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Q9Y261 (FOXA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hepatocyte nuclear factor 3-beta

Short name=HNF-3-beta
Short name=HNF-3B
Alternative name(s):
Forkhead box protein A2
Transcription factor 3B
Short name=TCF-3B
Gene names
Name:FOXA2
Synonyms:HNF3B, TCF3B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length457 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Binds DNA as a monomer. Binds TLE1 By similarity. Interacts with FOXA1 and FOXA3. Interacts with PRKDC. Ref.8 Ref.9

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner; in response to insulin signaling via AKT1 is exported from the nucleus. Ref.6

Post-translational modification

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

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Sequence caution

The sequence AAH11780.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandDNA-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult locomotory behavior

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from electronic annotation. Source: Ensembl

cell differentiation in hindbrain

Inferred from electronic annotation. Source: Ensembl

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

connective tissue development

Inferred from electronic annotation. Source: Ensembl

dopaminergic neuron differentiation

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral neural tube patterning

Inferred from electronic annotation. Source: Ensembl

ectoderm formation

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Inferred from direct assay PubMed 12124776. Source: BHF-UCL

epithelial tube branching involved in lung morphogenesis

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from Biological aspect of Ancestor. Source: RefGenome

in utero embryonic development

Inferred from Biological aspect of Ancestor. Source: RefGenome

lung epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of detection of glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of epithelial to mesenchymal transition

Inferred from mutant phenotype PubMed 20160041. Source: BHF-UCL

negative regulation of glucokinase activity

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 12642491. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter by glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

neuron fate specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of cell-cell adhesion mediated by cadherin

Inferred by curator PubMed 20160041. Source: BHF-UCL

positive regulation of embryonic development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gastrulation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12124776PubMed 20160041. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter by glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of transcription from RNA polymerase III promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 9931457. Source: UniProtKB

primitive streak formation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of blood coagulation

Inferred from direct assay PubMed 12911579. Source: UniProtKB

regulation of hormone levels

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of steroid metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12911579. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter involved in detection of glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

response to interleukin-6

Traceable author statement Ref.7. Source: UniProtKB

signal transduction involved in regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

somite rostral/caudal axis specification

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 9931457. Source: UniProtKB

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from direct assay PubMed 9931457. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II core promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 12642491. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 9931457. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription regulatory region DNA binding

Inferred from mutant phenotype Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y261-1)

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.
Isoform 2 (identifier: Q9Y261-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MHSASSM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 457457Hepatocyte nuclear factor 3-beta
PRO_0000091795

Regions

DNA binding159 – 25294Fork-head
Region14 – 9380Transactivation domain 1 By similarity
Region361 – 45797Transactivation domain 2 By similarity
Motif106 – 1138Nuclear localization signal By similarity

Amino acid modifications

Modified residue1561Phosphothreonine By similarity
Modified residue2121Phosphoserine By similarity
Modified residue2831Phosphoserine By similarity
Modified residue3031Phosphoserine By similarity
Modified residue3061Phosphoserine By similarity
Modified residue3071Phosphoserine By similarity
Modified residue3091Phosphoserine By similarity
Modified residue4361Phosphoserine By similarity
Modified residue4571Phosphoserine By similarity

Natural variations

Alternative sequence11M → MHSASSM in isoform 2.
VSP_041212
Natural variant3281A → V in Japanese subjects with maturity-onset diabetes of the young; pathological significance unknown. Ref.1
Corresponds to variant rs199796119 [ dbSNP | Ensembl ].
VAR_008858

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 61DDE4C75C70680A

FASTA45748,306
        10         20         30         40         50         60 
MLGAVKMEGH EPSDWSSYYA EPEGYSSVSN MNAGLGMNGM NTYMSMSAAA MGSGSGNMSA 

        70         80         90        100        110        120 
GSMNMSSYVG AGMSPSLAGM SPGAGAMAGM GGSAGAAGVA GMGPHLSPSL SPLGGQAAGA 

       130        140        150        160        170        180 
MGGLAPYANM NSMSPMYGQA GLSRARDPKT YRRSYTHAKP PYSYISLITM AIQQSPNKML 

       190        200        210        220        230        240 
TLSEIYQWIM DLFPFYRQNQ QRWQNSIRHS LSFNDCFLKV PRSPDKPGKG SFWTLHPDSG 

       250        260        270        280        290        300 
NMFENGCYLR RQKRFKCEKQ LALKEAAGAA GSGKKAAAGA QASQAQLGEA AGPASETPAG 

       310        320        330        340        350        360 
TESPHSSASP CQEHKRGGLG ELKGTPAAAL SPPEPAPSPG QQQQAAAHLL GPPHHPGLPP 

       370        380        390        400        410        420 
EAHLKPEHHY AFNHPFSINN LMSSEQQHHH SHHHHQPHKM DLKAYEQVMH YPGYGSPMPG 

       430        440        450 
SLAMGPVTNK TGLDASPLAA DTSYYQGVYS RPIMNSS 

« Hide

Isoform 2 [UniParc].

Checksum: 726495A18CAE1677
Show »

FASTA46348,907

References

« Hide 'large scale' references
[1]"Cloning of cDNA and the gene encoding human hepatocyte nuclear factor (HNF)-3 beta and mutation screening in Japanese subjects with maturity-onset diabetes of the young."
Yamada S., Zhu Q., Aihara Y., Onda H., Zhang Z., Yu L., Jin L., Si Y.J., Nishigori H., Tomura H., Inoue I., Morikawa A., Yamagata K., Hanafusa T., Matsuzawa Y., Takeda J.
Diabetologia 43:121-124(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT VAL-328.
Tissue: Liver.
[2]"No evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3 beta gene in Japanese patients with MODY."
Hinokio Y., Horikawa Y., Furuta H., Cox N.J., Iwasaki N., Honda M., Ogata M., Iwamoto Y., Bell G.I.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The human HNF-3 genes: cloning, partial sequence and mutation screening in patients with impaired glucose homeostasis."
Navas M.A., Vaisse C., Boger S., Heimesaat M., Kollee L.A., Stoffel M.
Hum. Hered. 50:370-381(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[6]"Insulin regulates the activity of forkhead transcription factor Hnf-3beta/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization."
Wolfrum C., Besser D., Luca E., Stoffel M.
Proc. Natl. Acad. Sci. U.S.A. 100:11624-11629(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important for interleukin 6-induced expression, and its activity is influenced by the adjacent -148C/T polymorphism."
Verschuur M., de Jong M., Felida L., de Maat M.P., Vos H.L.
J. Biol. Chem. 280:16763-16771(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROMOTER-BINDING.
[8]"Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq."
Motallebipour M., Ameur A., Reddy Bysani M.S., Patra K., Wallerman O., Mangion J., Barker M.A., McKernan K.J., Komorowski J., Wadelius C.
Genome Biol. 10:R129.0-R129.0(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FOXA1 AND FOXA3.
[9]"Identification of DNA-dependent protein kinase as a cofactor for the forkhead transcription factor FoxA2."
Nock A., Ascano J.M., Jones T., Barrero M.J., Sugiyama N., Tomita M., Ishihama Y., Malik S.
J. Biol. Chem. 284:19915-19926(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKDC.
+Additional computationally mapped references.

Web resources

Wikipedia

Hepatocyte nuclear factors entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB028021 mRNA. Translation: BAA78106.1.
AF147787 Genomic DNA. Translation: AAD41081.1.
AF176110 Genomic DNA. Translation: AAD51978.1.
AL121722 Genomic DNA. Translation: CAB89773.1.
BC006545 mRNA. Translation: AAH06545.2.
BC011780 mRNA. Translation: AAH11780.1. Different initiation.
BC019288 mRNA. Translation: AAH19288.1.
CCDSCCDS13147.1. [Q9Y261-1]
CCDS46585.1. [Q9Y261-2]
RefSeqNP_068556.2. NM_021784.4. [Q9Y261-2]
NP_710141.1. NM_153675.2. [Q9Y261-1]
XP_006723625.1. XM_006723562.1. [Q9Y261-1]
UniGeneHs.155651.

3D structure databases

ProteinModelPortalQ9Y261.
SMRQ9Y261. Positions 157-256.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109412. 10 interactions.
IntActQ9Y261. 1 interaction.
MINTMINT-6610868.
STRING9606.ENSP00000315955.

PTM databases

PhosphoSiteQ9Y261.

Polymorphism databases

DMDM8134491.

Proteomic databases

MaxQBQ9Y261.
PaxDbQ9Y261.
PRIDEQ9Y261.

Protocols and materials databases

DNASU3170.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377115; ENSP00000366319; ENSG00000125798. [Q9Y261-1]
ENST00000419308; ENSP00000400341; ENSG00000125798. [Q9Y261-2]
GeneID3170.
KEGGhsa:3170.
UCSCuc002wsn.3. human. [Q9Y261-1]

Organism-specific databases

CTD3170.
GeneCardsGC20M022561.
HGNCHGNC:5022. FOXA2.
HPACAB001388.
MIM600288. gene.
neXtProtNX_Q9Y261.
PharmGKBPA201091.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000231817.
HOVERGENHBG006621.
InParanoidQ9Y261.
KOK08035.
OMATYEQVMH.
OrthoDBEOG7C8GHD.
PhylomeDBQ9Y261.
TreeFamTF316127.

Enzyme and pathway databases

SignaLinkQ9Y261.

Gene expression databases

ArrayExpressQ9Y261.
BgeeQ9Y261.
CleanExHS_FOXA2.
GenevestigatorQ9Y261.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR013638. Fork-head_N.
IPR018533. Forkhead_box_C.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
PF08430. Fork_head_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFOXA2. human.
GeneWikiFOXA2.
GenomeRNAi3170.
NextBio12568.
PROQ9Y261.
SOURCESearch...

Entry information

Entry nameFOXA2_HUMAN
AccessionPrimary (citable) accession number: Q9Y261
Secondary accession number(s): Q8WUW4, Q96DF7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM