HEYL_HUMAN
ID HEYL_HUMAN Reviewed; 328 AA.
AC Q9NQ87; Q5TG99;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Hairy/enhancer-of-split related with YRPW motif-like protein;
DE Short=hHeyL;
DE AltName: Full=Class B basic helix-loop-helix protein 33;
DE Short=bHLHb33;
DE AltName: Full=Hairy-related transcription factor 3;
DE Short=HRT-3;
DE Short=hHRT3;
GN Name=HEYL; Synonyms=BHLHB33, HRT3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-47.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-47.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [5]
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 [6]
RP FUNCTION.
RX PubMed=15485867; DOI=10.1074/jbc.m409879200;
RA Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M.,
RA Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O.;
RT "Hairy-related transcription factors inhibit GATA-dependent cardiac gene
RT expression through a signal-responsive mechanism.";
RL J. Biol. Chem. 279:54937-54943(2004).
CC -!- FUNCTION: Downstream effector of Notch signaling which may be required
CC for cardiovascular development (By similarity). Transcriptional
CC repressor which binds preferentially to the canonical E box sequence
CC 5'-CACGTG-3' (By similarity). Represses transcription by the cardiac
CC transcriptional activators GATA4 and GATA6. {ECO:0000250,
CC ECO:0000269|PubMed:15485867}.
CC -!- SUBUNIT: Self-associates. Interacts with GATA4, GATA6, HES1, HEY1 and
CC HEY2. Interacts with HDAC1, NCOR1 and SIN3A. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9NQ87; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-751092, EBI-11524452;
CC Q9NQ87; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-751092, EBI-11962084;
CC Q9NQ87; Q99750: MDFI; NbExp=7; IntAct=EBI-751092, EBI-724076;
CC Q9NQ87; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-751092, EBI-373552;
CC Q9NQ87; Q93062: RBPMS; NbExp=4; IntAct=EBI-751092, EBI-740322;
CC Q9NQ87; Q96KN7: RPGRIP1; NbExp=3; IntAct=EBI-751092, EBI-1050213;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- INDUCTION: By activation of the Notch signaling pathway.
CC {ECO:0000269|PubMed:10964718}.
CC -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR EMBL; AJ272215; CAB75716.1; -; mRNA.
DR EMBL; AF311885; AAG31158.1; -; mRNA.
DR EMBL; AL035404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006087; AAH06087.1; -; mRNA.
DR CCDS; CCDS439.1; -.
DR RefSeq; NP_055386.1; NM_014571.3.
DR AlphaFoldDB; Q9NQ87; -.
DR SMR; Q9NQ87; -.
DR BioGRID; 117714; 27.
DR IntAct; Q9NQ87; 22.
DR MINT; Q9NQ87; -.
DR STRING; 9606.ENSP00000361943; -.
DR iPTMnet; Q9NQ87; -.
DR PhosphoSitePlus; Q9NQ87; -.
DR BioMuta; HEYL; -.
DR DMDM; 146286205; -.
DR MassIVE; Q9NQ87; -.
DR PaxDb; Q9NQ87; -.
DR PeptideAtlas; Q9NQ87; -.
DR PRIDE; Q9NQ87; -.
DR ProteomicsDB; 82105; -.
DR Antibodypedia; 643; 333 antibodies from 25 providers.
DR DNASU; 26508; -.
DR Ensembl; ENST00000372852.4; ENSP00000361943.3; ENSG00000163909.8.
DR GeneID; 26508; -.
DR KEGG; hsa:26508; -.
DR MANE-Select; ENST00000372852.4; ENSP00000361943.3; NM_014571.4; NP_055386.2.
DR UCSC; uc001cdp.4; human.
DR CTD; 26508; -.
DR DisGeNET; 26508; -.
DR GeneCards; HEYL; -.
DR HGNC; HGNC:4882; HEYL.
DR HPA; ENSG00000163909; Tissue enhanced (pancreas).
DR MIM; 609034; gene.
DR neXtProt; NX_Q9NQ87; -.
DR OpenTargets; ENSG00000163909; -.
DR PharmGKB; PA29260; -.
DR VEuPathDB; HostDB:ENSG00000163909; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000161351; -.
DR HOGENOM; CLU_048294_1_1_1; -.
DR InParanoid; Q9NQ87; -.
DR OMA; FLPCPAW; -.
DR OrthoDB; 1201152at2759; -.
DR PhylomeDB; Q9NQ87; -.
DR TreeFam; TF323617; -.
DR PathwayCommons; Q9NQ87; -.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR SignaLink; Q9NQ87; -.
DR SIGNOR; Q9NQ87; -.
DR BioGRID-ORCS; 26508; 6 hits in 1087 CRISPR screens.
DR ChiTaRS; HEYL; human.
DR GeneWiki; HEYL; -.
DR GenomeRNAi; 26508; -.
DR Pharos; Q9NQ87; Tbio.
DR PRO; PR:Q9NQ87; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NQ87; protein.
DR Bgee; ENSG00000163909; Expressed in right coronary artery and 146 other tissues.
DR Genevisible; Q9NQ87; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0050683; F:AF-1 domain binding; IPI:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
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:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0003180; P:aortic valve morphogenesis; TAS:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IEA:Ensembl.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:UniProtKB.
DR GO; GO:0032835; P:glomerulus development; IEA:Ensembl.
DR GO; GO:0014031; P:mesenchymal cell development; ISS:BHF-UCL.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0061314; P:Notch signaling involved in heart development; TAS:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0072014; P:proximal tubule development; IEA:Ensembl.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS: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; IBA:GO_Central.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS: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..328
FT /note="Hairy/enhancer-of-split related with YRPW motif-like
FT protein"
FT /id="PRO_0000286429"
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..57
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 239..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 47
FT /note="H -> R (in dbSNP:rs784625)"
FT /evidence="ECO:0000269|PubMed:10860664,
FT ECO:0000269|PubMed:11095750"
FT /id="VAR_032112"
SQ SEQUENCE 328 AA; 35087 MW; C11A1EAB18611F43 CRC64;
MKRPKEPSGS DGESDGPIDV GQEGQLSQMA RPLSTPSSSQ MQARKKHRGI IEKRRRDRIN
SSLSELRRLV PTAFEKQGSS KLEKAEVLQM TVDHLKMLHA TGGTGFFDAR ALAVDFRSIG
FRECLTEVIR YLGVLEGPSS RADPVRIRLL SHLNSYAAEM EPSPTPTGPL AFPAWPWSFF
HSCPGLPALS NQLAILGRVP SPVLPGVSSP AYPIPALRTA PLRRATGIIL PARRNVLPSR
GASSTRRARP LERPATPVPV APSSRAARSS HIAPLLQSSS PTPPGPTGSA AYVAVPTPNS
SSPGPAGRPA GAMLYHSWVS EITEIGAF
