BioPAX pathway converted from "HNF1A-dependent synthesis of HNF4A" in the Reactome database. HNF1A-dependent synthesis of HNF4A HNF1A-dependent synthesis of HNF4A The HNF4A gene is transcribed from either of two promoters, P1 and P2, the resulting mRNA is translated, and the protein products localize in the nucleoplasm. Transcription is positively regulated by HNF1A. Many of the molecular details of these events have not been studied experimentally in humans, but are inferred from mouse model systems (Boj et al. 2001). Transcription in mouse and human pancreatic beta cells is P2-dependent and in humans yields three isoforms of mature HNF4A protein. A point mutation in the human P2 genomic DNA sequence is associated with MODY (maturity onset diabetes of the young), consistent with the hypothesis that P2-mediated transcription is essential for HNF4A expression and normal beta cell function (Hansen et al. 2002). Authored: Ferrer, J, Tello-Ruiz, MK, 2008-05-23 Reviewed: Jensen, J, 2008-05-12 21:46:53 Edited: D'Eustachio, P, 2008-05-12 21:43:33 Reactome DB_ID: 9606122 1 nucleoplasm GO 0005654 ENSEMBL:ENSG00000101076 HNF4A HNF4 TCF14 HNF4A NR2A1 Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 ENSEMBL ENSG00000101076 Converted from EntitySet in Reactome Reactome DB_ID: 211468 1 HNF4A (pancreas-specific) [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HNF4A-7 [nucleoplasm] HNF4A-6 [nucleoplasm] HNF4A-5 [nucleoplasm] UniProt P41235-7 UniProt P41235-6 UniProt P41235-5 Reactome Database ID Release 82 211466 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=211466 Reactome R-HSA-211466 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-211466.2 12235114 Pubmed 2002 Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function Hansen, SK Parrizas, M Jensen, ML Pruhova, S Ek, J Boj, SF Johansen, A Maestro, MA Rivera, F Eiberg, H Andel, M Lebl, J Pedersen, O Ferrer, Jorge Hansen, T J Clin Invest 110:827-33 11717395 Pubmed 2001 A transcription factor regulatory circuit in differentiated pancreatic cells Boj, SF Parrizas, M Maestro, MA Ferrer, Jorge Proc Natl Acad Sci U S A 98:14481-6 ACTIVATION Reactome Database ID Release 82 211494 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=211494 Reactome R-HSA-211494 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-211494.1 Reactome DB_ID: 3004629 UniProt:P20823 HNF1A HNF1A HNF1A TCF1 FUNCTION Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). Binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:12453420, PubMed:10966642). Activates the transcription of CYP1A2, CYP2E1 and CYP3A11 (By similarity).SUBUNIT Binds DNA as a dimer (PubMed:12453420). Heterotetramer with PCBD1; formed by a dimer of dimers (By similarity). Interacts with PCBD1 (PubMed:10966642). Interacts with BHLHE41 (By similarity).TISSUE SPECIFICITY Liver.POLYMORPHISM The Ala-98/Val-98 polymorphism is associated with a reduction in glucose-induced serum C-peptide and insulin responses.SIMILARITY Belongs to the HNF1 homeobox family. UniProt P20823 Chain Coordinates 1 EQUAL 631 EQUAL