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Q9DBX7

- HEYL_MOUSE

UniProt

Q9DBX7 - HEYL_MOUSE

Protein

Hairy/enhancer-of-split related with YRPW motif-like protein

Gene

Heyl

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 98 (01 Oct 2014)
      Sequence version 2 (01 May 2007)
      Previous versions | rss
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    Functioni

    Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' By similarity. Downstream effector of Notch signaling required for cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.By similarity2 Publications

    GO - Molecular functioni

    1. microsatellite binding Source: Ensembl
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: UniProtKB
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: UniProtKB
    5. RNA polymerase II core promoter sequence-specific DNA binding Source: UniProtKB
    6. RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Source: UniProtKB
    7. RNA polymerase II transcription corepressor activity Source: UniProtKB
    8. sequence-specific DNA binding Source: MGI
    9. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    10. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

    1. atrioventricular valve morphogenesis Source: BHF-UCL
    2. cardiac epithelial to mesenchymal transition Source: BHF-UCL
    3. cardiac ventricle morphogenesis Source: BHF-UCL
    4. cellular response to BMP stimulus Source: UniProtKB
    5. endocardial cushion morphogenesis Source: BHF-UCL
    6. epithelial to mesenchymal transition involved in endocardial cushion formation Source: MGI
    7. glomerulus development Source: UniProtKB
    8. mesenchymal cell development Source: BHF-UCL
    9. negative regulation of androgen receptor activity Source: UniProtKB
    10. negative regulation of androgen receptor signaling pathway Source: UniProtKB
    11. negative regulation of gene expression Source: MGI
    12. negative regulation of transcription, DNA-templated Source: UniProtKB
    13. negative regulation of transcription from RNA polymerase II promoter Source: GOC
    14. Notch signaling pathway Source: UniProtKB
    15. outflow tract morphogenesis Source: BHF-UCL
    16. peripheral nervous system development Source: UniProtKB
    17. positive regulation of neuron differentiation Source: UniProtKB
    18. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    19. proximal tubule development Source: UniProtKB
    20. pulmonary valve morphogenesis Source: BHF-UCL
    21. regulation of transcription from RNA polymerase II promoter Source: MGI
    22. skeletal muscle cell differentiation Source: MGI
    23. transcription from RNA polymerase II promoter Source: GOC
    24. ventricular septum morphogenesis Source: BHF-UCL

    Keywords - Molecular functioni

    Developmental protein, Repressor

    Keywords - Biological processi

    Notch signaling pathway, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_196464. NOTCH1 Intracellular Domain Regulates Transcription.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hairy/enhancer-of-split related with YRPW motif-like protein
    Alternative name(s):
    Hairy and enhancer of split-related protein 3
    Hairy-related transcription factor 3
    Short name:
    HRT-3
    Short name:
    mHRT3
    Gene namesi
    Name:Heyl
    Synonyms:Hesr3, Hrt3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 4

    Organism-specific databases

    MGIiMGI:1860511. Heyl.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleoplasm Source: Reactome
    3. nucleus Source: UniProtKB
    4. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 326326Hairy/enhancer-of-split related with YRPW motif-like proteinPRO_0000286430Add
    BLAST

    Proteomic databases

    PRIDEiQ9DBX7.

    PTM databases

    PhosphoSiteiQ9DBX7.

    Expressioni

    Tissue specificityi

    Expressed in heart and at lower levels in brain, lung, muscle, ovary and testis.1 Publication

    Developmental stagei

    Expressed in the presmitic mesoderm, the somites, the developing peripheral nervous system and arterial smooth muscle. Expressed in atrioventricular cushions from E9.5 to E12.5. Also expressed in developing retina.3 Publications

    Inductioni

    By activation of the Notch signaling pathway.

    Gene expression databases

    BgeeiQ9DBX7.
    GenevestigatoriQ9DBX7.

    Interactioni

    Subunit structurei

    Interacts with HES1, HDAC1, NCOR1 and SIN3A By similarity. Self-associates. Interacts with GATA4, GATA6, HEY1 and HEY2.By similarity2 Publications

    Protein-protein interaction databases

    IntActiQ9DBX7. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9DBX7.
    SMRiQ9DBX7. Positions 42-99, 105-159.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini43 – 9856bHLHPROSITE-ProRule annotationAdd
    BLAST
    Domaini116 – 15338OrangePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni42 – 11170Transcriptional repression and interaction with NCOR1 and SIN3ABy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi162 – 307146Pro-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the HEY family.Curated
    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
    Contains 1 Orange domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG310123.
    GeneTreeiENSGT00700000104130.
    HOGENOMiHOG000286035.
    HOVERGENiHBG003275.
    InParanoidiQ9DBX7.
    KOiK09091.
    OMAiHSWVSEI.
    OrthoDBiEOG76MK98.
    PhylomeDBiQ9DBX7.
    TreeFamiTF323617.

    Family and domain databases

    Gene3Di4.10.280.10. 1 hit.
    InterProiIPR011598. bHLH_dom.
    IPR003650. Orange.
    IPR018352. Orange_subgr.
    [Graphical view]
    PfamiPF07527. Hairy_orange. 1 hit.
    PF00010. HLH. 1 hit.
    [Graphical view]
    SMARTiSM00353. HLH. 1 hit.
    SM00511. ORANGE. 1 hit.
    [Graphical view]
    SUPFAMiSSF47459. SSF47459. 1 hit.
    PROSITEiPS50888. BHLH. 1 hit.
    PS51054. ORANGE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9DBX7-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKRPRAPSGS DGESDGPIDV GQENDLSQMA RPLTTPSPSQ MQARKKRRGI    50
    IEKRRRDRIN SSLSELRRLV PTAFEKQGSS KLEKAEVLQM TVDHLKMLHA 100
    SGGTGFFDAR ALAVDFRSIG FRECLTEVIR YLGVLEGPSS HADPVRIRLL 150
    SHLKSYAAEM EPSPTTTSAL AFPVWPWSFL HSCPGLPSLN SQLAILGRVP 200
    GPVLPSISSP PYPISALRSA PVHRPAGTIP PTRRNLLPSR GVTSTQRAHL 250
    PERPAAPPPT ALDARAARSI VPIPPCSPTT APGAGKSDDN VSGSISSPCP 300
    SGPTGRPAGA VFYHSWVSEI TEIGAF 326
    Length:326
    Mass (Da):34,929
    Last modified:May 1, 2007 - v2
    Checksum:iE7F71F1A1F8E00A3
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti29 – 291M → V in BAB23482. (PubMed:16141072)Curated
    Sequence conflicti201 – 2011G → S in AAF14547. (PubMed:10588864)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF172288 mRNA. Translation: AAF14547.1.
    AJ271868 mRNA. Translation: CAB71347.1.
    AB093590 mRNA. Translation: BAC55067.1.
    AK004697 mRNA. Translation: BAB23482.1.
    AK028596 mRNA. Translation: BAC26024.1.
    AK080822 mRNA. Translation: BAC38037.1.
    AL606934 Genomic DNA. No translation available.
    BC130263 mRNA. Translation: AAI30264.1.
    CCDSiCCDS18613.1.
    RefSeqiNP_038933.2. NM_013905.3.
    UniGeneiMm.103615.

    Genome annotation databases

    EnsembliENSMUST00000040821; ENSMUSP00000040576; ENSMUSG00000032744.
    GeneIDi56198.
    KEGGimmu:56198.
    UCSCiuc008uoz.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF172288 mRNA. Translation: AAF14547.1 .
    AJ271868 mRNA. Translation: CAB71347.1 .
    AB093590 mRNA. Translation: BAC55067.1 .
    AK004697 mRNA. Translation: BAB23482.1 .
    AK028596 mRNA. Translation: BAC26024.1 .
    AK080822 mRNA. Translation: BAC38037.1 .
    AL606934 Genomic DNA. No translation available.
    BC130263 mRNA. Translation: AAI30264.1 .
    CCDSi CCDS18613.1.
    RefSeqi NP_038933.2. NM_013905.3.
    UniGenei Mm.103615.

    3D structure databases

    ProteinModelPortali Q9DBX7.
    SMRi Q9DBX7. Positions 42-99, 105-159.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9DBX7. 2 interactions.

    PTM databases

    PhosphoSitei Q9DBX7.

    Proteomic databases

    PRIDEi Q9DBX7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000040821 ; ENSMUSP00000040576 ; ENSMUSG00000032744 .
    GeneIDi 56198.
    KEGGi mmu:56198.
    UCSCi uc008uoz.1. mouse.

    Organism-specific databases

    CTDi 26508.
    MGIi MGI:1860511. Heyl.

    Phylogenomic databases

    eggNOGi NOG310123.
    GeneTreei ENSGT00700000104130.
    HOGENOMi HOG000286035.
    HOVERGENi HBG003275.
    InParanoidi Q9DBX7.
    KOi K09091.
    OMAi HSWVSEI.
    OrthoDBi EOG76MK98.
    PhylomeDBi Q9DBX7.
    TreeFami TF323617.

    Enzyme and pathway databases

    Reactomei REACT_196464. NOTCH1 Intracellular Domain Regulates Transcription.

    Miscellaneous databases

    NextBioi 312018.
    PROi Q9DBX7.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9DBX7.
    Genevestigatori Q9DBX7.

    Family and domain databases

    Gene3Di 4.10.280.10. 1 hit.
    InterProi IPR011598. bHLH_dom.
    IPR003650. Orange.
    IPR018352. Orange_subgr.
    [Graphical view ]
    Pfami PF07527. Hairy_orange. 1 hit.
    PF00010. HLH. 1 hit.
    [Graphical view ]
    SMARTi SM00353. HLH. 1 hit.
    SM00511. ORANGE. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47459. SSF47459. 1 hit.
    PROSITEi PS50888. BHLH. 1 hit.
    PS51054. ORANGE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "HRT1, HRT2 and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic and pharyngeal arch segments."
      Nakagawa O., Nakagawa M., Richardson J.A., Olson E.N., Srivastava D.
      Dev. Biol. 216:72-84(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family."
      Steidl C., Leimeister C., Klamt B., Maier M., Nanda I., Dixon M., Clarke R., Schmid M., Gessler M.
      Genomics 66:195-203(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    3. "Cloning of hesr2 gene."
      Kokubo H., Johnson R.L.
      Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Corpora quadrigemina, Lung and Skin.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. "Analysis of HeyL expression in wild-type and Notch pathway mutant mouse embryos."
      Leimeister C., Schumacher N., Steidl C., Gessler M.
      Mech. Dev. 98:175-178(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.
    8. "The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse retina."
      Satow T., Bae S.-K., Inoue T., Inoue C., Miyoshi G., Tomita K., Bessho Y., Hashimoto N., Kageyama R.
      J. Neurosci. 21:1265-1273(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.
    9. "Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts."
      Fischer A., Klattig J., Kneitz B., Diez H., Maier M., Holtmann B., Englert C., Gessler M.
      Mol. Cell. Biol. 25:8960-8970(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH GATA4 AND GATA6.
    10. "Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition."
      Fischer A., Steidl C., Wagner T.U., Lang E., Jakob P.M., Friedl P., Knobeloch K.-P., Gessler M.
      Circ. Res. 100:856-863(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH HEY1 AND HEY2, DEVELOPMENTAL STAGE.

    Entry informationi

    Entry nameiHEYL_MOUSE
    AccessioniPrimary (citable) accession number: Q9DBX7
    Secondary accession number(s): Q9JJV6, Q9QXW8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 2007
    Last sequence update: May 1, 2007
    Last modified: October 1, 2014
    This is version 98 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Expression in nascent somites is reduced in mice lacking Notch signaling.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3