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P22449

- HNF4A_RAT

UniProt

P22449 - HNF4A_RAT

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Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi57 – 13276Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: RGD
  2. fatty acid binding Source: RGD
  3. fatty-acyl-CoA binding Source: RGD
  4. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
  5. palmitoyl-CoA hydrolase activity Source: RGD
  6. protein homodimerization activity Source: RGD
  7. repressing transcription factor binding Source: BHF-UCL
  8. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  9. sequence-specific DNA binding Source: RGD
  10. sequence-specific DNA binding transcription factor activity Source: RGD
  11. steroid hormone receptor activity Source: RGD
  12. transcription factor binding Source: RGD
  13. zinc ion binding Source: InterPro

GO - Biological processi

  1. acyl-CoA metabolic process Source: RGD
  2. cell-cell junction organization Source: RGD
  3. cell differentiation Source: RGD
  4. establishment of tissue polarity Source: RGD
  5. negative regulation of cell proliferation Source: RGD
  6. negative regulation of mitotic cell cycle Source: RGD
  7. negative regulation of peptidyl-tyrosine phosphorylation Source: RGD
  8. negative regulation of protein import into nucleus, translocation Source: RGD
  9. negative regulation of sequence-specific DNA binding transcription factor activity Source: RGD
  10. negative regulation of tyrosine phosphorylation of Stat5 protein Source: RGD
  11. positive regulation of fatty acid biosynthetic process Source: RGD
  12. positive regulation of gluconeogenesis Source: RGD
  13. positive regulation of transcription, DNA-templated Source: BHF-UCL
  14. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  15. regulation of microvillus assembly Source: RGD
  16. regulation of transcription, DNA-templated Source: RGD
  17. response to cAMP Source: RGD
  18. response to drug Source: RGD
  19. response to glucose Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Hnf4a
Synonyms:Hnf-4, Hnf4, Nr2a1, Tcf14
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2810. Hnf4a.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. nucleus Source: BHF-UCL
  3. transcription factor complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi142 – 1432SS → AG: Loss of phosphorylation, no effect on DNA-binding. 1 Publication
Mutagenesisi142 – 1432SS → LE: Loss of phosphorylation, no effect on DNA-binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 474474Hepatocyte nuclear factor 4-alphaPRO_0000053560Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei142 – 1421Phosphoserine; by PKA1 Publication
Modified residuei143 – 1431Phosphoserine; by PKA1 Publication
Modified residuei166 – 1661PhosphothreonineBy similarity
Modified residuei167 – 1671PhosphoserineBy similarity
Cross-linki234 – 234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki307 – 307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei313 – 3131Phosphoserine; by AMPKBy similarity
Modified residuei429 – 4291PhosphothreonineBy similarity
Modified residuei432 – 4321PhosphothreonineBy similarity
Modified residuei436 – 4361PhosphoserineBy similarity
Modified residuei458 – 4581N6-acetyllysineBy similarity

Post-translational modificationi

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.By similarity1 Publication
The N-terminus is blocked.
Acetylation at Lys-458 lowers transcriptional activation by about two-fold.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP22449.

PTM databases

PhosphoSiteiP22449.

Expressioni

Tissue specificityi

Liver, kidney and intestine.

Gene expression databases

GenevestigatoriP22449.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Fabp1P026923EBI-5261592,EBI-1209448

Protein-protein interaction databases

BioGridi247763. 1 interaction.
IntActiP22449. 3 interactions.

Structurei

Secondary structure

1
474
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi152 – 16413Combined sources
Helixi184 – 20320Combined sources
Helixi206 – 2094Combined sources
Helixi213 – 22210Combined sources
Helixi224 – 23411Combined sources
Turni235 – 2384Combined sources
Beta strandi239 – 2446Combined sources
Beta strandi250 – 2545Combined sources
Helixi256 – 2583Combined sources
Turni259 – 2613Combined sources
Helixi262 – 27110Combined sources
Helixi273 – 2797Combined sources
Helixi283 – 29412Combined sources
Helixi305 – 32420Combined sources
Beta strandi326 – 3283Combined sources
Helixi333 – 3386Combined sources
Helixi341 – 36020Combined sources
Helixi368 – 3736Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M7WX-ray2.80A/B/C/D142-391[»]
ProteinModelPortaliP22449.
SMRiP22449. Positions 59-134, 151-376.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22449.

Family & Domainsi

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG241134.
HOGENOMiHOG000260822.
HOVERGENiHBG005606.
InParanoidiP22449.
KOiK07292.
PhylomeDBiP22449.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. 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]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform Long (identifier: P22449-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MRLSKTLADM 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 DAPHAHHPLH PHLMQEHMGT
410 420 430 440 450
NVIVANTMPS HLSNGQMCEW PRPRGQAATP ETPQPSPPSG SGSESYKLLP
460 470
GAITTIVKPP SAIPQPTITK QEAI
Length:474
Mass (Da):52,712
Last modified:May 29, 2007 - v3
Checksum:iE6DECA74FEA65E75
GO
Isoform Short (identifier: P22449-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:464
Mass (Da):51,546
Checksum:i6B0961382FB9A0F7
GO

Sequence cautioni

The sequence BAA01411.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA40412.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801K → R in CAA40412. (PubMed:2279702)Curated
Sequence conflicti183 – 1831N → S in CAA40412. (PubMed:2279702)Curated
Sequence conflicti378 – 3781S → L in ABM69090. 1 PublicationCurated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei418 – 42811CEWPRPRGQAA → S in isoform Short. 2 PublicationsVSP_003677Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10554 mRNA. Translation: BAA01411.1. Different initiation.
X57133 mRNA. Translation: CAA40412.1. Different initiation.
EF193392 mRNA. Translation: ABM69090.1.
PIRiA36471.
S23502.
RefSeqiNP_071516.2. NM_022180.2.
UniGeneiRn.12238.

Genome annotation databases

GeneIDi25735.
KEGGirno:25735.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10554 mRNA. Translation: BAA01411.1 . Different initiation.
X57133 mRNA. Translation: CAA40412.1 . Different initiation.
EF193392 mRNA. Translation: ABM69090.1 .
PIRi A36471.
S23502.
RefSeqi NP_071516.2. NM_022180.2.
UniGenei Rn.12238.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1M7W X-ray 2.80 A/B/C/D 142-391 [» ]
ProteinModelPortali P22449.
SMRi P22449. Positions 59-134, 151-376.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247763. 1 interaction.
IntActi P22449. 3 interactions.

PTM databases

PhosphoSitei P22449.

Proteomic databases

PRIDEi P22449.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25735.
KEGGi rno:25735.

Organism-specific databases

CTDi 3172.
RGDi 2810. Hnf4a.

Phylogenomic databases

eggNOGi NOG241134.
HOGENOMi HOG000260822.
HOVERGENi HBG005606.
InParanoidi P22449.
KOi K07292.
PhylomeDBi P22449.

Miscellaneous databases

EvolutionaryTracei P22449.
NextBioi 607871.
PROi P22449.

Gene expression databases

Genevestigatori P22449.

Family and domain databases

Gene3Di 1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProi IPR003068. 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 ]
Pfami PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PRINTSi PR01282. COUPTNFACTOR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 1 hit.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiHNF4A_RAT
AccessioniPrimary (citable) accession number: P22449
Secondary accession number(s): A2ICG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 29, 2007
Last modified: November 26, 2014
This is version 148 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3