UniProtKB - Q9Y261 (FOXA2_HUMAN)
Hepatocyte nuclear factor 3-beta
FOXA2
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. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation.
By similarityRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 159 – 252 | Fork-headPROSITE-ProRule annotationAdd BLAST | 94 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- protein domain specific binding Source: InterPro
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- adult locomotory behavior Source: ParkinsonsUK-UCL
- anatomical structure morphogenesis Source: GO_Central
- cell differentiation Source: GO_Central
- cell fate specification Source: ParkinsonsUK-UCL
- chromatin organization Source: UniProtKB-KW
- dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- endocrine pancreas development Source: BHF-UCL
- negative regulation of detection of glucose Source: BHF-UCL
- negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
- negative regulation of epithelial to mesenchymal transition Source: BHF-UCL
- negative regulation of glucokinase activity Source: BHF-UCL
- negative regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
- positive regulation of cell-cell adhesion mediated by cadherin Source: BHF-UCL
- positive regulation of embryonic development Source: UniProtKB
- positive regulation of gastrulation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of transcription from RNA polymerase II promoter by glucose Source: BHF-UCL
- primitive streak formation Source: UniProtKB
- regulation of blood coagulation Source: UniProtKB
- regulation of insulin secretion involved in cellular response to glucose stimulus Source: BHF-UCL
- regulation of transcription by RNA polymerase II Source: BHF-UCL
- response to interleukin-6 Source: UniProtKB
Keywordsi
Molecular function | Activator, Chromatin regulator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q9Y261 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells |
SignaLinki | Q9Y261 |
SIGNORi | Q9Y261 |
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 Transcription factor 3B Short name: TCF-3B |
Gene namesi | Name:FOXA2 Synonyms:HNF3B, TCF3B |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5022, FOXA2 |
MIMi | 600288, gene |
neXtProti | NX_Q9Y261 |
VEuPathDBi | HostDB:ENSG00000125798 |
Subcellular locationi
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cell junction Source: HPA
- chromatin Source: NTNU_SB
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 3170 |
MalaCardsi | FOXA2 |
OpenTargetsi | ENSG00000125798 |
Orphaneti | 95494, Combined pituitary hormone deficiencies, genetic forms |
PharmGKBi | PA201091 |
Miscellaneous databases
Pharosi | Q9Y261, Tbio |
Genetic variation databases
BioMutai | FOXA2 |
DMDMi | 8134491 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000091795 | 1 – 457 | Hepatocyte nuclear factor 3-betaAdd BLAST | 457 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 156 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 212 | PhosphoserineBy similarity | 1 | |
Modified residuei | 283 | PhosphoserineBy similarity | 1 | |
Modified residuei | 301 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 303 | PhosphoserineCombined sources | 1 | |
Modified residuei | 306 | PhosphoserineBy similarity | 1 | |
Modified residuei | 307 | PhosphoserineBy similarity | 1 | |
Modified residuei | 309 | PhosphoserineCombined sources | 1 | |
Modified residuei | 436 | PhosphoserineBy similarity | 1 | |
Modified residuei | 457 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q9Y261 |
MassIVEi | Q9Y261 |
MaxQBi | Q9Y261 |
PaxDbi | Q9Y261 |
PeptideAtlasi | Q9Y261 |
PRIDEi | Q9Y261 |
ProteomicsDBi | 85664 [Q9Y261-1] 85665 [Q9Y261-2] |
PTM databases
iPTMneti | Q9Y261 |
PhosphoSitePlusi | Q9Y261 |
Expressioni
Gene expression databases
Bgeei | ENSG00000125798, Expressed in endometrium and 87 other tissues |
ExpressionAtlasi | Q9Y261, baseline and differential |
Genevisiblei | Q9Y261, HS |
Organism-specific databases
HPAi | ENSG00000125798, Tissue enhanced (liver, pancreas, stomach) |
Interactioni
Subunit structurei
Binds DNA as a monomer. Binds TLE1 (By similarity).
Interacts with FOXA1 and FOXA3.
Interacts with PRKDC.
By similarity2 PublicationsBinary interactionsi
Isoform 2 [Q9Y261-2]
GO - Molecular functioni
- protein domain specific binding Source: InterPro
Protein-protein interaction databases
BioGRIDi | 109412, 22 interactors |
IntActi | Q9Y261, 16 interactors |
MINTi | Q9Y261 |
STRINGi | 9606.ENSP00000400341 |
Miscellaneous databases
RNActi | Q9Y261, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9Y261 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 14 – 93 | Transactivation domain 1By similarityAdd BLAST | 80 | |
Regioni | 280 – 365 | DisorderedSequence analysisAdd BLAST | 86 | |
Regioni | 361 – 457 | Transactivation domain 2By similarityAdd BLAST | 97 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 106 – 113 | Nuclear localization signalBy similarity | 8 |
Phylogenomic databases
eggNOGi | KOG3563, Eukaryota |
GeneTreei | ENSGT00940000155999 |
HOGENOMi | CLU_027910_4_1_1 |
InParanoidi | Q9Y261 |
OMAi | GMGASMT |
PhylomeDBi | Q9Y261 |
TreeFami | TF316127 |
Family and domain databases
CDDi | cd00059, FH, 1 hit |
DisProti | DP01124 |
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 |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLGAVKMEGH EPSDWSSYYA EPEGYSSVSN MNAGLGMNGM NTYMSMSAAA
60 70 80 90 100
MGSGSGNMSA GSMNMSSYVG AGMSPSLAGM SPGAGAMAGM GGSAGAAGVA
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 GSGKKAAAGA QASQAQLGEA AGPASETPAG
310 320 330 340 350
TESPHSSASP CQEHKRGGLG ELKGTPAAAL SPPEPAPSPG QQQQAAAHLL
360 370 380 390 400
GPPHHPGLPP EAHLKPEHHY AFNHPFSINN LMSSEQQHHH SHHHHQPHKM
410 420 430 440 450
DLKAYEQVMH YPGYGSPMPG SLAMGPVTNK TGLDASPLAA DTSYYQGVYS
RPIMNSS
Sequence cautioni
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008858 | 328 | A → V in Japanese subjects with maturity-onset diabetes of the young; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199796119Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041212 | 1 | M → MHSASSM in isoform 2. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB028021 mRNA Translation: BAA78106.1 AF147787 Genomic DNA Translation: AAD41081.1 AF176110 Genomic DNA Translation: AAD51978.1 AL121722 Genomic DNA No translation available. BC006545 mRNA Translation: AAH06545.2 BC011780 mRNA Translation: AAH11780.1 Different initiation. BC019288 mRNA Translation: AAH19288.1 |
CCDSi | CCDS13147.1 [Q9Y261-1] CCDS46585.1 [Q9Y261-2] |
RefSeqi | NP_068556.2, NM_021784.4 [Q9Y261-2] NP_710141.1, NM_153675.2 [Q9Y261-1] |
Genome annotation databases
Ensembli | ENST00000377115; ENSP00000366319; ENSG00000125798 ENST00000419308; ENSP00000400341; ENSG00000125798 [Q9Y261-2] |
GeneIDi | 3170 |
KEGGi | hsa:3170 |
MANE-Selecti | ENST00000419308.7; ENSP00000400341.3; NM_021784.5; NP_068556.2 [Q9Y261-2] |
UCSCi | uc002wsm.4, human [Q9Y261-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Hepatocyte nuclear factors entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB028021 mRNA Translation: BAA78106.1 AF147787 Genomic DNA Translation: AAD41081.1 AF176110 Genomic DNA Translation: AAD51978.1 AL121722 Genomic DNA No translation available. BC006545 mRNA Translation: AAH06545.2 BC011780 mRNA Translation: AAH11780.1 Different initiation. BC019288 mRNA Translation: AAH19288.1 |
CCDSi | CCDS13147.1 [Q9Y261-1] CCDS46585.1 [Q9Y261-2] |
RefSeqi | NP_068556.2, NM_021784.4 [Q9Y261-2] NP_710141.1, NM_153675.2 [Q9Y261-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5X07 | X-ray | 2.80 | C/F/I/L | 157-258 | [»] | |
SMRi | Q9Y261 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109412, 22 interactors |
IntActi | Q9Y261, 16 interactors |
MINTi | Q9Y261 |
STRINGi | 9606.ENSP00000400341 |
PTM databases
iPTMneti | Q9Y261 |
PhosphoSitePlusi | Q9Y261 |
Genetic variation databases
BioMutai | FOXA2 |
DMDMi | 8134491 |
Proteomic databases
jPOSTi | Q9Y261 |
MassIVEi | Q9Y261 |
MaxQBi | Q9Y261 |
PaxDbi | Q9Y261 |
PeptideAtlasi | Q9Y261 |
PRIDEi | Q9Y261 |
ProteomicsDBi | 85664 [Q9Y261-1] 85665 [Q9Y261-2] |
Protocols and materials databases
Antibodypediai | 3772, 861 antibodies from 47 providers |
DNASUi | 3170 |
Genome annotation databases
Ensembli | ENST00000377115; ENSP00000366319; ENSG00000125798 ENST00000419308; ENSP00000400341; ENSG00000125798 [Q9Y261-2] |
GeneIDi | 3170 |
KEGGi | hsa:3170 |
MANE-Selecti | ENST00000419308.7; ENSP00000400341.3; NM_021784.5; NP_068556.2 [Q9Y261-2] |
UCSCi | uc002wsm.4, human [Q9Y261-1] |
Organism-specific databases
CTDi | 3170 |
DisGeNETi | 3170 |
GeneCardsi | FOXA2 |
HGNCi | HGNC:5022, FOXA2 |
HPAi | ENSG00000125798, Tissue enhanced (liver, pancreas, stomach) |
MalaCardsi | FOXA2 |
MIMi | 600288, gene |
neXtProti | NX_Q9Y261 |
OpenTargetsi | ENSG00000125798 |
Orphaneti | 95494, Combined pituitary hormone deficiencies, genetic forms |
PharmGKBi | PA201091 |
VEuPathDBi | HostDB:ENSG00000125798 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3563, Eukaryota |
GeneTreei | ENSGT00940000155999 |
HOGENOMi | CLU_027910_4_1_1 |
InParanoidi | Q9Y261 |
OMAi | GMGASMT |
PhylomeDBi | Q9Y261 |
TreeFami | TF316127 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y261 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells |
SignaLinki | Q9Y261 |
SIGNORi | Q9Y261 |
Miscellaneous databases
BioGRID-ORCSi | 3170, 29 hits in 1056 CRISPR screens |
ChiTaRSi | FOXA2, human |
GeneWikii | FOXA2 |
GenomeRNAii | 3170 |
Pharosi | Q9Y261, Tbio |
PROi | PR:Q9Y261 |
RNActi | Q9Y261, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125798, Expressed in endometrium and 87 other tissues |
ExpressionAtlasi | Q9Y261, baseline and differential |
Genevisiblei | Q9Y261, HS |
Family and domain databases
CDDi | cd00059, FH, 1 hit |
DisProti | DP01124 |
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | FOXA2_HUMAN | |
Accessioni | Q9Y261Primary (citable) accession number: Q9Y261 Secondary accession number(s): Q8WUW4, Q96DF7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 1, 1999 | |
Last modified: | February 23, 2022 | |
This is version 204 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references