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Protein

Hepatocyte nuclear factor 3-beta

Gene

FOXA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi159 – 252Fork-headPROSITE-ProRule annotationAdd BLAST94

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
SignaLinkiQ9Y261.
SIGNORiQ9Y261.

Names & Taxonomyi

Protein namesi
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 namesi
Name:FOXA2
Synonyms:HNF3B, TCF3B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:5022. FOXA2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication
  • Cytoplasm 1 Publication

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

GO - Cellular componenti

  • cell junction Source: HPA
  • cytoplasm Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3170.
OpenTargetsiENSG00000125798.
PharmGKBiPA201091.

Polymorphism and mutation databases

BioMutaiFOXA2.
DMDMi8134491.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000917951 – 457Hepatocyte nuclear factor 3-betaAdd BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156PhosphothreonineBy similarity1
Modified residuei212PhosphoserineBy similarity1
Modified residuei283PhosphoserineBy similarity1
Modified residuei301PhosphothreonineBy similarity1
Modified residuei303PhosphoserineCombined sources1
Modified residuei306PhosphoserineBy similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei309PhosphoserineCombined sources1
Modified residuei436PhosphoserineBy similarity1
Modified residuei457PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y261.
PaxDbiQ9Y261.
PeptideAtlasiQ9Y261.
PRIDEiQ9Y261.

PTM databases

iPTMnetiQ9Y261.
PhosphoSitePlusiQ9Y261.

Expressioni

Gene expression databases

BgeeiENSG00000125798.
CleanExiHS_FOXA2.
ExpressionAtlasiQ9Y261. baseline and differential.
GenevisibleiQ9Y261. HS.

Organism-specific databases

HPAiCAB001388.
HPA066846.

Interactioni

Subunit structurei

Binds DNA as a monomer. Binds TLE1 (By similarity). Interacts with FOXA1 and FOXA3. Interacts with PRKDC.By similarity2 Publications

Protein-protein interaction databases

BioGridi109412. 18 interactors.
IntActiQ9Y261. 10 interactors.
MINTiMINT-6610868.
STRINGi9606.ENSP00000315955.

Structurei

3D structure databases

ProteinModelPortaliQ9Y261.
SMRiQ9Y261.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 93Transactivation domain 1By similarityAdd BLAST80
Regioni361 – 457Transactivation domain 2By similarityAdd BLAST97

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi106 – 113Nuclear localization signalBy similarity8

Phylogenomic databases

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiQ9Y261.
KOiK08035.
OMAiTYEQVMH.
PhylomeDBiQ9Y261.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView 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.
IPR011991. WHTH_DNA-bd_dom.
PfamiView protein in Pfam
PF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
PRINTSiPR00053. FORKHEAD.
SMARTiView protein in SMART
SM00339. FH. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiView protein in PROSITE
PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative 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.

« Hide

        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
Length:457
Mass (Da):48,306
Last modified:November 1, 1999 - v1
Checksum:i61DDE4C75C70680A
GO
Isoform 2 (identifier: Q9Y261-2) [UniParc]FASTAAdd to basket

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

Show »
Length:463
Mass (Da):48,907
Checksum:i726495A18CAE1677
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_008858328A → V in Japanese subjects with maturity-onset diabetes of the young; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199796119Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0412121M → MHSASSM in isoform 2. 1 Publication1

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. Translation: CAB89773.1.
BC006545 mRNA. Translation: AAH06545.2.
BC011780 mRNA. Translation: AAH11780.1. Different initiation.
BC019288 mRNA. Translation: AAH19288.1.
CCDSiCCDS13147.1. [Q9Y261-1]
CCDS46585.1. [Q9Y261-2]
RefSeqiNP_068556.2. NM_021784.4. [Q9Y261-2]
NP_710141.1. NM_153675.2. [Q9Y261-1]
UniGeneiHs.155651.

Genome annotation databases

EnsembliENST00000377115; ENSP00000366319; ENSG00000125798. [Q9Y261-1]
ENST00000419308; ENSP00000400341; ENSG00000125798. [Q9Y261-2]
GeneIDi3170.
KEGGihsa:3170.
UCSCiuc002wsm.4. human. [Q9Y261-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAB89773.1.
BC006545 mRNA. Translation: AAH06545.2.
BC011780 mRNA. Translation: AAH11780.1. Different initiation.
BC019288 mRNA. Translation: AAH19288.1.
CCDSiCCDS13147.1. [Q9Y261-1]
CCDS46585.1. [Q9Y261-2]
RefSeqiNP_068556.2. NM_021784.4. [Q9Y261-2]
NP_710141.1. NM_153675.2. [Q9Y261-1]
UniGeneiHs.155651.

3D structure databases

ProteinModelPortaliQ9Y261.
SMRiQ9Y261.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109412. 18 interactors.
IntActiQ9Y261. 10 interactors.
MINTiMINT-6610868.
STRINGi9606.ENSP00000315955.

PTM databases

iPTMnetiQ9Y261.
PhosphoSitePlusiQ9Y261.

Polymorphism and mutation databases

BioMutaiFOXA2.
DMDMi8134491.

Proteomic databases

EPDiQ9Y261.
PaxDbiQ9Y261.
PeptideAtlasiQ9Y261.
PRIDEiQ9Y261.

Protocols and materials databases

DNASUi3170.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377115; ENSP00000366319; ENSG00000125798. [Q9Y261-1]
ENST00000419308; ENSP00000400341; ENSG00000125798. [Q9Y261-2]
GeneIDi3170.
KEGGihsa:3170.
UCSCiuc002wsm.4. human. [Q9Y261-1]

Organism-specific databases

CTDi3170.
DisGeNETi3170.
GeneCardsiFOXA2.
HGNCiHGNC:5022. FOXA2.
HPAiCAB001388.
HPA066846.
MIMi600288. gene.
neXtProtiNX_Q9Y261.
OpenTargetsiENSG00000125798.
PharmGKBiPA201091.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiQ9Y261.
KOiK08035.
OMAiTYEQVMH.
PhylomeDBiQ9Y261.
TreeFamiTF316127.

Enzyme and pathway databases

ReactomeiR-HSA-210745. Regulation of gene expression in beta cells.
SignaLinkiQ9Y261.
SIGNORiQ9Y261.

Miscellaneous databases

ChiTaRSiFOXA2. human.
GeneWikiiFOXA2.
GenomeRNAii3170.
PROiQ9Y261.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125798.
CleanExiHS_FOXA2.
ExpressionAtlasiQ9Y261. baseline and differential.
GenevisibleiQ9Y261. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView 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.
IPR011991. WHTH_DNA-bd_dom.
PfamiView protein in Pfam
PF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
PRINTSiPR00053. FORKHEAD.
SMARTiView protein in SMART
SM00339. FH. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiView protein in PROSITE
PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFOXA2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y261
Secondary accession number(s): Q8WUW4, Q96DF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: March 15, 2017
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.