P55318 (FOXA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	FOXA3
Synonyms:	HNF3G, TCF3G

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	350 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Spermatogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding
Molecular function	Activator Chromatin regulator Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from Biological aspect of Ancestor. Source: RefGenome cellular glucose homeostasis Traceable author statement Ref.8. Source: UniProtKB cellular response to starvation Inferred from Biological aspect of Ancestor. Source: RefGenome 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 cell proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome neural plate anterior/posterior regionalization Inferred from Biological aspect of Ancestor. Source: RefGenome neuron fate specification Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of hepatocyte 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 sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA 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 protein domain specific binding Inferred from Biological aspect of Ancestor. Source: RefGenome sequence-specific DNA binding Inferred from electronic annotation. Source: Compara 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 350

350

Hepatocyte nuclear factor 3-gamma

PRO_0000091800

Regions

DNA binding

116 – 207

92

Fork-head

Natural variations

Natural variant

91

1

G → R.

VAR_008859

Experimental info

Sequence conflict

52

1

Missing in AAA58477. Ref.1

Sequence conflict

83

1

V → L in AAA58477. Ref.1

Sequence conflict

107

1

K → M in BAD97193. Ref.4

Sequence conflict

111 – 113

3

RPL → AP in AAA58477. Ref.1

Sequence conflict

137

1

M → V in AAA58477. Ref.1

Sequence conflict

156

1

E → D in AAA58477. Ref.1

Sequence conflict

227 – 228

2

AT → S in AAA58477. Ref.1

Sequence conflict

291

1

E → D in AAA58477. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

350

Helix Strand Turn

Details...

Helix

122 – 131

10

Helix

140 – 150

11

Helix

152 – 155

4

Helix

158 – 171

14

Beta strand

175 – 178

4

Beta strand

190 – 193

4

Helix

195 – 197

3

Beta strand

206 – 208

3

Sequences

	Sequence		Length	Mass (Da)
	P55318 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 07657D41B0867101	FASTA	350	37,140
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00024388.

PIR

C48924.

RefSeq

NP_004488.2. NM_004497.2.

UniGene

Hs.36137.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1VTN	X-ray	2.50	C	115-215	[»]

ProteinModelPortal

P55318.

ModBase

Search...

Protein-protein interaction databases

IntAct

P55318. 1 interaction.

STRING

9606.ENSP00000304004.

PTM databases

PhosphoSite

P55318.

Polymorphism databases

DMDM

8247938.

Proteomic databases

PaxDb

P55318.

PRIDE

P55318.

Protocols and materials databases

DNASU

3171.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000302177; ENSP00000304004; ENSG00000170608.

GeneID

3171.

KEGG

hsa:3171.

UCSC

uc002pdr.3. human.

Organism-specific databases

CTD

3171.

GeneCards

GC19P046368.

HGNC

HGNC:5023. FOXA3.

HPA

CAB015154.

MIM

602295. gene.

neXtProt

NX_P55318.

PharmGKB

PA201092.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5025.

HOGENOM

HOG000231817.

HOVERGEN

HBG006621.

InParanoid

P55318.

KO

K08038.

OMA

VYYQGVY.

OrthoDB

EOG43R3NB.

PhylomeDB

P55318.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3pathway. FOXA transcription factor networks.
hnf3apathway. FOXA1 transcription factor network.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

Bgee

P55318.

CleanEx

HS_FOXA3.

Genevestigator

P55318.

GermOnline

ENSG00000170608. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.

InterPro

IPR013638. Fork-head_N.
IPR018533. Forkhead_box_C.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00250. Fork_head. 1 hit.
PF08430. Fork_head_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]

PRINTS

PR00053. FORKHEAD.

SMART

SM00339. FH. 1 hit.
[Graphical view]

PROSITE

PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

3171.

NextBio

12574.

SOURCE

Search...

Entry information

Entry name

FOXA3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.