HEYL_MOUSE
ID HEYL_MOUSE Reviewed; 326 AA.
AC Q9DBX7; Q9JJV6; Q9QXW8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Hairy/enhancer-of-split related with YRPW motif-like protein;
DE AltName: Full=Hairy and enhancer of split-related protein 3;
DE AltName: Full=Hairy-related transcription factor 3;
DE Short=HRT-3;
DE Short=mHRT3;
GN Name=Heyl; Synonyms=Hesr3, Hrt3;
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].
RX PubMed=10588864; DOI=10.1006/dbio.1999.9454;
RA Nakagawa O., Nakagawa M., Richardson J.A., Olson E.N., Srivastava D.;
RT "HRT1, HRT2 and HRT3: a new subclass of bHLH transcription factors marking
RT specific cardiac, somitic and pharyngeal arch segments.";
RL Dev. Biol. 216:72-84(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kokubo H., Johnson R.L.;
RT "Cloning of hesr2 gene.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, Lung, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=11044625; DOI=10.1016/s0925-4773(00)00459-7;
RA Leimeister C., Schumacher N., Steidl C., Gessler M.;
RT "Analysis of HeyL expression in wild-type and Notch pathway mutant mouse
RT embryos.";
RL Mech. Dev. 98:175-178(2000).
RN [8]
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 [9]
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 [10]
RP FUNCTION, SELF-ASSOCIATION, INTERACTION WITH HEY1 AND HEY2, AND
RP 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).
CC -!- FUNCTION: Transcriptional repressor which binds preferentially to the
CC canonical E box sequence 5'-CACGTG-3' (By similarity). Downstream
CC effector of Notch signaling required for cardiovascular development.
CC Specifically required for the Notch-induced endocardial epithelial to
CC mesenchymal transition, which is itself criticial for cardiac valve and
CC septum development. Represses transcription by the cardiac
CC transcriptional activators GATA4 and GATA6. {ECO:0000250,
CC ECO:0000269|PubMed:16199874, ECO:0000269|PubMed:17303760}.
CC -!- SUBUNIT: Interacts with HES1, HDAC1, NCOR1 and SIN3A (By similarity).
CC Self-associates. Interacts with GATA4, GATA6, HEY1 and HEY2.
CC {ECO:0000250, ECO:0000269|PubMed:16199874,
CC ECO:0000269|PubMed:17303760}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Expressed in heart and at lower levels in brain,
CC lung, muscle, ovary and testis. {ECO:0000269|PubMed:10860664}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the presmitic mesoderm, the somites,
CC the developing peripheral nervous system and arterial smooth muscle.
CC Expressed in atrioventricular cushions from 9.5 dpc to 12.5 dpc. Also
CC expressed in developing retina. {ECO:0000269|PubMed:11044625,
CC ECO:0000269|PubMed:11160397, ECO:0000269|PubMed:17303760}.
CC -!- INDUCTION: By activation of the Notch signaling pathway.
CC -!- MISCELLANEOUS: Expression in nascent somites is reduced in mice lacking
CC Notch signaling.
CC -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR EMBL; AF172288; AAF14547.1; -; mRNA.
DR EMBL; AJ271868; CAB71347.1; -; mRNA.
DR EMBL; AB093590; BAC55067.1; -; mRNA.
DR EMBL; AK004697; BAB23482.1; -; mRNA.
DR EMBL; AK028596; BAC26024.1; -; mRNA.
DR EMBL; AK080822; BAC38037.1; -; mRNA.
DR EMBL; AL606934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC130263; AAI30264.1; -; mRNA.
DR CCDS; CCDS18613.1; -.
DR RefSeq; NP_038933.2; NM_013905.3.
DR AlphaFoldDB; Q9DBX7; -.
DR SMR; Q9DBX7; -.
DR IntAct; Q9DBX7; 2.
DR STRING; 10090.ENSMUSP00000040576; -.
DR PhosphoSitePlus; Q9DBX7; -.
DR PaxDb; Q9DBX7; -.
DR PRIDE; Q9DBX7; -.
DR ProteomicsDB; 269783; -.
DR Antibodypedia; 643; 333 antibodies from 25 providers.
DR DNASU; 56198; -.
DR Ensembl; ENSMUST00000040821; ENSMUSP00000040576; ENSMUSG00000032744.
DR GeneID; 56198; -.
DR KEGG; mmu:56198; -.
DR UCSC; uc008uoz.1; mouse.
DR CTD; 26508; -.
DR MGI; MGI:1860511; Heyl.
DR VEuPathDB; HostDB:ENSMUSG00000032744; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000161351; -.
DR HOGENOM; CLU_048294_1_1_1; -.
DR InParanoid; Q9DBX7; -.
DR OMA; FLPCPAW; -.
DR OrthoDB; 1201152at2759; -.
DR PhylomeDB; Q9DBX7; -.
DR TreeFam; TF323617; -.
DR BioGRID-ORCS; 56198; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9DBX7; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9DBX7; protein.
DR Bgee; ENSMUSG00000032744; Expressed in ascending aorta and 217 other tissues.
DR Genevisible; Q9DBX7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:MGI.
DR GO; GO:0050683; F:AF-1 domain binding; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IGI:BHF-UCL.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IGI:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IEP:UniProtKB.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IGI:MGI.
DR GO; GO:0032835; P:glomerulus development; IEP:UniProtKB.
DR GO; GO:0014031; P:mesenchymal cell development; IGI:BHF-UCL.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:BHF-UCL.
DR GO; GO:0007422; P:peripheral nervous system development; NAS:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0072014; P:proximal tubule development; IEP:UniProtKB.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IGI:BHF-UCL.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IGI:BHF-UCL.
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..326
FT /note="Hairy/enhancer-of-split related with YRPW motif-like
FT protein"
FT /id="PRO_0000286430"
FT DOMAIN 43..98
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 116..153
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..111
FT /note="Transcriptional repression and interaction with
FT NCOR1 and SIN3A"
FT /evidence="ECO:0000250"
FT REGION 223..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..306
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 29
FT /note="M -> V (in Ref. 4; BAB23482)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="G -> S (in Ref. 1; AAF14547)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 326 AA; 34929 MW; E7F71F1A1F8E00A3 CRC64;
MKRPRAPSGS DGESDGPIDV GQENDLSQMA RPLTTPSPSQ MQARKKRRGI IEKRRRDRIN
SSLSELRRLV PTAFEKQGSS KLEKAEVLQM TVDHLKMLHA SGGTGFFDAR ALAVDFRSIG
FRECLTEVIR YLGVLEGPSS HADPVRIRLL SHLKSYAAEM EPSPTTTSAL AFPVWPWSFL
HSCPGLPSLN SQLAILGRVP GPVLPSISSP PYPISALRSA PVHRPAGTIP PTRRNLLPSR
GVTSTQRAHL PERPAAPPPT ALDARAARSI VPIPPCSPTT APGAGKSDDN VSGSISSPCP
SGPTGRPAGA VFYHSWVSEI TEIGAF
