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P22449 (HNF4A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte nuclear factor 4-alpha

Short 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 names
Name:Hnf4a
Synonyms:Hnf-4, Hnf4, Nr2a1, Tcf14
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length474 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.

Subunit structure

Homodimerization is required for HNF4-alpha to bind to its recognition site. Interacts with PER2.

Subcellular location

Nucleus.

Tissue specificity

Liver, kidney and intestine.

Post-translational modification

Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA By similarity. Phosphorylated in the recognition sequence R-R-S-S near the DNA-binding domain; phosphorylation results in decrease in DNA-binding activity. Phosphorylation of HNF4 depends on the diet and is decreased by a carbohydrate-rich diet and is increased by fasting. Ref.4

The N-terminus is blocked.

Acetylation at Lys-458 lowers transcriptional activation by about two-fold By similarity.

Miscellaneous

DNA-binding activity of phosphorylated protein is reduced by fasting and by inducers of intracellular cyclic AMP.

Binds fatty acids.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence BAA01411.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAA40412.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacyl-CoA metabolic process

Inferred from direct assay PubMed 15870076. Source: RGD

cell differentiation

Inferred from mutant phenotype PubMed 16563856. Source: RGD

cell-cell junction organization

Inferred from direct assay PubMed 12749857. Source: RGD

establishment of tissue polarity

Inferred from direct assay PubMed 12749857. Source: RGD

negative regulation of cell proliferation

Inferred from direct assay PubMed 15541721. Source: RGD

negative regulation of mitotic cell cycle

Inferred from direct assay PubMed 15541721. Source: RGD

negative regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 16584384. Source: RGD

negative regulation of protein import into nucleus, translocation

Inferred from direct assay PubMed 16584384. Source: RGD

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 16584384. Source: RGD

negative regulation of tyrosine phosphorylation of Stat5 protein

Inferred from direct assay PubMed 16584384. Source: RGD

positive regulation of fatty acid biosynthetic process

Inferred from mutant phenotype PubMed 16800817. Source: RGD

positive regulation of gluconeogenesis

Inferred from mutant phenotype PubMed 16893891. Source: RGD

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20735474. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19651776. Source: BHF-UCL

regulation of microvillus assembly

Inferred from mutant phenotype PubMed 17178913. Source: RGD

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11741883. Source: RGD

response to cAMP

Inferred from expression pattern PubMed 16799975. Source: RGD

response to drug

Inferred from expression pattern PubMed 16799975. Source: RGD

response to glucose

Inferred from direct assay PubMed 16800817. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16799975. Source: RGD

nucleus

Inferred from direct assay PubMed 19651776. Source: BHF-UCL

transcription factor complex

Inferred from direct assay PubMed 11741883. Source: RGD

   Molecular_functionDNA binding

Inferred from direct assay PubMed 11741883. Source: RGD

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 20735474. Source: BHF-UCL

fatty acid binding

Inferred from physical interaction PubMed 15870076. Source: RGD

fatty-acyl-CoA binding

Inferred from physical interaction PubMed 15870076. Source: RGD

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from electronic annotation. Source: InterPro

palmitoyl-CoA hydrolase activity

Inferred from direct assay PubMed 15870076. Source: RGD

protein binding

Inferred from physical interaction PubMed 24140341. Source: IntAct

protein homodimerization activity

Inferred from mutant phenotype Ref.1. Source: RGD

repressing transcription factor binding

Inferred from physical interaction PubMed 19651776. Source: BHF-UCL

sequence-specific DNA binding

Inferred from mutant phenotype PubMed 16893891. Source: RGD

sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 16893891. Source: RGD

steroid hormone receptor activity

Traceable author statement PubMed 11741883. Source: RGD

transcription factor binding

Inferred from physical interaction PubMed 16800817. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Fabp1P026923EBI-5261592,EBI-1209448

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P22449-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: P22449-2)

The sequence of this isoform differs from the canonical sequence as follows:
     418-428: CEWPRPRGQAA → S

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 474474Hepatocyte nuclear factor 4-alpha
PRO_0000053560

Regions

DNA binding57 – 13276Nuclear receptor
Zinc finger60 – 8021NR C4-type
Zinc finger96 – 12025NR C4-type

Amino acid modifications

Modified residue1421Phosphoserine; by PKA Probable
Modified residue1431Phosphoserine; by PKA Probable
Modified residue1661Phosphothreonine By similarity
Modified residue1671Phosphoserine By similarity
Modified residue3131Phosphoserine; by AMPK By similarity
Modified residue4291Phosphothreonine By similarity
Modified residue4321Phosphothreonine By similarity
Modified residue4361Phosphoserine By similarity
Modified residue4581N6-acetyllysine By similarity
Cross-link234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence418 – 42811CEWPRPRGQAA → S in isoform Short.
VSP_003677

Experimental info

Mutagenesis142 – 1432SS → AG: Loss of phosphorylation, no effect on DNA-binding.
Mutagenesis142 – 1432SS → LE: Loss of phosphorylation, no effect on DNA-binding.
Sequence conflict1801K → R in CAA40412. Ref.1
Sequence conflict1831N → S in CAA40412. Ref.1
Sequence conflict3781S → L in ABM69090. Ref.3

Secondary structure

................................. 474
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified May 29, 2007. Version 3.
Checksum: E6DECA74FEA65E75

FASTA47452,712
        10         20         30         40         50         60 
MRLSKTLADM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS SNSLGVSALC 

        70         80         90        100        110        120 
AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC 

       130        140        150        160        170        180 
FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSQQITSPIS GINGDIRAKK 

       190        200        210        220        230        240 
IANITDVCES MKEQLLVLVE WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK 

       250        260        270        280        290        300 
DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK 

       310        320        330        340        350        360 
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL 

       370        380        390        400        410        420 
FGMAKIDNLL QEMLLGGSAS DAPHAHHPLH PHLMQEHMGT NVIVANTMPS HLSNGQMCEW 

       430        440        450        460        470 
PRPRGQAATP ETPQPSPPSG SGSESYKLLP GAITTIVKPP SAIPQPTITK QEAI 

« Hide

Isoform Short [UniParc].

Checksum: 6B0961382FB9A0F7
Show »

FASTA46451,546

References

[1]"Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily."
Sladek F.M., Zhong W., Lai E., Darnell J.E. Jr.
Genes Dev. 4:2353-2365(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[2]"A novel isoform of rat hepatocyte nuclear factor 4 (HNF-4)."
Hata S., Tsukamoto T., Osumi T.
Biochim. Biophys. Acta 1131:211-213(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
Strain: Wistar.
Tissue: Liver.
[3]"Expression of HNF4 alpha 3 in pancreatic islets and Ins-1 beta cells."
Huang J., Karakucuk V., Levitsky L.L., Rhoads D.B.
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-378 (ISOFORMS LONG AND SHORT).
Strain: New England Deaconess Hospital.
Tissue: Liver.
[4]"Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4."
Viollet B., Kahn A., Raymondjean M.
Mol. Cell. Biol. 17:4208-4219(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS, PHOSPHORYLATION AT SER-142 AND SER-143.
[5]"Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand."
Dhe-Paganon S., Duda K., Iwamoto M., Chi Y.I., Shoelson S.E.
J. Biol. Chem. 277:37973-37976(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 142-391, FATTY ACID BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D10554 mRNA. Translation: BAA01411.1. Different initiation.
X57133 mRNA. Translation: CAA40412.1. Different initiation.
EF193392 mRNA. Translation: ABM69090.1.
PIRA36471.
S23502.
RefSeqNP_071516.2. NM_022180.2.
UniGeneRn.12238.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7WX-ray2.80A/B/C/D142-391[»]
ProteinModelPortalP22449.
SMRP22449. Positions 59-134, 151-376.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247763. 1 interaction.
IntActP22449. 3 interactions.

PTM databases

PhosphoSiteP22449.

Proteomic databases

PRIDEP22449.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25735.
KEGGrno:25735.

Organism-specific databases

CTD3172.
RGD2810. Hnf4a.

Phylogenomic databases

eggNOGNOG241134.
HOGENOMHOG000260822.
HOVERGENHBG005606.
InParanoidP22449.
KOK07292.
PhylomeDBP22449.

Gene expression databases

GenevestigatorP22449.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR003068. COUP_TF.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22449.
NextBio607871.
PROP22449.

Entry information

Entry nameHNF4A_RAT
AccessionPrimary (citable) accession number: P22449
Secondary accession number(s): A2ICG9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 29, 2007
Last modified: July 9, 2014
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references