HNF1A

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HNF1A
Protein TCF1 PDB 1ic8.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HNF1A, HNF-1A, HNF1, IDDM20, LFB1, MODY3, TCF-1, TCF1, HNF1 homeobox A
External IDs MGI: 98504 HomoloGene: 459 GeneCards: 6927
Genetically Related Diseases
Disease Name References
diabetes mellitus type 2
RNA expression pattern
PBB GE TCF1 210515 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000545
NM_001306179

NM_009327

RefSeq (protein)

NP_000536.5
NP_001293108.1
NP_000536.5
NP_001293108.1

NP_033353.2

Location (UCSC) Chr 12: 120.98 – 121 Mb Chr 5: 114.95 – 114.97 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

HNF1 homeobox A (hepatocyte nuclear factor 1 homeobox A), also known as HNF1A, is a human gene.[4][5]

The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes.[6]

Function[edit]

HNF-1α is a transcription factor expressed in organs of endoderm origin, including liver, kidneys, pancreas, intestines, stomach, spleen, thymus, testis, and keratinocytes and melanocytes in human skin.[7] It has been shown to affect intestinal epithelial cell growth and cell lineages differentiation. For instance, HNF1A is an important cell-intrinsic transcription factor in adult B lymphopoiesis.[8][9][10] The participation of HNF-1α in glucose metabolism and diabetes has been reported, including the involvement in GLUT1 and GLUT2 transporter expression in pancreatic β-cells and angiotensin-converting enzyme 2 gene expression in pancreatic islets.[11][12] HNF-1α could promote the transcription of several proteins involved in the management of type II diabetes including dipeptidyl peptidase-IV (DPP-IV/CD26).[13][14] HNF-1α is also involved in various metabolic pathways of other organs, such as being a transcriptional regulator of bile acid transporters in the intestine and kidneys.[15] HNF-1α is involved in the promotion of hepatic organic cation transporters, which uptake certain classes of pharmaceuticals; hence, the loss of its function can lead to drug metabolism problems.[16] In addition, HNF-1α regulates the expression of acute phase proteins, such as fibrinogen, c-reactive protein, and interleukin 1 receptor, which are involved with inflammation.[17] Moreover, significantly lower levels of HNF-1α in pancreatic tumors and hepatocellular adenomas than in normal adjacent tissues was observed, suggesting that HNF-1α might play a possible tumor suppressor role.[18][19]

Clinical significance[edit]

HNF1A mutations can cause maturity onset diabetes of the young type 3, one of the forms of "monogenic diabetes",[5] as well as hepatocellular adenoma. HNF-1 protein is present in clear cell carcinoma of ovary [20][21]

Interactions[edit]

HNF1A has been shown to interact with:

See also[edit]

References[edit]

  1. ^ "chibi.ubc.ca/Gemma/phenotypes.html?phenotypeUrlId=DOID_9352&geneId=158550". 
  2. ^ "Human PubMed Reference:". 
  3. ^ "Mouse PubMed Reference:". 
  4. ^ Szpirer C, Riviere M, Cortese R, Nakamura T, Islam MQ, Levan G, Szpirer J (June 1992). "Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF)". Genomics. 13 (2): 293–300. doi:10.1016/0888-7543(92)90245-N. PMID 1535333. 
  5. ^ a b Vaxillaire M, Boccio V, Philippi A, Vigouroux C, Terwilliger J, Passa P, Beckmann JS, Velho G, Lathrop GM, Froguel P (April 1995). "A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q". Nature Genetics. 9 (4): 418–23. doi:10.1038/ng0495-418. PMID 7795649. 
  6. ^ Courtois G, Morgan JG, Campbell LA, Fourel G, Crabtree GR (October 1987). "Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters". Science. 238 (4827): 688–92. doi:10.1126/science.3499668. PMID 3499668. 
  7. ^ Real Hernandez LM, Fan J, Johnson MH, Gonzalez de Mejia E (2015-01-01). "Berry Phenolic Compounds Increase Expression of Hepatocyte Nuclear Factor-1α (HNF-1α) in Caco-2 and Normal Colon Cells Due to High Affinities with Transcription and Dimerization Domains of HNF-1α". PloS One. 10 (9): e0138768. doi:10.1371/journal.pone.0138768. PMC 4587667free to read. PMID 26413797. 
  8. ^ Lussier CR, Brial F, Roy SA, Langlois MJ, Verdu EF, Rivard N, Perreault N, Boudreau F (2010-01-01). "Loss of hepatocyte-nuclear-factor-1alpha impacts on adult mouse intestinal epithelial cell growth and cell lineages differentiation". PloS One. 5 (8): e12378. doi:10.1371/journal.pone.0012378. PMC 2927538free to read. PMID 20808783. 
  9. ^ D'Angelo A, Bluteau O, Garcia-Gonzalez MA, Gresh L, Doyen A, Garbay S, Robine S, Pontoglio M (May 2010). "Hepatocyte nuclear factor 1alpha and beta control terminal differentiation and cell fate commitment in the gut epithelium". Development. 137 (9): 1573–82. doi:10.1242/dev.044420. PMID 20388655. 
  10. ^ von Wnuck Lipinski K, Sattler K, Peters S, Weske S, Keul P, Klump H, Heusch G, Göthert JR, Levkau B (February 2016). "Hepatocyte Nuclear Factor 1A Is a Cell-Intrinsic Transcription Factor Required for B Cell Differentiation and Development in Mice". Journal of Immunology. 196 (4): 1655–65. doi:10.4049/jimmunol.1500897. PMID 26800876. 
  11. ^ Luni C, Marth JD, Doyle FJ (2012-01-01). "Computational modeling of glucose transport in pancreatic β-cells identifies metabolic thresholds and therapeutic targets in diabetes". PloS One. 7 (12): e53130. doi:10.1371/journal.pone.0053130. PMC 3531366free to read. PMID 23300881. 
  12. ^ Pedersen KB, Chhabra KH, Nguyen VK, Xia H, Lazartigues E (November 2013). "The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs". Biochimica et Biophysica Acta. 1829 (11): 1225–35. doi:10.1016/j.bbagrm.2013.09.007. PMC 3838857free to read. PMID 24100303. 
  13. ^ Gu N, Adachi T, Matsunaga T, Takeda J, Tsujimoto G, Ishihara A, Yasuda K, Tsuda K (August 2006). "Mutant HNF-1alpha and mutant HNF-1beta identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells". Biochemical and Biophysical Research Communications. 346 (3): 1016–23. doi:10.1016/j.bbrc.2006.06.010. PMID 16781669. 
  14. ^ Gu N, Tsuda M, Matsunaga T, Adachi T, Yasuda K, Ishihara A, Tsuda K (December 2008). "Glucose regulation of dipeptidyl peptidase IV gene expression is mediated by hepatocyte nuclear factor-1alpha in epithelial intestinal cells". Clinical and Experimental Pharmacology & Physiology. 35 (12): 1433–9. doi:10.1111/j.1440-1681.2008.05015.x. PMID 18671716. 
  15. ^ Shih DQ, Bussen M, Sehayek E, Ananthanarayanan M, Shneider BL, Suchy FJ, Shefer S, Bollileni JS, Gonzalez FJ, Breslow JL, Stoffel M (April 2001). "Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism". Nature Genetics. 27 (4): 375–82. doi:10.1038/86871. PMID 11279518. 
  16. ^ O'Brien VP, Bokelmann K, Ramírez J, Jobst K, Ratain MJ, Brockmöller J, Tzvetkov MV (October 2013). "Hepatocyte nuclear factor 1 regulates the expression of the organic cation transporter 1 via binding to an evolutionary conserved region in intron 1 of the OCT1 gene". The Journal of Pharmacology and Experimental Therapeutics. 347 (1): 181–92. doi:10.1124/jpet.113.206359. PMC 3781413free to read. PMID 23922447. 
  17. ^ Armendariz AD, Krauss RM (April 2009). "Hepatic nuclear factor 1-alpha: inflammation, genetics, and atherosclerosis". Current Opinion in Lipidology. 20 (2): 106–11. PMID 19280766. 
  18. ^ Luo Z, Li Y, Wang H, Fleming J, Li M, Kang Y, Zhang R, Li D (2015-01-01). "Hepatocyte nuclear factor 1A (HNF1A) as a possible tumor suppressor in pancreatic cancer". PloS One. 10 (3): e0121082. doi:10.1371/journal.pone.0121082. PMC 4368635free to read. PMID 25793983. 
  19. ^ Bluteau O, Jeannot E, Bioulac-Sage P, Marqués JM, Blanc JF, Bui H, Beaudoin JC, Franco D, Balabaud C, Laurent-Puig P, Zucman-Rossi J (October 2002). "Bi-allelic inactivation of TCF1 in hepatic adenomas". Nature Genetics. 32 (2): 312–5. doi:10.1038/ng1001. PMID 12355088. 
  20. ^ Köbel M, Kalloger SE, Carrick J, Huntsman D, Asad H, Oliva E, Ewanowich CA, Soslow RA, Gilks CB (January 2009). "A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary". The American Journal of Surgical Pathology. 33 (1): 14–21. doi:10.1097/PAS.0b013e3181788546. PMID 18830127. 
  21. ^ Offman SL, Longacre TA (September 2012). "Clear cell carcinoma of the female genital tract (not everything is as clear as it seems)". Advances in Anatomic Pathology. 19 (5): 296–312. doi:10.1097/PAP.0b013e31826663b1. PMID 22885379. 
  22. ^ a b c d Soutoglou E, Papafotiou G, Katrakili N, Talianidis I (April 2000). "Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins". The Journal of Biological Chemistry. 275 (17): 12515–20. doi:10.1074/jbc.275.17.12515. PMID 10777539. 
  23. ^ Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, Toyokuni S, Tsuda K, Seino Y (May 2002). "Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter". Diabetes. 51 (5): 1409–18. doi:10.2337/diabetes.51.5.1409. PMID 11978637. 
  24. ^ Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3: 89. doi:10.1038/msb4100134. PMC 1847948free to read. PMID 17353931. 
  25. ^ Sourdive DJ, Transy C, Garbay S, Yaniv M (April 1997). "The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity". Nucleic Acids Research. 25 (8): 1476–84. doi:10.1093/nar/25.8.1476. PMC 146627free to read. PMID 9092652. 
  26. ^ Hines RN, Luo Z, Cresteil T, Ding X, Prough RA, Fitzpatrick JL, Ripp SL, Falkner KC, Ge NL, Levine A, Elferink CJ (May 2001). "Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors". Drug Metabolism and Disposition. 29 (5): 623–33. PMID 11302926. 
  27. ^ Rufibach LE, Duncan SA, Battle M, Deeb SS (July 2006). "Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter". Journal of Lipid Research. 47 (7): 1463–77. doi:10.1194/jlr.M600082-JLR200. PMID 16603721. 
  28. ^ a b Bulla GA, Kraus DM (December 2004). "Dissociation of the hepatic phenotype from HNF4 and HNF1alpha expression". Bioscience Reports. 24 (6): 595–608. doi:10.1007/s10540-005-2794-8. PMID 16158197. 

Further reading[edit]

  • Eastman Q, Grosschedl R (April 1999). "Regulation of LEF-1/TCF transcription factors by Wnt and other signals". Current Opinion in Cell Biology. 11 (2): 233–40. doi:10.1016/S0955-0674(99)80031-3. PMID 10209158. 
  • Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J (May 2007). "Genotype phenotype classification of hepatocellular adenoma". World Journal of Gastroenterology. 13 (19): 2649–54. doi:10.3748/wjg.v13.i19.2649. PMID 17569132.