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Protein

Hepatocyte nuclear factor 3-beta

Gene

Foxa2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis (By similarity). Involved in regulation of fat metabolism. Acts synergistically with ONECUT1 to activate transcription of female-specific CYP2C12; the function is inhibited by growth hormone-activated STAT5B. Acts synergistically with HNF4A to activate transcription of APOA1.By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi159 – 252Fork-headPROSITE-ProRule annotationAdd BLAST94

GO - Molecular functioni

  • DNA binding transcription factor activity Source: RGD
  • double-stranded DNA binding Source: RGD
  • kinase binding Source: RGD
  • protein domain specific binding Source: InterPro
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: RGD
  • SMAD binding Source: RGD
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: RGD
  • transcription factor binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte nuclear factor 3-beta
Short name:
HNF-3-beta
Short name:
HNF-3B
Alternative name(s):
Forkhead box protein A2
Gene namesi
Name:Foxa2
Synonyms:Hnf3b, Tcf-3b, Tcf3b
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2808 Foxa2

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

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18Y → P: Reduces transcriptional activation. 1 Publication1
Mutagenesisi110L → A: Inhibits nuclear export; when associated with A-113. 1 Publication1
Mutagenesisi113L → A: Inhibits nuclear export; when associated with A-110. 1 Publication1
Mutagenesisi153R → K: Abolishes interaction with AKT1. 1 Publication1
Mutagenesisi156T → A: Constitutive active. Abolishes phosphorylation by PKB/AKT1; inhibits nuclear export; no effect on DNA binding. 2 Publications1
Mutagenesisi280T → A: Impairs transcriptional activation; when associated with A-283. 1 Publication1
Mutagenesisi283S → A: Abolishes in vitro phosphorylation by PRKDC. Impairs transcriptional activation; when associated with A-280. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000917971 – 458Hepatocyte nuclear factor 3-betaAdd BLAST458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei212Phosphoserine1 Publication1
Modified residuei283Phosphoserine1 Publication1
Modified residuei301PhosphothreonineBy similarity1
Modified residuei303Phosphoserine1 Publication1
Modified residuei306Phosphoserine1 Publication1
Modified residuei307Phosphoserine1 Publication1
Modified residuei309Phosphoserine1 Publication1
Modified residuei437Phosphoserine1 Publication1
Modified residuei458Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation on Thr-156 abolishes binding to target promoters and subsequent transcription activation upon insulin stimulation.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP32182
PRIDEiP32182

PTM databases

iPTMnetiP32182
PhosphoSitePlusiP32182

Expressioni

Tissue specificityi

Liver.

Interactioni

Subunit structurei

Binds DNA as a monomer. Binds TLE1. Interacts with FOXA1 and FOXA3 (By similarity). Interacts with PRKDC.By similarity3 Publications

GO - Molecular functioni

  • kinase binding Source: RGD
  • protein domain specific binding Source: InterPro
  • SMAD binding Source: RGD
  • transcription factor binding Source: InterPro

Protein-protein interaction databases

IntActiP32182, 1 interactor
STRINGi10116.ENSRNOP00000017742

Structurei

3D structure databases

ProteinModelPortaliP32182
SMRiP32182
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 93Transactivation domain 1Add BLAST80
Regioni361 – 458Transactivation domain 2Add BLAST98

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi106 – 113Nuclear localization signal1 Publication8

Phylogenomic databases

eggNOGiKOG3563 Eukaryota
COG5025 LUCA
HOGENOMiHOG000231817
HOVERGENiHBG006621
InParanoidiP32182
KOiK08035
PhylomeDBiP32182

Family and domain databases

CDDicd00059 FH, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR013638 Fork-head_N
IPR001766 Fork_head_dom
IPR018533 Forkhead_box_C
IPR018122 TF_fork_head_CS_1
IPR030456 TF_fork_head_CS_2
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00250 Forkhead, 1 hit
PF08430 Forkhead_N, 1 hit
PF09354 HNF_C, 1 hit
PRINTSiPR00053 FORKHEAD
SMARTiView protein in SMART
SM00339 FH, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00657 FORK_HEAD_1, 1 hit
PS00658 FORK_HEAD_2, 1 hit
PS50039 FORK_HEAD_3, 1 hit

Sequencei

Sequence statusi: Complete.

P32182-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGAVKMEGH EPSDWSSYYA EPEGYSSVSN MNASLGMNGM NTYMSMSAAA
60 70 80 90 100
MGSGSGNMSA GSMNMSSYVG AGMSPSLAGM SPGAGAMAGM SGSAGAAGVA
110 120 130 140 150
GMGPHLSPSL SPLGGQAAGA MGGLAPYANM NSMSPMYGQA GLSRARDPKT
160 170 180 190 200
YRRSYTHAKP PYSYISLITM AIQQSPNKML TLSEIYQWIM DLFPFYRQNQ
210 220 230 240 250
QRWQNSIRHS LSFNDFLKVP RAPDKPGKGS FWTLHPDSGN MFENGCYLRR
260 270 280 290 300
QKRFKCENEL ALKEAAGAGS GGGKKTAPGT QASQVQLGEA AGSASETPAG
310 320 330 340 350
TESPHSSASP CQEHKRGGLS ELKGTPASAL SPPEPAPSPG QQQQAAAHLL
360 370 380 390 400
GPPHHPGLPP EAHLKPEHHY AFNHPFSINN LMSSEQQHHH SHHHHQPHKM
410 420 430 440 450
DLKTYEQVMH YPGGYGSPMP GSLAMGPVTN KAGLDASPLA ADTSYYQGVY

SRPIMNSS
Length:458
Mass (Da):48,484
Last modified:October 1, 1993 - v1
Checksum:i9FF754142C194055
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L09647 mRNA Translation: AAA41338.1
PIRiB39533
RefSeqiNP_036875.1, NM_012743.1
UniGeneiRn.10948

Genome annotation databases

GeneIDi25099
KEGGirno:25099

Similar proteinsi

Entry informationi

Entry nameiFOXA2_RAT
AccessioniPrimary (citable) accession number: P32182
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 20, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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