FOXA1_RAT
ID FOXA1_RAT Reviewed; 466 AA.
AC P23512;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 25-MAY-2022, entry version 162.
DE RecName: Full=Hepatocyte nuclear factor 3-alpha;
DE Short=HNF-3-alpha;
DE Short=HNF-3A;
DE AltName: Full=Forkhead box protein A1;
GN Name=Foxa1; Synonyms=Hnf3a, Tcf-3a, Tcf3a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 313-337 AND 413-434.
RC TISSUE=Liver;
RX PubMed=2227418; DOI=10.1101/gad.4.8.1427;
RA Lai E., Prezioso V.R., Smith E., Litvin O., Costa R.H., Darnell J.E. Jr.;
RT "HNF-3A, a hepatocyte-enriched transcription factor of novel structure is
RT regulated transcriptionally.";
RL Genes Dev. 4:1427-1436(1990).
RN [2]
RP FUNCTION IN PROSTATE AR ACTIVATION, AND INTERACTION WITH AR.
RX PubMed=12750453; DOI=10.1210/me.2003-0020;
RA Gao N., Zhang J., Rao M.A., Case T.C., Mirosevich J., Wang Y., Jin R.,
RA Gupta A., Rennie P.S., Matusik R.J.;
RT "The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and
RT androgen receptor in transcriptional regulation of prostatic genes.";
RL Mol. Endocrinol. 17:1484-1507(2003).
RN [3]
RP FUNCTION, AND INTERACTION WITH NR0B2.
RX PubMed=15358835; DOI=10.1210/me.2004-0211;
RA Kim J.Y., Kim H.J., Kim K.T., Park Y.Y., Seong H.A., Park K.C., Lee I.K.,
RA Ha H., Shong M., Park S.C., Choi H.S.;
RT "Orphan nuclear receptor small heterodimer partner represses hepatocyte
RT nuclear factor 3/Foxa transactivation via inhibition of its DNA binding.";
RL Mol. Endocrinol. 18:2880-2894(2004).
RN [4]
RP DNA-BINDING, AND SUBUNIT.
RX PubMed=17189638; DOI=10.1016/j.jmb.2006.11.087;
RA Cirillo L.A., Zaret K.S.;
RT "Specific interactions of the wing domains of FOXA1 transcription factor
RT with DNA.";
RL J. Mol. Biol. 366:720-724(2007).
RN [5]
RP FUNCTION, AND INTERACTION WITH NKX2-1.
RX PubMed=17220277; DOI=10.1128/mcb.01133-06;
RA Minoo P., Hu L., Xing Y., Zhu N.L., Chen H., Li M., Borok Z., Li C.;
RT "Physical and functional interactions between homeodomain NKX2.1 and winged
RT helix/forkhead FOXA1 in lung epithelial cells.";
RL Mol. Cell. Biol. 27:2155-2165(2007).
RN [6]
RP FUNCTION IN PROSTATE AR ACTIVATION, AND INTERACTION WITH AR.
RX PubMed=18178153; DOI=10.1016/j.bbrc.2007.12.162;
RA Lee H.J., Hwang M., Chattopadhyay S., Choi H.S., Lee K.;
RT "Hepatocyte nuclear factor-3 alpha (HNF-3alpha) negatively regulates
RT androgen receptor transactivation in prostate cancer cells.";
RL Biochem. Biophys. Res. Commun. 367:481-486(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcription factor that is involved in embryonic
CC development, establishment of tissue-specific gene expression and
CC regulation of gene expression in differentiated tissues. Is thought to
CC act as a 'pioneer' factor opening the compacted chromatin for other
CC proteins through interactions with nucleosomal core histones and
CC thereby replacing linker histones at target enhancer and/or promoter
CC sites. Binds DNA with the consensus sequence 5'-
CC [AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'. Proposed to play a role in
CC translating the epigenetic signatures into cell type-specific enhancer-
CC driven transcriptional programs. Involved in glucose homeostasis;
CC activates the GCG promoter. Involved in the development of multiple
CC endoderm-derived organ systems such as the liver, pancreas, lungs and
CC prostate; FOXA1 and FOXA2 seem to have at least in part redundant
CC roles. Modulates the transcriptional activity of nuclear hormone
CC receptors. Is required for maximal gene activation mediated by AR in
CC the prostate. Negatively regulates AR transactivation via competition
CC with coactivators such as NCOA2. Is involved in ESR1-mediated
CC transcription. Involved in regulation of apoptosis. Involved in cell
CC cycle regulation. Originally described as a transcription activator for
CC a number of liver genes such as AFP, albumin, tyrosine
CC aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory
CC regions of these genes. {ECO:0000269|PubMed:12750453,
CC ECO:0000269|PubMed:15358835, ECO:0000269|PubMed:17220277,
CC ECO:0000269|PubMed:18178153}.
CC -!- SUBUNIT: Binds DNA as a monomer. Interacts with FOXA2. Interacts with
CC NKX2-1. Interacts with HDAC7. Interacts with the histone H3-H4
CC heterodimer. Associates with nucleosomes containing histone H2A (By
CC similarity). Interacts with AR. Interacts with NR0B2. {ECO:0000250,
CC ECO:0000269|PubMed:12750453, ECO:0000269|PubMed:15358835,
CC ECO:0000269|PubMed:17189638, ECO:0000269|PubMed:17220277,
CC ECO:0000269|PubMed:18178153}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Liver.
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DR EMBL; X55955; CAA39418.1; -; mRNA.
DR PIR; A36674; A36674.
DR RefSeq; NP_036874.1; NM_012742.1.
DR AlphaFoldDB; P23512; -.
DR SMR; P23512; -.
DR IntAct; P23512; 1.
DR STRING; 10116.ENSRNOP00000009940; -.
DR iPTMnet; P23512; -.
DR PhosphoSitePlus; P23512; -.
DR PaxDb; P23512; -.
DR GeneID; 25098; -.
DR KEGG; rno:25098; -.
DR UCSC; RGD:2807; rat.
DR CTD; 3169; -.
DR RGD; 2807; Foxa1.
DR eggNOG; KOG3563; Eukaryota.
DR InParanoid; P23512; -.
DR OrthoDB; 1181467at2759; -.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR PRO; PR:P23512; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005902; C:microvillus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0061144; P:alveolar secondary septum development; ISO:RGD.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; ISO:RGD.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0061448; P:connective tissue development; ISO:RGD.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; ISO:RGD.
DR GO; GO:0060743; P:epithelial cell maturation involved in prostate gland development; ISO:RGD.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; ISO:RGD.
DR GO; GO:0060738; P:epithelial-mesenchymal signaling involved in prostate gland development; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0042445; P:hormone metabolic process; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0060487; P:lung epithelial cell differentiation; ISO:RGD.
DR GO; GO:0060425; P:lung morphogenesis; ISO:RGD.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0048665; P:neuron fate specification; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; ISO:RGD.
DR GO; GO:0060741; P:prostate gland stromal morphogenesis; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1902691; P:respiratory basal cell differentiation; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; ISO:RGD.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; ISO:RGD.
DR GO; GO:0035239; P:tube morphogenesis; ISO:RGD.
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; IPR018533; Forkhead_box_C.
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 Pfam; PF09354; HNF_C; 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;
KW Direct protein sequencing; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..466
FT /note="Hepatocyte nuclear factor 3-alpha"
FT /id="PRO_0000091794"
FT DNA_BIND 169..260
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 251..288
FT /note="Essential for DNA binding"
FT REGION 269..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..357
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55317"
SQ SEQUENCE 466 AA; 48775 MW; 06555BA74BD9B7DC CRC64;
MLGTVKMEGH ESNDWNSYYA DTQEAYSSVP VSNMNSGLGS MNSMNTYMTM NTMTTSGNMT
PASFNMSYAN PGLGAGLSPG AVAGMPGGSA GAMNSMTAAG VTAMGAALSP GGMGSMGAQP
AASMNGLGPY AAAMNPCMSP MAYAPSNLGR SRAGGGGDAK TFKRSYPHAK PPYSYISLIT
MAIQQAPSKM LTLSEIYQWI MDLFPYYRQN QQRWQNSIRH SLSFNACFVK VARSPDKPGK
GSYWTLHPDS GNMFENGCYL RRQKRFKCEK QPGAGGGSGG GGSKGVPENR KDPSGPVNPS
AESPIHRGVH GKASQLEGAP APGPAASPQT LDHSGATATG GGSELKSPAS SSAPPISSGP
GGWICTPLSP TWLAPHESQL HLKGAPHYSF NHPFSINNLM SSSEQQHKLD FKAYEQALQY
SPYGATLPAS LPLGGASVAT RSPIEPSALE PAYYQGVYSR PVLNTS
