Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Hnf1a. (This text reflects annotations as of Wednesday, January 23, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of January 2, 2008. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

This gene encodes a hepatic transcription factor. The encoded protein is not a member of the T-cell factor family, and is distinct from T-cell specific transcription factor 7 which has also been referred to by the symbol Tcf1. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Hnf1a
  • participates in the following biological processes:
    • glucose homeostasis ^[30]
    • glucose import ^[30]
    • positive regulation of transcription from RNA polymerase II promoter ^[17]
    • positive regulation of transcription, DNA-dependent ^{[1, 7, 9, 14, 15, 18, 21, 23, 26, 30, 36]}
    • regulation of transcription from RNA polymerase II promoter ^[38]
    • renal glucose absorption ^[30]
    • SMAD protein signal transduction ^[37]
  • performs the following molecular functions:
    • DNA binding ^{[2, 3, 5, 6, 7, 14, 15, 17, 18, 19, 22, 23, 25, 29, 30, 31, 35, 36, 38, 39, 40]}
    • sequence-specific DNA binding transcription factor activity ^{[6, 7, 14, 15, 18, 23, 30, 36]}
  • is located in the following cellular components:
    • cytoplasm ^[40]
    • nucleus ^{[2, 3, 4, 5, 6, 7, 13, 15, 18, 23, 24, 26, 28, 30, 31, 35, 38]}
    • pronucleus ^[40]
• The gene product of Hnf1a has been shown to bind to the gene products of Hnf1b, Pcbd1, Pcbd2, Sirt1, Slc5a2, Smarca5. ^{[12, 30, 31, 35, 40]} Researchers have inferred, based on physical interactions, that the gene product of Hnf1a
  • performs the following molecular functions:
    • protein dimerization activity ^[34]
    • protein heterodimerization activity ^{[7, 23]}
    • protein homodimerization activity ^{[2, 23, 35]}
  • is located in the following cellular components:
    • transcription factor complex ^[22]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Hnf1a
  • participates in the following biological processes:
    • bile acid and bile salt transport ^[36]
    • bile acid biosynthetic process ^[36]
    • blastocyst development ^[40]
    • cholesterol metabolic process ^[36]
    • chromatin remodeling ^{[6, 32]}
    • endocrine pancreas development ^[16]
    • fatty acid biosynthetic process ^[1]
    • fatty acid transport ^[1]
    • glucose homeostasis ^{[15, 30, 33]}
    • heme biosynthetic process ^[27]
    • insulin secretion ^{[8, 33, 41]}
    • liver development ^[20]
    • positive regulation of transcription from RNA polymerase II promoter ^[4]
    • positive regulation of transcription, DNA-dependent ^{[3, 6, 21, 26, 27, 31, 32, 42]}
    • protein localization ^[40]
    • regulation of hormone secretion ^[20]
    • regulation of insulin secretion ^[20]
    • regulation of transcription, DNA-dependent ^[40]
    • reproductive structure development ^[20]
    • response to glucose stimulus ^[8]
    • response to oxidative stress ^[27]
    • reverse cholesterol transport ^[42]
  • performs the following molecular functions:
    • sequence-specific DNA binding transcription factor activity ^{[31, 40]}
• Researchers have inferred, based on genetic interactions, that the gene product of Hnf1a
  • participates in the following biological processes:
    • bone resorption based on interactions with Ctnnb1 ^[11]
    • embryonic limb morphogenesis based on interactions with Lef1 ^[10]
    • paraxial mesoderm formation based on interactions with Lef1 ^[10]
    • placenta development based on interactions with Lef1 ^[10]
    • regulation of Wnt receptor signaling pathway based on interactions with Lef1 ^[10]
  • is located in the following cellular components:
    • photoreceptor outer segment based on interactions with Lef1 ^[10]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Hnf1a:
  • participates in the following biological processes:
    • glucose homeostasis
    • glucose import
    • insulin secretion
    • negative regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription initiation from RNA polymerase II promoter
    • positive regulation of transcription, DNA-dependent
    • regulation of transcription from RNA polymerase II promoter
    • renal glucose absorption
    • transcription from RNA polymerase II promoter
  • performs the following molecular functions:
    • DNA binding
    • double-stranded DNA binding
    • protein dimerization activity
    • protein heterodimerization activity
    • protein homodimerization activity
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
    • sequence-specific DNA binding
    • sequence-specific DNA binding transcription factor activity
    • transcription factor binding
    • transcription regulatory region DNA binding
  • is located in the following cellular components:
    • cytoplasm
    • nucleus
    • protein complex

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Hnf1a indicates that it:
  • participates in the following biological processes:
    • transcription, DNA-dependent

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References

1. Akiyama TE et al. (2000) Regulation of the liver fatty acid-binding protein gene by hepatocyte nuclear factor 1alpha (HNF1alpha). Alterations in fatty acid homeostasis in HNF1alpha-deficient mice. J Biol Chem, 275:27117-22. (PubMed:10852923)
2. Blumenfeld M et al. (1991) Hepatic nuclear factor 1 (HNF1) shows a wider distribution than products of its known target genes in developing mouse. Development, 113:589-99. (PubMed:1685988)
3. Bosse T et al. (2006) Hepatocyte nuclear factor-1alpha is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo. Am J Physiol Gastrointest Liver Physiol, 290:G1016-24. (PubMed:16223943)
4. Bosse T et al. (2007) Gata4 and Hnf1alpha are partially required for the expression of specific intestinal genes during development. Am J Physiol Gastrointest Liver Physiol, 292:G1302-14. (PubMed:17272516)
5. Cereghini S et al. (1992) Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles. Development, 116:783-97. (PubMed:1363228)
6. Cheret C et al. (2002) Hepatocyte Nuclear Factor 1 alpha Controls Renal Expression of the Npt1-Npt4 Anionic Transporter Locus. J Mol Biol, 322:929. (PubMed:12367519)
7. De Simone V et al. (1991) LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia. EMBO J, 10:1435-43. (PubMed:1673925)
8. Dukes ID et al. (1998) Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor-1alpha-deficient mice. J Biol Chem, 273:24457-64. (PubMed:9733737)
9. Galceran J et al. (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development, 127:469-82. (PubMed:10631168)
10. Galceran J et al. (1999) Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev, 13:709-17. (PubMed:10090727)
11. Glass DA 2nd et al. (2005) Canonical wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell, 8:751-64. (PubMed:15866165)
12. Grimm AA et al. (2011) A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates Crp expression. Aging Cell, 10:305-17. (PubMed:21176092)
13. Hiesberger T et al. (2005) Role of the hepatocyte nuclear factor-1beta (HNF-1beta) C-terminal domain in Pkhd1 (ARPKD) gene transcription and renal cystogenesis. J Biol Chem, 280:10578-86. (PubMed:15647252)
14. Hiesberger T et al. (2004) Mutation of hepatocyte nuclear factor-1beta inhibits Pkhd1 gene expression and produces renal cysts in mice. J Clin Invest, 113:814-25. (PubMed:15067314)
15. Hiraiwa H et al. (2001) A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1alpha-null mice. J Biol Chem, 276:7963-7. (PubMed:11121425)
16. Jakowlew SB et al. (1998) Reduction in transforming growth factor-beta type II receptor in mouse lung carcinogenesis. Mol Carcinog, 22:46-56. (PubMed:9609100)
17. Kamiya A et al. (2004) Hepatocyte nuclear factors 1alpha and 4alpha control expression of proline oxidase in adult liver. FEBS Lett, 578:63-8. (PubMed:15581617)
18. Kuo CJ et al. (1990) Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1. Proc Natl Acad Sci U S A, 87:9838-42. (PubMed:2263635)
19. Kyrmizi I et al. (2006) Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev, 20:2293-305. (PubMed:16912278)
20. Lee YH et al. (1998) Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse. Mol Cell Biol, 18:3059-68. (PubMed:9566924)
21. Luco RF et al. (2006) A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious. Diabetes, 55:2202-11. (PubMed:16873682)
22. Maestro MA et al. (2003) Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet, 12:3307-14. (PubMed:14570708)
23. Mendel DB et al. (1991) HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev, 5:1042-56. (PubMed:2044952)
24. Miura N et al. (1993) Immunological characterization of hepatocyte nuclear factor 1 protein: appearance of hepatocyte nuclear factor 1 protein in developing mouse embryos. Eur J Cell Biol, 60:376-82. (PubMed:8330635)
25. Miura N et al. (1993) MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme. FEBS Lett, 326:171-6. (PubMed:8325367)
26. Mouchel N et al. (2004) HNF1alpha is involved in tissue-specific regulation of CFTR gene expression. Biochem J, 378:909-18. (PubMed:14656222)
27. Muppala V et al. (2000) The role of HNF-1alpha in controlling hepatic catalase activity. Mol Pharmacol, 57:93-100. (PubMed:10617683)
28. Nammo T et al. (2002) Expression profile of MODY3/HNF-1alpha protein in the developing mouse pancreas. Diabetologia, 45:1142-53. (PubMed:12189445)
29. Pare JF et al. (2004) The fetoprotein transcription factor (FTF) gene is essential to embryogenesis and cholesterol homeostasis and is regulated by a DR4 element. J Biol Chem, 279:21206-16. (PubMed:15014077)
30. Pontoglio M et al. (2000) HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep, 1:359-65. (PubMed:11269503)
31. Pontoglio M et al. (1996) Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell, 84:575-85. (PubMed:8598044)
32. Pontoglio M et al. (2001) Hepatocyte nuclear factor 1alpha controls the expression of terminal complement genes. J Exp Med, 194:1683-9. (PubMed:11733582)
33. Pontoglio M et al. (1998) Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. J Clin Invest, 101:2215-22. (PubMed:9593777)
34. Rose RB et al. (2000) High-resolution structure of the HNF-1alpha dimerization domain. Biochemistry, 39:15062-70. (PubMed:11106484)
35. Rose RB et al. (2004) Biochemical and structural basis for partially redundant enzymatic and transcriptional functions of DCoH and DCoH2. Biochemistry, 43:7345-55. (PubMed:15182178)
36. Shih DQ et al. (2001) Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet, 27:375-82. (PubMed:11279518)
37. Sirard C et al. (1998) The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev, 12:107-19. (PubMed:9420335)
38. Streeper RS et al. (1998) Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. Proc Natl Acad Sci U S A, 95:9208-13. (PubMed:9689059)
39. Tomomura M et al. (1994) Abnormal gene expression and regulation in the liver of jvs mice with systemic carnitine deficiency. Biochim Biophys Acta, 1226:307-14. (PubMed:7914432)
40. Torres-Padilla ME et al. (2006) Role of TIF1{alpha} as a modulator of embryonic transcription in the mouse zygote. J Cell Biol, 174:329-38. (PubMed:16880268)
41. Wang L et al. (2004) Selective deletion of the Hnf1beta (MODY5) gene in beta-cells leads to altered gene expression and defective insulin release. Endocrinology, 145:3941-9. (PubMed:15142986)
42. Wolfrum C et al. (2005) Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med, 11:418-22. (PubMed:15793583)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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