FOXA3_MOUSE
ID FOXA3_MOUSE Reviewed; 353 AA.
AC P35584;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Hepatocyte nuclear factor 3-gamma;
DE Short=HNF-3-gamma;
DE Short=HNF-3G;
DE AltName: Full=Forkhead box protein A3;
GN Name=Foxa3; Synonyms=Hnf3g, Tcf-3g, Tcf3g;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8034310; DOI=10.1006/geno.1994.1191;
RA Kaestner K., Hiemisch H., Luckow B., Schuetz G.;
RT "The HNF-3 gene family of transcription factors in mice: gene structure,
RT cDNA sequence, and mRNA distribution.";
RL Genomics 20:377-385(1994).
RN [2]
RP FUNCTION IN LIVER-SPECIFIC TRANSCRIPTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9632808; DOI=10.1128/mcb.18.7.4245;
RA Kaestner K.H., Hiemisch H., Schutz G.;
RT "Targeted disruption of the gene encoding hepatocyte nuclear factor 3gamma
RT results in reduced transcription of hepatocyte-specific genes.";
RL Mol. Cell. Biol. 18:4245-4251(1998).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11546810; DOI=10.1074/jbc.m106344200;
RA Shen W., Scearce L.M., Brestelli J.E., Sund N.J., Kaestner K.H.;
RT "Foxa3 (hepatocyte nuclear factor 3gamma) is required for the regulation of
RT hepatic GLUT2 expression and the maintenance of glucose homeostasis during
RT a prolonged fast.";
RL J. Biol. Chem. 276:42812-42817(2001).
RN [4]
RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND FUNCTION
RP IN SPERMATOGENESIS.
RX PubMed=17488644; DOI=10.1016/j.ydbio.2007.03.525;
RA Behr R., Sackett S.D., Bochkis I.M., Le P.P., Kaestner K.H.;
RT "Impaired male fertility and atrophy of seminiferous tubules caused by
RT haploinsufficiency for Foxa3.";
RL Dev. Biol. 306:636-645(2007).
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; activates GLUT2 transcription.
CC Involved in regulation of neuronal-specific transcription. Involved in
CC regulation of spermatogenesis; required for the maintenance of the
CC testicular germ cell population and male fertility. {ECO:0000250,
CC ECO:0000269|PubMed:11546810, ECO:0000269|PubMed:17488644,
CC ECO:0000269|PubMed:9632808}.
CC -!- SUBUNIT: Interacts with FOXA2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Restricted mainly to endoderm-derived tissues
CC (lung, liver, stomach, and small intestine), also present additionally
CC in ovary, testis, heart, and adipose tissue, but missing from lung.
CC {ECO:0000269|PubMed:17488644}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks around day 15.5 of gestation.
CC Expressed from day 6 to day 70 during postnatal testicular development.
CC {ECO:0000269|PubMed:17488644}.
CC -!- DISRUPTION PHENOTYPE: Reduced expression levels of several HNF3 target
CC genes (phosphoenolpyruvate carboxykinase, transferrin, tyrosine
CC aminotransferase) by 50 to 70%,. The germinal epithelium of testes is
CC characterized by a loss of germ cells secondary to an increase in germ
CC cell apoptosis that ultimately leads to a Sertoli cell-only syndrome.
CC Significantly lower blood glucose in fasted mice.
CC {ECO:0000269|PubMed:11546810, ECO:0000269|PubMed:17488644,
CC ECO:0000269|PubMed:9632808}.
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DR EMBL; X74938; CAA52892.1; -; mRNA.
DR CCDS; CCDS20886.1; -.
DR PIR; C54258; C54258.
DR RefSeq; NP_032286.1; NM_008260.2.
DR AlphaFoldDB; P35584; -.
DR SMR; P35584; -.
DR STRING; 10090.ENSMUSP00000043173; -.
DR iPTMnet; P35584; -.
DR PhosphoSitePlus; P35584; -.
DR MaxQB; P35584; -.
DR PaxDb; P35584; -.
DR PeptideAtlas; P35584; -.
DR PRIDE; P35584; -.
DR ProteomicsDB; 267614; -.
DR Antibodypedia; 4191; 100 antibodies from 25 providers.
DR DNASU; 15377; -.
DR Ensembl; ENSMUST00000036018; ENSMUSP00000043173; ENSMUSG00000040891.
DR GeneID; 15377; -.
DR KEGG; mmu:15377; -.
DR UCSC; uc009fkd.1; mouse.
DR CTD; 3171; -.
DR MGI; MGI:1347477; Foxa3.
DR VEuPathDB; HostDB:ENSMUSG00000040891; -.
DR eggNOG; KOG3563; Eukaryota.
DR GeneTree; ENSGT00940000162453; -.
DR HOGENOM; CLU_027910_0_0_1; -.
DR InParanoid; P35584; -.
DR OMA; NNLMSEP; -.
DR OrthoDB; 1181467at2759; -.
DR PhylomeDB; P35584; -.
DR TreeFam; TF316127; -.
DR BioGRID-ORCS; 15377; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Foxa3; mouse.
DR PRO; PR:P35584; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P35584; protein.
DR Bgee; ENSMUSG00000040891; Expressed in mucous cell of stomach and 112 other tissues.
DR Genevisible; P35584; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; IMP:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IMP:MGI.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0070368; P:positive regulation of hepatocyte differentiation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
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 Pfam; PF00250; Forkhead; 1.
DR Pfam; PF08430; Forkhead_N; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Activator; Chromatin regulator; Developmental protein; Differentiation;
KW DNA-binding; Nucleus; Reference proteome; Spermatogenesis; Transcription;
KW Transcription regulation.
FT CHAIN 1..353
FT /note="Hepatocyte nuclear factor 3-gamma"
FT /id="PRO_0000091801"
FT DNA_BIND 118..209
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 52..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 52..75
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..255
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 353 AA; 37601 MW; 28F060A8E944D5B9 CRC64;
MLGSVKMEAH DLAEWSYYPE AGEVYSPVNP VPTMAPLNSY MTLNPLSSPY PPGGLQASPL
PTGPLAPPAP TAPLGPTFPS LGTGGSTGGS ASGYVAPGPG LVHGKEMAKG YRRPLAHAKP
PYSYISLITM AIQQAPGKML TLSEIYQWIM DLFPYYRENQ QRWQNSIRHS LSFNDCFVKV
ARSPDKPGKG SYWALHPSSG NMFENGCYLR RQKRFKLEEK AKKGNSATSA SRNGTAGSAT
SATTTAATAV TSPAQPQPTP SEPEAQSGDD VGGLDCASPP SSTPYFSGLE LPGELKLDAP
YNFNHPFSIN NLMSEQTSTP SKLDVGFGGY GAESGEPGVY YQSLYSRSLL NAS
