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

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "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]
• DNA-binding transcription factor activity Source: RGDInferred from sequence orthologyⁱ
  • "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]
• DNA-binding transcription factor activity, RNA polymerase II-specific Source: RGDInferred from sequence orthologyⁱ
  • "Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats."
    Kanno K., Ishiura S.
    J. Neurosci. Res. 89:562-575(2011) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription repressor activity, RNA polymerase II-specific Source: RGDInferred from sequence orthologyⁱ
  • "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]
• histone deacetylase binding Source: RGDInferred from sequence orthologyⁱ
  • "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
    Takata T., Ishikawa F.
    Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
• protein heterodimerization activity Source: RGDInferred from sequence orthologyⁱ
  • "Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors."
    Leimeister C., Dale K., Fischer A., Klamt B., Hrabe de Angelis M., Radtke F., McGrew M.J., Pourquie O., Gessler M.
    Dev. Biol. 227:91-103(2000) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: RGDInferred from sequence orthologyⁱ
  • "Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors."
    Leimeister C., Dale K., Fischer A., Klamt B., Hrabe de Angelis M., Radtke F., McGrew M.J., Pourquie O., Gessler M.
    Dev. Biol. 227:91-103(2000) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II activating transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6."
    Shirvani S., Xiang F., Koibuchi N., Chin M.T.
    Biochem. Biophys. Res. Commun. 339:151-156(2006) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II regulatory region sequence-specific DNA binding Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• sequence-specific DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors."
    Heisig J., Weber D., Englberger E., Winkler A., Kneitz S., Sung W.K., Wolf E., Eilers M., Wei C.L., Gessler M.
    PLoS Genet. 8:e1002728-e1002728(2012) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4."
    Xiang F., Sakata Y., Cui L., Youngblood J.M., Nakagami H., Liao J.K., Liao R., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 290:H1997-2006(2006) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• anterior/posterior axis specification Source: RGDInferred from sequence orthologyⁱ
  • "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]
• anterior/posterior pattern specification Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• arterial endothelial cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "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]
• artery development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• ascending aorta morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• atrial septum morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• atrioventricular valve development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• blood vessel development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cardiac epithelial to mesenchymal transition Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cardiac left ventricle morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cardiac muscle hypertrophy Source: RGDInferred from sequence orthologyⁱ
  • "The bHLH transcription factor CHF1/Hey2 regulates susceptibility to apoptosis and heart failure after pressure overload."
    Liu Y., Yu M., Wu L., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 298:H2082-92(2010) [PubMed] [Europe PMC] [Abstract]
• cardiac muscle hypertrophy in response to stress Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4."
    Xiang F., Sakata Y., Cui L., Youngblood J.M., Nakagami H., Liao J.K., Liao R., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 290:H1997-2006(2006) [PubMed] [Europe PMC] [Abstract]
• cardiac right ventricle morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cardiac septum morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cardiac vascular smooth muscle cell development Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 regulates coronary vascular maturation."
    Watanabe T., Koibuchi N., Chin M.T.
    Mech. Dev. 127:418-427(2010) [PubMed] [Europe PMC] [Abstract]
• cardiac ventricle morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• cell differentiation Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• cell fate commitment Source: RGDInferred from sequence orthologyⁱ
  • "Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti."
    Doetzlhofer A., Basch M.L., Ohyama T., Gessler M., Groves A.K., Segil N.
    Dev. Cell 16:58-69(2009) [PubMed] [Europe PMC] [Abstract]
• circulatory system development Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• cochlea development Source: RGDInferred from sequence orthologyⁱ
  • "Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development."
    Li S., Mark S., Radde-Gallwitz K., Schlisner R., Chin M.T., Chen P.
    BMC Dev. Biol. 8:20-20(2008) [PubMed] [Europe PMC] [Abstract]
• coronary vasculature morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 regulates coronary vascular maturation."
    Watanabe T., Koibuchi N., Chin M.T.
    Mech. Dev. 127:418-427(2010) [PubMed] [Europe PMC] [Abstract]
• dorsal aorta morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• endocardial cushion to mesenchymal transition involved in heart valve formation Source: RGDInferred from sequence orthologyⁱ
  • "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]
• heart development Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "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]
• heart trabecula formation Source: RGDInferred from sequence orthologyⁱ
  • "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]
• labyrinthine layer blood vessel development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• mesenchymal cell development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• muscular septum morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• negative regulation of biomineral tissue development Source: RGDInferred from sequence orthologyⁱ
  • "Inhibitory role of Notch1 in calcific aortic valve disease."
    Acharya A., Hans C.P., Koenig S.N., Nichols H.A., Galindo C.L., Garner H.R., Merrill W.H., Hinton R.B., Garg V.
    PLoS ONE 6:e27743-e27743(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cardiac muscle cell apoptotic process Source: RGDInferred from sequence orthologyⁱ
  • "The bHLH transcription factor CHF1/Hey2 regulates susceptibility to apoptosis and heart failure after pressure overload."
    Liu Y., Yu M., Wu L., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 298:H2082-92(2010) [PubMed] [Europe PMC] [Abstract]
• negative regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "Mutations in NOTCH1 cause aortic valve disease."
    Garg V., Muth A.N., Ransom J.F., Schluterman M.K., Barnes R., King I.N., Grossfeld P.D., Srivastava D.
    Nature 437:270-274(2005) [PubMed] [Europe PMC] [Abstract]
  • "The bHLH transcription factor CHF1/Hey2 regulates susceptibility to apoptosis and heart failure after pressure overload."
    Liu Y., Yu M., Wu L., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 298:H2082-92(2010) [PubMed] [Europe PMC] [Abstract]
  • "Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors."
    Heisig J., Weber D., Englberger E., Winkler A., Kneitz S., Sung W.K., Wolf E., Eilers M., Wei C.L., Gessler M.
    PLoS Genet. 8:e1002728-e1002728(2012) [PubMed] [Europe PMC] [Abstract]
• negative regulation of Notch signaling pathway Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site."
    Tang Y., Urs S., Liaw L.
    Circ. Res. 102:661-668(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
    Takata T., Ishikawa F.
    Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
  • "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]
  • "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]
• negative regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "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]
  • "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
    Takata T., Ishikawa F.
    Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
  • "Mutations in NOTCH1 cause aortic valve disease."
    Garg V., Muth A.N., Ransom J.F., Schluterman M.K., Barnes R., King I.N., Grossfeld P.D., Srivastava D.
    Nature 437:270-274(2005) [PubMed] [Europe PMC] [Abstract]
  • "MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters."
    Morin S., Pozzulo G., Robitaille L., Cross J., Nemer M.
    J. Biol. Chem. 280:32272-32278(2005) [PubMed] [Europe PMC] [Abstract]
  • "CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6."
    Shirvani S., Xiang F., Koibuchi N., Chin M.T.
    Biochem. Biophys. Res. Commun. 339:151-156(2006) [PubMed] [Europe PMC] [Abstract]
  • "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]
  • "Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation."
    Tokuzawa Y., Yagi K., Yamashita Y., Nakachi Y., Nikaido I., Bono H., Ninomiya Y., Kanesaki-Yatsuka Y., Akita M., Motegi H., Wakana S., Noda T., Sablitzky F., Arai S., Kurokawa R., Fukuda T., Katagiri T., Schonbach C.

    , Suda T., Mizuno Y., Okazaki Y.
    PLoS Genet. 6:e1001019-e1001019(2010) [PubMed] [Europe PMC] [Abstract]
  • "Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats."
    Kanno K., Ishiura S.
    J. Neurosci. Res. 89:562-575(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site."
    Tang Y., Urs S., Liaw L.
    Circ. Res. 102:661-668(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription initiation from RNA polymerase II promoter Source: RGDInferred from sequence orthologyⁱ
  • "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]
• negative regulation of transcription regulatory region DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site."
    Tang Y., Urs S., Liaw L.
    Circ. Res. 102:661-668(2008) [PubMed] [Europe PMC] [Abstract]
• Notch signaling pathway Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "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]
• outflow tract morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• pattern specification process Source: RGDInferred from sequence orthologyⁱ
  • "Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development."
    Li S., Mark S., Radde-Gallwitz K., Schlisner R., Chin M.T., Chen P.
    BMC Dev. Biol. 8:20-20(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cardiac muscle cell proliferation Source: RGDInferred from sequence orthologyⁱ
  • "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]
• positive regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "Inhibitory role of Notch1 in calcific aortic valve disease."
    Acharya A., Hans C.P., Koenig S.N., Nichols H.A., Galindo C.L., Garner H.R., Merrill W.H., Hinton R.B., Garg V.
    PLoS ONE 6:e27743-e27743(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of heart rate Source: RGDInferred from sequence orthologyⁱ
  • "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]
• positive regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "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]
• protein-DNA complex assembly Source: RGDInferred from sequence orthologyⁱ
  • "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]
  • "Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4."
    Xiang F., Sakata Y., Cui L., Youngblood J.M., Nakagami H., Liao J.K., Liao R., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 290:H1997-2006(2006) [PubMed] [Europe PMC] [Abstract]
• pulmonary artery morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• pulmonary valve morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• regulation of gene expression Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 regulates coronary vascular maturation."
    Watanabe T., Koibuchi N., Chin M.T.
    Mech. Dev. 127:418-427(2010) [PubMed] [Europe PMC] [Abstract]
• regulation of inner ear auditory receptor cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti."
    Doetzlhofer A., Basch M.L., Ohyama T., Gessler M., Groves A.K., Segil N.
    Dev. Cell 16:58-69(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of neurogenesis Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• regulation of vasculogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• tricuspid valve formation Source: RGDInferred from sequence orthologyⁱ
  • "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]
• tricuspid valve morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• umbilical cord morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• vascular smooth muscle cell development Source: RGDInferred from sequence orthologyⁱ
  • "Segmental expression of Notch and Hairy genes in nephrogenesis."
    Chen L., Al-Awqati Q.
    Am. J. Physiol. Renal Physiol. 288:F939-52(2005) [PubMed] [Europe PMC] [Abstract]
• vasculogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• ventricular cardiac muscle cell development Source: RGDInferred from sequence orthologyⁱ
  • "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]
• ventricular septum morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]
• ventricular trabecula myocardium morphogenesis Source: RGDInferred from sequence orthologyⁱ
  • "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]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

GO - Molecular functionⁱ

• histone deacetylase binding Source: RGDInferred from sequence orthologyⁱ
  • "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
    Takata T., Ishikawa F.
    Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]
• protein heterodimerization activity Source: RGDInferred from sequence orthologyⁱ
  • "Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors."
    Leimeister C., Dale K., Fischer A., Klamt B., Hrabe de Angelis M., Radtke F., McGrew M.J., Pourquie O., Gessler M.
    Dev. Biol. 227:91-103(2000) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: RGDInferred from sequence orthologyⁱ
  • "Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors."
    Leimeister C., Dale K., Fischer A., Klamt B., Hrabe de Angelis M., Radtke F., McGrew M.J., Pourquie O., Gessler M.
    Dev. Biol. 227:91-103(2000) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II activating transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6."
    Shirvani S., Xiang F., Koibuchi N., Chin M.T.
    Biochem. Biophys. Res. Commun. 339:151-156(2006) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4."
    Xiang F., Sakata Y., Cui L., Youngblood J.M., Nakagami H., Liao J.K., Liao R., Chin M.T.
    Am. J. Physiol. Heart Circ. Physiol. 290:H1997-2006(2006) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

Compositional bias

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MKRPCEETTS ESDLDETIDV GSENNYSGHS ASSVMRSNSP 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 SSMSHHHHPL HPHHWAAAFH HLPTSLLQPN 
       210        220        230        240        250
GLHTSESTPC RLSTSSEVPP AHGSALLTAT FAHADSALRM PSTGTVAPCV 
       260        270        280        290        300
PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA 
       310        320        330 
AATAISPPLS VSAASSPQQT SSGTNSKPYR PWGTEVGAF             

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ