Menu
Home
People
Places
Arts
History
Plants & Animals
Science
Life & Culture
Technology
Reference.org
Hepatocyte nuclear factor 4
open-in-new
<h2 id="ligands">Ligands</h2> <p>HNF4 was originally classified as an <a href="/facts/Orphan_receptor/30Xum2PA">orphan receptor</a> that exhibits constitutive transactivation activity apparently by being continuously bound to a variety of fatty acids.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a><a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> The existence of a ligand for HNF4 has been somewhat controversial, but <a href="/facts/Linoleic_acid/E3zEMyb6">linoleic acid</a> (LA) has been identified as the endogenous ligand of native HNF4 expressed in mouse liver; the binding of LA to HNF4 is reversible.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p><p>The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich <a href="/facts/Protein_domains/oUpFcSsl">fold</a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> and interacts with <a href="/facts/Coactivation_(Transcription)/0lVABmQx">co-activator</a> proteins.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p><p>HNF4 binds to the consensus sequence AGGTCAaAGGTCA in order to activate transcription. </p> <h2 id="pathology">Pathology</h2> <p>Mutations in the <i>HNF4A</i> gene have been linked to <a href="/facts/MODY_1/f2ND6VSH">maturity onset diabetes of the young 1</a> (MODY1).<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>This seems to be caused by HNF4-a's <a href="http://jme.endocrinology-journals.org/content/43/1/19.full.pdf">[1]</a> role in the synthesis of <a href="/facts/SHBG/9gVoXJMz">SHBG</a>, which is known to be severely diminished in patients with <a href="/facts/Insulin_resistance/cz6oFqke">insulin-resistance</a>. </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Hepatocyte_nuclear_factors/JDnRdtt9">Hepatocyte nuclear factors</a></li> <li><a href="/facts/HNF4A/o5u6pla7">Hepatocyte nuclear factor 4A</a></li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=Hepatocyte+Nuclear+Factor+4">Hepatocyte+Nuclear+Factor+4</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (1994). "Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver". Gene. 147 (2): 269–72. doi:10.1016/0378-1119(94)90079-5. PMID 7926813. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Sladek F (August 2002). "Desperately seeking...something". Mol. Cell. 10 (2): 219–21. doi:10.1016/S1097-2765(02)00605-6. PMID 12191466. <a href="https://doi.org/10.1016%2FS1097-2765%2802%2900605-6" target="_blank">https://doi.org/10.1016%2FS1097-2765%2802%2900605-6</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O (November 2005). "Fatty acid regulation of hepatic gene transcription". J. Nutr. 135 (11): 2503–6. doi:10.1093/jn/135.11.2503. PMID 16251601. <a href="https://doi.org/10.1093%2Fjn%2F135.11.2503" target="_blank">https://doi.org/10.1093%2Fjn%2F135.11.2503</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Yuan X, Ta TC, Lin M, Evans JR, Dong Y, Bolotin E, Sherman MA, Forman BM, Sladek FM (2009). Laudet V (ed.). "Identification of an endogenous ligand bound to a native orphan nuclear receptor". PLOS ONE. 4 (5): e5609. Bibcode:2009PLoSO...4.5609Y. doi:10.1371/journal.pone.0005609. PMC 2680617. PMID 19440305. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680617" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680617</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Wisely GB, Miller AB, Davis RG, Thornquest AD, Johnson R, Spitzer T, Sefler A, Shearer B, Moore JT, Miller AB, Willson TM, Williams SP (September 2002). "Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids". Structure. 10 (9): 1225–34. doi:10.1016/S0969-2126(02)00829-8. PMID 12220494. <a href="https://doi.org/10.1016%2FS0969-2126%2802%2900829-8" target="_blank">https://doi.org/10.1016%2FS0969-2126%2802%2900829-8</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Dhe-Paganon S, Duda K, Iwamoto M, Chi YI, Shoelson SE (October 2002). "Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand". J. Biol. Chem. 277 (41): 37973–6. doi:10.1074/jbc.C200420200. PMID 12193589. <a href="https://doi.org/10.1074%2Fjbc.C200420200" target="_blank">https://doi.org/10.1074%2Fjbc.C200420200</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Duda K, Chi YI, Shoelson SE (May 2004). "Structural basis for HNF-4alpha activation by ligand and coactivator binding". J. Biol. Chem. 279 (22): 23311–6. doi:10.1074/jbc.M400864200. PMID 14982928. <a href="https://doi.org/10.1074%2Fjbc.M400864200" target="_blank">https://doi.org/10.1074%2Fjbc.M400864200</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Fajans SS, Bell GI, Polonsky KS (2001). "Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young". N Engl J Med. 345 (13): 971–80. doi:10.1056/NEJMra002168. PMID 11575290. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> </ol>