UniProtKB - P35583 (FOXA2_MOUSE)
Protein
Hepatocyte nuclear factor 3-beta
Gene
Foxa2
Organism
Mus musculus (Mouse)
Status
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. FOXA1 and FOXA2 are essential for hepatic specification. FOXA1 and FOXA2 are required for morphogenesis and cell differentiation during formation of the lung. FOXA1 and FOXA2 are involved in bile duct formation; they positively regulate the binding glucocorticoid receptor/NR3C1 to the IL6 promoter. FOXA1 and FOXA2 regulate multiple phases of midbrain dopaminergic neuron development; they regulate expression of NEUROG2 at the beginning of mDA neurogenesis and of NR4A2 and EN1 in immature mDA neurons. Modulates the transcriptional activity of nuclear hormone receptors; inhibits AR-mediated transcription from the LCN5 promoter. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. 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. In pancreatic beta cells activates transcription of potassium channel subunits KCNJ11 and ABCC8. Involved in regulation of fat metabolism; activates transcriptional programs of lipid metabolism and ketogenesis at low insulin state. Involved in transcriptional regulation of MUC2 in the intestine.By similarity11 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 159 – 252 | Fork-headPROSITE-ProRule annotationAdd BLAST | 94 |
GO - Molecular functioni
- chromatin binding Source: MGI
- core promoter binding Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor activity Source: MGI
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- double-stranded DNA binding Source: MGI
- kinase binding Source: MGI
- protein domain specific binding Source: InterPro
- RNA polymerase II distal enhancer sequence-specific DNA binding Source: MGI
- RNA polymerase II proximal promoter sequence-specific DNA binding Source: MGI
- sequence-specific DNA binding Source: MGI
- SMAD binding Source: MGI
- transcription factor binding Source: InterPro
- transcription regulatory region DNA binding Source: MGI
GO - Biological processi
- adult locomotory behavior Source: MGI
- anatomical structure formation involved in morphogenesis Source: MGI
- anatomical structure morphogenesis Source: MGI
- anterior/posterior pattern specification Source: MGI
- cell development Source: MGI
- cell differentiation Source: GO_Central
- cell differentiation in hindbrain Source: MGI
- cell fate specification Source: MGI
- chromatin organization Source: UniProtKB-KW
- connective tissue development Source: MGI
- dopaminergic neuron differentiation Source: MGI
- dorsal/ventral neural tube patterning Source: MGI
- dorsal/ventral pattern formation Source: MGI
- ectoderm formation Source: MGI
- endocrine pancreas development Source: MGI
- epithelial tube branching involved in lung morphogenesis Source: MGI
- in utero embryonic development Source: MGI
- lung development Source: MGI
- lung epithelial cell differentiation Source: MGI
- mesendoderm development Source: MGI
- negative regulation of detection of glucose Source: BHF-UCL
- negative regulation of DNA-binding transcription factor activity Source: MGI
- negative regulation of epithelial to mesenchymal transition Source: MGI
- negative regulation of glucokinase activity Source: BHF-UCL
- negative regulation of neuron differentiation Source: MGI
- negative regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
- neuron fate specification Source: MGI
- Notch signaling pathway Source: MGI
- pattern specification process Source: MGI
- positive regulation of embryonic development Source: UniProtKB
- positive regulation of gastrulation Source: UniProtKB
- positive regulation of neuron differentiation Source: MGI
- positive regulation of smoothened signaling pathway Source: MGI
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of transcription by RNA polymerase III Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
- primitive streak formation Source: UniProtKB
- regulation of blood coagulation Source: MGI
- regulation of gene expression Source: MGI
- regulation of insulin secretion involved in cellular response to glucose stimulus Source: BHF-UCL
- regulation of lipid metabolic process Source: MGI
- regulation of steroid metabolic process Source: MGI
- regulation of transcription, DNA-templated Source: MGI
- regulation of transcription by RNA polymerase II Source: MGI
- response to interleukin-6 Source: UniProtKB
- signal transduction involved in regulation of gene expression Source: MGI
- somite rostral/caudal axis specification Source: MGI
Keywordsi
Molecular function | Activator, Chromatin regulator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Names & Taxonomyi
Protein namesi | Recommended name: Hepatocyte nuclear factor 3-betaShort name: HNF-3-beta Short name: HNF-3B Alternative name(s): Forkhead box protein A2 |
Gene namesi | Name:Foxa2 Synonyms:Hnf3b, Tcf-3b, Tcf3b |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1347476 Foxa2 |
Subcellular locationi
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- cell junction Source: MGI
- cytoplasm Source: UniProtKB-SubCell
- transcription factor complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Embryonic lethal; absence of organized node and notochord formation, which leads to secondary defects in dorsal-ventral patterning of the neural tube. Mice deficient for Fox1a and deficient for Foxa2 in the endoderm from 8.5 dpc onwards do not show hepatic bud formation. Mice deficient for Fox1a and deficient for Foxa2 in the midbrain from 10.5 dpc onwards show almost complete loss of mDA neurons. Mice deficient for Fox1a and deficient for Foxa2 in the embryonic liver show hyperplasia of the biliary tree due to at least in part activation of IL-6 expression, a proliferative signal for cholangiocytes. Mice deficient for Fox2a in pancreatic beta cell show hypoglycemia and disorganized islets arrangements.2 Publications
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000091796 | 1 – 459 | Hepatocyte nuclear factor 3-betaAdd BLAST | 459 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 156 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 212 | PhosphoserineBy similarity | 1 | |
Modified residuei | 284 | PhosphoserineBy similarity | 1 | |
Modified residuei | 302 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 304 | PhosphoserineBy similarity | 1 | |
Modified residuei | 307 | PhosphoserineBy similarity | 1 | |
Modified residuei | 308 | PhosphoserineBy similarity | 1 | |
Modified residuei | 310 | PhosphoserineBy similarity | 1 | |
Modified residuei | 438 | PhosphoserineBy similarity | 1 | |
Modified residuei | 459 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylation on Thr-156 abolishes binding to target promoters and subsequent transcription activation upon insulin stimulation.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | P35583 |
PaxDbi | P35583 |
PRIDEi | P35583 |
PTM databases
iPTMneti | P35583 |
PhosphoSitePlusi | P35583 |
Expressioni
Tissue specificityi
Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine). Expressed in epididymis with region-specific expression pattern: no expression is observed in initial segment, low expression in proximal caput, gradiently higher levels of expression in middle and distal caput and highest level in corpus and cauda (at protein level).1 Publication
Developmental stagei
Most abundant in midgestation embryos (day 9.5).
Gene expression databases
Bgeei | ENSMUSG00000037025 Expressed in 170 organ(s), highest expression level in islet of Langerhans |
ExpressionAtlasi | P35583 baseline and differential |
Genevisiblei | P35583 MM |
Interactioni
Subunit structurei
Binds DNA as a monomer. Binds TLE1.
Interacts with FOXA1 and FOXA3.
Interacts with PRKDC (By similarity).
By similarityBinary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
Q61221 | 5 | EBI-2893341,EBI-298954 |
GO - Molecular functioni
- kinase binding Source: MGI
- protein domain specific binding Source: InterPro
- SMAD binding Source: MGI
- transcription factor binding Source: InterPro
Protein-protein interaction databases
IntActi | P35583, 7 interactors |
STRINGi | 10090.ENSMUSP00000045918 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 14 – 93 | Transactivation domain 1By similarityAdd BLAST | 80 | |
Regioni | 362 – 459 | Transactivation domain 2By similarityAdd BLAST | 98 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 106 – 113 | Nuclear localization signalBy similarity | 8 |
Phylogenomic databases
eggNOGi | KOG3563 Eukaryota COG5025 LUCA |
GeneTreei | ENSGT00940000155999 |
HOGENOMi | HOG000231817 |
InParanoidi | P35583 |
KOi | K08035 |
OrthoDBi | 1181467at2759 |
TreeFami | TF316127 |
Family and domain databases
CDDi | cd00059 FH, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00250 Forkhead, 1 hit PF08430 Forkhead_N, 1 hit PF09354 HNF_C, 1 hit |
PRINTSi | PR00053 FORKHEAD |
SMARTi | View protein in SMART SM00339 FH, 1 hit |
SUPFAMi | SSF46785 SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00657 FORK_HEAD_1, 1 hit PS00658 FORK_HEAD_2, 1 hit PS50039 FORK_HEAD_3, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P35583-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLGAVKMEGH EPSDWSSYYA EPEGYSSVSN MNAGLGMNGM NTYMSMSAAA
60 70 80 90 100
MGGGSGNMSA 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 LSFNDCFLKV PRSPDKPGKG SFWTLHPDSG NMFENGCYLR
260 270 280 290 300
RQKRFKCEKQ LALKEAAGAA SSGGKKTAPG SQASQAQLGE AAGSASETPA
310 320 330 340 350
GTESPHSSAS PCQEHKRGGL SELKGAPASA LSPPEPAPSP GQQQQAAAHL
360 370 380 390 400
LGPPHHPGLP PEAHLKPEHH YAFNHPFSIN NLMSSEQQHH HSHHHHQPHK
410 420 430 440 450
MDLKAYEQVM HYPGGYGSPM PGSLAMGPVT NKAGLDASPL AADTSYYQGV
YSRPIMNSS
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketG5E8P5 | G5E8P5_MOUSE | Hepatocyte nuclear factor 3-beta | Foxa2 | 465 | Annotation score: | ||
G3UYH0 | G3UYH0_MOUSE | Hepatocyte nuclear factor 3-beta | Foxa2 | 275 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 10 | H → L in CAA52891 (PubMed:8034310).Curated | 1 | |
Sequence conflicti | 434 | G → S in AAA03606 (PubMed:8306889).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X74937 mRNA Translation: CAA52891.1 L10409 mRNA Translation: AAA03161.1 AL845297 Genomic DNA No translation available. U04197 mRNA Translation: AAA03606.1 |
CCDSi | CCDS16836.1 |
PIRi | B54258 |
RefSeqi | NP_001277994.1, NM_001291065.1 NP_034576.2, NM_010446.3 |
Genome annotation databases
Ensembli | ENSMUST00000047315; ENSMUSP00000045918; ENSMUSG00000037025 |
GeneIDi | 15376 |
KEGGi | mmu:15376 |
UCSCi | uc008mtb.2 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X74937 mRNA Translation: CAA52891.1 L10409 mRNA Translation: AAA03161.1 AL845297 Genomic DNA No translation available. U04197 mRNA Translation: AAA03606.1 |
CCDSi | CCDS16836.1 |
PIRi | B54258 |
RefSeqi | NP_001277994.1, NM_001291065.1 NP_034576.2, NM_010446.3 |
3D structure databases
SMRi | P35583 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | P35583, 7 interactors |
STRINGi | 10090.ENSMUSP00000045918 |
PTM databases
iPTMneti | P35583 |
PhosphoSitePlusi | P35583 |
Proteomic databases
MaxQBi | P35583 |
PaxDbi | P35583 |
PRIDEi | P35583 |
Protocols and materials databases
DNASUi | 15376 |
Genome annotation databases
Ensembli | ENSMUST00000047315; ENSMUSP00000045918; ENSMUSG00000037025 |
GeneIDi | 15376 |
KEGGi | mmu:15376 |
UCSCi | uc008mtb.2 mouse |
Organism-specific databases
CTDi | 3170 |
MGIi | MGI:1347476 Foxa2 |
Phylogenomic databases
eggNOGi | KOG3563 Eukaryota COG5025 LUCA |
GeneTreei | ENSGT00940000155999 |
HOGENOMi | HOG000231817 |
InParanoidi | P35583 |
KOi | K08035 |
OrthoDBi | 1181467at2759 |
TreeFami | TF316127 |
Miscellaneous databases
ChiTaRSi | Foxa2 mouse |
PROi | PR:P35583 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000037025 Expressed in 170 organ(s), highest expression level in islet of Langerhans |
ExpressionAtlasi | P35583 baseline and differential |
Genevisiblei | P35583 MM |
Family and domain databases
CDDi | cd00059 FH, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00250 Forkhead, 1 hit PF08430 Forkhead_N, 1 hit PF09354 HNF_C, 1 hit |
PRINTSi | PR00053 FORKHEAD |
SMARTi | View protein in SMART SM00339 FH, 1 hit |
SUPFAMi | SSF46785 SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00657 FORK_HEAD_1, 1 hit PS00658 FORK_HEAD_2, 1 hit PS50039 FORK_HEAD_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | FOXA2_MOUSE | |
Accessioni | P35583Primary (citable) accession number: P35583 Secondary accession number(s): A2AR89, Q60602 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | July 27, 2011 | |
Last modified: | November 13, 2019 | |
This is version 175 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot