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P55318 (FOXA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FOXA3
Synonyms:HNF3G, TCF3G
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length350 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9

Subunit structure

Interacts with FOXA2. Ref.10

Subcellular location

Nucleus Ref.11.

Tissue specificity

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

Developmental stage

Detected in prenatal liver nuclear extracts (12.4-27 weeks estimated gestational age). Not detected in postnatal liver samples. Ref.11

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Spermatogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
   Molecular functionActivator
Chromatin regulator
Developmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular glucose homeostasis

Traceable author statement Ref.8. Source: UniProtKB

cellular response to starvation

Inferred from electronic annotation. Source: Ensembl

chromatin modification

Inferred from electronic annotation. Source: UniProtKB-KW

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

endocrine pancreas development

Traceable author statement. Source: Reactome

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

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 neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of hormone levels

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

spermatogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentnucleus

Traceable author statement PubMed 7739897. Source: ProtInc

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.9. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription regulatory region DNA binding

Inferred from mutant phenotype Ref.9PubMed 18239190Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 350350Hepatocyte nuclear factor 3-gamma
PRO_0000091800

Regions

DNA binding116 – 20792Fork-head

Natural variations

Natural variant911G → R.
VAR_008859

Experimental info

Sequence conflict521Missing in AAA58477. Ref.1
Sequence conflict831V → L in AAA58477. Ref.1
Sequence conflict1071K → M in BAD97193. Ref.4
Sequence conflict111 – 1133RPL → AP in AAA58477. Ref.1
Sequence conflict1371M → V in AAA58477. Ref.1
Sequence conflict1561E → D in AAA58477. Ref.1
Sequence conflict227 – 2282AT → S in AAA58477. Ref.1
Sequence conflict2911E → D in AAA58477. Ref.1

Secondary structure

................. 350
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P55318 [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 07657D41B0867101

FASTA35037,140
        10         20         30         40         50         60 
MLGSVKMEAH DLAEWSYYPE AGEVYSPVTP VPTMAPLNSY MTLNPLSSPY PPGGLPASPL 

        70         80         90        100        110        120 
PSGPLAPPAP AAPLGPTFPG LGVSGGSSSS GYGAPGPGLV HGKEMPKGYR RPLAHAKPPY 

       130        140        150        160        170        180 
SYISLITMAI QQAPGKMLTL SEIYQWIMDL FPYYRENQQR WQNSIRHSLS FNDCFVKVAR 

       190        200        210        220        230        240 
SPDKPGKGSY WALHPSSGNM FENGCYLRRQ KRFKLEEKVK KGGSGAATTT RNGTGSAAST 

       250        260        270        280        290        300 
TTPAATVTSP PQPPPPAPEP EAQGGEDVGA LDCGSPASST PYFTGLELPG ELKLDAPYNF 

       310        320        330        340        350 
NHPFSINNLM SEQTPAPPKL DVGFGGYGAE GGEPGVYYQG LYSRSLLNAS 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Web resources

Wikipedia

Hepatocyte nuclear factors entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRC48924.
RefSeqNP_004488.2. NM_004497.2.
UniGeneHs.36137.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1VTNX-ray2.50C115-215[»]
ProteinModelPortalP55318.
SMRP55318. Positions 115-215.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109413. 4 interactions.
IntActP55318. 1 interaction.
STRING9606.ENSP00000304004.

PTM databases

PhosphoSiteP55318.

Polymorphism databases

DMDM8247938.

Proteomic databases

PaxDbP55318.
PRIDEP55318.

Protocols and materials databases

DNASU3171.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302177; ENSP00000304004; ENSG00000170608.
GeneID3171.
KEGGhsa:3171.
UCSCuc002pdr.3. human.

Organism-specific databases

CTD3171.
GeneCardsGC19P046368.
HGNCHGNC:5023. FOXA3.
HPACAB015154.
MIM602295. gene.
neXtProtNX_P55318.
PharmGKBPA201092.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000231817.
HOVERGENHBG006621.
InParanoidP55318.
KOK08038.
OMAVYYQGVY.
PhylomeDBP55318.
TreeFamTF316127.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressP55318.
BgeeP55318.
CleanExHS_FOXA3.
GenevestigatorP55318.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR013638. Fork-head_N.
IPR018533. Forkhead_box_C.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
PF08430. Fork_head_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFOXA3.
GenomeRNAi3171.
NextBio12574.
PROP55318.
SOURCESearch...

Entry information

Entry nameFOXA3_HUMAN
AccessionPrimary (citable) accession number: P55318
Secondary accession number(s): A9LYI5, Q53F16, Q9UMW9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM