HEY1_MOUSE
ID HEY1_MOUSE Reviewed; 299 AA.
AC Q9WV93;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 1;
DE AltName: Full=Hairy and enhancer of split-related protein 1;
DE Short=HESR-1;
DE AltName: Full=Hairy-related transcription factor 1;
DE Short=HRT-1;
DE Short=mHRT1;
GN Name=Hey1; Synonyms=Herp2, Hesr1, Hrt1;
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 STRAIN=C57BL/6J;
RX PubMed=10403790; DOI=10.1006/bbrc.1999.0880;
RA Kokubo H., Lun Y., Johnson R.L.;
RT "Identification and expression of a novel family of bHLH cDNAs related to
RT Drosophila hairy and enhancer of split.";
RL Biochem. Biophys. Res. Commun. 260:459-465(1999).
RN [2]
RP DEVELOPMENTAL STAGE.
RX PubMed=10415358; DOI=10.1016/s0925-4773(99)00080-5;
RA Leimeister C., Externbrinck A., Klamt B., Gessler M.;
RT "Hey genes: a novel subfamily of hairy- and enhancer of split related genes
RT specifically expressed during mouse embryogenesis.";
RL Mech. Dev. 85:173-177(1999).
RN [3]
RP INDUCTION.
RX PubMed=10964718; DOI=10.1006/bbrc.2000.3354;
RA Maier M.M., Gessler M.;
RT "Comparative analysis of the human and mouse Hey1 promoter: Hey genes are
RT new Notch target genes.";
RL Biochem. Biophys. Res. Commun. 275:652-660(2000).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10860664; DOI=10.1006/geno.2000.6200;
RA Steidl C., Leimeister C., Klamt B., Maier M., Nanda I., Dixon M.,
RA Clarke R., Schmid M., Gessler M.;
RT "Characterization of the human and mouse HEY1, HEY2, and HEYL genes:
RT cloning, mapping, and mutation screening of a new bHLH gene family.";
RL Genomics 66:195-203(2000).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=11095750; DOI=10.1073/pnas.250485597;
RA Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T.,
RA Srivastava D., Olson E.N.;
RT "Members of the HRT family of basic helix-loop-helix proteins act as
RT transcriptional repressors downstream of Notch signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=11160397; DOI=10.1523/jneurosci.21-04-01265.2001;
RA Satow T., Bae S.-K., Inoue T., Inoue C., Miyoshi G., Tomita K., Bessho Y.,
RA Hashimoto N., Kageyama R.;
RT "The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse
RT retina.";
RL J. Neurosci. 21:1265-1273(2001).
RN [7]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=11486044; DOI=10.1128/mcb.21.17.6071-6079.2001;
RA Iso T., Sartorelli V., Chung G., Shichinohe T., Kedes L., Hamamori Y.;
RT "HERP, a new primary target of Notch regulated by ligand binding.";
RL Mol. Cell. Biol. 21:6071-6079(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH HDAC1.
RX PubMed=11486045; DOI=10.1128/mcb.21.17.6080-6089.2001;
RA Iso T., Sartorelli V., Poizat C., Iezzi S., Wu H.-Y., Chung G., Kedes L.,
RA Hamamori Y.;
RT "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling.";
RL Mol. Cell. Biol. 21:6080-6089(2001).
RN [9]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11741889; DOI=10.1074/jbc.m110495200;
RA Iso T., Chung G., Hamamori Y., Kedes L.;
RT "HERP1 is a cell type-specific primary target of Notch.";
RL J. Biol. Chem. 277:6598-6607(2002).
RN [10]
RP INTERACTION WITH CCDC89.
RX PubMed=14648848; DOI=10.1002/dvdy.10406;
RA Van Wayenbergh R., Taelman V., Pichon B., Fischer A., Kricha S.,
RA Gessler M., Christophe D., Bellefroid E.J.;
RT "Identification of BOIP, a novel cDNA highly expressed during
RT spermatogenesis that encodes a protein interacting with the orange domain
RT of the hairy-related transcription factor HRT1/Hey1 in Xenopus and mouse.";
RL Dev. Dyn. 228:716-725(2003).
RN [11]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12947105; DOI=10.1074/jbc.m300448200;
RA Sakamoto M., Hirata H., Ohtsuka T., Bessho Y., Kageyama R.;
RT "The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate
RT maintenance of neural precursor cells in the brain.";
RL J. Biol. Chem. 278:44808-44815(2003).
RN [12]
RP FUNCTION.
RX PubMed=15107403; DOI=10.1101/gad.291004;
RA Fischer A., Schumacher N., Maier M., Sendtner M., Gessler M.;
RT "The Notch target genes Hey1 and Hey2 are required for embryonic vascular
RT development.";
RL Genes Dev. 18:901-911(2004).
RN [13]
RP FUNCTION.
RX PubMed=15680351; DOI=10.1016/j.ydbio.2004.10.025;
RA Kokubo H., Miyagawa-Tomita S., Nakazawa M., Saga Y., Johnson R.L.;
RT "Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch
RT signaling in the developing cardiovascular system.";
RL Dev. Biol. 278:301-309(2005).
RN [14]
RP FUNCTION, AND INTERACTION WITH GATA4 AND GATA6.
RX PubMed=16199874; DOI=10.1128/mcb.25.20.8960-8970.2005;
RA Fischer A., Klattig J., Kneitz B., Diez H., Maier M., Holtmann B.,
RA Englert C., Gessler M.;
RT "Hey basic helix-loop-helix transcription factors are repressors of GATA4
RT and GATA6 and restrict expression of the GATA target gene ANF in fetal
RT hearts.";
RL Mol. Cell. Biol. 25:8960-8970(2005).
RN [15]
RP FUNCTION, INTERACTION WITH HEYL, AND DEVELOPMENTAL STAGE.
RX PubMed=17303760; DOI=10.1161/01.res.0000260913.95642.3b;
RA Fischer A., Steidl C., Wagner T.U., Lang E., Jakob P.M., Friedl P.,
RA Knobeloch K.-P., Gessler M.;
RT "Combined loss of Hey1 and HeyL causes congenital heart defects because of
RT impaired epithelial to mesenchymal transition.";
RL Circ. Res. 100:856-863(2007).
RN [16]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17259303; DOI=10.1242/dev.02777;
RA Kokubo H., Tomita-Miyagawa S., Hamada Y., Saga Y.;
RT "Hesr1 and Hesr2 regulate atrioventricular boundary formation in the
RT developing heart through the repression of Tbx2.";
RL Development 134:747-755(2007).
CC -!- FUNCTION: Transcriptional repressor which binds preferentially to the
CC canonical E box sequence 5'-CACGTG-3'. Downstream effector of Notch
CC signaling required for cardiovascular development. Specifically
CC required for the Notch-induced endocardial epithelial to mesenchymal
CC transition, which is itself criticial for cardiac valve and septum
CC development. May be required in conjunction with HEY2 to specify
CC arterial cell fate or identity. Promotes maintenance of neuronal
CC precursor cells and glial versus neuronal fate specification. Represses
CC transcription by the cardiac transcriptional activators GATA4 and GATA6
CC and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3.
CC {ECO:0000269|PubMed:11095750, ECO:0000269|PubMed:11486045,
CC ECO:0000269|PubMed:12947105, ECO:0000269|PubMed:15107403,
CC ECO:0000269|PubMed:15680351, ECO:0000269|PubMed:16199874,
CC ECO:0000269|PubMed:17259303, ECO:0000269|PubMed:17303760}.
CC -!- SUBUNIT: May self-associate (By similarity). Interacts with HES1, NCOR1
CC and SIN3A (By similarity). Interacts with GATA4, GATA6 and HDAC1 and
CC HEYL. Interacts with CCDC89/BOIP. {ECO:0000250,
CC ECO:0000269|PubMed:11486045, ECO:0000269|PubMed:14648848,
CC ECO:0000269|PubMed:16199874, ECO:0000269|PubMed:17303760}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:11486044,
CC ECO:0000269|PubMed:11741889}.
CC -!- TISSUE SPECIFICITY: Expressed in somitic mesoderm, brain, central
CC nervous system, kidney, heart, nasal epithelium, limbs, lung, muscle,
CC ovary and testis. {ECO:0000269|PubMed:10860664,
CC ECO:0000269|PubMed:12947105}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing nervous system, the
CC somites, heart and craniofacial region. Expressed in the myocardium of
CC the atrium at 9.5 dpc and in the atrioventricular cushions from 9.5 dpc
CC to 12.5 dpc. Also expressed in developing and adult retina. Expressed
CC in the ventricular zone of the ventral spinal cord at 12 dpc and in the
CC ventricular zone of the telencephalon at 12 dpc and 15 dpc. Weakly
CC expressed in the cortical plate at 15 dpc.
CC {ECO:0000269|PubMed:10415358, ECO:0000269|PubMed:11160397,
CC ECO:0000269|PubMed:12947105, ECO:0000269|PubMed:17259303,
CC ECO:0000269|PubMed:17303760}.
CC -!- INDUCTION: By activation of the Notch signaling pathway.
CC {ECO:0000269|PubMed:10964718, ECO:0000269|PubMed:11095750,
CC ECO:0000269|PubMed:11486044, ECO:0000269|PubMed:11741889}.
CC -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR EMBL; AF151521; AAD38966.1; -; mRNA.
DR CCDS; CCDS17232.1; -.
DR AlphaFoldDB; Q9WV93; -.
DR SMR; Q9WV93; -.
DR ELM; Q9WV93; -.
DR IntAct; Q9WV93; 1.
DR STRING; 10090.ENSMUSP00000038014; -.
DR iPTMnet; Q9WV93; -.
DR PhosphoSitePlus; Q9WV93; -.
DR PaxDb; Q9WV93; -.
DR PRIDE; Q9WV93; -.
DR ProteomicsDB; 269564; -.
DR MGI; MGI:1341800; Hey1.
DR eggNOG; KOG4304; Eukaryota.
DR InParanoid; Q9WV93; -.
DR PhylomeDB; Q9WV93; -.
DR PRO; PR:Q9WV93; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9WV93; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
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:MGI.
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:0009948; P:anterior/posterior axis specification; IGI:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0003180; P:aortic valve morphogenesis; IDA:BHF-UCL.
DR GO; GO:0060842; P:arterial endothelial cell differentiation; IGI:BHF-UCL.
DR GO; GO:0060840; P:artery development; IGI:MGI.
DR GO; GO:0003190; P:atrioventricular valve formation; IMP:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IGI:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IGI:MGI.
DR GO; GO:0060837; P:blood vessel endothelial cell differentiation; IGI:MGI.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IGI:BHF-UCL.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0072359; P:circulatory system development; IBA:GO_Central.
DR GO; GO:0072049; P:comma-shaped body morphogenesis; IEP:UniProtKB.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003199; P:endocardial cushion to mesenchymal transition involved in heart valve formation; IGI:MGI.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IGI:MGI.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; 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; IGI:BHF-UCL.
DR GO; GO:0014031; P:mesenchymal cell development; IGI:BHF-UCL.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000820; P:negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; ISO:MGI.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0061314; P:Notch signaling involved in heart development; IC:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0002076; P:osteoblast development; IGI:MGI.
DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IGI:BHF-UCL.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IGI:MGI.
DR GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; IGI:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:2001212; P:regulation of vasculogenesis; IGI:BHF-UCL.
DR GO; GO:0072087; P:renal vesicle development; IEP:UniProtKB.
DR GO; GO:0072050; P:S-shaped body morphogenesis; IEP:UniProtKB.
DR GO; GO:0036304; P:umbilical cord morphogenesis; IGI:BHF-UCL.
DR GO; GO:0060675; P:ureteric bud morphogenesis; IEP:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IGI:MGI.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IGI:MGI.
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 Developmental protein; DNA-binding; Notch signaling pathway; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..299
FT /note="Hairy/enhancer-of-split related with YRPW motif
FT protein 1"
FT /id="PRO_0000127218"
FT DOMAIN 49..104
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 122..158
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 48..117
FT /note="Transcriptional repression and interaction with
FT NCOR1 and SIN3A"
FT /evidence="ECO:0000250"
FT REGION 194..234
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 289..292
FT /note="YRPW motif"
FT COMPBIAS 28..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 299 AA; 32063 MW; 99111DD24ACEE819 CRC64;
MKRAHPDYSS SDSELDETIE VEKESADENG NLSSALCSMS PTTSSQVLAR KRRRGIIEKR
RRDRINNSLS ELRRLVPSAF EKQGSAKLEK AEILQMTVDH LKMLHTAGGK GYFDAHALAM
DYRSLGFREC LAEVARYLSI IEGLDASDPL LVRLVSHLNN YASQREAASG AHGGLGHIPW
GSAFGHHPHI AHPLLLPQNG HGNAGTAASP TEPHHQGRLA SAHPEAPALR APPSGGLGPV
LPVVTSASKL SPPLLSSVAS LSAFPFSFSS FHLLSPSTPT QAANLGKPYR PWGTEIGAF
