ID   FOXA3_HUMAN             Reviewed;         350 AA.
AC   P55318; A9LYI5; Q53F16; Q9UMW9;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   24-JAN-2024, entry version 202.
DE   RecName: Full=Hepatocyte nuclear factor 3-gamma;
DE            Short=HNF-3-gamma;
DE            Short=HNF-3G;
DE   AltName: Full=Fork head-related protein FKH H3;
DE   AltName: Full=Forkhead box protein A3;
DE   AltName: Full=Transcription factor 3G;
DE            Short=TCF-3G;
GN   Name=FOXA3; Synonyms=HNF3G, TCF3G;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=8499623;
RA   Hromas R., Moore J., Johnston T., Socha C., Klemsz M.;
RT   "Drosophila forkhead homologues are expressed in a lineage-restricted
RT   manner in human hematopoietic cells.";
RL   Blood 81:2854-2859(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10899756; DOI=10.1159/000022943;
RA   Navas M.A., Vaisse C., Boger S., Heimesaat M., Kollee L.A., Stoffel M.;
RT   "The human HNF-3 genes: cloning, partial sequence and mutation screening in
RT   patients with impaired glucose homeostasis.";
RL   Hum. Hered. 50:370-381(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Gastric mucosa;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   SeattleSNPs variation discovery resource;
RL   Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Uterus;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   PROMOTER BINDING.
RX   PubMed=9369482; DOI=10.1021/bi9703249;
RA   Lin B., Morris D.W., Chou J.Y.;
RT   "The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase
RT   gene activation.";
RL   Biochemistry 36:14096-14106(1997).
RN   [9]
RP   FUNCTION.
RX   PubMed=12695546; DOI=10.1124/mol.63.5.1180;
RA   Rodriguez-Antona C., Bort R., Jover R., Tindberg N., Ingelman-Sundberg M.,
RA   Gomez-Lechon M.J., Castell J.V.;
RT   "Transcriptional regulation of human CYP3A4 basal expression by CCAAT
RT   enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma.";
RL   Mol. Pharmacol. 63:1180-1189(2003).
RN   [10]
RP   INTERACTION WITH FOXA2.
RX   PubMed=19919681; DOI=10.1186/gb-2009-10-11-r129;
RA   Motallebipour M., Ameur A., Reddy Bysani M.S., Patra K., Wallerman O.,
RA   Mangion J., Barker M.A., McKernan K.J., Komorowski J., Wadelius C.;
RT   "Differential binding and co-binding pattern of FOXA1 and FOXA3 and their
RT   relation to H3K4me3 in HepG2 cells revealed by ChIP-seq.";
RL   Genome Biol. 10:R129.0-R129.0(2009).
RN   [11]
RP   PROMOTER-BINDING, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX   PubMed=19706729; DOI=10.1124/mol.109.055699;
RA   Riffel A.K., Schuenemann E., Vyhlidal C.A.;
RT   "Regulation of the CYP3A4 and CYP3A7 promoters by members of the nuclear
RT   factor I transcription factor family.";
RL   Mol. Pharmacol. 76:1104-1114(2009).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 115-215 IN COMPLEX WITH DNA.
RX   PubMed=8332212; DOI=10.1038/364412a0;
RA   Clark K.L., Halay E.D., Lai E., Burley S.K.;
RT   "Co-crystal structure of the HNF-3/fork head DNA-recognition motif
RT   resembles histone H5.";
RL   Nature 364:412-420(1993).
CC   -!- FUNCTION: Transcription factor that is thought to act as a 'pioneer'
CC       factor opening the compacted chromatin for other proteins through
CC       interactions with nucleosomal core histones and thereby replacing
CC       linker histones at target enhancer and/or promoter sites (By
CC       similarity). Originally described as a transcription activator for a
CC       number of liver genes such as AFP, albumin, tyrosine aminotransferase,
CC       PEPCK, etc. Interacts with the cis-acting regulatory regions of these
CC       genes. Involved in glucose homeostasis; binds to and activates
CC       transcription from the G6PC1 promoter. Binds to the CYP3A4 promoter and
CC       activates its transcription in cooperation with CEBPA. Binds to the
CC       CYP3A7 promoter together with members of the CTF/NF-I family. Involved
CC       in regulation of neuronal-specific transcription. May be involved in
CC       regulation of spermatogenesis. {ECO:0000250,
CC       ECO:0000269|PubMed:12695546}.
CC   -!- SUBUNIT: Interacts with FOXA2. {ECO:0000269|PubMed:19919681,
CC       ECO:0000269|PubMed:8332212}.
CC   -!- INTERACTION:
CC       P55318; P28329-3: CHAT; NbExp=3; IntAct=EBI-3910364, EBI-25837549;
CC       P55318; P22607: FGFR3; NbExp=3; IntAct=EBI-3910364, EBI-348399;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC       ECO:0000269|PubMed:19706729}.
CC   -!- TISSUE SPECIFICITY: Expressed in erythroleukemia and hepatoma cell
CC       lines and in liver and pancreas. Not expressed in any other cell lines
CC       or tissues examined. {ECO:0000269|PubMed:8499623}.
CC   -!- DEVELOPMENTAL STAGE: Detected in prenatal liver nuclear extracts (12.4-
CC       27 weeks estimated gestational age). Not detected in postnatal liver
CC       samples. {ECO:0000269|PubMed:19706729}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Hepatocyte nuclear factors entry;
CC       URL="https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/foxa3/";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L12141; AAA58477.1; -; mRNA.
DR   EMBL; AF176114; AAD51980.1; -; Genomic_DNA.
DR   EMBL; AF176113; AAD51980.1; JOINED; Genomic_DNA.
DR   EMBL; BT006720; AAP35366.1; -; mRNA.
DR   EMBL; AK223473; BAD97193.1; -; mRNA.
DR   EMBL; EU275778; ABX44664.1; -; Genomic_DNA.
DR   EMBL; CH471126; EAW57394.1; -; Genomic_DNA.
DR   EMBL; BC016024; AAH16024.1; -; mRNA.
DR   CCDS; CCDS12677.1; -.
DR   PIR; C48924; C48924.
DR   RefSeq; NP_004488.2; NM_004497.2.
DR   PDB; 1VTN; X-ray; 2.50 A; C=115-215.
DR   PDBsum; 1VTN; -.
DR   AlphaFoldDB; P55318; -.
DR   SMR; P55318; -.
DR   BioGRID; 109413; 52.
DR   IntAct; P55318; 51.
DR   MINT; P55318; -.
DR   STRING; 9606.ENSP00000304004; -.
DR   iPTMnet; P55318; -.
DR   PhosphoSitePlus; P55318; -.
DR   BioMuta; FOXA3; -.
DR   DMDM; 8247938; -.
DR   EPD; P55318; -.
DR   jPOST; P55318; -.
DR   MassIVE; P55318; -.
DR   MaxQB; P55318; -.
DR   PaxDb; 9606-ENSP00000304004; -.
DR   PeptideAtlas; P55318; -.
DR   ProteomicsDB; 56846; -.
DR   Antibodypedia; 4191; 107 antibodies from 26 providers.
DR   DNASU; 3171; -.
DR   Ensembl; ENST00000302177.3; ENSP00000304004.1; ENSG00000170608.3.
DR   GeneID; 3171; -.
DR   KEGG; hsa:3171; -.
DR   MANE-Select; ENST00000302177.3; ENSP00000304004.1; NM_004497.3; NP_004488.2.
DR   UCSC; uc002pdr.3; human.
DR   AGR; HGNC:5023; -.
DR   CTD; 3171; -.
DR   DisGeNET; 3171; -.
DR   GeneCards; FOXA3; -.
DR   HGNC; HGNC:5023; FOXA3.
DR   HPA; ENSG00000170608; Group enriched (intestine, liver, pancreas, stomach).
DR   MIM; 602295; gene.
DR   neXtProt; NX_P55318; -.
DR   OpenTargets; ENSG00000170608; -.
DR   PharmGKB; PA201092; -.
DR   VEuPathDB; HostDB:ENSG00000170608; -.
DR   eggNOG; KOG3563; Eukaryota.
DR   GeneTree; ENSGT00940000162453; -.
DR   HOGENOM; CLU_027910_0_0_1; -.
DR   InParanoid; P55318; -.
DR   OMA; SHDISEW; -.
DR   OrthoDB; 5385885at2759; -.
DR   PhylomeDB; P55318; -.
DR   TreeFam; TF316127; -.
DR   PathwayCommons; P55318; -.
DR   Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR   SignaLink; P55318; -.
DR   BioGRID-ORCS; 3171; 26 hits in 1186 CRISPR screens.
DR   ChiTaRS; FOXA3; human.
DR   GeneWiki; FOXA3; -.
DR   GenomeRNAi; 3171; -.
DR   Pharos; P55318; Tbio.
DR   PRO; PR:P55318; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; P55318; Protein.
DR   Bgee; ENSG00000170608; Expressed in ileal mucosa and 76 other cell types or tissues.
DR   ExpressionAtlas; P55318; baseline and differential.
DR   GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:InterPro.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:UniProtKB.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR   GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR   GO; GO:0061484; P:hematopoietic stem cell homeostasis; IEA:Ensembl.
DR   GO; GO:0001678; P:intracellular glucose homeostasis; TAS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR   CDD; cd20040; FH_FOXA3; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR047366; FH_FOXA3.
DR   InterPro; IPR013638; Fork-head_N.
DR   InterPro; IPR001766; Fork_head_dom.
DR   InterPro; IPR018122; TF_fork_head_CS_1.
DR   InterPro; IPR030456; TF_fork_head_CS_2.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR11829; FORKHEAD BOX PROTEIN; 1.
DR   PANTHER; PTHR11829:SF201; HEPATOCYTE NUCLEAR FACTOR 3-GAMMA; 1.
DR   Pfam; PF00250; Forkhead; 1.
DR   Pfam; PF08430; Forkhead_N; 1.
DR   PRINTS; PR00053; FORKHEAD.
DR   SMART; SM00339; FH; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00657; FORK_HEAD_1; 1.
DR   PROSITE; PS00658; FORK_HEAD_2; 1.
DR   PROSITE; PS50039; FORK_HEAD_3; 1.
DR   Genevisible; P55318; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Chromatin regulator; Developmental protein;
KW   Differentiation; DNA-binding; Nucleus; Reference proteome; Spermatogenesis;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..350
FT                   /note="Hepatocyte nuclear factor 3-gamma"
FT                   /id="PRO_0000091800"
FT   DNA_BIND        116..207
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          217..276
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        225..246
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        247..261
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         91
FT                   /note="G -> R (in dbSNP:rs758330593)"
FT                   /id="VAR_008859"
FT   CONFLICT        52
FT                   /note="Missing (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        83
FT                   /note="V -> L (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        107
FT                   /note="K -> M (in Ref. 4; BAD97193)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        111..113
FT                   /note="RPL -> AP (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        137
FT                   /note="M -> V (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        156
FT                   /note="E -> D (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        227..228
FT                   /note="AT -> S (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        291
FT                   /note="E -> D (in Ref. 1; AAA58477)"
FT                   /evidence="ECO:0000305"
FT   HELIX           122..131
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   HELIX           140..150
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   HELIX           152..155
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   HELIX           158..171
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   STRAND          175..178
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   STRAND          190..193
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   HELIX           195..197
FT                   /evidence="ECO:0007829|PDB:1VTN"
FT   STRAND          206..208
FT                   /evidence="ECO:0007829|PDB:1VTN"
SQ   SEQUENCE   350 AA;  37140 MW;  07657D41B0867101 CRC64;
     MLGSVKMEAH DLAEWSYYPE AGEVYSPVTP VPTMAPLNSY MTLNPLSSPY PPGGLPASPL
     PSGPLAPPAP AAPLGPTFPG LGVSGGSSSS GYGAPGPGLV HGKEMPKGYR RPLAHAKPPY
     SYISLITMAI QQAPGKMLTL SEIYQWIMDL FPYYRENQQR WQNSIRHSLS FNDCFVKVAR
     SPDKPGKGSY WALHPSSGNM FENGCYLRRQ KRFKLEEKVK KGGSGAATTT RNGTGSAAST
     TTPAATVTSP PQPPPPAPEP EAQGGEDVGA LDCGSPASST PYFTGLELPG ELKLDAPYNF
     NHPFSINNLM SEQTPAPPKL DVGFGGYGAE GGEPGVYYQG LYSRSLLNAS
//