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Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Mus musculus (Mouse)
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

Binds fatty acids.By similarity

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

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:109128 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

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 residuei143PhosphoserineBy 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
SwissPalmiP49698

Expressioni

Gene expression databases

BgeeiENSMUSG00000017950 Expressed in 144 organ(s), highest expression level in ileum
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
CORUMiP49698
IntActiP49698, 3 interactors
MINTiP49698
STRINGi10090.ENSMUSP00000018094

Structurei

3D structure databases

ProteinModelPortaliP49698
SMRiP49698
ModBaseiSearch...
MobiDBiSearch...

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
GeneTreeiENSGT00760000118948
HOGENOMiHOG000260822
HOVERGENiHBG005606
InParanoidiP49698
KOiK07292
OrthoDBiEOG091G0A89
PhylomeDBiP49698
TreeFamiTF352097

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR003068 COUP_TF
IPR039067 HNF4A
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PANTHERiPTHR24083:SF41 PTHR24083:SF41, 1 hit
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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2A5I6A2A5I6_MOUSE
Hepatocyte nuclear factor 4-alpha
Hnf4a
191Annotation score:
Z4YKX0Z4YKX0_MOUSE
Hepatic nuclear factor 4, alpha, is...
Hnf4a mCG_5450
465Annotation score:
A2A5I4A2A5I4_MOUSE
Hepatocyte nuclear factor 4-alpha
Hnf4a
100Annotation score:

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

Similar proteinsi

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
CORUMiP49698
IntActiP49698, 3 interactors
MINTiP49698
STRINGi10090.ENSMUSP00000018094

PTM databases

iPTMnetiP49698
PhosphoSitePlusiP49698
SwissPalmiP49698

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
OrthoDBiEOG091G0A89
PhylomeDBiP49698
TreeFamiTF352097

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway

Miscellaneous databases

ChiTaRSiHnf4a mouse
PROiPR:P49698
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000017950 Expressed in 144 organ(s), highest expression level in ileum
CleanExiMM_HNF4A
ExpressionAtlasiP49698 baseline and differential
GenevisibleiP49698 MM

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR003068 COUP_TF
IPR039067 HNF4A
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PANTHERiPTHR24083:SF41 PTHR24083:SF41, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiHNF4A_MOUSE
AccessioniPrimary (citable) accession number: P49698
Secondary accession number(s): A2A5I5
, A2ICH0, Q3UNX3, Q8CFY1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: May 29, 2007
Last modified: November 7, 2018
This is version 177 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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