Hepatocyte nuclear factor 1-alpha

Details

Name
Hepatocyte nuclear factor 1-alpha
Synonyms
  • HNF-1-alpha
  • LFB1
  • Liver-specific transcription factor LF-B1
  • TCF-1
  • TCF1
  • Transcription factor 1
Gene Name
HNF1A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009435|Hepatocyte nuclear factor 1-alpha
MVSKLSQLQTELLAALLESGLSKEALIQALGEPGPYLLAGEGPLDKGESCGGGRGELAEL
PNGLGETRGSEDETDDDGEDFTPPILKELENLSPEEAAHQKAVVETLLQEDPWRVAKMVK
SYLQQHNIPQREVVDTTGLNQSHLSQHLNKGTPMKTQKRAALYTWYVRKQREVAQQFTHA
GQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKEERETLVEECNRAE
CIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYSGPPPGPGPGPALP
AHSSPGLPPPALSPSKVHGVRYGQPATSETAEVPSSSGGPLVTVSTPLHQVSPTGLEPSH
SLLSTEAKLVSAAGGPLPPVSTLTALHSLEQTSPGLNQQPQNLIMASLPGVMTIGPGEPA
SLGPTFTNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPV
QSHVTQSPFMATMAQLQSPHALYSHKPEVAQYTHTGLLPQTMLITDTTNLSALASLTPTK
QVFTSDTEASSESGLHTPASQATTLHVPSQDPAGIQHLQPAHRLSASPTVSSSSLVLYQS
SDSSNGQSHLLPSNHSVIETFISTQMASSSQ
Number of residues
631
Molecular Weight
67356.01
Theoretical pI
Not Available
GO Classification
Functions
DNA binding / protein dimerization activity / protein heterodimerization activity / protein homodimerization activity / transcription factor activity, sequence-specific DNA binding / transcription regulatory region DNA binding / transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
Processes
glucose homeostasis / glucose import / insulin secretion / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription initiation from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / regulation of transcription from RNA polymerase II promoter / renal glucose absorption / transcription from RNA polymerase II promoter
Components
cytoplasm / nucleus / protein complex
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0017459|Hepatocyte nuclear factor 1-alpha (HNF1A)
ATGGTTTCTAAACTGAGCCAGCTGCAGACGGAGCTCCTGGCGGCCCTGCTCGAGTCAGGG
CTGAGCAAAGAGGCACTGATCCAGGCACTGGGTGAGCCGGGGCCCTACCTCCTGGCTGGA
GAAGGCCCCCTGGACAAGGGGGAGTCCTGCGGCGGCGGTCGAGGGGAGCTGGCTGAGCTG
CCCAATGGGCTGGGGGAGACTCGGGGCTCCGAGGACGAGACGGACGACGATGGGGAAGAC
TTCACGCCACCCATCCTCAAAGAGCTGGAGAACCTCAGCCCTGAGGAGGCGGCCCACCAG
AAAGCCGTGGTGGAGACCCTTCTGCAGGAGGACCCGTGGCGTGTGGCGAAGATGGTCAAG
TCCTACCTGCAGCAGCACAACATCCCACAGCGGGAGGTGGTCGATACCACTGGCCTCAAC
CAGTCCCACCTGTCCCAACACCTCAACAAGGGCACTCCCATGAAGACGCAGAAGCGGGCC
GCCCTGTACACCTGGTACGTCCGCAAGCAGCGAGAGGTGGCGCAGCAGTTCACCCATGCA
GGGCAGGGAGGGCTGATTGAAGAGCCCACAGGTGATGAGCTACCAACCAAGAAGGGGCGG
AGGAACCGTTTCAAGTGGGGCCCAGCATCCCAGCAGATCCTGTTCCAGGCCTATGAGAGG
CAGAAGAACCCTAGCAAGGAGGAGCGAGAGACGCTAGTGGAGGAGTGCAATAGGGCGGAA
TGCATCCAGAGAGGGGTGTCCCCATCACAGGCACAGGGGCTGGGCTCCAACCTCGTCACG
GAGGTGCGTGTCTACAACTGGTTTGCCAACCGGCGCAAAGAAGAAGCCTTCCGGCACAAG
CTGGCCATGGACACGTACAGCGGGCCCCCCCCAGGGCCAGGCCCGGGACCTGCGCTGCCC
GCTCACAGCTCCCCTGGCCTGCCTCCACCTGCCCTCTCCCCCAGTAAGGTCCACGGTGTG
CGCTATGGACAGCCTGCGACCAGTGAGACTGCAGAAGTACCCTCAAGCAGCGGCGGTCCC
TTAGTGACAGTGTCTACACCCCTCCACCAAGTGTCCCCCACGGGCCTGGAGCCCAGCCAC
AGCCTGCTGAGTACAGAAGCCAAGCTGGTCTCAGCAGCTGGGGGCCCCCTCCCCCCTGTC
AGCACCCTGACAGCACTGCACAGCTTGGAGCAGACATCCCCAGGCCTCAACCAGCAGCCC
CAGAACCTCATCATGGCCTCACTTCCTGGGGTCATGACCATCGGGCCTGGTGAGCCTGCC
TCCCTGGGTCCTACGTTCACCAACACAGGTGCCTCCACCCTGGTCATCGGCCTGGCCTCC
ACGCAGGCACAGAGTGTGCCGGTCATCAACAGCATGGGCAGCAGCCTGACCACCCTGCAG
CCCGTCCAGTTCTCCCAGCCGCTGCACCCCTCCTACCAGCAGCCGCTCATGCCACCTGTG
CAGAGCCATGTGACCCAGAGCCCCTTCATGGCCACCATGGCTCAGCTGCAGAGCCCCCAC
GCCCTCTACAGCCACAAGCCCGAGGTGGCCCAGTACACCCACACGGGCCTGCTCCCGCAG
ACTATGCTCATCACCGACACCACCAACCTGAGCGCCCTGGCCAGCCTCACGCCCACCAAG
CAGGTCTTCACCTCAGACACTGAGGCCTCCAGTGAGTCCGGGCTTCACACGCCGGCATCT
CAGGCCACCACCCTCCACGTCCCCAGCCAGGACCCTGCCGGCATCCAGCACCTGCAGCCG
GCCCACCGGCTCAGCGCCAGCCCCACAGTGTCCTCCAGCAGCCTGGTGCTGTACCAGAGC
TCAGACTCCAGCAATGGCCAGAGCCACCTGCTGCCATCCAACCACAGCGTCATCGAGACC
TTCATCTCCACCCAGATGGCCTCTTCCTCCCAGTAA
Chromosome Location
12
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP20823
UniProtKB Entry NameHNF1A_HUMAN
HGNC IDHGNC:11621
General References
  1. Bach I, Galcheva-Gargova Z, Mattei MG, Simon-Chazottes D, Guenet JL, Cereghini S, Yaniv M: Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse. Genomics. 1990 Sep;8(1):155-64. [Article]
  2. Bach I, Yaniv M: More potent transcriptional activators or a transdominant inhibitor of the HNF1 homeoprotein family are generated by alternative RNA processing. EMBO J. 1993 Nov;12(11):4229-42. [Article]
  3. Yamagata K, Oda N, Kaisaki PJ, Menzel S, Furuta H, Vaxillaire M, Southam L, Cox RD, Lathrop GM, Boriraj VV, Chen X, Cox NJ, Oda Y, Yano H, Le Beau MM, Yamada S, Nishigori H, Takeda J, Fajans SS, Hattersley AT, Iwasaki N, Hansen T, Pedersen O, Polonsky KS, Bell GI, et al.: Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3) Nature. 1996 Dec 5;384(6608):455-8. [Article]
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  7. Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE: Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol Cell. 2002 Nov;10(5):1129-37. [Article]
  8. Narayana N, Phillips NB, Hua QX, Jia W, Weiss MA: Diabetes mellitus due to misfolding of a beta-cell transcription factor: stereospecific frustration of a Schellman motif in HNF-1alpha. J Mol Biol. 2006 Sep 22;362(3):414-29. Epub 2006 Jul 27. [Article]
  9. Glucksmann MA, Lehto M, Tayber O, Scotti S, Berkemeier L, Pulido JC, Wu Y, Nir WJ, Fang L, Markel P, Munnelly KD, Goranson J, Orho M, Young BM, Whitacre JL, McMenimen C, Wantman M, Tuomi T, Warram J, Forsblom CM, Carlsson M, Rosenzweig J, Kennedy G, Duyk GM, Thomas JD, et al.: Novel mutations and a mutational hotspot in the MODY3 gene. Diabetes. 1997 Jun;46(6):1081-6. [Article]
  10. Iwasaki N, Oda N, Ogata M, Hara M, Hinokio Y, Oda Y, Yamagata K, Kanematsu S, Ohgawara H, Omori Y, Bell GI: Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM. Diabetes. 1997 Sep;46(9):1504-8. [Article]
  11. Yamada S, Nishigori H, Onda H, Takahashi K, Kitano N, Morikawa A, Takeuchi T, Takeda J: Mutations in the hepatocyte nuclear factor-1alpha gene (MODY3) are not a major cause of late-onset NIDDM in Japanese subjects. Diabetes. 1997 Sep;46(9):1512-3. [Article]
  12. Yamada S, Nishigori H, Onda H, Utsugi T, Yanagawa T, Maruyama T, Onigata K, Nagashima K, Nagai R, Morikawa A, Takeuchi T, Takeda J: Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM. Diabetes. 1997 Oct;46(10):1643-7. [Article]
  13. Boutin P, Chevre JC, Hani EH, Gomis R, Pardini VC, Guillausseau PJ, Vaxillaire M, Velho G, Froguel P: An automated fluorescent single-strand conformation polymorphism technique for screening mutations in the hepatocyte nuclear factor-1alpha gene (maturity-onset diabetes of the young). Diabetes. 1997 Dec;46(12):2108-9. [Article]
  14. Kaisaki PJ, Menzel S, Lindner T, Oda N, Rjasanowski I, Sahm J, Meincke G, Schulze J, Schmechel H, Petzold C, Ledermann HM, Sachse G, Boriraj VV, Menzel R, Kerner W, Turner RC, Yamagata K, Bell GI: Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4. Diabetes. 1997 Mar;46(3):528-35. [Article]
  15. Frayling TM, Bulamn MP, Ellard S, Appleton M, Dronsfield MJ, Mackie AD, Baird JD, Kaisaki PJ, Yamagata K, Bell GI, Bain SC, Hattersley AT: Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K. Diabetes. 1997 Apr;46(4):720-5. [Article]
  16. Hansen T, Eiberg H, Rouard M, Vaxillaire M, Moller AM, Rasmussen SK, Fridberg M, Urhammer SA, Holst JJ, Almind K, Echwald SM, Hansen L, Bell GI, Pedersen O: Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation. Diabetes. 1997 Apr;46(4):726-30. [Article]
  17. Urhammer SA, Fridberg M, Hansen T, Rasmussen SK, Moller AM, Clausen JO, Pedersen O: A prevalent amino acid polymorphism at codon 98 in the hepatocyte nuclear factor-1alpha gene is associated with reduced serum C-peptide and insulin responses to an oral glucose challenge. Diabetes. 1997 May;46(5):912-6. [Article]
  18. Urhammer SA, Rasmussen SK, Kaisaki PJ, Oda N, Yamagata K, Moller AM, Fridberg M, Hansen L, Hansen T, Bell GI, Pedersen O: Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM. Diabetologia. 1997 Apr;40(4):473-5. [Article]
  19. Vaxillaire M, Rouard M, Yamagata K, Oda N, Kaisaki PJ, Boriraj VV, Chevre JC, Boccio V, Cox RD, Lathrop GM, Dussoix P, Philippe J, Timsit J, Charpentier G, Velho G, Bell GI, Froguel P: Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3). Hum Mol Genet. 1997 Apr;6(4):583-6. [Article]
  20. Behn PS, Wasson J, Chayen S, Smolovitch I, Thomas J, Glaser B, Permutt MA: Hepatocyte nuclear factor 1alpha coding mutations are an uncommon contributor to early-onset type 2 diabetes in Ashkenazi Jews. Diabetes. 1998 Jun;47(6):967-9. [Article]
  21. Chevre JC, Hani EH, Boutin P, Vaxillaire M, Blanche H, Vionnet N, Pardini VC, Timsit J, Larger E, Charpentier G, Beckers D, Maes M, Bellanne-Chantelot C, Velho G, Froguel P: Mutation screening in 18 Caucasian families suggest the existence of other MODY genes. Diabetologia. 1998 Sep;41(9):1017-23. [Article]
  22. Moller AM, Dalgaard LT, Pociot F, Nerup J, Hansen T, Pedersen O: Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes. Diabetologia. 1998 Dec;41(12):1528-31. [Article]
  23. Elbein SC, Teng K, Yount P, Scroggin E: Linkage and molecular scanning analyses of MODY3/hepatocyte nuclear factor-1 alpha gene in typical familial type 2 diabetes: evidence for novel mutations in exons 8 and 10. J Clin Endocrinol Metab. 1998 Jun;83(6):2059-65. [Article]
  24. Nishigori H, Yamada S, Kohama T, Utsugi T, Shimizu H, Takeuchi T, Takeda J: Mutations in the hepatocyte nuclear factor-1 alpha gene (MODY3) are not a major cause of early-onset non-insulin-dependent (type 2) diabetes mellitus in Japanese. J Hum Genet. 1998;43(2):107-10. [Article]
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  26. Ellard S, Bulman MP, Frayling TM, Allen LI, Dronsfield MJ, Tack CJ, Hattersley AT: Allelic drop-out in exon 2 of the hepatocyte nuclear factor-1alpha gene hinders the identification of mutations in three families with maturity-onset diabetes of the young. Diabetes. 1999 Apr;48(4):921-3. [Article]
  27. Yoshiuchi I, Yamagata K, Yang Q, Iwahashi H, Okita K, Yamamoto K, Oue T, Imagawa A, Hamaguchi T, Yamasaki T, Horikawa Y, Satoh T, Nakajima H, Miyazaki J, Higashiyama S, Miyagawa J, Namba M, Hanafusa T, Matsuzawa Y: Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization. Diabetologia. 1999 May;42(5):621-6. [Article]
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  29. Miedzybrodzka Z, Hattersley AT, Ellard S, Pearson D, de Silva D, Harvey R, Haites N: Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1alpha gene: implications for predictive testing. Eur J Hum Genet. 1999 Sep;7(6):729-32. [Article]
  30. Hegele RA, Cao H, Harris SB, Hanley AJ, Zinman B: The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab. 1999 Mar;84(3):1077-82. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04419D-norleucineexperimentalunknownDetails