HES1_RAT
ID HES1_RAT Reviewed; 281 AA.
AC Q04666;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Transcription factor HES-1;
DE AltName: Full=Hairy and enhancer of split 1;
DE AltName: Full=Hairy-like protein;
DE AltName: Full=RHL;
GN Name=Hes1; Synonyms=Hes-1, Hl;
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].
RC STRAIN=Sprague-Dawley; TISSUE=Embryo;
RX PubMed=1340473; DOI=10.1101/gad.6.12b.2620;
RA Sasai Y., Kageyama R., Tagawa Y., Shigemoto R., Nakanishi S.;
RT "Two mammalian helix-loop-helix factors structurally related to Drosophila
RT hairy and Enhancer of split.";
RL Genes Dev. 6:2620-2634(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8417318; DOI=10.1128/mcb.13.1.105-113.1993;
RA Feder J.N., Jan L.Y., Jan Y.-N.;
RT "A rat gene with sequence homology to the Drosophila gene hairy is rapidly
RT induced by growth factors known to influence neuronal differentiation.";
RL Mol. Cell. Biol. 13:105-113(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [4]
RP INTERACTION WITH TLE1.
RX PubMed=8687460; DOI=10.1006/bbrc.1996.0959;
RA Grbavec D., Stifani S.;
RT "Molecular interaction between TLE1 and the carboxyl-terminal domain of
RT HES-1 containing the WRPW motif.";
RL Biochem. Biophys. Res. Commun. 223:701-705(1996).
RN [5]
RP FUNCTION, INTERACTION WITH TLE1, AND DOMAIN WRPW MOTIF.
RX PubMed=8649374; DOI=10.1128/mcb.16.6.2670;
RA Fisher A.L., Ohsako S., Caudy M.;
RT "The WRPW motif of the hairy-related basic helix-loop-helix repressor
RT proteins acts as a 4-amino-acid transcription repression and protein-
RT protein interaction domain.";
RL Mol. Cell. Biol. 16:2670-2677(1996).
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. Binds DNA on
CC N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-
CC CANNTG-3' with low affinity. May play a role in a functional FA core
CC complex response to DNA cross-link damage, being required for the
CC stability and nuclear localization of FA core complex proteins, as well
CC as for FANCD2 monoubiquitination in response to DNA damage (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:8649374}.
CC -!- SUBUNIT: Interacts with SIRT1. Interacts weakly with TLE2. Interacts
CC with HES6 (By similarity). Transcription repression requires formation
CC of a complex with a corepressor protein of the Groucho/TLE family.
CC Interacts (via WPRW motif) with TLE1. 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: Present in all tissues examined but highest in
CC epithelial cells and in mesoderm-derived tissues such as embryonal
CC muscle cells.
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). {ECO:0000269|PubMed:8649374}.
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. {ECO:0000269|PubMed:8649374}.
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}.
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; D13417; BAA02682.1; -; mRNA.
DR EMBL; L04527; AAA41307.1; -; mRNA.
DR EMBL; BC061730; AAH61730.1; -; mRNA.
DR PIR; S36748; S36748.
DR RefSeq; NP_077336.3; NM_024360.3.
DR AlphaFoldDB; Q04666; -.
DR BMRB; Q04666; -.
DR SMR; Q04666; -.
DR BioGRID; 248210; 8.
DR CORUM; Q04666; -.
DR ELM; Q04666; -.
DR IntAct; Q04666; 3.
DR MINT; Q04666; -.
DR STRING; 10116.ENSRNOP00000002346; -.
DR ChEMBL; CHEMBL4105998; -.
DR iPTMnet; Q04666; -.
DR PhosphoSitePlus; Q04666; -.
DR PaxDb; Q04666; -.
DR PRIDE; Q04666; -.
DR Ensembl; ENSRNOT00000002346; ENSRNOP00000002346; ENSRNOG00000001720.
DR GeneID; 29577; -.
DR KEGG; rno:29577; -.
DR UCSC; RGD:62081; rat.
DR CTD; 3280; -.
DR RGD; 62081; Hes1.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000159619; -.
DR InParanoid; Q04666; -.
DR OrthoDB; 1427802at2759; -.
DR PhylomeDB; Q04666; -.
DR PRO; PR:Q04666; -.
DR Proteomes; UP000002494; Chromosome 11.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016363; C:nuclear matrix; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0051087; F:chaperone binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0070888; F:E-box binding; IDA:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0043398; F:HLH domain binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0008432; F:JUN kinase binding; IPI:RGD.
DR GO; GO:0071820; F:N-box binding; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0021984; P:adenohypophysis development; ISO:RGD.
DR GO; GO:0035881; P:amacrine cell differentiation; IEA:Ensembl.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0035909; P:aorta morphogenesis; ISO:RGD.
DR GO; GO:0048844; P:artery morphogenesis; ISO:RGD.
DR GO; GO:0035910; P:ascending aorta morphogenesis; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0021870; P:Cajal-Retzius cell differentiation; IEA:Ensembl.
DR GO; GO:0061309; P:cardiac neural crest cell development involved in outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0001709; P:cell fate determination; IEA:Ensembl.
DR GO; GO:0048469; P:cell maturation; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; ISO:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IMP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0090102; P:cochlea development; ISO:RGD.
DR GO; GO:0072049; P:comma-shaped body morphogenesis; ISO:RGD.
DR GO; GO:0061009; P:common bile duct development; ISO:RGD.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISO:RGD.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; ISO:RGD.
DR GO; GO:0021861; P:forebrain radial glial cell differentiation; IDA:UniProtKB.
DR GO; GO:0072012; P:glomerulus vasculature development; ISO:RGD.
DR GO; GO:0035315; P:hair cell differentiation; IMP:RGD.
DR GO; GO:0021575; P:hindbrain morphogenesis; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; ISO:RGD.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0046331; P:lateral inhibition; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; ISO:RGD.
DR GO; GO:0030901; P:midbrain development; ISO:RGD.
DR GO; GO:0021555; P:midbrain-hindbrain boundary morphogenesis; ISO:RGD.
DR GO; GO:1902870; P:negative regulation of amacrine cell differentiation; IEA:Ensembl.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IMP:RGD.
DR GO; GO:0045596; P:negative regulation of cell differentiation; ISO:RGD.
DR GO; GO:1905934; P:negative regulation of cell fate determination; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:2000978; P:negative regulation of forebrain neuron differentiation; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; ISO:RGD.
DR GO; GO:2000981; P:negative regulation of inner ear receptor cell differentiation; ISO:RGD.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:RGD.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:RGD.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IMP:RGD.
DR GO; GO:2000227; P:negative regulation of pancreatic A cell differentiation; ISO:RGD.
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:RGD.
DR GO; GO:0061106; P:negative regulation of stomach neuroendocrine cell differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0021915; P:neural tube development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IEP:RGD.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0021557; P:oculomotor nerve development; ISO:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0031016; P:pancreas development; ISO:RGD.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; ISO:RGD.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISO:RGD.
DR GO; GO:0021983; P:pituitary gland development; ISO:RGD.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0045687; P:positive regulation of glial cell differentiation; IMP:RGD.
DR GO; GO:0045977; P:positive regulation of mitotic cell cycle, embryonic; ISO:RGD.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISO:RGD.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0045598; P:regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:RGD.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:RGD.
DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; ISO:RGD.
DR GO; GO:0048505; P:regulation of timing of cell differentiation; ISO:RGD.
DR GO; GO:0060164; P:regulation of timing of neuron differentiation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0072141; P:renal interstitial fibroblast development; ISO:RGD.
DR GO; GO:0043279; P:response to alkaloid; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0072050; P:S-shaped body morphogenesis; ISO:RGD.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD.
DR GO; GO:0035019; P:somatic stem cell population maintenance; ISO:RGD.
DR GO; GO:0061102; P:stomach neuroendocrine cell differentiation; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR GO; GO:0021537; P:telencephalon development; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR GO; GO:0021558; P:trochlear nerve development; ISO:RGD.
DR GO; GO:0060675; P:ureteric bud morphogenesis; ISO:RGD.
DR GO; GO:0097084; P:vascular associated smooth muscle cell development; ISO:RGD.
DR GO; GO:0003281; P:ventricular septum development; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..281
FT /note="Transcription factor HES-1"
FT /id="PRO_0000127204"
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..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 255..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..279
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..199
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..275
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 86
FT /note="K -> N (in Ref. 2; AAA41307)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="R -> W (in Ref. 2; AAA41307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 281 AA; 29622 MW; 8A98C8964F075B0D CRC64;
MPADIMEKNS SSPVAATPAS VNTTPDKPKT ASEHRKSSKP IMEKRRRARI NESLSQLKTL
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRAQMTAAL STDPSVLGKY RAGFSECMNE
VTRFLSTCEG VNTEVRTRLL GHLANCMTQI NAMTYPGQAH PALQAPPPPP PSGPGGPQHA
PFAPPPPLVP IPGGAAPPPG SAPCKLGSQA GEAAKVFGGF QVVPAPDGQF AFLIPNGAFA
HSGPVIPVYT SNSGTSVGPN AVSPSSGSSL TADSMWRPWR N
