ID   HEY1_HUMAN              Reviewed;         304 AA.
AC   Q9Y5J3; B2R883; Q5TZS3; Q8NAM2; Q9NYP4;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 208.
DE   RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 1;
DE   AltName: Full=Cardiovascular helix-loop-helix factor 2;
DE            Short=CHF-2;
DE   AltName: Full=Class B basic helix-loop-helix protein 31;
DE            Short=bHLHb31;
DE   AltName: Full=HES-related repressor 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=hHRT1;
GN   Name=HEY1; Synonyms=BHLHB31, CHF2, HERP2, HESR1, HRT1;
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] (ISOFORM 1).
RC   TISSUE=Brain;
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   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=10692439; DOI=10.1074/jbc.275.9.6381;
RA   Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D., Watanabe M.,
RA   Hsieh C.-M., Lee M.-E.;
RT   "Cardiovascular basic helix loop helix factor 1, a novel transcriptional
RT   repressor expressed preferentially in the developing and adult
RT   cardiovascular system.";
RL   J. Biol. Chem. 275:6381-6387(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Iso T., Sartorelli V., Poizat C., Chen T., Sucov H.M., Chung G., Wu H.-Y.,
RA   Kedes L., Hamamori Y.;
RT   "The HERP repressors, novel partners for HES/hairy in notch signaling.";
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND DNA-BINDING.
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16421571; DOI=10.1038/nature04406;
RA   Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA   Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA   Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA   Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA   Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA   Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA   Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA   Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA   Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA   O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA   Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA   Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA   Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA   Platzer M., Shimizu N., Lander E.S.;
RT   "DNA sequence and analysis of human chromosome 8.";
RL   Nature 439:331-335(2006).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung;
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   [12]
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).
RN   [13]
RP   FUNCTION.
RX   PubMed=25985737; DOI=10.1038/ncomms8122;
RA   Zhu P., Wang Y., Du Y., He L., Huang G., Zhang G., Yan X., Fan Z.;
RT   "C8orf4 negatively regulates self-renewal of liver cancer stem cells via
RT   suppression of NOTCH2 signalling.";
RL   Nat. Commun. 6:7122-7122(2015).
RN   [14]
RP   FUNCTION, INTERACTION WITH FBXO45, AND SUBCELLULAR LOCATION.
RX   PubMed=26068074; DOI=10.1371/journal.pone.0130288;
RA   Salat D., Winkler A., Urlaub H., Gessler M.;
RT   "Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase
RT   Complex and Induce Its Translocation into the Nucleus.";
RL   PLoS ONE 10:e0130288-e0130288(2015).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 111-167.
RG   RIKEN structural genomics initiative (RSGI);
RT   "Crystal structure of hypothetical protein MS0332.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Transcriptional repressor which binds preferentially to the
CC       canonical E box sequence 5'-CACGTG-3' (PubMed:11095750). 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. 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       (PubMed:15485867). Involved in the regulation of liver cancer cells
CC       self-renewal (PubMed:25985737). {ECO:0000250|UniProtKB:Q9WV93,
CC       ECO:0000269|PubMed:11095750, ECO:0000269|PubMed:15485867,
CC       ECO:0000269|PubMed:25985737}.
CC   -!- SUBUNIT: Self-associates. Interacts with HES1 and HEYL. Interacts with
CC       HDAC1, NCOR1 and SIN3A. Interacts with GATA4 and GATA6. Interacts with
CC       CCDC89/BOIP. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q9Y5J3; Q15038: DAZAP2; NbExp=3; IntAct=EBI-7231130, EBI-724310;
CC       Q9Y5J3; O75593: FOXH1; NbExp=3; IntAct=EBI-7231130, EBI-1759806;
CC       Q9Y5J3; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-7231130, EBI-11962084;
CC       Q9Y5J3; Q99697-2: PITX2; NbExp=3; IntAct=EBI-7231130, EBI-12138495;
CC       Q9Y5J3; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-7231130, EBI-373552;
CC       Q9Y5J3; Q8NEK8: TENT5D; NbExp=3; IntAct=EBI-7231130, EBI-744726;
CC       Q9Y5J3; Q9BYJ9: YTHDF1; NbExp=3; IntAct=EBI-7231130, EBI-1051237;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC       ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:26068074}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9Y5J3-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9Y5J3-2; Sequence=VSP_040997;
CC   -!- TISSUE SPECIFICITY: Expressed in the somitic mesoderm, the central
CC       nervous system, the kidney, the heart, nasal epithelium, and limbs.
CC   -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR   EMBL; AF151522; AAD38967.1; -; mRNA.
DR   EMBL; AF176422; AAD51749.1; -; mRNA.
DR   EMBL; AJ272214; CAB75715.1; -; mRNA.
DR   EMBL; AF232239; AAF37297.1; -; mRNA.
DR   EMBL; AF311883; AAG31156.1; -; mRNA.
DR   EMBL; BT020065; AAV38868.1; -; mRNA.
DR   EMBL; AK092437; BAC03890.1; -; mRNA.
DR   EMBL; AK313271; BAG36080.1; -; mRNA.
DR   EMBL; AC016240; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471068; EAW87066.1; -; Genomic_DNA.
DR   EMBL; BC001873; AAH01873.1; -; mRNA.
DR   CCDS; CCDS43749.1; -. [Q9Y5J3-2]
DR   CCDS; CCDS6225.1; -. [Q9Y5J3-1]
DR   RefSeq; NP_001035798.1; NM_001040708.1. [Q9Y5J3-2]
DR   RefSeq; NP_001269780.1; NM_001282851.1.
DR   RefSeq; NP_036390.3; NM_012258.3. [Q9Y5J3-1]
DR   PDB; 2DB7; X-ray; 1.90 A; A/B=111-167.
DR   PDBsum; 2DB7; -.
DR   AlphaFoldDB; Q9Y5J3; -.
DR   SMR; Q9Y5J3; -.
DR   BioGRID; 117025; 138.
DR   ELM; Q9Y5J3; -.
DR   IntAct; Q9Y5J3; 16.
DR   MINT; Q9Y5J3; -.
DR   STRING; 9606.ENSP00000338272; -.
DR   TCDB; 3.A.16.1.4; the endoplasmic reticular retrotranslocon (er-rt) family.
DR   iPTMnet; Q9Y5J3; -.
DR   PhosphoSitePlus; Q9Y5J3; -.
DR   BioMuta; HEY1; -.
DR   DMDM; 13124298; -.
DR   MassIVE; Q9Y5J3; -.
DR   MaxQB; Q9Y5J3; -.
DR   PaxDb; 9606-ENSP00000338272; -.
DR   PeptideAtlas; Q9Y5J3; -.
DR   ProteomicsDB; 86418; -. [Q9Y5J3-1]
DR   ProteomicsDB; 86419; -. [Q9Y5J3-2]
DR   Pumba; Q9Y5J3; -.
DR   Antibodypedia; 12406; 464 antibodies from 32 providers.
DR   DNASU; 23462; -.
DR   Ensembl; ENST00000337919.9; ENSP00000338272.5; ENSG00000164683.19. [Q9Y5J3-2]
DR   Ensembl; ENST00000354724.8; ENSP00000346761.3; ENSG00000164683.19. [Q9Y5J3-1]
DR   GeneID; 23462; -.
DR   KEGG; hsa:23462; -.
DR   MANE-Select; ENST00000354724.8; ENSP00000346761.3; NM_012258.4; NP_036390.3.
DR   UCSC; uc003ybl.4; human. [Q9Y5J3-1]
DR   AGR; HGNC:4880; -.
DR   CTD; 23462; -.
DR   DisGeNET; 23462; -.
DR   GeneCards; HEY1; -.
DR   HGNC; HGNC:4880; HEY1.
DR   HPA; ENSG00000164683; Tissue enhanced (brain).
DR   MIM; 602953; gene.
DR   neXtProt; NX_Q9Y5J3; -.
DR   OpenTargets; ENSG00000164683; -.
DR   PharmGKB; PA29258; -.
DR   VEuPathDB; HostDB:ENSG00000164683; -.
DR   eggNOG; KOG4304; Eukaryota.
DR   GeneTree; ENSGT00940000157068; -.
DR   HOGENOM; CLU_048294_2_0_1; -.
DR   InParanoid; Q9Y5J3; -.
DR   OMA; PFAFGAC; -.
DR   OrthoDB; 5405528at2759; -.
DR   PhylomeDB; Q9Y5J3; -.
DR   TreeFam; TF323617; -.
DR   PathwayCommons; Q9Y5J3; -.
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-8940973; RUNX2 regulates osteoblast differentiation.
DR   Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR   Reactome; R-HSA-9733709; Cardiogenesis.
DR   SignaLink; Q9Y5J3; -.
DR   SIGNOR; Q9Y5J3; -.
DR   BioGRID-ORCS; 23462; 10 hits in 1176 CRISPR screens.
DR   ChiTaRS; HEY1; human.
DR   EvolutionaryTrace; Q9Y5J3; -.
DR   GeneWiki; HEY1; -.
DR   GenomeRNAi; 23462; -.
DR   Pharos; Q9Y5J3; Tbio.
DR   PRO; PR:Q9Y5J3; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q9Y5J3; Protein.
DR   Bgee; ENSG00000164683; Expressed in endothelial cell and 207 other cell types or tissues.
DR   ExpressionAtlas; Q9Y5J3; baseline and differential.
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; ISS:UniProtKB.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
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:BHF-UCL.
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; IPI:BHF-UCL.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEP:UniProtKB.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR   GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060842; P:arterial endothelial cell differentiation; ISS:BHF-UCL.
DR   GO; GO:0003190; P:atrioventricular valve formation; ISS:BHF-UCL.
DR   GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL.
DR   GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:BHF-UCL.
DR   GO; GO:0060411; P:cardiac septum morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003208; P:cardiac ventricle morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0072359; P:circulatory system development; IBA:GO_Central.
DR   GO; GO:0035912; P:dorsal aorta morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL.
DR   GO; GO:0060716; P:labyrinthine layer blood vessel development; ISS:BHF-UCL.
DR   GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:BHF-UCL.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IBA:GO_Central.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; IDA:BHF-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
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:2001212; P:regulation of vasculogenesis; ISS:BHF-UCL.
DR   GO; GO:0036304; P:umbilical cord morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL.
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:SF78; HAIRY_ENHANCER-OF-SPLIT RELATED WITH YRPW MOTIF PROTEIN 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; Q9Y5J3; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Developmental protein; DNA-binding;
KW   Notch signaling pathway; Nucleus; Reference proteome; Repressor;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..304
FT                   /note="Hairy/enhancer-of-split related with YRPW motif
FT                   protein 1"
FT                   /id="PRO_0000127217"
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..52
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          196..234
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           294..297
FT                   /note="YRPW motif"
FT   COMPBIAS        28..49
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        200..214
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         82
FT                   /note="K -> KQVME (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_040997"
FT   CONFLICT        237
FT                   /note="L -> F (in Ref. 5; AAF37297)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        237
FT                   /note="L -> P (in Ref. 8; BAC03890)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        252
FT                   /note="P -> L (in Ref. 5; AAF37297)"
FT                   /evidence="ECO:0000305"
FT   HELIX           115..120
FT                   /evidence="ECO:0007829|PDB:2DB7"
FT   HELIX           122..140
FT                   /evidence="ECO:0007829|PDB:2DB7"
FT   HELIX           149..164
FT                   /evidence="ECO:0007829|PDB:2DB7"
SQ   SEQUENCE   304 AA;  32613 MW;  F130991A99E9CA54 CRC64;
     MKRAHPEYSS SDSELDETIE VEKESADENG NLSSALGSMS PTTSSQILAR KRRRGIIEKR
     RRDRINNSLS ELRRLVPSAF EKQGSAKLEK AEILQMTVDH LKMLHTAGGK GYFDAHALAM
     DYRSLGFREC LAEVARYLSI IEGLDASDPL RVRLVSHLNN YASQREAASG AHAGLGHIPW
     GTVFGHHPHI AHPLLLPQNG HGNAGTTASP TEPHHQGRLG SAHPEAPALR APPSGSLGPV
     LPVVTSASKL SPPLLSSVAS LSAFPFSFGS FHLLSPNALS PSAPTQAANL GKPYRPWGTE
     IGAF
//