Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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)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

GO - Biological processi

  • blood coagulation Source: MGI
  • endocrine pancreas development Source: Reactome
  • glucose homeostasis Source: BHF-UCL
  • lipid homeostasis Source: MGI
  • lipid metabolic process Source: MGI
  • negative regulation of cell growth Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • ornithine metabolic process Source: MGI
  • phospholipid homeostasis Source: BHF-UCL
  • positive regulation of cholesterol homeostasis Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of gastrulation Source: MGI
  • regulation of insulin secretion Source: BHF-UCL
  • regulation of lipid metabolic process Source: MGI
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to glucose Source: BHF-UCL
  • 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
  • xenobiotic metabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-210745. Regulation of gene expression in beta cells.
R-MMU-383280. Nuclear Receptor transcription pathway.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:109128. Hnf4a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: Reactome
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Pancreatic beta-cells-specific knockout results in hyperinsulinemia and hypoglycemia.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535591 – 474Hepatocyte nuclear factor 4-alphaAdd BLAST474

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei142PhosphoserineBy similarity1
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 residuei429PhosphothreonineCombined sources1
Modified residuei432PhosphothreonineCombined sources1
Modified residuei436PhosphoserineCombined sources1
Modified residuei458N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA (By similarity).By similarity
Acetylation at Lys-458 lowers transcriptional activation by about two-fold.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP49698.
PaxDbiP49698.
PeptideAtlasiP49698.
PRIDEiP49698.

PTM databases

iPTMnetiP49698.
PhosphoSitePlusiP49698.

Expressioni

Gene expression databases

BgeeiENSMUSG00000017950.
CleanExiMM_HNF4A.
ExpressionAtlasiP49698. baseline and differential.
GenevisibleiP49698. MM.

Interactioni

Subunit structurei

Homodimerization is required for HNF4-alpha to bind to its recognition site. Interacts with PER2.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200354. 4 interactors.
IntActiP49698. 3 interactors.
MINTiMINT-5027670.
STRINGi10090.ENSMUSP00000018094.

Structurei

3D structure databases

ProteinModelPortaliP49698.
SMRiP49698.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

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.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260822.
HOVERGENiHBG005606.
InParanoidiP49698.
KOiK07292.
OMAiANTMPSH.
OrthoDBiEOG091G0A89.
PhylomeDBiP49698.
TreeFamiTF352097.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. COUP_TF.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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. AlignAdd to basket

Isoform Long (identifier: P49698-1) [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
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
Length:474
Mass (Da):52,684
Last modified:May 29, 2007 - v2
Checksum:i10843D528EAE87EE
GO
Isoform Short (identifier: P49698-2) [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):51,518
Checksum:i4C293463C33B2D76
GO

Sequence cautioni

The sequence BAA06101 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55G → S in BAA06101 (PubMed:7999795).Curated1
Sequence conflicti365K → R in BAE25624 (PubMed:16141072).Curated1
Sequence conflicti378S → L in ABM69091 (Ref. 6) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003676418 – 428CEWPRPRGQAA → S in isoform Short. 1 PublicationAdd BLAST11

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.
CCDSiCCDS17012.1. [P49698-1]
PIRiS52074.
RefSeqiNP_032287.2. NM_008261.3. [P49698-1]
XP_006498850.1. XM_006498787.1. [P49698-2]
UniGeneiMm.202383.

Genome annotation databases

EnsembliENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. [P49698-1]
GeneIDi15378.
KEGGimmu:15378.
UCSCiuc008nta.2. mouse. [P49698-1]
uc012cit.1. mouse. [P49698-2]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS17012.1. [P49698-1]
PIRiS52074.
RefSeqiNP_032287.2. NM_008261.3. [P49698-1]
XP_006498850.1. XM_006498787.1. [P49698-2]
UniGeneiMm.202383.

3D structure databases

ProteinModelPortaliP49698.
SMRiP49698.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200354. 4 interactors.
IntActiP49698. 3 interactors.
MINTiMINT-5027670.
STRINGi10090.ENSMUSP00000018094.

PTM databases

iPTMnetiP49698.
PhosphoSitePlusiP49698.

Proteomic databases

MaxQBiP49698.
PaxDbiP49698.
PeptideAtlasiP49698.
PRIDEiP49698.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. [P49698-1]
GeneIDi15378.
KEGGimmu:15378.
UCSCiuc008nta.2. mouse. [P49698-1]
uc012cit.1. mouse. [P49698-2]

Organism-specific databases

CTDi3172.
MGIiMGI:109128. Hnf4a.

Phylogenomic databases

eggNOGiKOG4215. Eukaryota.
ENOG410XQT8. LUCA.
GeneTreeiENSGT00760000118948.
HOGENOMiHOG000260822.
HOVERGENiHBG005606.
InParanoidiP49698.
KOiK07292.
OMAiANTMPSH.
OrthoDBiEOG091G0A89.
PhylomeDBiP49698.
TreeFamiTF352097.

Enzyme and pathway databases

ReactomeiR-MMU-210745. Regulation of gene expression in beta cells.
R-MMU-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

ChiTaRSiHnf4a. mouse.
PROiP49698.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000017950.
CleanExiMM_HNF4A.
ExpressionAtlasiP49698. baseline and differential.
GenevisibleiP49698. MM.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003068. COUP_TF.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_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]
ProtoNetiSearch...

Entry informationi

Entry nameiHNF4A_MOUSE
AccessioniPrimary (citable) accession number: P49698
Secondary accession number(s): A2A5I5
, A2ICH0, Q3UNX3, Q8CFY1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 29, 2007
Last modified: November 2, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Binds fatty acids.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.