Hepatocyte nuclear factor 4

Hepatocyte nuclear factor 4

protein
Name=hepatocyte nuclear factor 4 alpha
caption=


width=
HGNCid=5024
Symbol=HNF4A
AltSymbols=TCF14, MODY, MODY1
EntrezGene=3172
OMIM=600281
RefSeq=NM_001030004
UniProt=P41235
PDB=1M7W
ECnumber=
Chromosome=20
Arm=q
Band=12
LocusSupplementaryData=-20q13.1
protein
Name=hepatocyte nuclear factor 4 gamma
caption=


width=
HGNCid=5026
Symbol=HNF4G
AltSymbols=
EntrezGene=3174
OMIM=605966
RefSeq=NM_004133
UniProt=Q14541
PDB=1LV2
ECnumber=
Chromosome=8
Arm=q
Band=21
LocusSupplementaryData=-q22

HNF4 (Hepatocyte Nuclear Factor 4) is a nuclear receptor protein mostly expressed in the liver, gut, kidney, and pancreatic beta cells that is critical for liver development. In humans, there are two isoforms of NHF4, alpha and gamma encoded by two separate genes Gene|HNF4A and Gene|HNF4G respectively.cite journal |author=Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B|title=Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver|journal= Gene |volume= 147 |issue= 2 |pages= 269–72 |year= 1994| doi = 10.1016/0378-1119(94)90079-5 |pmid= 7926813]

Ligands

HNF4 was originally classified as an orphan receptor. However HNF4 was found later to be constitutively active by virtue of being continuously bound to a variety of fatty acids.cite journal |author=Sladek F|title=Desperately seeking...something|journal= Mol Cell |volume= 10 |issue= 2 |pages= 219–21 |year= 2002| doi = 10.1016/S1097-2765(02)00605-6 |pmid= 12191466] cite journal |author=Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O|title=Fatty acid regulation of hepatic gene transcription|journal= J Nutr |volume= 135 |issue= 11 |pages= 2503–6 |year= 2005| doi = |pmid= 16251601] The ligand binding domain of HNF4, as with other nuclear receptors, adopts a canonical alpha helical sandwich foldcite journal |author=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|title=Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids|journal= Structure |volume= 10 |issue= 9 |pages= 1225–34 |year= 2002| doi = 10.1016/S0969-2126(02)00829-8 |pmid= 12220494] cite journal |author=Dhe-Paganon S, Duda K, Iwamoto M, Chi YI, Shoelson SE|title=Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand|journal= J Biol Chem |volume= 277 |issue= 41 |pages= 37973–6 |year= 2002| doi = 10.1074/jbc.C200420200 |pmid= 12193589] and interacts with co-activator proteins.cite journal |author=Duda K, Chi YI, Shoelson SE|title=Structural basis for HNF-4alpha activation by ligand and coactivator binding|journal= J Biol Chem |volume= 279 |issue= 22 |pages= 23311–6 |year= 2004| doi = 10.1074/jbc.M400864200 |pmid= 14982928]

Pathology

Mutations in the HNF4-α gene have been linked to maturity onset diabetes of the young (MODY).cite journal |author=Fajans SS, Bell GI, Polonsky KS|title=Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young|journal= N Engl J Med |volume= 345 |issue= 13 |pages= 971–80 |year= 2001| doi = 10.1056/NEJMra002168 |pmid= 11575290]

ee also

* Hepatocyte nuclear factors
* Hepatocyte nuclear factor 4A

References

External links

*


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