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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

Keywordsi

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

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000129514.5.
HGNCiHGNC:5021. FOXA1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 residuei223PhosphoserineBy similarity1
Modified residuei293PhosphoserineBy similarity1
Modified residuei307PhosphoserineCombined sources1
Modified residuei331PhosphoserineCombined sources1
Modified residuei472PhosphoserineBy similarity1

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

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102753EBI-3918034,EBI-608057

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109411. 40 interactors.
DIPiDIP-57138N.
ELMiP55317.
IntActiP55317. 37 interactors.
MINTiMINT-2804254.
STRINGi9606.ENSP00000250448.

Structurei

3D structure databases

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

Family & Domainsi

Phylogenomic databases

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

Family and domain databases

CDDicd00059. FH. 1 hit.
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.
IPR036388. WH-like_DNA-bd_sf.
IPR036390. WH_DNA-bd_sf.
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: 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 → A2 Publications1
Natural variantiVAR_01345783A → T1 PublicationCorresponds to variant dbSNP:rs7144658Ensembl.1
Natural variantiVAR_05583587G → E. Corresponds to variant dbSNP:rs35220193Ensembl.1
Natural variantiVAR_015184124M → MM2 Publications1
Natural variantiVAR_015185185Q → R2 Publications1
Natural variantiVAR_013458448S → N1 PublicationCorresponds to variant dbSNP:rs33984772Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiFOXA1_HUMAN
AccessioniPrimary (citable) accession number: P55317
Secondary accession number(s): B2R9H6, B7ZAP5, Q9H2A0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 18, 2010
Last modified: October 25, 2017
This is version 172 of the entry and version 2 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 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