Q9Y261 (FOXA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	457 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator Chromatin regulator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult 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_component	cytoplasm 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_function	DNA 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 457	457	Hepatocyte nuclear factor 3-beta		PRO_0000091795
Regions
	DNA binding	159 – 252	94	Fork-head
	Region	14 – 93	80	Transactivation domain 1 By similarity
	Region	361 – 457	97	Transactivation domain 2 By similarity
	Motif	106 – 113	8	Nuclear localization signal By similarity
Amino acid modifications
	Modified residue	156	1	Phosphothreonine By similarity
	Modified residue	212	1	Phosphoserine By similarity
	Modified residue	283	1	Phosphoserine By similarity
	Modified residue	303	1	Phosphoserine By similarity
	Modified residue	306	1	Phosphoserine By similarity
	Modified residue	307	1	Phosphoserine By similarity
	Modified residue	309	1	Phosphoserine By similarity
	Modified residue	436	1	Phosphoserine By similarity
	Modified residue	457	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1	1	M → MHSASSM in isoform 2.		VSP_041212
	Natural variant	328	1	A → 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		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 61DDE4C75C70680A	FASTA	457	48,306
	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
	Isoform 2 [UniParc]. Checksum: 726495A18CAE1677	FASTA	463	48,907
	10 20 30 40 50 60 MHSASSMLGA VKMEGHEPSD WSSYYAEPEG YSSVSNMNAG LGMNGMNTYM SMSAAAMGSG 70 80 90 100 110 120 SGNMSAGSMN MSSYVGAGMS PSLAGMSPGA GAMAGMGGSA GAAGVAGMGP HLSPSLSPLG 130 140 150 160 170 180 GQAAGAMGGL APYANMNSMS PMYGQAGLSR ARDPKTYRRS YTHAKPPYSY ISLITMAIQQ 190 200 210 220 230 240 SPNKMLTLSE IYQWIMDLFP FYRQNQQRWQ NSIRHSLSFN DCFLKVPRSP DKPGKGSFWT 250 260 270 280 290 300 LHPDSGNMFE NGCYLRRQKR FKCEKQLALK EAAGAAGSGK KAAAGAQASQ AQLGEAAGPA 310 320 330 340 350 360 SETPAGTESP HSSASPCQEH KRGGLGELKG TPAAALSPPE PAPSPGQQQQ AAAHLLGPPH 370 380 390 400 410 420 HPGLPPEAHL KPEHHYAFNH PFSINNLMSS EQQHHHSHHH HQPHKMDLKA YEQVMHYPGY 430 440 450 460 GSPMPGSLAM GPVTNKTGLD ASPLAADTSY YQGVYSRPIM NSS

References

	« Hide 'large scale' referencesShow '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. , 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.
RefSeq	NP_068556.2. NM_021784.4. NP_710141.1. NM_153675.2.
UniGene	Hs.155651.
3D structure databases
ProteinModelPortal	Q9Y261.
SMR	Q9Y261. Positions 157-256.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	109412. 10 interactions.
IntAct	Q9Y261. 1 interaction.
MINT	MINT-6610868.
STRING	9606.ENSP00000315955.
PTM databases
PhosphoSite	Q9Y261.
Polymorphism databases
DMDM	8134491.
Proteomic databases
PaxDb	Q9Y261.
PRIDE	Q9Y261.
Protocols and materials databases
DNASU	3170.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000377115; ENSP00000366319; ENSG00000125798. [Q9Y261-1] ENST00000419308; ENSP00000400341; ENSG00000125798. [Q9Y261-2]
GeneID	3170.
KEGG	hsa:3170.
UCSC	uc002wsn.3. human. [Q9Y261-1]
Organism-specific databases
CTD	3170.
GeneCards	GC20M022561.
HGNC	HGNC:5022. FOXA2.
HPA	CAB001388.
MIM	600288. gene.
neXtProt	NX_Q9Y261.
PharmGKB	PA201091.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5025.
HOGENOM	HOG000231817.
HOVERGEN	HBG006621.
InParanoid	Q9Y261.
KO	K08035.
OMA	TYEQVMH.
OrthoDB	EOG7C8GHD.
PhylomeDB	Q9Y261.
TreeFam	TF316127.
Enzyme and pathway databases
SignaLink	Q9Y261.
Gene expression databases
ArrayExpress	Q9Y261.
Bgee	Q9Y261.
CleanEx	HS_FOXA2.
Genevestigator	Q9Y261.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR013638. Fork-head_N. IPR018533. Forkhead_box_C. IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. PF08430. Fork_head_N. 1 hit. PF09354. HNF_C. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FOXA2. human.
GeneWiki	FOXA2.
GenomeRNAi	3170.
NextBio	12568.
PRO	Q9Y261.
SOURCE	Search...

Entry information

Entry name

FOXA2_HUMAN

Accession

Primary (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:	April 16, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.