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P49698 (HNF4A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. 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·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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. Ref.8

Subcellular location

Nucleus.

Post-translational modification

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.

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

Miscellaneous

Binds fatty acids By similarity.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence BAA06101.1 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 termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from direct assay PubMed 9420335. Source: MGI

blood coagulation

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Traceable author statement. Source: Reactome

glucose homeostasis

Inferred from mutant phenotype PubMed 15761495. Source: BHF-UCL

lipid metabolic process

Inferred from mutant phenotype PubMed 16498401. Source: MGI

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

ornithine metabolic process

Inferred from electronic annotation. Source: Ensembl

phospholipid homeostasis

Inferred from mutant phenotype PubMed 11158324. Source: BHF-UCL

positive regulation of cholesterol homeostasis

Inferred from mutant phenotype PubMed 11158324. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15761495. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 9408084PubMed 9421506. Source: MGI

regulation of gastrulation

Inferred from mutant phenotype PubMed 7958910. Source: MGI

regulation of insulin secretion

Inferred from mutant phenotype PubMed 15761495. Source: BHF-UCL

regulation of lipid metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 9053305. Source: MGI

response to glucose

Inferred from mutant phenotype PubMed 15761495. Source: BHF-UCL

sex differentiation

Inferred from mutant phenotype PubMed 17412818. Source: MGI

signal transduction involved in regulation of gene expression

Inferred from direct assay PubMed 18462699. Source: MGI

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10859308. Source: GOC

triglyceride homeostasis

Inferred from mutant phenotype PubMed 11158324. Source: BHF-UCL

xenobiotic metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 15767668PubMed 16537911PubMed 17021047PubMed 8306889PubMed 9408084PubMed 9421506. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 15014077PubMed 15581617PubMed 16912278. Source: MGI

RNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 17932483. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 10859308. Source: MGI

fatty acid binding

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 8306889. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 15761495. Source: BHF-UCL

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region DNA binding

Inferred from direct assay PubMed 15761495. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P49698-1)

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: P49698-2)

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_0000053559

Regions

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

Amino acid modifications

Modified residue1421Phosphoserine By similarity
Modified residue1661Phosphothreonine By similarity
Modified residue1671Phosphoserine By similarity
Modified residue3131Phosphoserine; by AMPK By similarity
Modified residue4291Phosphothreonine Ref.7
Modified residue4321Phosphothreonine Ref.7
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_003676

Experimental info

Sequence conflict551G → S in BAA06101. Ref.1
Sequence conflict3651K → R in BAE25624. Ref.3
Sequence conflict3781S → L in ABM69091. Ref.6

Sequences

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

Last modified May 29, 2007. Version 2.
Checksum: 10843D528EAE87EE

FASTA47452,684
        10         20         30         40         50         60 
MRLSKTLAGM 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 DAPHTHHPLH PHLMQEHMGT NVIVANTMPS HLSNGQMCEW 

       430        440        450        460        470 
PRPRGQAATP ETPQPSPPSG SGSESYKLLP GAITTIVKPP SAIPQPTITK QEAI 

« Hide

Isoform Short [UniParc].

Checksum: 4C293463C33B2D76
Show »

FASTA46451,518

References

« Hide 'large scale' references
[1]"Identification of two splice isoforms of mRNA for mouse hepatocyte nuclear factor 4 (HNF-4)."
Hata S., Inoue T., Kosuga K., Nakashima T., Tsukamoto T., Osumi T.
Biochim. Biophys. Acta 1260:55-61(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
Strain: C57BL/6 X CBA.
Tissue: Liver.
[2]"Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains."
Farber C.R., Corva P.M., Medrano J.F.
BMC Genomics 7:102-102(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: CAST/Ei.
Tissue: Liver.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Kidney.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Kidney.
[6]"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.
Strain: C57BL/6.
Tissue: Liver.
[7]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429 AND THR-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PER2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17012.1. [P49698-1]
PIRS52074.
RefSeqNP_032287.2. NM_008261.2. [P49698-1]
XP_006498850.1. XM_006498787.1. [P49698-2]
UniGeneMm.202383.

3D structure databases

ProteinModelPortalP49698.
SMRP49698. Positions 58-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200354. 4 interactions.
IntActP49698. 3 interactions.
MINTMINT-5027670.

PTM databases

PhosphoSiteP49698.

Proteomic databases

MaxQBP49698.
PaxDbP49698.
PRIDEP49698.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. [P49698-1]
GeneID15378.
KEGGmmu:15378.
UCSCuc008nta.2. mouse. [P49698-1]
uc012cit.1. mouse. [P49698-2]

Organism-specific databases

CTD3172.
MGIMGI:109128. Hnf4a.

Phylogenomic databases

eggNOGNOG241134.
GeneTreeENSGT00740000115493.
HOGENOMHOG000260822.
HOVERGENHBG005606.
InParanoidP49698.
KOK07292.
OMAANTMPSH.
PhylomeDBP49698.
TreeFamTF352097.

Enzyme and pathway databases

ReactomeREACT_13641. Regulation of Beta-Cell Development.
REACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP49698.
BgeeP49698.
CleanExMM_HNF4A.
GenevestigatorP49698.

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

ChiTaRSHNF4A. mouse.
NextBio288038.
PROP49698.
SOURCESearch...

Entry information

Entry nameHNF4A_MOUSE
AccessionPrimary (citable) accession number: P49698
Secondary accession number(s): A2A5I5 expand/collapse secondary AC list , A2ICH0, Q3UNX3, Q8CFY1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 29, 2007
Last modified: July 9, 2014
This is version 139 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot