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P49698

- HNF4A_MOUSE

UniProt

P49698 - HNF4A_MOUSE

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Protein

Hepatocyte nuclear factor 4-alpha

Gene
Hnf4a, Hnf-4, Hnf4, Nr2a1, Tcf14
Organism
Mus musculus (Mouse)
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 receptorAdd
BLAST
Zinc fingeri60 – 8021NR C4-typeAdd
BLAST
Zinc fingeri96 – 12025NR C4-typeAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. fatty acid binding Source: Ensembl
  3. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
  4. protein binding Source: UniProtKB
  5. RNA polymerase II activating transcription factor binding Source: BHF-UCL
  6. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
  8. sequence-specific DNA binding Source: MGI
  9. sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  10. steroid hormone receptor activity Source: InterPro
  11. transcription regulatory region DNA binding Source: BHF-UCL
  12. zinc ion binding Source: InterPro

GO - Biological processi

  1. blood coagulation Source: Ensembl
  2. endocrine pancreas development Source: Reactome
  3. glucose homeostasis Source: BHF-UCL
  4. lipid metabolic process Source: MGI
  5. negative regulation of cell growth Source: Ensembl
  6. negative regulation of cell proliferation Source: Ensembl
  7. ornithine metabolic process Source: Ensembl
  8. phospholipid homeostasis Source: BHF-UCL
  9. positive regulation of cholesterol homeostasis Source: BHF-UCL
  10. positive regulation of transcription, DNA-templated Source: MGI
  11. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  12. regulation of gastrulation Source: MGI
  13. regulation of insulin secretion Source: BHF-UCL
  14. regulation of lipid metabolic process Source: Ensembl
  15. regulation of transcription, DNA-templated Source: MGI
  16. regulation of transcription from RNA polymerase II promoter Source: MGI
  17. response to glucose Source: BHF-UCL
  18. sex differentiation Source: MGI
  19. signal transduction involved in regulation of gene expression Source: MGI
  20. SMAD protein signal transduction Source: MGI
  21. transcription from RNA polymerase II promoter Source: GOC
  22. triglyceride homeostasis Source: BHF-UCL
  23. xenobiotic metabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_214529. Regulation of gene expression in beta cells.

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
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:109128. Hnf4a.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 474474Hepatocyte nuclear factor 4-alphaPRO_0000053559Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei142 – 1421Phosphoserine By similarity
Modified residuei166 – 1661Phosphothreonine By similarity
Modified residuei167 – 1671Phosphoserine By 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 AMPK By similarity
Modified residuei429 – 4291Phosphothreonine1 Publication
Modified residuei432 – 4321Phosphothreonine1 Publication
Modified residuei436 – 4361Phosphoserine By similarity
Modified residuei458 – 4581N6-acetyllysine By similarity

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.
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.
PRIDEiP49698.

PTM databases

PhosphoSiteiP49698.

Expressioni

Gene expression databases

ArrayExpressiP49698.
BgeeiP49698.
CleanExiMM_HNF4A.
GenevestigatoriP49698.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi200354. 4 interactions.
IntActiP49698. 3 interactions.
MINTiMINT-5027670.

Structurei

3D structure databases

ProteinModelPortaliP49698.
SMRiP49698. Positions 58-377.

Family & Domainsi

Sequence similaritiesi

Zinc finger

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

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG241134.
GeneTreeiENSGT00740000115493.
HOGENOMiHOG000260822.
HOVERGENiHBG005606.
InParanoidiP49698.
KOiK07292.
OMAiANTMPSH.
PhylomeDBiP49698.
TreeFamiTF352097.

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: 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

MRLSKTLAGM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS    50
SNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR 100
QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP 150
SINALLQAEV LSQQITSPIS GINGDIRAKK IANITDVCES MKEQLLVLVE 200
WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI 250
VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK 300
GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ 350
MIEQIQFIKL FGMAKIDNLL QEMLLGGSAS DAPHTHHPLH PHLMQEHMGT 400
NVIVANTMPS HLSNGQMCEW PRPRGQAATP ETPQPSPPSG SGSESYKLLP 450
GAITTIVKPP SAIPQPTITK QEAI 474
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 BAA06101.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei418 – 42811CEWPRPRGQAA → S in isoform Short. VSP_003676Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551G → S in BAA06101. 1 Publication
Sequence conflicti365 – 3651K → R in BAE25624. 1 Publication
Sequence conflicti378 – 3781S → L in ABM69091. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_008261.2. [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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS17012.1. [P49698-1 ]
PIRi S52074.
RefSeqi NP_032287.2. NM_008261.2. [P49698-1 ]
XP_006498850.1. XM_006498787.1. [P49698-2 ]
UniGenei Mm.202383.

3D structure databases

ProteinModelPortali P49698.
SMRi P49698. Positions 58-377.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200354. 4 interactions.
IntActi P49698. 3 interactions.
MINTi MINT-5027670.

PTM databases

PhosphoSitei P49698.

Proteomic databases

MaxQBi P49698.
PaxDbi P49698.
PRIDEi P49698.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000018094 ; ENSMUSP00000018094 ; ENSMUSG00000017950 . [P49698-1 ]
GeneIDi 15378.
KEGGi mmu:15378.
UCSCi uc008nta.2. mouse. [P49698-1 ]
uc012cit.1. mouse. [P49698-2 ]

Organism-specific databases

CTDi 3172.
MGIi MGI:109128. Hnf4a.

Phylogenomic databases

eggNOGi NOG241134.
GeneTreei ENSGT00740000115493.
HOGENOMi HOG000260822.
HOVERGENi HBG005606.
InParanoidi P49698.
KOi K07292.
OMAi ANTMPSH.
PhylomeDBi P49698.
TreeFami TF352097.

Enzyme and pathway databases

Reactomei REACT_214529. Regulation of gene expression in beta cells.

Miscellaneous databases

ChiTaRSi HNF4A. mouse.
NextBioi 288038.
PROi P49698.
SOURCEi Search...

Gene expression databases

ArrayExpressi P49698.
Bgeei P49698.
CleanExi MM_HNF4A.
Genevestigatori P49698.

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

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

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: September 3, 2014
This is version 140 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

External Data

Dasty 3

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