UniProtKB - Q9Y261 (FOXA2_HUMAN)
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Protein
Hepatocyte nuclear factor 3-beta
Gene
FOXA2
Organism
Homo sapiens (Human)
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. 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 similarity
Regions
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
- protein domain specific binding Source: InterPro
- RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
- RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
- transcription factor binding Source: InterPro
- transcription regulatory region DNA binding Source: UniProtKB
GO - Biological processi
- adult locomotory behavior Source: ParkinsonsUK-UCL
- anatomical structure morphogenesis 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
- transcription, DNA-templated Source: UniProtKB-KW
Keywordsi
Molecular function | Activator, Chromatin regulator, Developmental protein, DNA-binding |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
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
EuPathDBi | HostDB:ENSG00000125798.14 |
HGNCi | HGNC:5022 FOXA2 |
MIMi | 600288 gene |
neXtProti | NX_Q9Y261 |
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 3170 |
OpenTargetsi | ENSG00000125798 |
PharmGKBi | PA201091 |
Polymorphism and mutation 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
Phosphorylation on Thr-156 abolishes binding to target promoters and subsequent transcription activation upon insulin stimulation.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q9Y261 |
PeptideAtlasi | Q9Y261 |
PRIDEi | Q9Y261 |
PTM databases
iPTMneti | Q9Y261 |
PhosphoSitePlusi | Q9Y261 |
Expressioni
Gene expression databases
Bgeei | ENSG00000125798 |
CleanExi | HS_FOXA2 |
ExpressionAtlasi | Q9Y261 baseline and differential |
Genevisiblei | Q9Y261 HS |
Organism-specific databases
HPAi | CAB001388 HPA066846 |
Interactioni
Subunit structurei
Binds DNA as a monomer. Binds TLE1 (By similarity). Interacts with FOXA1 and FOXA3. Interacts with PRKDC.By similarity2 Publications
GO - Molecular functioni
- protein domain specific binding Source: InterPro
- transcription factor binding Source: InterPro
Protein-protein interaction databases
BioGridi | 10941218 interactors. |
IntActi | Q9Y261 10 interactors. |
MINTi | Q9Y261 |
STRINGi | 9606.ENSP00000315955 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 164 – 173 | Combined sources | 10 | |
Beta strandi | 178 – 180 | Combined sources | 3 | |
Helixi | 182 – 192 | Combined sources | 11 | |
Helixi | 194 – 197 | Combined sources | 4 | |
Helixi | 200 – 213 | Combined sources | 14 | |
Beta strandi | 217 – 220 | Combined sources | 4 | |
Beta strandi | 224 – 226 | Combined sources | 3 | |
Beta strandi | 232 – 235 | Combined sources | 4 |
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 | [»] | |
ProteinModelPortali | Q9Y261 | |||||
SMRi | Q9Y261 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 14 – 93 | Transactivation domain 1By similarityAdd BLAST | 80 | |
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 COG5025 LUCA |
GeneTreei | ENSGT00760000118904 |
HOGENOMi | HOG000231817 |
HOVERGENi | HBG006621 |
InParanoidi | Q9Y261 |
KOi | K08035 |
OMAi | QEHKRGG |
PhylomeDBi | Q9Y261 |
TreeFami | TF316127 |
Family and domain databases
CDDi | cd00059 FH, 1 hit |
Gene3Di | 1.10.10.101 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 basket
Isoform 1 (identifier: Q9Y261-1) [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.
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
The sequence AAH11780 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
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] |
UniGenei | Hs.155651 |
Genome annotation databases
Ensembli | ENST00000377115; ENSP00000366319; ENSG00000125798 [Q9Y261-1] ENST00000419308; ENSP00000400341; ENSG00000125798 [Q9Y261-2] |
GeneIDi | 3170 |
KEGGi | hsa:3170 |
UCSCi | uc002wsm.4 human [Q9Y261-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
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: | April 25, 2018 | |
This is version 179 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. |