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Protein

Hepatocyte nuclear factor 3-gamma

Gene

FOXA3

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

Functioni

Transcription factor that 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 (By similarity). 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; binds to and activates transcription from the G6PC promoter. Binds to the CYP3A4 promoter and activates its transcription in cooperation with CEBPA. Binds to the CYP3A7 promoter together with members of the CTF/NF-I family. Involved in regulation of neuronal-specific transcription. May be involved in regulation of spermatogenesis.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi116 – 20792Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. sequence-specific DNA binding Source: Ensembl
  2. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central
  3. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  4. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. cellular glucose homeostasis Source: UniProtKB
  3. cellular response to starvation Source: Ensembl
  4. chromatin modification Source: UniProtKB-KW
  5. endocrine pancreas development Source: Reactome
  6. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  7. spermatogenesis Source: UniProtKB-KW
  8. transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Developmental protein

Keywords - Biological processi

Differentiation, Spermatogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_13819. Regulation of gene expression in beta cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte nuclear factor 3-gamma
Short name:
HNF-3-gamma
Short name:
HNF-3G
Alternative name(s):
Fork head-related protein FKH H3
Forkhead box protein A3
Transcription factor 3G
Short name:
TCF-3G
Gene namesi
Name:FOXA3
Synonyms:HNF3G, TCF3G
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:5023. FOXA3.

Subcellular locationi

Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA201092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 350350Hepatocyte nuclear factor 3-gammaPRO_0000091800Add
BLAST

Proteomic databases

MaxQBiP55318.
PaxDbiP55318.
PRIDEiP55318.

PTM databases

PhosphoSiteiP55318.

Expressioni

Tissue specificityi

Expressed in erythroleukemia and hepatoma cell lines and in liver and pancreas. Not expressed in any other cell lines or tissues examined.1 Publication

Developmental stagei

Detected in prenatal liver nuclear extracts (12.4-27 weeks estimated gestational age). Not detected in postnatal liver samples.1 Publication

Gene expression databases

BgeeiP55318.
CleanExiHS_FOXA3.
ExpressionAtlasiP55318. baseline and differential.
GenevestigatoriP55318.

Organism-specific databases

HPAiCAB015154.

Interactioni

Subunit structurei

Interacts with FOXA2.2 Publications

Protein-protein interaction databases

BioGridi109413. 4 interactions.
IntActiP55318. 1 interaction.
STRINGi9606.ENSP00000304004.

Structurei

Secondary structure

1
350
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi122 – 13110Combined sources
Helixi140 – 15011Combined sources
Helixi152 – 1554Combined sources
Helixi158 – 17114Combined sources
Beta strandi175 – 1784Combined sources
Beta strandi190 – 1934Combined sources
Helixi195 – 1973Combined sources
Beta strandi206 – 2083Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VTNX-ray2.50C115-215[»]
ProteinModelPortaliP55318.
SMRiP55318. Positions 115-215.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP55318.
KOiK08038.
OMAiVYYQGVY.
PhylomeDBiP55318.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. Fork-head_N.
IPR018533. Forkhead_box_C.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
PF08430. Fork_head_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P55318-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGSVKMEAH DLAEWSYYPE AGEVYSPVTP VPTMAPLNSY MTLNPLSSPY
60 70 80 90 100
PPGGLPASPL PSGPLAPPAP AAPLGPTFPG LGVSGGSSSS GYGAPGPGLV
110 120 130 140 150
HGKEMPKGYR RPLAHAKPPY SYISLITMAI QQAPGKMLTL SEIYQWIMDL
160 170 180 190 200
FPYYRENQQR WQNSIRHSLS FNDCFVKVAR SPDKPGKGSY WALHPSSGNM
210 220 230 240 250
FENGCYLRRQ KRFKLEEKVK KGGSGAATTT RNGTGSAAST TTPAATVTSP
260 270 280 290 300
PQPPPPAPEP EAQGGEDVGA LDCGSPASST PYFTGLELPG ELKLDAPYNF
310 320 330 340 350
NHPFSINNLM SEQTPAPPKL DVGFGGYGAE GGEPGVYYQG LYSRSLLNAS
Length:350
Mass (Da):37,140
Last modified:May 30, 2000 - v2
Checksum:i07657D41B0867101
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti52 – 521Missing in AAA58477 (PubMed:8499623).Curated
Sequence conflicti83 – 831V → L in AAA58477 (PubMed:8499623).Curated
Sequence conflicti107 – 1071K → M in BAD97193 (Ref. 4) Curated
Sequence conflicti111 – 1133RPL → AP in AAA58477 (PubMed:8499623).Curated
Sequence conflicti137 – 1371M → V in AAA58477 (PubMed:8499623).Curated
Sequence conflicti156 – 1561E → D in AAA58477 (PubMed:8499623).Curated
Sequence conflicti227 – 2282AT → S in AAA58477 (PubMed:8499623).Curated
Sequence conflicti291 – 2911E → D in AAA58477 (PubMed:8499623).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti91 – 911G → R.
VAR_008859

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12141 mRNA. Translation: AAA58477.1.
AF176114, AF176113 Genomic DNA. Translation: AAD51980.1.
BT006720 mRNA. Translation: AAP35366.1.
AK223473 mRNA. Translation: BAD97193.1.
EU275778 Genomic DNA. Translation: ABX44664.1.
CH471126 Genomic DNA. Translation: EAW57394.1.
BC016024 mRNA. Translation: AAH16024.1.
CCDSiCCDS12677.1.
PIRiC48924.
RefSeqiNP_004488.2. NM_004497.2.
UniGeneiHs.36137.

Genome annotation databases

EnsembliENST00000302177; ENSP00000304004; ENSG00000170608.
GeneIDi3171.
KEGGihsa:3171.
UCSCiuc002pdr.3. human.

Polymorphism databases

DMDMi8247938.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hepatocyte nuclear factors entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12141 mRNA. Translation: AAA58477.1.
AF176114, AF176113 Genomic DNA. Translation: AAD51980.1.
BT006720 mRNA. Translation: AAP35366.1.
AK223473 mRNA. Translation: BAD97193.1.
EU275778 Genomic DNA. Translation: ABX44664.1.
CH471126 Genomic DNA. Translation: EAW57394.1.
BC016024 mRNA. Translation: AAH16024.1.
CCDSiCCDS12677.1.
PIRiC48924.
RefSeqiNP_004488.2. NM_004497.2.
UniGeneiHs.36137.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VTNX-ray2.50C115-215[»]
ProteinModelPortaliP55318.
SMRiP55318. Positions 115-215.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109413. 4 interactions.
IntActiP55318. 1 interaction.
STRINGi9606.ENSP00000304004.

PTM databases

PhosphoSiteiP55318.

Polymorphism databases

DMDMi8247938.

Proteomic databases

MaxQBiP55318.
PaxDbiP55318.
PRIDEiP55318.

Protocols and materials databases

DNASUi3171.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302177; ENSP00000304004; ENSG00000170608.
GeneIDi3171.
KEGGihsa:3171.
UCSCiuc002pdr.3. human.

Organism-specific databases

CTDi3171.
GeneCardsiGC19P046368.
HGNCiHGNC:5023. FOXA3.
HPAiCAB015154.
MIMi602295. gene.
neXtProtiNX_P55318.
PharmGKBiPA201092.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00760000118904.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP55318.
KOiK08038.
OMAiVYYQGVY.
PhylomeDBiP55318.
TreeFamiTF316127.

Enzyme and pathway databases

ReactomeiREACT_13819. Regulation of gene expression in beta cells.

Miscellaneous databases

GeneWikiiFOXA3.
GenomeRNAii3171.
NextBioi12574.
PROiP55318.
SOURCEiSearch...

Gene expression databases

BgeeiP55318.
CleanExiHS_FOXA3.
ExpressionAtlasiP55318. baseline and differential.
GenevestigatoriP55318.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. Fork-head_N.
IPR018533. Forkhead_box_C.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Fork_head. 1 hit.
PF08430. Fork_head_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells."
    Hromas R., Moore J., Johnston T., Socha C., Klemsz M.
    Blood 81:2854-2859(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Liver.
  2. "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].
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
    Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Gastric mucosa.
  5. SeattleSNPs variation discovery resource
    Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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].
    Tissue: Uterus.
  8. "The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase gene activation."
    Lin B., Morris D.W., Chou J.Y.
    Biochemistry 36:14096-14106(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROMOTER BINDING.
  9. "Transcriptional regulation of human CYP3A4 basal expression by CCAAT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma."
    Rodriguez-Antona C., Bort R., Jover R., Tindberg N., Ingelman-Sundberg M., Gomez-Lechon M.J., Castell J.V.
    Mol. Pharmacol. 63:1180-1189(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "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 FOXA2.
  11. "Regulation of the CYP3A4 and CYP3A7 promoters by members of the nuclear factor I transcription factor family."
    Riffel A.K., Schuenemann E., Vyhlidal C.A.
    Mol. Pharmacol. 76:1104-1114(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROMOTER-BINDING, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  12. "Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5."
    Clark K.L., Halay E.D., Lai E., Burley S.K.
    Nature 364:412-420(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 115-215 IN COMPLEX WITH DNA.

Entry informationi

Entry nameiFOXA3_HUMAN
AccessioniPrimary (citable) accession number: P55318
Secondary accession number(s): A9LYI5, Q53F16, Q9UMW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: February 4, 2015
This is version 140 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.