ID   HNF4A_MOUSE             Reviewed;         474 AA.
AC   P49698; A2A5I5; A2ICH0; Q3UNX3; Q8CFY1;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   29-MAY-2007, sequence version 2.
DT   04-NOV-2026, entry version 219.
DE   RecName: Full=Hepatocyte nuclear factor 4-alpha;
DE            Short=HNF-4-alpha;
DE   AltName: Full=Nuclear receptor subfamily 2 group A member 1;
DE   AltName: Full=Transcription factor 14;
DE            Short=TCF-14;
DE   AltName: Full=Transcription factor HNF-4;
GN   Name=Hnf4a; Synonyms=Hnf-4, Hnf4, Nr2a1, Tcf14;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC   STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX   PubMed=7999795; DOI=10.1016/0167-4781(94)00177-5;
RA   Hata S., Inoue T., Kosuga K., Nakashima T., Tsukamoto T., Osumi T.;
RT   "Identification of two splice isoforms of mRNA for mouse hepatocyte nuclear
RT   factor 4 (HNF-4).";
RL   Biochim. Biophys. Acta 1260:55-61(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=CAST/EiJ; TISSUE=Liver;
RX   PubMed=16670015; DOI=10.1186/1471-2164-7-102;
RA   Farber C.R., Corva P.M., Medrano J.F.;
RT   "Genome-wide isolation of growth and obesity QTL using mouse speed congenic
RT   strains.";
RL   BMC Genomics 7:102-102(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 21-378.
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RA   Huang J., Karakucuk V., Levitsky L.L., Rhoads D.B.;
RT   "Expression of HNF4 alpha 3 in pancreatic islets and Ins-1 beta cells.";
RL   Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=17407387; DOI=10.1371/journal.pmed.0040118;
RA   Pearson E.R., Boj S.F., Steele A.M., Barrett T., Stals K., Shield J.P.,
RA   Ellard S., Ferrer J., Hattersley A.T.;
RT   "Macrosomia and hyperinsulinaemic hypoglycaemia in patients with
RT   heterozygous mutations in the HNF4A gene.";
RL   PLoS Med. 4:E118-E118(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429 AND THR-432, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429 AND SER-436, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [10]
RP   INTERACTION WITH PER2.
RX   PubMed=20159955; DOI=10.1101/gad.564110;
RA   Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.;
RT   "The mammalian clock component PERIOD2 coordinates circadian output by
RT   interaction with nuclear receptors.";
RL   Genes Dev. 24:345-357(2010).
RN   [11]
RP   INTERACTION WITH CRY1 AND CRY2.
RX   PubMed=28751364; DOI=10.1073/pnas.1704955114;
RA   Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E.,
RA   Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T.,
RA   Zhao X., Downes M., Evans R.M., Lamia K.A.;
RT   "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors
RT   and modulate transcriptional activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017).
RN   [12]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=30530698; DOI=10.1073/pnas.1816411115;
RA   Qu M., Duffy T., Hirota T., Kay S.A.;
RT   "Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-
RT   specific circadian networks.";
RL   Proc. Natl. Acad. Sci. U.S.A. 115:E12305-E12312(2018).
RN   [13]
RP   FUNCTION.
RX   PubMed=30555544; DOI=10.7150/thno.28676;
RA   Zhang T., Yu F., Guo L., Chen M., Yuan X., Wu B.;
RT   "Small heterodimer partner regulates circadian cytochromes p450 and drug-
RT   induced hepatotoxicity.";
RL   Theranostics 8:5246-5258(2018).
CC   -!- FUNCTION: Transcriptional regulator which controls the expression of
CC       hepatic genes during the transition of endodermal cells to hepatic
CC       progenitor cells, facilitatating the recruitment of RNA pol II to the
CC       promoters of target genes (By similarity). Activates the transcription
CC       of CYP2C38 (PubMed:30555544). Represses the CLOCK-BMAL1 transcriptional
CC       activity and is essential for circadian rhythm maintenance and period
CC       regulation in the liver and colon cells (PubMed:30530698).
CC       {ECO:0000250|UniProtKB:P41235, ECO:0000269|PubMed:30530698,
CC       ECO:0000269|PubMed:30555544}.
CC   -!- SUBUNIT: Homodimerization is required for HNF4-alpha to bind to its
CC       recognition site (By similarity). Interacts with CLOCK, BMAL1 and PER1
CC       (By similarity). Interacts with PER2 (PubMed:20159955). Interacts with
CC       CRY1 and CRY2 (PubMed:28751364). Interacts with NR0B2/SHP; the
CC       resulting heterodimer is transcriptionally inactive (By similarity).
CC       Interacts with DDX3X; this interaction disrupts the interaction between
CC       HNF4 and NR0B2 that forms inactive heterodimers and enhances the
CC       formation of active HNF4 homodimers (By similarity).
CC       {ECO:0000250|UniProtKB:P41235, ECO:0000269|PubMed:20159955,
CC       ECO:0000269|PubMed:28751364}.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=P49698-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=P49698-2; Sequence=VSP_003676;
CC   -!- TISSUE SPECIFICITY: Expressed in the liver, pancreas and colon in a
CC       circadian manner. {ECO:0000269|PubMed:30530698}.
CC   -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC       number of yeast and animal transcription factors.
CC       {ECO:0000250|UniProtKB:P41235}.
CC   -!- PTM: Phosphorylated on tyrosine residue(s); phosphorylation is
CC       important for its DNA-binding activity. Phosphorylation may directly or
CC       indirectly play a regulatory role in the subnuclear distribution.
CC       Phosphorylation at Ser-313 by AMPK reduces the ability to form
CC       homodimers and bind DNA (By similarity). {ECO:0000250}.
CC   -!- PTM: Acetylation at Lys-458 lowers transcriptional activation by about
CC       two-fold. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Pancreatic beta-cells-specific knockout results
CC       in hyperinsulinemia and hypoglycemia. {ECO:0000269|PubMed:17407387}.
CC   -!- MISCELLANEOUS: Binds fatty acids. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC       subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA06101.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; D29015; BAA06101.1; ALT_INIT; mRNA.
DR   EMBL; AY902317; AAX90602.1; -; Genomic_DNA.
DR   EMBL; AK143948; BAE25624.1; -; mRNA.
DR   EMBL; AL591488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC039220; AAH39220.1; -; mRNA.
DR   EMBL; EF193393; ABM69091.1; -; mRNA.
DR   CCDS; CCDS17012.1; -. [P49698-1]
DR   PIR; S52074; S52074.
DR   RefSeq; NP_032287.2; NM_008261.3. [P49698-1]
DR   RefSeq; XP_006498850.1; XM_006498787.1. [P49698-2]
DR   AlphaFoldDB; P49698; -.
DR   SMR; P49698; -.
DR   BioGRID; 200354; 8.
DR   CORUM; P49698; -.
DR   FunCoup; P49698; 2080.
DR   IntAct; P49698; 2.
DR   STRING; 10090.ENSMUSP00000018094; -.
DR   iPTMnet; P49698; -.
DR   PhosphoSitePlus; P49698; -.
DR   SwissPalm; P49698; -.
DR   PaxDb; 10090-ENSMUSP00000018094; -.
DR   PeptideAtlas; P49698; -.
DR   ProteomicsDB; 273158; -. [P49698-1]
DR   ProteomicsDB; 273159; -. [P49698-2]
DR   Antibodypedia; 1326; 1159 antibodies from 47 providers.
DR   DNASU; 15378; -.
DR   Ensembl; ENSMPUT00000017816; ENSMPUP00000017557; ENSMPUG00000017669.
DR   Ensembl; ENSMUST00000018094.13; ENSMUSP00000018094.7; ENSMUSG00000017950.17. [P49698-1]
DR   GeneID; 15378; -.
DR   KEGG; mmu:15378; -.
DR   UCSC; uc008nta.2; mouse. [P49698-1]
DR   UCSC; uc012cit.1; mouse. [P49698-2]
DR   AGR; MGI:109128; -.
DR   CTD; 3172; -.
DR   MGI; MGI:109128; Hnf4a.
DR   VEuPathDB; HostDB:ENSMUSG00000017950; -.
DR   eggNOG; KOG4215; Eukaryota.
DR   GeneTree; ENSGT00940000157965; -.
DR   InParanoid; P49698; -.
DR   OMA; AEMMSRQ; -.
DR   OrthoDB; 5771769at2759; -.
DR   PhylomeDB; P49698; -.
DR   Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR   BioGRID-ORCS; 15378; 0 hits in 78 CRISPR screens.
DR   PRO; PR:P49698; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P49698; protein.
DR   Bgee; ENSMUSG00000017950; Expressed in paneth cell and 112 other cell types or tissues.
DR   ExpressionAtlas; P49698; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IC:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; ISO:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0050544; F:arachidonate binding; ISO:GO_Central.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:GO_Central.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR   GO; GO:0005504; F:fatty acid binding; ISO:GO_Central.
DR   GO; GO:0000062; F:fatty-acyl-CoA binding; ISO:GO_Central.
DR   GO; GO:0036042; F:long-chain fatty acyl-CoA binding; ISO:GO_Central.
DR   GO; GO:0052816; F:long-chain fatty acyl-CoA hydrolase activity; ISO:GO_Central.
DR   GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:GO_Central.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:GO_Central.
DR   GO; GO:0005102; F:signaling receptor binding; ISO:GO_Central.
DR   GO; GO:0070540; F:stearic acid binding; ISO:GO_Central.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR   GO; GO:0001221; F:transcription coregulator binding; ISO:GO_Central.
DR   GO; GO:0001222; F:transcription corepressor binding; ISO:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006637; P:acyl-CoA metabolic process; ISO:GO_Central.
DR   GO; GO:0007596; P:blood coagulation; ISO:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; ISO:GO_Central.
DR   GO; GO:0045216; P:cell-cell junction organization; ISO:GO_Central.
DR   GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR   GO; GO:0007164; P:establishment of tissue polarity; ISO:GO_Central.
DR   GO; GO:0010467; P:gene expression; IMP:MGI.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:BHF-UCL.
DR   GO; GO:0055088; P:lipid homeostasis; ISO:GO_Central.
DR   GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISO:GO_Central.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISO:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:GO_Central.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:GO_Central.
DR   GO; GO:0042308; P:negative regulation of protein import into nucleus; ISO:GO_Central.
DR   GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; ISO:GO_Central.
DR   GO; GO:0055091; P:phospholipid homeostasis; IMP:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; ISO:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:GO_Central.
DR   GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:GO_Central.
DR   GO; GO:1903268; P:positive regulation of ornithine catabolic process; ISO:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:MGI.
DR   GO; GO:0010470; P:regulation of gastrulation; IMP:MGI.
DR   GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; ISO:GO_Central.
DR   GO; GO:0032534; P:regulation of microvillus assembly; ISO:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR   GO; GO:0009749; P:response to glucose; IMP:BHF-UCL.
DR   GO; GO:0035983; P:response to trichostatin A; ISO:GO_Central.
DR   GO; GO:0007548; P:sex differentiation; IMP:MGI.
DR   GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IDA:MGI.
DR   GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
DR   GO; GO:0006805; P:xenobiotic metabolic process; ISO:GO_Central.
DR   CDD; cd06960; NR_DBD_HNF4A; 1.
DR   CDD; cd06931; NR_LBD_HNF4_like; 1.
DR   FunFam; 1.10.565.10:FF:000007; Hepatocyte nuclear factor 4 alpha; 1.
DR   FunFam; 3.30.50.10:FF:000012; Hepatocyte nuclear factor 4, alpha; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
DR   InterPro; IPR049636; HNF4-like_DBD.
DR   InterPro; IPR049635; HNF4_LBD.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR   InterPro; IPR050274; Nuclear_hormone_rcpt_NR2.
DR   InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR   InterPro; IPR001628; Znf_hrmn_rcpt.
DR   InterPro; IPR013088; Znf_NHR/GATA.
DR   PANTHER; PTHR24083; NUCLEAR HORMONE RECEPTOR; 1.
DR   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF00105; zf-C4; 1.
DR   PRINTS; PR01282; COUPTNFACTOR.
DR   PRINTS; PR00398; STRDHORMONER.
DR   PRINTS; PR00047; STROIDFINGER.
DR   SMART; SM00430; HOLI; 1.
DR   SMART; SM00399; ZnF_C4; 1.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Activator; Alternative splicing; Biological rhythms;
KW   DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW   Receptor; Reference proteome; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..474
FT                   /note="Hepatocyte nuclear factor 4-alpha"
FT                   /id="PRO_0000053559"
FT   DOMAIN          147..377
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        57..132
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         60..80
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         96..120
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          413..450
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           368..376
FT                   /note="9aaTAD"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   MOD_RES         142
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22449"
FT   MOD_RES         143
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22449"
FT   MOD_RES         144
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   MOD_RES         166
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   MOD_RES         167
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   MOD_RES         313
FT                   /note="Phosphoserine; by AMPK"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   MOD_RES         429
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         432
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17242355"
FT   MOD_RES         436
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         458
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   CROSSLNK        234
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   CROSSLNK        307
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P41235"
FT   VAR_SEQ         418..428
FT                   /note="CEWPRPRGQAA -> S (in isoform Short)"
FT                   /evidence="ECO:0000303|PubMed:7999795"
FT                   /id="VSP_003676"
FT   CONFLICT        55
FT                   /note="G -> S (in Ref. 1; BAA06101)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        365
FT                   /note="K -> R (in Ref. 3; BAE25624)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        378
FT                   /note="S -> L (in Ref. 6; ABM69091)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   474 AA;  52684 MW;  10843D528EAE87EE CRC64;
     MRLSKTLAGM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS SNSLGVSALC
     AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC
     FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSQQITSPIS GINGDIRAKK
     IANITDVCES MKEQLLVLVE WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK
     DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK
     GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL
     FGMAKIDNLL QEMLLGGSAS DAPHTHHPLH PHLMQEHMGT NVIVANTMPS HLSNGQMCEW
     PRPRGQAATP ETPQPSPPSG SGSESYKLLP GAITTIVKPP SAIPQPTITK QEAI
//