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Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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.

Miscellaneous

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi57 – 132Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri60 – 80NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri96 – 120NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • arachidonic acid binding Source: RGD
  • DNA binding transcription factor activity Source: RGD
  • fatty acid binding Source: RGD
  • fatty-acyl-CoA binding Source: RGD
  • long-chain fatty acyl-CoA binding Source: RGD
  • nuclear receptor activity Source: InterPro
  • palmitoyl-CoA hydrolase activity Source: RGD
  • protein homodimerization activity Source: RGD
  • proximal promoter sequence-specific DNA binding Source: RGD
  • repressing transcription factor binding Source: BHF-UCL
  • sequence-specific DNA binding Source: RGD
  • stearic acid binding Source: RGD
  • steroid hormone receptor activity Source: InterPro
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • acyl-CoA metabolic process Source: RGD
  • aging Source: RGD
  • cell-cell junction organization Source: RGD
  • cell differentiation Source: RGD
  • cellular response to hypoxia Source: RGD
  • establishment of tissue polarity Source: RGD
  • hepatocyte differentiation Source: RGD
  • negative regulation of activation of Janus kinase activity Source: RGD
  • negative regulation of cell migration Source: RGD
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of DNA binding transcription factor activity Source: RGD
  • negative regulation of mitotic cell cycle Source: RGD
  • negative regulation of protein import into nucleus, translocation Source: RGD
  • negative regulation of tyrosine phosphorylation of STAT protein Source: RGD
  • positive regulation of fatty acid biosynthetic process Source: RGD
  • positive regulation of gluconeogenesis Source: RGD
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • regulation of microvillus assembly Source: RGD
  • response to cAMP Source: RGD
  • response to dexamethasone Source: RGD
  • response to drug Source: RGD
  • response to glucose Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to nutrient levels Source: RGD

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2810 Hnf4a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi142 – 143SS → AG: Loss of phosphorylation, no effect on DNA-binding. 1 Publication2
Mutagenesisi142 – 143SS → LE: Loss of phosphorylation, no effect on DNA-binding. 1 Publication2

Chemistry databases

ChEMBLiCHEMBL3714705

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535601 – 474Hepatocyte nuclear factor 4-alphaAdd BLAST474

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei142Phosphoserine; by PKA1 Publication1
Modified residuei143Phosphoserine; by PKA1 Publication1
Modified residuei144PhosphotyrosineBy similarity1
Modified residuei166PhosphothreonineBy similarity1
Modified residuei167PhosphoserineBy similarity1
Cross-linki234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei313Phosphoserine; by AMPKBy similarity1
Modified residuei429PhosphothreonineBy similarity1
Modified residuei432PhosphothreonineCombined sources1
Modified residuei436PhosphoserineCombined sources1
Modified residuei458N6-acetyllysineBy similarity1

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

PaxDbiP22449
PRIDEiP22449

PTM databases

iPTMnetiP22449
PhosphoSitePlusiP22449

Expressioni

Tissue specificityi

Liver, kidney and intestine.

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

GO - Molecular functioni

  • protein homodimerization activity Source: RGD
  • repressing transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi247763, 1 interactor
IntActiP22449, 2 interactors
MINTiP22449
STRINGi10116.ENSRNOP00000011978

Structurei

Secondary structure

1474
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi152 – 164Combined sources13
Helixi184 – 203Combined sources20
Helixi206 – 209Combined sources4
Helixi213 – 222Combined sources10
Helixi224 – 234Combined sources11
Turni235 – 238Combined sources4
Beta strandi239 – 244Combined sources6
Beta strandi250 – 254Combined sources5
Helixi256 – 258Combined sources3
Turni259 – 261Combined sources3
Helixi262 – 271Combined sources10
Helixi273 – 279Combined sources7
Helixi283 – 294Combined sources12
Helixi305 – 324Combined sources20
Beta strandi326 – 328Combined sources3
Helixi333 – 338Combined sources6
Helixi341 – 360Combined sources20
Helixi368 – 373Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M7WX-ray2.80A/B/C/D142-391[»]
ProteinModelPortaliP22449
SMRiP22449
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22449

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini147 – 377NR LBDPROSITE-ProRule annotationAdd BLAST231

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri60 – 80NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri96 – 120NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4215 Eukaryota
ENOG410XQT8 LUCA
HOGENOMiHOG000260822
HOVERGENiHBG005606
InParanoidiP22449
KOiK07292
PhylomeDBiP22449

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR003068 COUP_TF
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01282 COUPTNFACTOR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti180K → R in CAA40412 (PubMed:2279702).Curated1
Sequence conflicti183N → S in CAA40412 (PubMed:2279702).Curated1
Sequence conflicti378S → L in ABM69090 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003677418 – 428CEWPRPRGQAA → S in isoform Short. 2 PublicationsAdd BLAST11

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

Similar proteinsi

Entry informationi

Entry nameiHNF4A_RAT
AccessioniPrimary (citable) accession number: P22449
Secondary accession number(s): A2ICG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 29, 2007
Last modified: May 23, 2018
This is version 175 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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