ID   HES1_MOUSE              Reviewed;         282 AA.
AC   P35428;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   24-JAN-2024, entry version 195.
DE   RecName: Full=Transcription factor HES-1;
DE   AltName: Full=Hairy and enhancer of split 1;
GN   Name=Hes1; Synonyms=Hes-1;
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 [GENOMIC DNA].
RX   PubMed=7906273; DOI=10.1016/s0021-9258(17)37668-8;
RA   Takebayashi K., Sasai Y., Sakai Y., Watanabe T., Nakanishi S., Kageyama R.;
RT   "Structure, chromosomal locus, and promoter analysis of the gene encoding
RT   the mouse helix-loop-helix factor HES-1. Negative autoregulation through
RT   the multiple N box elements.";
RL   J. Biol. Chem. 269:5150-5156(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Colon, and Eye;
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   [3]
RP   INTERACTION WITH TLE1 AND TLE2.
RX   PubMed=9874198; DOI=10.1046/j.1432-1327.1998.2580339.x;
RA   Grbavec D., Lo R., Liu Y., Stifani S.;
RT   "Transducin-like Enhancer of split 2, a mammalian homologue of Drosophila
RT   Groucho, acts as a transcriptional repressor, interacts with Hairy/Enhancer
RT   of split proteins, and is expressed during neuronal development.";
RL   Eur. J. Biochem. 258:339-349(1998).
RN   [4]
RP   DNA-BINDING, AND INTERACTION WITH HES6.
RX   PubMed=10851137; DOI=10.1242/dev.127.13.2933;
RA   Bae S.-K., Bessho Y., Hojo M., Kageyama R.;
RT   "The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal
RT   differentiation.";
RL   Development 127:2933-2943(2000).
CC   -!- FUNCTION: Transcriptional repressor of genes that require a bHLH
CC       protein for their transcription. May act as a negative regulator of
CC       myogenesis by inhibiting the functions of MYOD1 and ASH1 (By
CC       similarity). Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity
CC       and on E-box motifs: 5'-CANNTG-3' with low affinity. May play a role in
CC       a functional FA core complex response to DNA cross-link damage, being
CC       required for the stability and nuclear localization of FA core complex
CC       proteins, as well as for FANCD2 monoubiquitination in response to DNA
CC       damage (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with SIRT1 (By similarity). Transcription repression
CC       requires formation of a complex with a corepressor protein of the
CC       Groucho/TLE family. Interacts (via WPRW motif) with TLE1, and more
CC       weakly with TLE2. Interacts with HES6. Interacts with an FA complex,
CC       composed of FANCA, FANCF, FANCG and FANCL, but not of FANCC, nor FANCE
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Expressed at high levels in undifferentiated neural
CC       precursor cells, but the level of expression decreases as neural
CC       differentiation proceeds.
CC   -!- DOMAIN: Has a particular type of basic domain (presence of a helix-
CC       interrupting proline) that binds to the N-box (CACNAG), rather than the
CC       canonical E-box (CANNTG).
CC   -!- DOMAIN: The C-terminal WRPW motif is a transcriptional repression
CC       domain necessary for the interaction with Groucho/TLE family members,
CC       transcriptional corepressors recruited to specific target DNA by Hairy-
CC       related proteins.
CC   -!- DOMAIN: The bHLH, as well as cooperation between the central Orange
CC       domain and the C-terminal WRPW motif, is required for transcriptional
CC       repressor activity. {ECO:0000250}.
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DR   EMBL; D16464; BAA03931.1; -; Genomic_DNA.
DR   EMBL; BC018375; AAH18375.1; -; mRNA.
DR   EMBL; BC051428; AAH51428.1; -; mRNA.
DR   CCDS; CCDS28098.1; -.
DR   PIR; A53336; A53336.
DR   RefSeq; NP_032261.1; NM_008235.2.
DR   AlphaFoldDB; P35428; -.
DR   BMRB; P35428; -.
DR   SMR; P35428; -.
DR   BioGRID; 200275; 8.
DR   ELM; P35428; -.
DR   STRING; 10090.ENSMUSP00000023171; -.
DR   BindingDB; P35428; -.
DR   ChEMBL; CHEMBL1075292; -.
DR   iPTMnet; P35428; -.
DR   PhosphoSitePlus; P35428; -.
DR   PaxDb; 10090-ENSMUSP00000023171; -.
DR   PeptideAtlas; P35428; -.
DR   ProteomicsDB; 269593; -.
DR   Pumba; P35428; -.
DR   Antibodypedia; 19442; 767 antibodies from 40 providers.
DR   DNASU; 15205; -.
DR   Ensembl; ENSMUST00000023171.8; ENSMUSP00000023171.8; ENSMUSG00000022528.9.
DR   GeneID; 15205; -.
DR   KEGG; mmu:15205; -.
DR   UCSC; uc007ywl.1; mouse.
DR   AGR; MGI:104853; -.
DR   CTD; 3280; -.
DR   MGI; MGI:104853; Hes1.
DR   VEuPathDB; HostDB:ENSMUSG00000022528; -.
DR   eggNOG; KOG4304; Eukaryota.
DR   GeneTree; ENSGT00940000159619; -.
DR   HOGENOM; CLU_068550_1_0_1; -.
DR   InParanoid; P35428; -.
DR   OMA; AMNYPAQ; -.
DR   OrthoDB; 2907677at2759; -.
DR   PhylomeDB; P35428; -.
DR   TreeFam; TF351373; -.
DR   BioGRID-ORCS; 15205; 5 hits in 79 CRISPR screens.
DR   ChiTaRS; Hes1; mouse.
DR   PRO; PR:P35428; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; P35428; Protein.
DR   Bgee; ENSMUSG00000022528; Expressed in lip and 289 other cell types or tissues.
DR   ExpressionAtlas; P35428; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR   GO; GO:0001217; F:DNA-binding transcription repressor activity; IDA:UniProtKB.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR   GO; GO:0070888; F:E-box binding; IDA:ARUK-UCL.
DR   GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR   GO; GO:0043398; F:HLH domain binding; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0008432; F:JUN kinase binding; ISO:MGI.
DR   GO; GO:0071820; F:N-box binding; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0051087; F:protein-folding chaperone binding; IDA:MGI.
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; ISS:UniProtKB.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR   GO; GO:0021984; P:adenohypophysis development; IMP:MGI.
DR   GO; GO:0035881; P:amacrine cell differentiation; IMP:MGI.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR   GO; GO:0035909; P:aorta morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0048844; P:artery morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0035910; P:ascending aorta morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0030509; P:BMP signaling pathway; IGI:MGI.
DR   GO; GO:0021870; P:Cajal-Retzius cell differentiation; IGI:MGI.
DR   GO; GO:0061309; P:cardiac neural crest cell development involved in outflow tract morphogenesis; IMP:MGI.
DR   GO; GO:0007155; P:cell adhesion; IGI:MGI.
DR   GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR   GO; GO:0001709; P:cell fate determination; IMP:MGI.
DR   GO; GO:0048469; P:cell maturation; IGI:MGI.
DR   GO; GO:0016477; P:cell migration; IGI:MGI.
DR   GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IGI:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR   GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR   GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISO:MGI.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0090102; P:cochlea development; IMP:MGI.
DR   GO; GO:0072049; P:comma-shaped body morphogenesis; IEP:UniProtKB.
DR   GO; GO:0061009; P:common bile duct development; IMP:MGI.
DR   GO; GO:0003143; P:embryonic heart tube morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0090162; P:establishment of epithelial cell polarity; IGI:MGI.
DR   GO; GO:0021861; P:forebrain radial glial cell differentiation; ISS:UniProtKB.
DR   GO; GO:0072012; P:glomerulus vasculature development; IEP:UniProtKB.
DR   GO; GO:0035315; P:hair cell differentiation; ISO:MGI.
DR   GO; GO:0021575; P:hindbrain morphogenesis; IGI:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR   GO; GO:0002085; P:inhibition of neuroepithelial cell differentiation; IMP:MGI.
DR   GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IGI:MGI.
DR   GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IGI:MGI.
DR   GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:BHF-UCL.
DR   GO; GO:0046331; P:lateral inhibition; IMP:MGI.
DR   GO; GO:0001889; P:liver development; IMP:MGI.
DR   GO; GO:0030324; P:lung development; IMP:MGI.
DR   GO; GO:0072282; P:metanephric nephron tubule morphogenesis; IEP:UniProtKB.
DR   GO; GO:0030901; P:midbrain development; IGI:MGI.
DR   GO; GO:0021555; P:midbrain-hindbrain boundary morphogenesis; IGI:MGI.
DR   GO; GO:1902870; P:negative regulation of amacrine cell differentiation; IMP:MGI.
DR   GO; GO:0090281; P:negative regulation of calcium ion import; ISO:MGI.
DR   GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI.
DR   GO; GO:1905934; P:negative regulation of cell fate determination; IMP:MGI.
DR   GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:ARUK-UCL.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:2000978; P:negative regulation of forebrain neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR   GO; GO:0060253; P:negative regulation of glial cell proliferation; IDA:UniProtKB.
DR   GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IMP:MGI.
DR   GO; GO:2000981; P:negative regulation of inner ear receptor cell differentiation; IMP:UniProtKB.
DR   GO; GO:0050768; P:negative regulation of neurogenesis; ISO:MGI.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI.
DR   GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IDA:UniProtKB.
DR   GO; GO:2000227; P:negative regulation of pancreatic A cell differentiation; IMP:MGI.
DR   GO; GO:2000974; P:negative regulation of pro-B cell differentiation; ISS:UniProtKB.
DR   GO; GO:2000737; P:negative regulation of stem cell differentiation; ISO:MGI.
DR   GO; GO:0061106; P:negative regulation of stomach neuroendocrine cell differentiation; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0021915; P:neural tube development; IGI:MGI.
DR   GO; GO:0061101; P:neuroendocrine cell differentiation; IMP:MGI.
DR   GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:UniProtKB.
DR   GO; GO:0007219; P:Notch signaling pathway; IDA:MGI.
DR   GO; GO:0021557; P:oculomotor nerve development; IGI:MGI.
DR   GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0031016; P:pancreas development; IMP:MGI.
DR   GO; GO:0003310; P:pancreatic A cell differentiation; IMP:MGI.
DR   GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR   GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0021983; P:pituitary gland development; IMP:MGI.
DR   GO; GO:0048711; P:positive regulation of astrocyte differentiation; IDA:UniProtKB.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; IGI:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR   GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0045687; P:positive regulation of glial cell differentiation; ISO:MGI.
DR   GO; GO:0045977; P:positive regulation of mitotic cell cycle, embryonic; IMP:BHF-UCL.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:UniProtKB.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR   GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR   GO; GO:0050678; P:regulation of epithelial cell proliferation; IGI:MGI.
DR   GO; GO:0045598; P:regulation of fat cell differentiation; IMP:MGI.
DR   GO; GO:0050767; P:regulation of neurogenesis; IGI:MGI.
DR   GO; GO:0045664; P:regulation of neuron differentiation; IGI:MGI.
DR   GO; GO:0043254; P:regulation of protein-containing complex assembly; ISO:MGI.
DR   GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR   GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; IMP:MGI.
DR   GO; GO:0048505; P:regulation of timing of cell differentiation; IMP:MGI.
DR   GO; GO:0060164; P:regulation of timing of neuron differentiation; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0072141; P:renal interstitial fibroblast development; IEP:UniProtKB.
DR   GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl.
DR   GO; GO:0072050; P:S-shaped body morphogenesis; IEP:UniProtKB.
DR   GO; GO:0007224; P:smoothened signaling pathway; IDA:MGI.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR   GO; GO:0061102; P:stomach neuroendocrine cell differentiation; IMP:MGI.
DR   GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR   GO; GO:0021537; P:telencephalon development; IMP:MGI.
DR   GO; GO:0048538; P:thymus development; IMP:BHF-UCL.
DR   GO; GO:0021558; P:trochlear nerve development; IGI:MGI.
DR   GO; GO:0060675; P:ureteric bud morphogenesis; IEP:UniProtKB.
DR   GO; GO:0097084; P:vascular associated smooth muscle cell development; IMP:BHF-UCL.
DR   GO; GO:0003281; P:ventricular septum development; IMP:BHF-UCL.
DR   GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR   CDD; cd11459; bHLH-O_HES1_4; 1.
DR   Gene3D; 6.10.250.980; -; 1.
DR   Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR003650; Orange_dom.
DR   PANTHER; PTHR10985; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, HES-RELATED; 1.
DR   PANTHER; PTHR10985:SF77; TRANSCRIPTION FACTOR HES-1; 1.
DR   Pfam; PF07527; Hairy_orange; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SMART; SM00511; ORANGE; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   SUPFAM; SSF158457; Orange domain-like; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS51054; ORANGE; 1.
DR   Genevisible; P35428; MM.
PE   1: Evidence at protein level;
KW   DNA-binding; Nucleus; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..282
FT                   /note="Transcription factor HES-1"
FT                   /id="PRO_0000127203"
FT   DOMAIN          34..91
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   DOMAIN          110..143
FT                   /note="Orange"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          158..204
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          256..282
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           277..280
FT                   /note="WRPW motif"
FT   COMPBIAS        10..27
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        28..44
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        161..200
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   282 AA;  29749 MW;  88C7700C5EF7DA26 CRC64;
     MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI NESLSQLKTL
     ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL STDPSVLGKY RAGFSECMNE
     VTRFLSTCEG VNTEVRTRLL GHLANCMTQI NAMTYPGQAH PALQAPPPPP PSGPAGPQHA
     PFAPPPPPLV PIPGGAAPPP GSAPCKLGSQ AGEAAKVFGG FQVVPAPDGQ FAFLIPNGAF
     AHSGPVIPVY TSNSGTSVGP NAVSPSSGSS LTSDSMWRPW RN
//