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Protein

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

Gene

Heyl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. AF-1 domain binding Source: MGI
  2. microsatellite binding Source: MGI
  3. protein heterodimerization activity Source: MGI
  4. protein homodimerization activity Source: UniProtKB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: UniProtKB
  6. RNA polymerase II core promoter sequence-specific DNA binding Source: UniProtKB
  7. RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Source: UniProtKB
  8. RNA polymerase II transcription corepressor activity Source: UniProtKB
  9. sequence-specific DNA binding Source: MGI
  10. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  11. 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. Notch signaling pathway Source: UniProtKB
  14. outflow tract morphogenesis Source: BHF-UCL
  15. peripheral nervous system development Source: UniProtKB
  16. positive regulation of neuron differentiation Source: UniProtKB
  17. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  18. proximal tubule development Source: UniProtKB
  19. pulmonary valve morphogenesis Source: BHF-UCL
  20. regulation of transcription from RNA polymerase II promoter Source: MGI
  21. skeletal muscle cell differentiation Source: MGI
  22. transcription from RNA polymerase II promoter Source: GOC
  23. ventricular septum morphogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Notch signaling pathway, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_334977. 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 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1860511. Heyl.

Subcellular locationi

  1. 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
Complete GO annotation...

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.
[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

        10         20         30         40         50
MKRPRAPSGS DGESDGPIDV GQENDLSQMA RPLTTPSPSQ MQARKKRRGI
60 70 80 90 100
IEKRRRDRIN SSLSELRRLV PTAFEKQGSS KLEKAEVLQM TVDHLKMLHA
110 120 130 140 150
SGGTGFFDAR ALAVDFRSIG FRECLTEVIR YLGVLEGPSS HADPVRIRLL
160 170 180 190 200
SHLKSYAAEM EPSPTTTSAL AFPVWPWSFL HSCPGLPSLN SQLAILGRVP
210 220 230 240 250
GPVLPSISSP PYPISALRSA PVHRPAGTIP PTRRNLLPSR GVTSTQRAHL
260 270 280 290 300
PERPAAPPPT ALDARAARSI VPIPPCSPTT APGAGKSDDN VSGSISSPCP
310 320
SGPTGRPAGA VFYHSWVSEI TEIGAF
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

IntActiQ9DBX7. 2 interactions.

PTM databases

PhosphoSiteiQ9DBX7.

Proteomic databases

PRIDEiQ9DBX7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi26508.
MGIiMGI:1860511. Heyl.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.

Miscellaneous databases

NextBioi312018.
PROiQ9DBX7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9DBX7.
GenevestigatoriQ9DBX7.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR003650. Orange.
[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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 1, 2015
This is version 102 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.