids Res. 2003 Apr 15;31(8):2168-77. PMID:12682367
6. ↑ Squatrito M, Mancino M, Donzelli M, Areces LB, Draetta GF. EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes. Oncogene. 2004 May 27;23(25):4454-65. PMID:15064750 doi:http://dx.doi.org/10.1038/sj.onc.1207579
7. ↑ Zhang Y, Hamburger AW. Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling. Br J Cancer. 2005 Jan 17;92(1):140-6. PMID:15583694 doi:http://dx.doi.org/6602257