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Q9QUS4

- HEY2_MOUSE

UniProt

Q9QUS4 - HEY2_MOUSE

Protein

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

Gene

Hey2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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

    1. DNA binding Source: UniProtKB
    2. microsatellite binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity Source: UniProtKB
    5. sequence-specific DNA binding Source: MGI
    6. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    7. transcription factor binding Source: MGI

    GO - Biological processi

    1. anterior/posterior axis specification Source: MGI
    2. arterial endothelial cell differentiation Source: BHF-UCL
    3. artery development Source: MGI
    4. ascending aorta morphogenesis Source: BHF-UCL
    5. atrial septum morphogenesis Source: BHF-UCL
    6. atrioventricular valve development Source: MGI
    7. blood vessel development Source: MGI
    8. cardiac epithelial to mesenchymal transition Source: BHF-UCL
    9. cardiac left ventricle morphogenesis Source: BHF-UCL
    10. cardiac muscle hypertrophy Source: MGI
    11. cardiac muscle hypertrophy in response to stress Source: MGI
    12. cardiac right ventricle morphogenesis Source: BHF-UCL
    13. cardiac septum morphogenesis Source: BHF-UCL
    14. cardiac vascular smooth muscle cell development Source: MGI
    15. cardiac ventricle morphogenesis Source: UniProtKB
    16. cell fate commitment Source: MGI
    17. cochlea development Source: MGI
    18. coronary vasculature morphogenesis Source: MGI
    19. dorsal aorta morphogenesis Source: BHF-UCL
    20. endocardial cushion to mesenchymal transition involved in heart valve formation Source: MGI
    21. heart trabecula formation Source: BHF-UCL
    22. labyrinthine layer blood vessel development Source: BHF-UCL
    23. mesenchymal cell development Source: BHF-UCL
    24. muscular septum morphogenesis Source: BHF-UCL
    25. negative regulation of cardiac muscle cell apoptotic process Source: MGI
    26. negative regulation of gene expression Source: BHF-UCL
    27. negative regulation of Notch signaling pathway Source: UniProtKB
    28. negative regulation of transcription, DNA-templated Source: UniProtKB
    29. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    30. negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation Source: BHF-UCL
    31. negative regulation of transcription initiation from RNA polymerase II promoter Source: Ensembl
    32. negative regulation of transcription regulatory region DNA binding Source: BHF-UCL
    33. Notch signaling involved in heart development Source: BHF-UCL
    34. Notch signaling pathway Source: UniProtKB
    35. outflow tract morphogenesis Source: BHF-UCL
    36. pattern specification process Source: MGI
    37. positive regulation of cardiac muscle cell proliferation Source: MGI
    38. positive regulation of heart rate Source: MGI
    39. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    40. protein-DNA complex assembly Source: MGI
    41. pulmonary artery morphogenesis Source: BHF-UCL
    42. pulmonary valve morphogenesis Source: BHF-UCL
    43. regulation of auditory receptor cell differentiation Source: MGI
    44. regulation of gene expression Source: MGI
    45. regulation of transcription from RNA polymerase II promoter Source: MGI
    46. regulation of vasculogenesis Source: BHF-UCL
    47. transcription from RNA polymerase II promoter Source: GOC
    48. tricuspid valve formation Source: MGI
    49. tricuspid valve morphogenesis Source: BHF-UCL
    50. umbilical cord morphogenesis Source: BHF-UCL
    51. vasculogenesis Source: MGI
    52. ventricular cardiac muscle cell development Source: BHF-UCL
    53. ventricular septum morphogenesis Source: BHF-UCL
    54. ventricular trabecula myocardium morphogenesis Source: MGI

    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 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: Chromosome 10

    Organism-specific databases

    MGIiMGI:1341884. Hey2.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleoplasm Source: Reactome
    3. nucleus Source: UniProtKB
    4. Sin3 complex Source: Ensembl
    5. transcriptional repressor complex Source: Ensembl
    6. transcription factor complex Source: MGI

    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.
    Mutagenesisi49 – 6113RKKRR…EKRRR → LE: Abrogates DNA-binding and transcriptional repression. Add
    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

    ArrayExpressiQ9QUS4.
    BgeeiQ9QUS4.
    CleanExiMM_HEY2.
    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.
    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.

    Q9QUS4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKRPCEETTS ESDLDETIDV GSENNYPGHA TSSVMRSNSP TTTSQIMARK    50
    KRRGIIEKRR RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL 100
    KMLQATGGKG YFDAHALATD FMSIGFRECL TEVARYLSSV EGLDPSDPLR 150
    VRLVSHLSTC ASQREAAVMT SSMAHHHHPL HPHHWAAAFH HLPTALLQPN 200
    GLHTSESTPC RLSTSSEVPS AHGSALLTAT FAHADSALRM PSGGTVAPCV 250
    PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA 300
    AATAISPPLS VSAASSPQQT STGTNNKPYQ PWGTEVGAF 339
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS23766.1.
    RefSeqi NP_038932.1. NM_013904.1.
    UniGenei Mm.103573.

    3D structure databases

    ProteinModelPortali Q9QUS4.
    SMRi Q9QUS4. Positions 40-104, 110-164.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200283. 1 interaction.
    IntActi Q9QUS4. 2 interactions.

    PTM databases

    PhosphoSitei Q9QUS4.

    Proteomic databases

    PRIDEi Q9QUS4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000019924 ; ENSMUSP00000019924 ; ENSMUSG00000019789 .
    GeneIDi 15214.
    KEGGi mmu:15214.
    UCSCi uc007etp.1. mouse.

    Organism-specific databases

    CTDi 23493.
    MGIi MGI:1341884. Hey2.

    Phylogenomic databases

    eggNOGi NOG324798.
    GeneTreei ENSGT00700000104130.
    HOGENOMi HOG000286035.
    HOVERGENi HBG003275.
    InParanoidi Q9QUS4.
    KOi K09091.
    OMAi STCASQR.
    OrthoDBi EOG76MK98.
    PhylomeDBi Q9QUS4.
    TreeFami TF323617.

    Enzyme and pathway databases

    Reactomei REACT_196464. NOTCH1 Intracellular Domain Regulates Transcription.

    Miscellaneous databases

    NextBioi 287789.
    PROi Q9QUS4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9QUS4.
    Bgeei Q9QUS4.
    CleanExi MM_HEY2.
    Genevestigatori Q9QUS4.

    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], 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: October 1, 2014
    This is version 114 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