UniProtKB - P49698 (HNF4A_MOUSE)
Hepatocyte nuclear factor 4-alpha
Hnf4a
Functioni
Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitatating the recruitment of RNA pol II to the promoters of target genes (By similarity).
Activates the transcription of CYP2C38 (PubMed:30555544).
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).
By similarity2 PublicationsMiscellaneous
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 57 – 132 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 76 | |
Zinc fingeri | 60 – 80 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 96 – 120 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- arachidonic acid binding Source: MGI
- chromatin binding Source: MGI
- cis-regulatory region sequence-specific DNA binding Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor activity Source: BHF-UCL
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor binding Source: MGI
- fatty acid binding Source: MGI
- fatty-acyl-CoA binding Source: MGI
- long-chain fatty acyl-CoA binding Source: MGI
- nuclear receptor activity Source: GO_Central
- palmitoyl-CoA hydrolase activity Source: MGI
- protein-containing complex binding Source: MGI
- protein homodimerization activity Source: MGI
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- sequence-specific DNA binding Source: MGI
- sequence-specific double-stranded DNA binding Source: MGI
- signaling receptor binding Source: MGI
- stearic acid binding Source: MGI
- transcription cis-regulatory region binding Source: BHF-UCL
- zinc ion binding Source: InterPro
GO - Biological processi
- acyl-CoA metabolic process Source: MGI
- anatomical structure development Source: GO_Central
- blood coagulation Source: MGI
- cell-cell junction organization Source: MGI
- cell differentiation Source: MGI
- cholesterol homeostasis Source: BHF-UCL
- establishment of tissue polarity Source: MGI
- glucose homeostasis Source: BHF-UCL
- hepatocyte differentiation Source: InterPro
- lipid homeostasis Source: MGI
- lipid metabolic process Source: MGI
- negative regulation of activation of Janus kinase activity Source: MGI
- negative regulation of cell growth Source: MGI
- negative regulation of cell migration Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of DNA-binding transcription factor activity Source: MGI
- negative regulation of mitotic cell cycle Source: MGI
- negative regulation of protein import into nucleus Source: MGI
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of tyrosine phosphorylation of STAT protein Source: MGI
- ornithine metabolic process Source: MGI
- phospholipid homeostasis Source: BHF-UCL
- positive regulation of fatty acid biosynthetic process Source: MGI
- positive regulation of gluconeogenesis Source: MGI
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- regulation of circadian rhythm Source: UniProtKB
- regulation of gastrulation Source: MGI
- regulation of insulin secretion Source: BHF-UCL
- regulation of lipid metabolic process Source: MGI
- regulation of microvillus assembly Source: MGI
- regulation of transcription, DNA-templated Source: MGI
- regulation of transcription by RNA polymerase II Source: MGI
- response to glucose Source: BHF-UCL
- rhythmic process Source: UniProtKB-KW
- sex differentiation Source: MGI
- signal transduction involved in regulation of gene expression Source: MGI
- SMAD protein signal transduction Source: MGI
- triglyceride homeostasis Source: BHF-UCL
- type B pancreatic cell development Source: InterPro
- xenobiotic metabolic process Source: MGI
Keywordsi
Molecular function | Activator, DNA-binding, Receptor, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-383280, Nuclear Receptor transcription pathway |
Names & Taxonomyi
Protein namesi | Recommended name: Hepatocyte nuclear factor 4-alphaShort name: HNF-4-alpha Alternative name(s): Nuclear receptor subfamily 2 group A member 1 Transcription factor 14 Short name: TCF-14 Transcription factor HNF-4 |
Gene namesi | Name:Hnf4a Synonyms:Hnf-4, Hnf4, Nr2a1, Tcf14 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109128, Hnf4a |
VEuPathDBi | HostDB:ENSMUSG00000017950 |
Subcellular locationi
Nucleus
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
Keywords - Cellular componenti
NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053559 | 1 – 474 | Hepatocyte nuclear factor 4-alphaAdd BLAST | 474 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 142 | PhosphoserineBy similarity | 1 | |
Modified residuei | 143 | PhosphoserineBy similarity | 1 | |
Modified residuei | 144 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 166 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 167 | PhosphoserineBy similarity | 1 | |
Cross-linki | 234 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 307 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 313 | Phosphoserine; by AMPKBy similarity | 1 | |
Modified residuei | 429 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 432 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 436 | PhosphoserineCombined sources | 1 | |
Modified residuei | 458 | N6-acetyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | P49698 |
PaxDbi | P49698 |
PeptideAtlasi | P49698 |
PRIDEi | P49698 |
ProteomicsDBi | 273158 [P49698-1] 273159 [P49698-2] |
PTM databases
iPTMneti | P49698 |
PhosphoSitePlusi | P49698 |
SwissPalmi | P49698 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000017950, Expressed in ileum and 168 other tissues |
ExpressionAtlasi | P49698, baseline and differential |
Genevisiblei | P49698, MM |
Interactioni
Subunit structurei
Homodimerization is required for HNF4-alpha to bind to its recognition site (By similarity).
Interacts with CLOCK, ARNTL and PER1 (By similarity).
Interacts with PER2 (PubMed:20159955).
Interacts with CRY1 and CRY2 (PubMed:28751364).
Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionnally inactive (By similarity).
Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- DNA-binding transcription factor binding Source: MGI
- protein homodimerization activity Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- signaling receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 200354, 8 interactors |
CORUMi | P49698 |
IntActi | P49698, 2 interactors |
STRINGi | 10090.ENSMUSP00000018094 |
Miscellaneous databases
RNActi | P49698, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 147 – 377 | NR LBDPROSITE-ProRule annotationAdd BLAST | 231 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 413 – 450 | DisorderedSequence analysisAdd BLAST | 38 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 368 – 376 | 9aaTADBy similarity | 9 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 60 – 80 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 96 – 120 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4215, Eukaryota |
GeneTreei | ENSGT00940000157965 |
InParanoidi | P49698 |
OMAi | PVMILRD |
OrthoDBi | 622732at2759 |
PhylomeDBi | P49698 |
TreeFami | TF352097 |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR039067, HNF4A IPR035500, NHR-like_dom_sf IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
PANTHERi | PTHR24083:SF41, PTHR24083:SF41, 1 hit |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRLSKTLAGM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS
60 70 80 90 100
SNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR
110 120 130 140 150
QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP
160 170 180 190 200
SINALLQAEV LSQQITSPIS GINGDIRAKK IANITDVCES MKEQLLVLVE
210 220 230 240 250
WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI
260 270 280 290 300
VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK
310 320 330 340 350
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ
360 370 380 390 400
MIEQIQFIKL FGMAKIDNLL QEMLLGGSAS DAPHTHHPLH PHLMQEHMGT
410 420 430 440 450
NVIVANTMPS HLSNGQMCEW PRPRGQAATP ETPQPSPPSG SGSESYKLLP
460 470
GAITTIVKPP SAIPQPTITK QEAI
The sequence of this isoform differs from the canonical sequence as follows:
418-428: CEWPRPRGQAA → S
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketZ4YKX0 | Z4YKX0_MOUSE | Hepatocyte nuclear factor 4-alpha | Hnf4a | 465 | Annotation score: | ||
A2A5I6 | A2A5I6_MOUSE | Hepatocyte nuclear factor 4-alpha | Hnf4a | 191 | Annotation score: | ||
A2A5I4 | A2A5I4_MOUSE | Hepatocyte nuclear factor 4-alpha | Hnf4a | 100 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 55 | G → S in BAA06101 (PubMed:7999795).Curated | 1 | |
Sequence conflicti | 365 | K → R in BAE25624 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 378 | S → L in ABM69091 (Ref. 6) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_003676 | 418 – 428 | CEWPRPRGQAA → S in isoform Short. 1 PublicationAdd BLAST | 11 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D29015 mRNA Translation: BAA06101.1 Different initiation. AY902317 Genomic DNA Translation: AAX90602.1 AK143948 mRNA Translation: BAE25624.1 AL591488 Genomic DNA No translation available. BC039220 mRNA Translation: AAH39220.1 EF193393 mRNA Translation: ABM69091.1 |
CCDSi | CCDS17012.1 [P49698-1] |
PIRi | S52074 |
RefSeqi | NP_032287.2, NM_008261.3 [P49698-1] XP_006498850.1, XM_006498787.1 [P49698-2] |
Genome annotation databases
Ensembli | ENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950 [P49698-1] |
GeneIDi | 15378 |
KEGGi | mmu:15378 |
UCSCi | uc008nta.2, mouse [P49698-1] uc012cit.1, mouse [P49698-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D29015 mRNA Translation: BAA06101.1 Different initiation. AY902317 Genomic DNA Translation: AAX90602.1 AK143948 mRNA Translation: BAE25624.1 AL591488 Genomic DNA No translation available. BC039220 mRNA Translation: AAH39220.1 EF193393 mRNA Translation: ABM69091.1 |
CCDSi | CCDS17012.1 [P49698-1] |
PIRi | S52074 |
RefSeqi | NP_032287.2, NM_008261.3 [P49698-1] XP_006498850.1, XM_006498787.1 [P49698-2] |
3D structure databases
SMRi | P49698 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200354, 8 interactors |
CORUMi | P49698 |
IntActi | P49698, 2 interactors |
STRINGi | 10090.ENSMUSP00000018094 |
PTM databases
iPTMneti | P49698 |
PhosphoSitePlusi | P49698 |
SwissPalmi | P49698 |
Proteomic databases
MaxQBi | P49698 |
PaxDbi | P49698 |
PeptideAtlasi | P49698 |
PRIDEi | P49698 |
ProteomicsDBi | 273158 [P49698-1] 273159 [P49698-2] |
Protocols and materials databases
Antibodypediai | 1326, 971 antibodies from 41 providers |
DNASUi | 15378 |
Genome annotation databases
Ensembli | ENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950 [P49698-1] |
GeneIDi | 15378 |
KEGGi | mmu:15378 |
UCSCi | uc008nta.2, mouse [P49698-1] uc012cit.1, mouse [P49698-2] |
Organism-specific databases
CTDi | 3172 |
MGIi | MGI:109128, Hnf4a |
VEuPathDBi | HostDB:ENSMUSG00000017950 |
Phylogenomic databases
eggNOGi | KOG4215, Eukaryota |
GeneTreei | ENSGT00940000157965 |
InParanoidi | P49698 |
OMAi | PVMILRD |
OrthoDBi | 622732at2759 |
PhylomeDBi | P49698 |
TreeFami | TF352097 |
Enzyme and pathway databases
Reactomei | R-MMU-383280, Nuclear Receptor transcription pathway |
Miscellaneous databases
BioGRID-ORCSi | 15378, 0 hits in 66 CRISPR screens |
ChiTaRSi | Hnf4a, mouse |
PROi | PR:P49698 |
RNActi | P49698, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000017950, Expressed in ileum and 168 other tissues |
ExpressionAtlasi | P49698, baseline and differential |
Genevisiblei | P49698, MM |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR039067, HNF4A IPR035500, NHR-like_dom_sf IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
PANTHERi | PTHR24083:SF41, PTHR24083:SF41, 1 hit |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HNF4A_MOUSE | |
Accessioni | P49698Primary (citable) accession number: P49698 Secondary accession number(s): A2A5I5 Q8CFY1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1996 |
Last sequence update: | May 29, 2007 | |
Last modified: | February 23, 2022 | |
This is version 197 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families