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Protein

Hairy/enhancer-of-split related with YRPW motif protein 2

Gene

Hey2

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

Functioni

Transcriptional repressor which functions as a downstream effector of Notch signaling in cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY1 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6 and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3.17 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • histone deacetylase binding Source: MGI
  • microsatellite binding Source: UniProtKB
  • protein binding transcription factor activity Source: Ensembl
  • RNA polymerase II activating transcription factor binding Source: MGI
  • RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • transcription factor binding Source: MGI

GO - Biological processi

  • anterior/posterior axis specification Source: MGI
  • arterial endothelial cell differentiation Source: BHF-UCL
  • artery development Source: MGI
  • ascending aorta morphogenesis Source: BHF-UCL
  • atrial septum morphogenesis Source: BHF-UCL
  • atrioventricular valve development Source: MGI
  • blood vessel development Source: MGI
  • cardiac epithelial to mesenchymal transition Source: BHF-UCL
  • cardiac left ventricle morphogenesis Source: BHF-UCL
  • cardiac muscle hypertrophy Source: MGI
  • cardiac muscle hypertrophy in response to stress Source: MGI
  • cardiac right ventricle morphogenesis Source: BHF-UCL
  • cardiac septum morphogenesis Source: BHF-UCL
  • cardiac vascular smooth muscle cell development Source: MGI
  • cardiac ventricle morphogenesis Source: UniProtKB
  • cell fate commitment Source: MGI
  • cochlea development Source: MGI
  • coronary vasculature morphogenesis Source: MGI
  • dorsal aorta morphogenesis Source: BHF-UCL
  • endocardial cushion to mesenchymal transition involved in heart valve formation Source: MGI
  • heart trabecula formation Source: BHF-UCL
  • labyrinthine layer blood vessel development Source: BHF-UCL
  • mesenchymal cell development Source: BHF-UCL
  • muscular septum morphogenesis Source: BHF-UCL
  • negative regulation of cardiac muscle cell apoptotic process Source: MGI
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of Notch signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation Source: BHF-UCL
  • negative regulation of transcription initiation from RNA polymerase II promoter Source: MGI
  • negative regulation of transcription regulatory region DNA binding Source: BHF-UCL
  • Notch signaling involved in heart development Source: BHF-UCL
  • Notch signaling pathway Source: UniProtKB
  • outflow tract morphogenesis Source: BHF-UCL
  • pattern specification process Source: MGI
  • positive regulation of cardiac muscle cell proliferation Source: MGI
  • positive regulation of heart rate Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein-DNA complex assembly Source: MGI
  • pulmonary artery morphogenesis Source: BHF-UCL
  • pulmonary valve morphogenesis Source: BHF-UCL
  • regulation of auditory receptor cell differentiation Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of vasculogenesis Source: BHF-UCL
  • transcription from RNA polymerase II promoter Source: GOC
  • tricuspid valve formation Source: MGI
  • tricuspid valve morphogenesis Source: BHF-UCL
  • umbilical cord morphogenesis Source: BHF-UCL
  • vasculogenesis Source: MGI
  • ventricular cardiac muscle cell development Source: BHF-UCL
  • ventricular septum morphogenesis Source: BHF-UCL
  • ventricular trabecula myocardium morphogenesis Source: MGI
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 protein 2
Alternative name(s):
HES-related repressor protein 2
Hairy and enhancer of split-related protein 2
Short name:
HESR-2
Hairy-related transcription factor 2
Short name:
HRT-2
Short name:
mHRT2
Protein gridlock homolog
Gene namesi
Name:Hey2
Synonyms:Chf1, Herp, Herp1, Hesr2, Hrt2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1341884. Hey2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • Sin3 complex Source: Ensembl
  • transcriptional repressor complex Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice display a spectrum of cardiac malformations including ventricular septal defects, tetralogy of Fallot and tricuspid atresia. The penetrance of the cardiac malformation phenotype varies according to the strain, suggesting the presence of modifier genes.7 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi33 – 375Missing : Abrogates interaction with GATA4 and repression of GATA4-mediated transcription. 1 Publication
Mutagenesisi49 – 6113RKKRR…EKRRR → LE: Abrogates DNA-binding and transcriptional repression. 1 PublicationAdd
BLAST

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 339339Hairy/enhancer-of-split related with YRPW motif protein 2PRO_0000245516Add
BLAST

Proteomic databases

PRIDEiQ9QUS4.

PTM databases

PhosphoSiteiQ9QUS4.

Expressioni

Tissue specificityi

Highly expressed in the aorta, lower expression detected in the heart, brain, kidney, lung, muscle, ovary and testis.4 Publications

Developmental stagei

Expressed in the developing somites and the ventricles of the heart. Expressed in the otic vesicles between E8.5 and E10.5. Expressed in the myocardium of the ventricles at E9.5 and in the atrioventricular cushions from E9.5 to E12.5. At E10.5, strongly expressed in the spinal nerves, the cranial ganglia and the telencephalon. At E11.5, expressed in the craniofacial region of the distal part of the maxillary arch, along the rostral mandibular arch and surrounding the lateral nasal processes. Expressed in the midbrain-hindbrain boundary and the posterior edge of the hand- and foot-paddle. Expressed in the mediodorsal region of the telencephalon and the ventricular zone of the ventral spinal cord at E12, then in the ventral region of the telencephalon and the cortical plate at E15. Expression in the heart is limited to the compact myocardial layer at E17.5. Also expressed in the developing retina up to P5, at which point expression decreases.10 Publications

Inductioni

By activation of the Notch signaling pathway.3 Publications

Gene expression databases

BgeeiQ9QUS4.
CleanExiMM_HEY2.
ExpressionAtlasiQ9QUS4. baseline and differential.
GenevestigatoriQ9QUS4.

Interactioni

Subunit structurei

May self-associate (By similarity). Interacts with ARNT (By similarity). Interacts with GATA4, GATA6, HES1 and HEYL. Interacts with HDAC1, NCOR1 and SIN3A.By similarity4 Publications

Protein-protein interaction databases

BioGridi200283. 1 interaction.
IntActiQ9QUS4. 2 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ9QUS4.
SMRiQ9QUS4. Positions 40-104, 110-164.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 10356bHLHPROSITE-ProRule annotationAdd
BLAST
Domaini122 – 15736OrangePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni47 – 11670Transcriptional repression and interaction with NCOR1 and SIN3AAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi329 – 3324YQPW motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi175 – 19117His-richAdd
BLAST
Compositional biasi262 – 30443Ala-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

eggNOGiNOG324798.
GeneTreeiENSGT00700000104130.
HOGENOMiHOG000286035.
HOVERGENiHBG003275.
InParanoidiQ9QUS4.
KOiK09091.
OMAiSTCASQR.
OrthoDBiEOG76MK98.
PhylomeDBiQ9QUS4.
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.

Q9QUS4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRPCEETTS ESDLDETIDV GSENNYPGHA TSSVMRSNSP TTTSQIMARK
60 70 80 90 100
KRRGIIEKRR RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL
110 120 130 140 150
KMLQATGGKG YFDAHALATD FMSIGFRECL TEVARYLSSV EGLDPSDPLR
160 170 180 190 200
VRLVSHLSTC ASQREAAVMT SSMAHHHHPL HPHHWAAAFH HLPTALLQPN
210 220 230 240 250
GLHTSESTPC RLSTSSEVPS AHGSALLTAT FAHADSALRM PSGGTVAPCV
260 270 280 290 300
PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA
310 320 330
AATAISPPLS VSAASSPQQT STGTNNKPYQ PWGTEVGAF
Length:339
Mass (Da):35,873
Last modified:May 1, 2000 - v1
Checksum:i105BEEA06DE50444
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71E → K in BAC27428 (PubMed:16141072).Curated
Sequence conflicti284 – 2841G → E in BAE34310 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172287 mRNA. Translation: AAF14546.1.
AJ271867 mRNA. Translation: CAB71346.1.
AF173902 mRNA. Translation: AAF20174.1.
AF232240 mRNA. Translation: AAF37298.1.
AB093589 mRNA. Translation: BAC55066.1.
AK031506 mRNA. Translation: BAC27428.1.
AK158000 mRNA. Translation: BAE34310.1.
BC103575 mRNA. Translation: AAI03576.1.
BC103576 mRNA. Translation: AAI03577.1.
CCDSiCCDS23766.1.
RefSeqiNP_038932.1. NM_013904.1.
UniGeneiMm.103573.

Genome annotation databases

EnsembliENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789.
GeneIDi15214.
KEGGimmu:15214.
UCSCiuc007etp.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172287 mRNA. Translation: AAF14546.1.
AJ271867 mRNA. Translation: CAB71346.1.
AF173902 mRNA. Translation: AAF20174.1.
AF232240 mRNA. Translation: AAF37298.1.
AB093589 mRNA. Translation: BAC55066.1.
AK031506 mRNA. Translation: BAC27428.1.
AK158000 mRNA. Translation: BAE34310.1.
BC103575 mRNA. Translation: AAI03576.1.
BC103576 mRNA. Translation: AAI03577.1.
CCDSiCCDS23766.1.
RefSeqiNP_038932.1. NM_013904.1.
UniGeneiMm.103573.

3D structure databases

ProteinModelPortaliQ9QUS4.
SMRiQ9QUS4. Positions 40-104, 110-164.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200283. 1 interaction.
IntActiQ9QUS4. 2 interactions.

PTM databases

PhosphoSiteiQ9QUS4.

Proteomic databases

PRIDEiQ9QUS4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789.
GeneIDi15214.
KEGGimmu:15214.
UCSCiuc007etp.1. mouse.

Organism-specific databases

CTDi23493.
MGIiMGI:1341884. Hey2.

Phylogenomic databases

eggNOGiNOG324798.
GeneTreeiENSGT00700000104130.
HOGENOMiHOG000286035.
HOVERGENiHBG003275.
InParanoidiQ9QUS4.
KOiK09091.
OMAiSTCASQR.
OrthoDBiEOG76MK98.
PhylomeDBiQ9QUS4.
TreeFamiTF323617.

Enzyme and pathway databases

ReactomeiREACT_334977. NOTCH1 Intracellular Domain Regulates Transcription.

Miscellaneous databases

NextBioi287789.
PROiQ9QUS4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QUS4.
CleanExiMM_HEY2.
ExpressionAtlasiQ9QUS4. baseline and differential.
GenevestigatoriQ9QUS4.

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], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  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, DEVELOPMENTAL STAGE.
  3. "Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system."
    Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D., Watanabe M., Hsieh C.-M., Lee M.-E.
    J. Biol. Chem. 275:6381-6387(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  4. "HERP, a new primary target of Notch regulated by ligand binding."
    Iso T., Sartorelli V., Chung G., Shichinohe T., Kedes L., Hamamori Y.
    Mol. Cell. Biol. 21:6071-6079(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Cloning of hesr2 gene."
    Kokubo H., Johnson R.L.
    Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "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: Inner ear and Testis.
  7. "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 [MRNA].
  8. "Hey genes: a novel subfamily of hairy- and enhancer of split related genes specifically expressed during mouse embryogenesis."
    Leimeister C., Externbrinck A., Klamt B., Gessler M.
    Mech. Dev. 85:173-177(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE.
  9. "Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes."
    Maier M.M., Gessler M.
    Biochem. Biophys. Res. Commun. 275:652-660(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  10. "Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling."
    Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T., Srivastava D., Olson E.N.
    Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, INDUCTION, MUTAGENESIS OF 49-ARG--ARG-61.
  11. "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: FUNCTION, DEVELOPMENTAL STAGE.
  12. "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling."
    Iso T., Sartorelli V., Poizat C., Iezzi S., Wu H.-Y., Chung G., Kedes L., Hamamori Y.
    Mol. Cell. Biol. 21:6080-6089(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH HDAC1; HES1; NCOR1 AND SIN3A.
  13. "Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2 -/- mice."
    Gessler M., Knobeloch K.-P., Helisch A., Amann K., Schumacher N., Rohde E., Fischer A., Leimeister C.
    Curr. Biol. 12:1601-1604(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  14. "Tetralogy of fallot and other congenital heart defects in Hey2 mutant mice."
    Donovan J., Kordylewska A., Jan Y.N., Utset M.F.
    Curr. Biol. 12:1605-1610(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  15. "HERP1 is a cell type-specific primary target of Notch."
    Iso T., Chung G., Hamamori Y., Kedes L.
    J. Biol. Chem. 277:6598-6607(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, SUBCELLULAR LOCATION.
  16. "Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2."
    Sakata Y., Kamei C.N., Nakagami H., Bronson R., Liao J.K., Chin M.T.
    Proc. Natl. Acad. Sci. U.S.A. 99:16197-16202(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  17. "The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain."
    Sakamoto M., Hirata H., Ohtsuka T., Bessho Y., Kageyama R.
    J. Biol. Chem. 278:44808-44815(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  18. "Transcription factor CHF1/Hey2 regulates neointimal formation in vivo and vascular smooth muscle proliferation and migration in vitro."
    Sakata Y., Xiang F., Chen Z., Kiriyama Y., Kamei C.N., Simon D.I., Chin M.T.
    Arterioscler. Thromb. Vasc. Biol. 24:2069-2074(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. "Targeted disruption of hesr2 results in atrioventricular valve anomalies that lead to heart dysfunction."
    Kokubo H., Miyagawa-Tomita S., Tomimatsu H., Nakashima Y., Nakazawa M., Saga Y., Johnson R.L.
    Circ. Res. 95:540-547(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  20. "The Notch target genes Hey1 and Hey2 are required for embryonic vascular development."
    Fischer A., Schumacher N., Maier M., Sendtner M., Gessler M.
    Genes Dev. 18:901-911(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  21. "Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism."
    Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M., Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O.
    J. Biol. Chem. 279:54937-54943(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GATA4, MUTAGENESIS OF 33-SER--SER-37.
  22. "Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system."
    Kokubo H., Miyagawa-Tomita S., Nakazawa M., Saga Y., Johnson R.L.
    Dev. Biol. 278:301-309(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  23. "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, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  24. "CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression."
    Koibuchi N., Chin M.T.
    Circ. Res. 100:850-855(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  25. "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, INTERACTION WITH HEYL, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  26. "Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2."
    Kokubo H., Tomita-Miyagawa S., Hamada Y., Saga Y.
    Development 134:747-755(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DEVELOPMENTAL STAGE.

Entry informationi

Entry nameiHEY2_MOUSE
AccessioniPrimary (citable) accession number: Q9QUS4
Secondary accession number(s): Q3TZ99, Q8CD44
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: May 1, 2000
Last modified: April 1, 2015
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.