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Protein

Hepatocyte nuclear factor 3-alpha

Gene

FOXA1

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). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. 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.By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi169 – 260Fork-headPROSITE-ProRule annotationAdd BLAST92

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129514-MONOMER.
SignaLinkiP55317.
SIGNORiP55317.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte nuclear factor 3-alpha
Short name:
HNF-3-alpha
Short name:
HNF-3A
Alternative name(s):
Forkhead box protein A1
Transcription factor 3A
Short name:
TCF-3A
Gene namesi
Name:FOXA1
Synonyms:HNF3A, TCF3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:5021. FOXA1.

Subcellular locationi

GO - Cellular componenti

  • microvillus Source: Ensembl
  • nucleolus Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3169.
OpenTargetsiENSG00000129514.
PharmGKBiPA201090.

Polymorphism and mutation databases

BioMutaiFOXA1.
DMDMi296434509.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000917921 – 472Hepatocyte nuclear factor 3-alphaAdd BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei307PhosphoserineCombined sources1
Modified residuei331PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP55317.
PaxDbiP55317.
PeptideAtlasiP55317.
PRIDEiP55317.

PTM databases

iPTMnetiP55317.
PhosphoSitePlusiP55317.

Expressioni

Tissue specificityi

Highly expressed in prostate and ESR1-positive breast tumors. Overexpressed in esophageal and lung adenocarcinomas.3 Publications

Gene expression databases

BgeeiENSG00000129514.
CleanExiHS_FOXA1.
ExpressionAtlasiP55317. baseline and differential.

Organism-specific databases

HPAiCAB011595.
HPA050505.

Interactioni

Subunit structurei

Binds DNA as a monomer (By similarity). Interacts with FOXA2. Interacts with NKX2-1. Interacts with HDAC7. Interacts with the histone H3-H4 heterodimer. Associates with nucleosomes containing histone H2A. Interacts with AR. Interacts with NR0B2 (By similarity).By similarity

Protein-protein interaction databases

BioGridi109411. 40 interactors.
DIPiDIP-57138N.
IntActiP55317. 37 interactors.
MINTiMINT-2804254.
STRINGi9606.ENSP00000250448.

Structurei

3D structure databases

ProteinModelPortaliP55317.
SMRiP55317.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP55317.
KOiK09387.
OMAiTMNTYMT.
OrthoDBiEOG091G0HW9.
PhylomeDBiP55317.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. 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.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55317-1) [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
MLGTVKMEGH ETSDWNSYYA DTQEAYSSVP VSNMNSGLGS MNSMNTYMTM
60 70 80 90 100
NTMTTSGNMT PASFNMSYAN PGLGAGLSPG AVAGMPGGSA GAMNSMTAAG
110 120 130 140 150
VTAMGTALSP SGMGAMGAQQ AASMNGLGPY AAAMNPCMSP MAYAPSNLGR
160 170 180 190 200
SRAGGGGDAK TFKRSYPHAK PPYSYISLIT MAIQQAPSKM LTLSEIYQWI
210 220 230 240 250
MDLFPYYRQN QQRWQNSIRH SLSFNDCFVK VARSPDKPGK GSYWTLHPDS
260 270 280 290 300
GNMFENGCYL RRQKRFKCEK QPGAGGGGGS GSGGSGAKGG PESRKDPSGA
310 320 330 340 350
SNPSADSPLH RGVHGKTGQL EGAPAPGPAA SPQTLDHSGA TATGGASELK
360 370 380 390 400
TPASSTAPPI SSGPGALASV PASHPAHGLA PHESQLHLKG DPHYSFNHPF
410 420 430 440 450
SINNLMSSSE QQHKLDFKAY EQALQYSPYG STLPASLPLG SASVTTRSPI
460 470
EPSALEPAYY QGVYSRPVLN TS
Length:472
Mass (Da):49,148
Last modified:May 18, 2010 - v2
Checksum:iB2489523459EEB4C
GO
Isoform 2 (identifier: P55317-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.

Note: No experimental confirmation available.
Show »
Length:439
Mass (Da):45,468
Checksum:i170DF8E54E6FC73C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01518372G → A.2 Publications1
Natural variantiVAR_01345783A → T.1 PublicationCorresponds to variant rs7144658dbSNPEnsembl.1
Natural variantiVAR_05583587G → E.Corresponds to variant rs35220193dbSNPEnsembl.1
Natural variantiVAR_015184124M → MM.2 Publications1
Natural variantiVAR_015185185Q → R.2 Publications1
Natural variantiVAR_013458448S → N.1 PublicationCorresponds to variant rs33984772dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0550941 – 33Missing in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39840 mRNA. Translation: AAB06493.1.
AF176112, AF176111 Genomic DNA. Translation: AAD51979.1.
AF303743, AF303742 Genomic DNA. Translation: AAG40847.1.
AK313785 mRNA. Translation: BAG36523.1.
AK316360 mRNA. Translation: BAH14731.1.
AL121790 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65844.1.
BC033890 mRNA. Translation: AAH33890.1.
CCDSiCCDS9665.1. [P55317-1]
PIRiS70357.
RefSeqiNP_004487.2. NM_004496.3. [P55317-1]
XP_016876735.1. XM_017021246.1. [P55317-2]
UniGeneiHs.163484.

Genome annotation databases

EnsembliENST00000250448; ENSP00000250448; ENSG00000129514. [P55317-1]
GeneIDi3169.
KEGGihsa:3169.
UCSCiuc001wuf.5. human. [P55317-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hepatocyte nuclear factors entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U39840 mRNA. Translation: AAB06493.1.
AF176112, AF176111 Genomic DNA. Translation: AAD51979.1.
AF303743, AF303742 Genomic DNA. Translation: AAG40847.1.
AK313785 mRNA. Translation: BAG36523.1.
AK316360 mRNA. Translation: BAH14731.1.
AL121790 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65844.1.
BC033890 mRNA. Translation: AAH33890.1.
CCDSiCCDS9665.1. [P55317-1]
PIRiS70357.
RefSeqiNP_004487.2. NM_004496.3. [P55317-1]
XP_016876735.1. XM_017021246.1. [P55317-2]
UniGeneiHs.163484.

3D structure databases

ProteinModelPortaliP55317.
SMRiP55317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109411. 40 interactors.
DIPiDIP-57138N.
IntActiP55317. 37 interactors.
MINTiMINT-2804254.
STRINGi9606.ENSP00000250448.

PTM databases

iPTMnetiP55317.
PhosphoSitePlusiP55317.

Polymorphism and mutation databases

BioMutaiFOXA1.
DMDMi296434509.

Proteomic databases

MaxQBiP55317.
PaxDbiP55317.
PeptideAtlasiP55317.
PRIDEiP55317.

Protocols and materials databases

DNASUi3169.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250448; ENSP00000250448; ENSG00000129514. [P55317-1]
GeneIDi3169.
KEGGihsa:3169.
UCSCiuc001wuf.5. human. [P55317-1]

Organism-specific databases

CTDi3169.
DisGeNETi3169.
GeneCardsiFOXA1.
H-InvDBHIX0011609.
HGNCiHGNC:5021. FOXA1.
HPAiCAB011595.
HPA050505.
MIMi602294. gene.
neXtProtiNX_P55317.
OpenTargetsiENSG00000129514.
PharmGKBiPA201090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP55317.
KOiK09387.
OMAiTMNTYMT.
OrthoDBiEOG091G0HW9.
PhylomeDBiP55317.
TreeFamiTF316127.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129514-MONOMER.
SignaLinkiP55317.
SIGNORiP55317.

Miscellaneous databases

ChiTaRSiFOXA1. human.
GeneWikiiFOXA1.
GenomeRNAii3169.
PROiP55317.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129514.
CleanExiHS_FOXA1.
ExpressionAtlasiP55317. baseline and differential.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. 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.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOXA1_HUMAN
AccessioniPrimary (citable) accession number: P55317
Secondary accession number(s): B2R9H6, B7ZAP5, Q9H2A0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 163 of the entry and version 2 of the sequence. [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 14
    Human chromosome 14: 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
  5. SIMILARITY comments
    Index of protein domains and families

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.