Hepatocyte nuclear factor 4-alpha

NameHepatocyte nuclear factor 4-alpha
SynonymsHNF-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
    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
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
Processes
    gene expression
SMAD protein signal transduction
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
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
Components
    cytoplasm
nucleoplasm
nucleus
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.
Transmembrane Regions
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 IDNone
GenAtlas ID
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 ]
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  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. Duda K, Chi YI, Shoelson SE: Structural basis for HNF-4alpha activation by ligand and coactivator binding. J Biol Chem. 2004 May 28;279(22):23311-6. Epub 2004 Feb 24.[14982928 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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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