Tmic
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NameHepatocyte nuclear factor 4-alpha
Synonyms
  • HNF-4-alpha
  • HNF4
  • NR2A1
  • Nuclear receptor subfamily 2 group A member 1
  • TCF-14
  • TCF14
  • Transcription factor 14
  • Transcription factor HNF-4
Gene NameHNF4A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0007682|Hepatocyte nuclear factor 4-alpha
MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGNDTSPSEGTNLNAPNSLGVSALC
AICGDRATGKHYGASSCDGCKGFFRRSVRKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKC
FRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRAKK
IASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFK
DVLLLGNDYIVPRHCPELAEMSRVSIRILDELVLPFQELQIDDNEYAYLKAIIFFDPDAK
GLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFIKL
FGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEW
PRPRGQAATPETPQPSPPGGSGSEPYKLLPGAVATIVKPLSAIPQPTITKQEVI
Number of residues474
Molecular Weight52784.205
Theoretical pI7.46
GO Classification
Functions
  • steroid hormone receptor activity
  • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
  • DNA binding
  • receptor binding
  • fatty acid binding
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • RNA polymerase II activating transcription factor binding
  • transcription regulatory region DNA binding
  • protein homodimerization activity
  • transcription factor activity, sequence-specific DNA binding
  • zinc ion binding
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
  • RNA polymerase II core promoter sequence-specific DNA binding
Processes
  • response to glucose
  • ornithine metabolic process
  • negative regulation of cell proliferation
  • positive regulation of cholesterol homeostasis
  • positive regulation of transcription from RNA polymerase II promoter
  • negative regulation of cell growth
  • regulation of gastrulation
  • lipid metabolic process
  • lipid homeostasis
  • regulation of growth hormone receptor signaling pathway
  • regulation of insulin secretion
  • sex differentiation
  • signal transduction involved in regulation of gene expression
  • phospholipid homeostasis
  • SMAD protein signal transduction
  • gene expression
  • xenobiotic metabolic process
  • transcription initiation from RNA polymerase II promoter
  • triglyceride homeostasis
  • regulation of lipid metabolic process
  • glucose homeostasis
  • regulation of transcription from RNA polymerase II promoter
  • endocrine pancreas development
  • blood coagulation
  • positive regulation of transcription, DNA-templated
Components
  • nucleus
  • cytoplasm
  • nucleoplasm
General FunctionZinc ion binding
Specific FunctionTranscriptionally 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1595752
UniProtKB IDP41235
UniProtKB Entry NameHNF4A_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0012799|Hepatocyte nuclear factor 4-alpha (HNF4A)
ATGCGACTCTCCAAAACCCTCGTCGACATGGACATGGCCGACTACAGTGCTGCACTGGAC
CCAGCCTACACCACCCTGGAATTTGAGAATGTGCAGGTGTTGACGATGGGCAATGACACG
TCCCCATCAGAAGGCACCAACCTCAACGCGCCCAACAGCCTGGGTGTCAGCGCCCTGTGT
GCCATCTGCGGGGACCGGGCCACGGGCAAACACTACGGTGCCTCGAGCTGTGACGGCTGC
AAGGGCTTCTTCCGGAGGAGCGTGCGGAAGAACCACATGTACTCCTGCAGATTTAGCCGG
CAGTGCGTGGTGGACAAAGACAAGAGGAACCAGTGCCGCTACTGCAGGCTCAAGAAATGC
TTCCGGGCTGGCATGAAGAAGGAAGCCGTCCAGAATGAGCGGGACCGGATCAGCACTCGA
AGGTCAAGCTATGAGGACAGCAGCCTGCCCTCCATCAATGCGCTCCTGCAGGCGGAGGTC
CTGTCCCGACAGATCACCTCCCCCGTCTCCGGGATCAACGGCGACATTCGGGCGAAGAAG
ATTGCCAGCATCGCAGATGTGTGTGAGTCCATGAAGGAGCAGCTGCTGGTTCTCGTTGAG
TGGGCCAAGTACATCCCAGCTTTCTGCGAGCTCCCCCTGGACGACCAGGTGGCCCTGCTC
AGAGCCCATGCTGGCGAGCACCTGCTGCTCGGAGCCACCAAGAGATCCATGGTGTTCAAG
GACGTGCTGCTCCTAGGCAATGACTACATTGTCCCTCGGCACTGCCCGGAGCTGGCGGAG
ATGAGCCGGGTGTCCATACGCATCCTTGACGAGCTGGTGCTGCCCTTCCAGGAGCTGCAG
ATCGATGACAATGAGTATGCCTACCTCAAAGCCATCATCTTCTTTGACCCAGATGCCAAG
GGGCTGAGCGATCCAGGGAAGATCAAGCGGCTGCGTTCCCAGGTGCAGGTGAGCTTGGAG
GACTACATCAACGACCGCCAGTATGACTCGCGTGGCCGCTTTGGAGAGCTGCTGCTGCTG
CTGCCCACCTTGCAGAGCATCACCTGGCAGATGATCGAGCAGATCCAGTTCATCAAGCTC
TTCGGCATGGCCAAGATTGACAACCTGTTGCAGGAGATGCTGCTGGGAGGGTCCCCCAGC
GATGCACCCCATGCCCACCACCCCCTGCACCCTCACCTGATGCAGGAACATATGGGAACC
AACGTCATCGTTGCCAACACAATGCCCACTCACCTCAGCAACGGACAGATGTGTGAGTGG
CCCCGACCCAGGGGACAGGCAGCCACCCCTGAGACCCCACAGCCCTCACCGCCAGGTGGC
TCAGGGTCTGAGCCCTATAAGCTCCTGCCGGGAGCCGTCGCCACAATCGTCAAGCCCCTC
TCTGCCATCCCCCAGCCGACCATCACCAAGCAGGAAGTTATCTAG
GenBank Gene IDX87870
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:5024
Chromosome Location20
Locus20q12-q13.1
References
  1. Kritis AA, Argyrokastritis A, Moschonas NK, Power S, Katrakili N, Zannis VI, Cereghini S, Talianidis I: Isolation and characterization of a third isoform of human hepatocyte nuclear factor 4. Gene. 1996 Sep 16;173(2):275-80. 8964514
  2. Drewes T, Senkel S, Holewa B, Ryffel GU: Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol. 1996 Mar;16(3):925-31. 8622695
  3. Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI: Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1) Nature. 1996 Dec 5;384(6608):458-60. 8945471
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  6. Chartier FL, Bossu JP, Laudet V, Fruchart JC, Laine B: Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. Gene. 1994 Sep 30;147(2):269-72. 7926813
  7. Ktistaki E, Ktistakis NT, Papadogeorgaki E, Talianidis I: 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. 1995 Oct 10;92(21):9876-80. 7568236
  8. Hong YH, Varanasi US, Yang W, Leff T: AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem. 2003 Jul 25;278(30):27495-501. Epub 2003 May 9. 12740371
  9. Yokoyama A, Katsura S, Ito R, Hashiba W, Sekine H, Fujiki R, Kato S: Multiple post-translational modifications in hepatocyte nuclear factor 4alpha. Biochem Biophys Res Commun. 2011 Jul 15;410(4):749-53. doi: 10.1016/j.bbrc.2011.06.033. Epub 2011 Jun 17. 21708125
  10. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
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  12. 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. 9313765
  13. 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. 9243109
  14. Moller AM, Urhammer SA, Dalgaard LT, Reneland R, Berglund L, Hansen T, Clausen JO, Lithell H, Pedersen O: Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM. Diabetologia. 1997 Aug;40(8):980-3. 9267996
  15. 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. 9449683
  16. Navas MA, Munoz-Elias EJ, Kim J, Shih D, Stoffel M: Functional characterization of the MODY1 gene mutations HNF4(R127W), HNF4(V255M), and HNF4(E276Q). Diabetes. 1999 Jul;48(7):1459-65. 10389854
  17. Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT: Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007 Apr;4(4):e118. 17407387
  18. Stanescu DE, Hughes N, Kaplan B, Stanley CA, De Leon DD: Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab. 2012 Oct;97(10):E2026-30. doi: 10.1210/jc.2012-1356. Epub 2012 Jul 16. 22802087
  19. Hamilton AJ, Bingham C, McDonald TJ, Cook PR, Caswell RC, Weedon MN, Oram RA, Shields BM, Shepherd M, Inward CD, Hamilton-Shield JP, Kohlhase J, Ellard S, Hattersley AT: The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a beta cell phenotype. J Med Genet. 2014 Mar;51(3):165-9. doi: 10.1136/jmedgenet-2013-102066. Epub 2013 Nov 27. 24285859