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Hepatocyte nuclear factor 4 alpha: Wikis


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Hepatocyte nuclear factor 4, alpha

PDB rendering based on 1m7w.
Available structures
1m7w, 1pzl
Symbols HNF4A; FLJ39654; HNF4; HNF4a7; HNF4a8; HNF4a9; MODY; MODY1; NR2A1; NR2A21; TCF; TCF14
External IDs OMIM600281 MGI109128 HomoloGene395 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 NM_008261
RefSeq (protein) NP_000448 NP_032287
Location (UCSC) Chr 20:
42.46 - 42.49 Mb
Chr 2:
163.2 - 163.26 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 encoded by the HNF4A gene.[1][2]



The protein encoded by this gene is a nuclear transcription factor which 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. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. 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]


Hepatocyte nuclear factor 4 alpha has been shown to interact with Berberine, [5]Beta-catenin,[6] Testicular receptor 4,[7] MED14,[8][9] CREB binding protein,[10][11] Small heterodimer partner[12] and MED1.[8][9]

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. ^ "Entrez Gene: HNF4A hepatocyte nuclear factor 4, alpha".  
  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, et al. Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity. October 2008 World J Gastroenterol. 14(39):6004-11. Free Full Text Free Full Text]
  6. ^ Mulholland, David J; Read Jason T, Rennie Paul S, Cox Michael E, Nelson Colleen C (Aug. 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 (England) 22 (36): 5602–13. doi:10.1038/sj.onc.1206802. ISSN 0950-9232. PMID 12944908.  
  7. ^ Lin, Wen-Jye; Li Jie, Lee Yi-Fen, Yeh Shauh-Der, Altuwaijri Saleh, Ou Jing-Hsiung, Chang Chawnshang (Mar. 2003). "Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4". J. Biol. Chem. (United States) 278 (11): 9353–60. doi:10.1074/jbc.M205944200. ISSN 0021-9258. PMID 12522137.  
  8. ^ a b Maeda, Yutaka; Rachez Christophe, Hawel Leo, Byus Craig V, Freedman Leonard P, Sladek Frances M (Jul. 2002). "Polyamines modulate the interaction between nuclear receptors and vitamin D receptor-interacting protein 205". Mol. Endocrinol. (United States) 16 (7): 1502–10. ISSN 0888-8809. PMID 12089346.  
  9. ^ a b Malik, Sohail; Wallberg Annika E, Kang Yun Kyoung, Roeder Robert G (Aug. 2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4". Mol. Cell. Biol. (United States) 22 (15): 5626–37. ISSN 0270-7306. PMID 12101254.  
  10. ^ Yoshida, E; Aratani S, Itou H, Miyagishi M, Takiguchi M, Osumu T, Murakami K, Fukamizu A (Dec. 1997). "Functional association between CBP and HNF4 in trans-activation". Biochem. Biophys. Res. Commun. (UNITED STATES) 241 (3): 664–9. doi:10.1006/bbrc.1997.7871. ISSN 0006-291X. PMID 9434765.  
  11. ^ Dell, H; Hadzopoulou-Cladaras M (Mar. 1999). "CREB-binding protein is a transcriptional coactivator for hepatocyte nuclear factor-4 and enhances apolipoprotein gene expression". J. Biol. Chem. (UNITED STATES) 274 (13): 9013–21. ISSN 0021-9258. PMID 10085149.  
  12. ^ Lee, Y K; Dell H, Dowhan D H, Hadzopoulou-Cladaras M, Moore D D (Jan. 2000). "The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression". Mol. Cell. Biol. (UNITED STATES) 20 (1): 187–95. ISSN 0270-7306. PMID 10594021.  

Further reading

  • Winter WE, Nakamura M, House DV (2000). "Monogenic diabetes mellitus in youth. The MODY syndromes.". Endocrinol. Metab. Clin. North Am. 28 (4): 765–85. doi:10.1016/S0889-8529(05)70101-8. PMID 10609119.  
  • Zannis VI, Kan HY, Kritis A, et al. (2001). "Transcriptional regulation of the human apolipoprotein genes.". Front. Biosci. 6: D456–504. doi:10.2741/Zannis. PMID 11229886.  
  • Gupta RK, Kaestner KH (2005). "HNF-4alpha: from MODY to late-onset type 2 diabetes.". Trends in molecular medicine 10 (11): 521–4. doi:10.1016/j.molmed.2004.09.004. PMID 15519277.  
  • Mohlke KL, Boehnke M (2005). "The role of HNF4A variants in the risk of type 2 diabetes.". Curr. Diab. Rep. 5 (2): 149–56. doi:10.1007/s11892-005-0043-y. PMID 15794920.  
  • Love-Gregory L, Permutt MA (2007). "HNF4A genetic variants: role in diabetes.". Current opinion in clinical nutrition and metabolic care 10 (4): 397–402. doi:10.1097/MCO.0b013e3281e3888d. PMID 17563455.  
  • Bell GI, Xiang KS, Newman MV, et al. (1991). "Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q.". Proc. Natl. Acad. Sci. U.S.A. 88 (4): 1484–8. doi:10.1073/pnas.88.4.1484. PMID 1899928.  
  • Ktistaki E, Ktistakis NT, Papadogeorgaki E, Talianidis I (1995). "Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA-binding and transactivation potential.". Proc. Natl. Acad. Sci. U.S.A. 92 (21): 9876–80. doi:10.1073/pnas.92.21.9876. PMID 7568236.  
  • Ginsburg GS, Ozer J, Karathanasis SK (1995). "Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, hepatocyte nuclear factor 4.". J. Clin. Invest. 96 (1): 528–38. doi:10.1172/JCI118065. PMID 7615825.  
  • Jiang G, Nepomuceno L, Hopkins K, Sladek FM (1995). "Exclusive homodimerization of the orphan receptor hepatocyte nuclear factor 4 defines a new subclass of nuclear receptors.". Mol. Cell. Biol. 15 (9): 5131–43. PMID 7651430.  
  • Chartier FL, Bossu JP, Laudet V, et al. (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.  
  • Drewes T, Senkel S, Holewa B, Ryffel GU (1996). "Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes.". Mol. Cell. Biol. 16 (3): 925–31. PMID 8622695.  
  • Yamagata K, Furuta H, Oda N, et al. (1997). "Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1)". Nature 384 (6608): 458–60. doi:10.1038/384458a0. PMID 8945471.  
  • Kritis AA, Argyrokastritis A, Moschonas NK, et al. (1996). "Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4.". Gene 173 (2): 275–80. doi:10.1016/0378-1119(96)00183-7. PMID 8964514.  
  • Argyrokastritis A, Kamakari S, Kapsetaki M, et al. (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.  
  • Thénot S, Henriquet C, Rochefort H, Cavaillès V (1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1.". J. Biol. Chem. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.  
  • Bulman MP, Dronsfield MJ, Frayling T, et al. (1997). "A missense mutation in the hepatocyte nuclear factor 4 alpha gene in a UK pedigree with maturity-onset diabetes of the young.". Diabetologia 40 (7): 859–62. doi:10.1007/s001250050760. PMID 9243109.  
  • Møller AM, Urhammer SA, Dalgaard LT, et al. (1998). "Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM.". Diabetologia 40 (8): 980–3. doi:10.1007/s001250050778. PMID 9267996.  
  • Lindner T, Gragnoli C, Furuta H, et al. (1997). "Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene.". J. Clin. Invest. 100 (6): 1400–5. doi:10.1172/JCI119660. PMID 9294105.  
  • Furuta H, Iwasaki N, Oda N, et al. (1997). "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 46 (10): 1652–7. doi:10.2337/diabetes.46.10.1652. PMID 9313765.  
  • Stoffel M, Duncan SA (1998). "The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism.". Proc. Natl. Acad. Sci. U.S.A. 94 (24): 13209–14. doi:10.1073/pnas.94.24.13209. PMID 9371825.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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