Hepatocyte nuclear factor 4 alpha

Hepatocyte nuclear factor 4 alpha
Hepatocyte nuclear factor 4, alpha

PDB rendering based on 1m7w.
Symbols HNF4A; FLJ39654; HNF4; HNF4a7; HNF4a8; HNF4a9; HNF4alpha; MODY; MODY1; NR2A1; NR2A21; TCF; TCF14
External IDs OMIM600281 MGI109128 HomoloGene395 IUPHAR: NR2A1 GeneCards: HNF4A Gene
RNA expression pattern
PBB GE HNF4A 216889 s at tn.png
PBB GE HNF4A 208429 x at tn.png
PBB GE HNF4A 214832 at tn.png
More reference expression data
Species Human Mouse
Entrez 3172 15378
Ensembl ENSG00000101076 ENSMUSG00000017950
UniProt P41235 Q3UNX3
RefSeq (mRNA) NM_000457.3 NM_008261.2
RefSeq (protein) NP_000448.3 NP_032287.2
Location (UCSC) Chr 20:
42.98 – 43.06 Mb
Chr 2:
163.33 – 163.4 Mb
PubMed search [1] [2]

Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the HNF4A gene.[1][2]



HNF-4α is a nuclear transcription factor that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene plays a role in development of the liver , kidney , and intestines . Alternative splicing of this gene results in multiple transcript variants.[3]

HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4.[4]

The alkaloid berberine upregulates the expression of HNF4A.[5]

Clinical significance

Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type II.[3]


Hepatocyte nuclear factor 4 alpha has been shown to interact with:

See also


  1. ^ Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B (September 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. 
  2. ^ Argyrokastritis A, Kamakari S, Kapsetaki M, Kritis A, Talianidis I, Moschonas NK (February 1997). "Human hepatocyte nuclear factor-4 (hHNF-4) gene maps to 20q12-q13.1 between PLCG1 and D20S17". Hum. Genet. 99 (2): 233–6. doi:10.1007/s004390050345. PMID 9048927. 
  3. ^ a b "Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3172. 
  4. ^ Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, Schuetz EG, Kim RB (February 2003). "The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4". Nat. Med. 9 (2): 220–4. doi:10.1038/nm815. PMID 12514743. 
  5. ^ Wang ZQ, Lu FE, Leng SH, Fang XS, Chen G, Wang ZS, Dong LP, Yan ZQ (October 2008). "Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity". World J. Gastroenterol. 14 (39): 6004–11. doi:10.3748/wjg.14.6004. PMC 2760199. PMID 18932278. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2760199. 
  6. ^ Mulholland DJ, Read JT, Rennie PS, Cox ME, Nelson CC (August 2003). "Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis". Oncogene 22 (36): 5602–13. doi:10.1038/sj.onc.1206802. PMID 12944908. 
  7. ^ Yoshida E, Aratani S, Itou H, Miyagishi M, Takiguchi M, Osumu T, Murakami K, Fukamizu A (December 1997). "Functional association between CBP and HNF4 in trans-activation". Biochem. Biophys. Res. Commun. 241 (3): 664–9. doi:10.1006/bbrc.1997.7871. PMID 9434765. 
  8. ^ Dell H, Hadzopoulou-Cladaras M (March 1999). "CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression". J. Biol. Chem. 274 (13): 9013–21. doi:10.1074/jbc.274.13.9013. PMID 10085149. 
  9. ^ a b Maeda Y, Rachez C, Hawel L, Byus CV, Freedman LP, Sladek FM (July 2002). "Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205". Mol. Endocrinol. 16 (7): 1502–10. doi:10.1210/me.16.7.1502. PMID 12089346. 
  10. ^ a b Malik S, Wallberg AE, Kang YK, Roeder RG (August 2002). "TRAP/SMCC/Mediator-Dependent Transcriptional Activation from DNA and Chromatin Templates by Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4". Mol. Cell. Biol. 22 (15): 5626–37. doi:10.1128/MCB.22.15.5626-5637.2002. PMC 133960. PMID 12101254. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133960. 
  11. ^ Lee YK, Dell H, Dowhan DH, Hadzopoulou-Cladaras M, Moore DD (January 2000). "The Orphan Nuclear Receptor SHP Inhibits Hepatocyte Nuclear Factor 4 and Retinoid X Receptor Transactivation: Two Mechanisms for Repression". Mol. Cell. Biol. 20 (1): 187–95. doi:10.1128/MCB.20.1.187-195.2000. PMC 85074. PMID 10594021. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85074. 
  12. ^ Lin WJ, Li J, Lee YF, Yeh SD, Altuwaijri S, Ou JH, Chang C (March 2003). "Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4". J. Biol. Chem. 278 (11): 9353–60. doi:10.1074/jbc.M205944200. PMID 12522137. 

Further reading

External links

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