3fs1

From Proteopedia

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Template:STRUCTURE 3fs1

Contents 1 Crystal structure of HNF4a LBD in complex with the ligand and the coactivator PGC-1a fragment 2 Disease 3 Function 4 About this Structure 5 Reference

Crystal structure of HNF4a LBD in complex with the ligand and the coactivator PGC-1a fragment

Template:ABSTRACT PUBMED 19846556

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.

About this Structure

3fs1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

• Rha GB, Wu G, Shoelson SE, Chi YI. Multiple binding modes between HNF4alpha and the LXXLL motifs of PGC-1alpha lead to full activation. J Biol Chem. 2009 Dec 11;284(50):35165-76. Epub 2009 Oct 21. PMID:19846556 doi:10.1074/jbc.M109.052506

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