BioPAX pathway converted from "HNF1A-dependent synthesis of HNF4A" in the Reactome database. LEFT-TO-RIGHT 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 HNF4A gene Reactome DB_ID: 9606122 nucleoplasm GENE ONTOLOGY GO:0005654 ENSEMBL:ENSG00000101076 HNF4A HNF4A HNF4 NR2A1 TCF14 Homo sapiens NCBI Taxonomy 9606 ENSEMBL ENSG00000101076 Reactome Database ID Release 82 9606122 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=9606122 Reactome R-HSA-9606122 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-9606122.1 Reactome http://www.reactome.org Converted from EntitySet in Reactome HNF-4-alpha HNF4A (pancreas-specific) Hepatocyte nuclear factor 4-alpha Transcription factor 14 Reactome DB_ID: 211468 HNF4A-5 HNF4A isoform 7 Reactome DB_ID: 211478 UniProt:P41235-5 HNF4A HNF4A HNF4 NR2A1 TCF14 FUNCTION Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).SUBUNIT Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:14982928). Interacts with CLOCK, ARNTL, CRY1, CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionnally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.PTM Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA.PTM Acetylation at Lys-458 lowers transcriptional activation by about two-fold.MISCELLANEOUS Binds fatty acids.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily. UniProt Isoform P41235-5 1 EQUAL 452 EQUAL Reactome Database ID Release 82 211478 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=211478 Reactome R-HSA-211478 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-211478.1 HNF4A-6 HNF4A isoform 8 Reactome DB_ID: 211463 UniProt:P41235-6 HNF4A HNF4A HNF4 NR2A1 TCF14 FUNCTION Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).SUBUNIT Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:14982928). Interacts with CLOCK, ARNTL, CRY1, CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionnally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.PTM Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA.PTM Acetylation at Lys-458 lowers transcriptional activation by about two-fold.MISCELLANEOUS Binds fatty acids.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily. UniProt Isoform P41235-6 1 EQUAL 442 EQUAL Reactome Database ID Release 82 211463 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=211463 Reactome R-HSA-211463 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-211463.1 HNF4A-7 HNF4A isoform 9 Reactome DB_ID: 211462 UniProt:P41235-7 HNF4A HNF4A HNF4 NR2A1 TCF14 FUNCTION Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-ARNTL/BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698).SUBUNIT Homodimerization is required for HNF4-alpha to bind to its recognition site (PubMed:14982928). Interacts with CLOCK, ARNTL, CRY1, CRY2, PER1 and PER2 (PubMed:30530698). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionnally inactive (PubMed:28128295). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.PTM Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA.PTM Acetylation at Lys-458 lowers transcriptional activation by about two-fold.MISCELLANEOUS Binds fatty acids.SIMILARITY Belongs to the nuclear hormone receptor family. NR2 subfamily. UniProt Isoform P41235-7 1 EQUAL 395 EQUAL Reactome Database ID Release 82 211462 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=211462 Reactome R-HSA-211462 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-211462.1 Reactome Database ID Release 82 211468 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=211468 Reactome R-HSA-211468 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-211468.1 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 HNF1A Hepatocyte nuclear factor 1-alpha HNF1A_HUMAN Reactome DB_ID: 3004629 UniProt:P20823 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 1 EQUAL 631 EQUAL Reactome Database ID Release 82 3004629 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=3004629 Reactome R-HSA-3004629 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-3004629.1