HNF4A_MOUSE
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 03-AUG-2022, entry version 199.
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-ARNTL/BMAL1
CC transcriptional activity and is essential for circadian rhythm
CC maintenance and period regulation in the liver and colon cells
CC (PubMed:30530698). {ECO:0000250|UniProtKB:P41235,
CC ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30555544}.
CC -!- SUBUNIT: Homodimerization is required for HNF4-alpha to bind to its
CC recognition site (By similarity). Interacts with CLOCK, ARNTL 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 transcriptionnally 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 IntAct; P49698; 2.
DR STRING; 10090.ENSMUSP00000018094; -.
DR iPTMnet; P49698; -.
DR PhosphoSitePlus; P49698; -.
DR SwissPalm; P49698; -.
DR MaxQB; P49698; -.
DR PaxDb; P49698; -.
DR PeptideAtlas; P49698; -.
DR PRIDE; P49698; -.
DR ProteomicsDB; 273158; -. [P49698-1]
DR ProteomicsDB; 273159; -. [P49698-2]
DR Antibodypedia; 1326; 996 antibodies from 43 providers.
DR DNASU; 15378; -.
DR Ensembl; ENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. [P49698-1]
DR GeneID; 15378; -.
DR KEGG; mmu:15378; -.
DR UCSC; uc008nta.2; mouse. [P49698-1]
DR UCSC; uc012cit.1; mouse. [P49698-2]
DR CTD; 3172; -.
DR MGI; MGI:109128; Hnf4a.
DR VEuPathDB; HostDB:ENSMUSG00000017950; -.
DR eggNOG; KOG4215; Eukaryota.
DR GeneTree; ENSGT00940000157965; -.
DR InParanoid; P49698; -.
DR OMA; PVMILRD; -.
DR OrthoDB; 622732at2759; -.
DR PhylomeDB; P49698; -.
DR TreeFam; TF352097; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 15378; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Hnf4a; mouse.
DR PRO; PR:P49698; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P49698; protein.
DR Bgee; ENSMUSG00000017950; Expressed in paneth cell and 111 other tissues.
DR ExpressionAtlas; P49698; baseline and differential.
DR Genevisible; P49698; MM.
DR GO; GO:0000785; C:chromatin; IC:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0050544; F:arachidonic acid binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
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:MGI.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISO:MGI.
DR GO; GO:0036042; F:long-chain fatty acyl-CoA binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
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:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0070540; F:stearic acid binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006637; P:acyl-CoA metabolic process; ISO:MGI.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0007596; P:blood coagulation; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; ISO:MGI.
DR GO; GO:0045216; P:cell-cell junction organization; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0007164; P:establishment of tissue polarity; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:BHF-UCL.
DR GO; GO:0070365; P:hepatocyte differentiation; IEA:InterPro.
DR GO; GO:0055088; P:lipid homeostasis; ISO:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR GO; GO:1902569; P:negative regulation of activation of Janus kinase activity; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0006591; P:ornithine metabolic process; ISO:MGI.
DR GO; GO:0055091; P:phospholipid homeostasis; IMP:BHF-UCL.
DR GO; GO:0045723; P:positive regulation of fatty acid biosynthetic process; ISO:MGI.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
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:MGI.
DR GO; GO:0032534; P:regulation of microvillus assembly; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0009749; P:response to glucose; IMP:BHF-UCL.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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:0060395; P:SMAD protein signal transduction; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
DR GO; GO:0003323; P:type B pancreatic cell development; IEA:InterPro.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR039067; HNF4A.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR24083:SF41; PTHR24083:SF41; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 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
