HEY2_MOUSE
ID HEY2_MOUSE Reviewed; 339 AA.
AC Q9QUS4; Q3TZ99; Q8CD44;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 2;
DE AltName: Full=HES-related repressor protein 2;
DE AltName: Full=Hairy and enhancer of split-related protein 2;
DE Short=HESR-2;
DE AltName: Full=Hairy-related transcription factor 2;
DE Short=HRT-2;
DE Short=mHRT2;
DE AltName: Full=Protein gridlock homolog;
GN Name=Hey2; Synonyms=Chf1, Herp, Herp1, Hesr2, Hrt2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10588864; DOI=10.1006/dbio.1999.9454;
RA Nakagawa O., Nakagawa M., Richardson J.A., Olson E.N., Srivastava D.;
RT "HRT1, HRT2 and HRT3: a new subclass of bHLH transcription factors marking
RT specific cardiac, somitic and pharyngeal arch segments.";
RL Dev. Biol. 216:72-84(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10860664; DOI=10.1006/geno.2000.6200;
RA Steidl C., Leimeister C., Klamt B., Maier M., Nanda I., Dixon M.,
RA Clarke R., Schmid M., Gessler M.;
RT "Characterization of the human and mouse HEY1, HEY2, and HEYL genes:
RT cloning, mapping, and mutation screening of a new bHLH gene family.";
RL Genomics 66:195-203(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=10692439; DOI=10.1074/jbc.275.9.6381;
RA Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D., Watanabe M.,
RA Hsieh C.-M., Lee M.-E.;
RT "Cardiovascular basic helix loop helix factor 1, a novel transcriptional
RT repressor expressed preferentially in the developing and adult
RT cardiovascular system.";
RL J. Biol. Chem. 275:6381-6387(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11486044; DOI=10.1128/mcb.21.17.6071-6079.2001;
RA Iso T., Sartorelli V., Chung G., Shichinohe T., Kedes L., Hamamori Y.;
RT "HERP, a new primary target of Notch regulated by ligand binding.";
RL Mol. Cell. Biol. 21:6071-6079(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kokubo H., Johnson R.L.;
RT "Cloning of hesr2 gene.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Inner ear, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=10415358; DOI=10.1016/s0925-4773(99)00080-5;
RA Leimeister C., Externbrinck A., Klamt B., Gessler M.;
RT "Hey genes: a novel subfamily of hairy- and enhancer of split related genes
RT specifically expressed during mouse embryogenesis.";
RL Mech. Dev. 85:173-177(1999).
RN [9]
RP INDUCTION.
RX PubMed=10964718; DOI=10.1006/bbrc.2000.3354;
RA Maier M.M., Gessler M.;
RT "Comparative analysis of the human and mouse Hey1 promoter: Hey genes are
RT new Notch target genes.";
RL Biochem. Biophys. Res. Commun. 275:652-660(2000).
RN [10]
RP FUNCTION, DNA-BINDING, INDUCTION, AND MUTAGENESIS OF 49-ARG--ARG-61.
RX PubMed=11095750; DOI=10.1073/pnas.250485597;
RA Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T.,
RA Srivastava D., Olson E.N.;
RT "Members of the HRT family of basic helix-loop-helix proteins act as
RT transcriptional repressors downstream of Notch signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000).
RN [11]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11160397; DOI=10.1523/jneurosci.21-04-01265.2001;
RA Satow T., Bae S.-K., Inoue T., Inoue C., Miyoshi G., Tomita K., Bessho Y.,
RA Hashimoto N., Kageyama R.;
RT "The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse
RT retina.";
RL J. Neurosci. 21:1265-1273(2001).
RN [12]
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH HDAC1; HES1; NCOR1 AND SIN3A.
RX PubMed=11486045; DOI=10.1128/mcb.21.17.6080-6089.2001;
RA Iso T., Sartorelli V., Poizat C., Iezzi S., Wu H.-Y., Chung G., Kedes L.,
RA Hamamori Y.;
RT "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling.";
RL Mol. Cell. Biol. 21:6080-6089(2001).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12372253; DOI=10.1016/s0960-9822(02)01150-8;
RA Gessler M., Knobeloch K.-P., Helisch A., Amann K., Schumacher N., Rohde E.,
RA Fischer A., Leimeister C.;
RT "Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac
RT defects in Hey2 -/- mice.";
RL Curr. Biol. 12:1601-1604(2002).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12372254; DOI=10.1016/s0960-9822(02)01149-1;
RA Donovan J., Kordylewska A., Jan Y.N., Utset M.F.;
RT "Tetralogy of fallot and other congenital heart defects in Hey2 mutant
RT mice.";
RL Curr. Biol. 12:1605-1610(2002).
RN [15]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11741889; DOI=10.1074/jbc.m110495200;
RA Iso T., Chung G., Hamamori Y., Kedes L.;
RT "HERP1 is a cell type-specific primary target of Notch.";
RL J. Biol. Chem. 277:6598-6607(2002).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12454287; DOI=10.1073/pnas.252648999;
RA Sakata Y., Kamei C.N., Nakagami H., Bronson R., Liao J.K., Chin M.T.;
RT "Ventricular septal defect and cardiomyopathy in mice lacking the
RT transcription factor CHF1/Hey2.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16197-16202(2002).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12947105; DOI=10.1074/jbc.m300448200;
RA Sakamoto M., Hirata H., Ohtsuka T., Bessho Y., Kageyama R.;
RT "The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate
RT maintenance of neural precursor cells in the brain.";
RL J. Biol. Chem. 278:44808-44815(2003).
RN [18]
RP FUNCTION.
RX PubMed=15345511; DOI=10.1161/01.atv.0000143936.77094.a4;
RA Sakata Y., Xiang F., Chen Z., Kiriyama Y., Kamei C.N., Simon D.I.,
RA Chin M.T.;
RT "Transcription factor CHF1/Hey2 regulates neointimal formation in vivo and
RT vascular smooth muscle proliferation and migration in vitro.";
RL Arterioscler. Thromb. Vasc. Biol. 24:2069-2074(2004).
RN [19]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15297376; DOI=10.1161/01.res.0000141136.85194.f0;
RA Kokubo H., Miyagawa-Tomita S., Tomimatsu H., Nakashima Y., Nakazawa M.,
RA Saga Y., Johnson R.L.;
RT "Targeted disruption of hesr2 results in atrioventricular valve anomalies
RT that lead to heart dysfunction.";
RL Circ. Res. 95:540-547(2004).
RN [20]
RP FUNCTION.
RX PubMed=15107403; DOI=10.1101/gad.291004;
RA Fischer A., Schumacher N., Maier M., Sendtner M., Gessler M.;
RT "The Notch target genes Hey1 and Hey2 are required for embryonic vascular
RT development.";
RL Genes Dev. 18:901-911(2004).
RN [21]
RP FUNCTION, INTERACTION WITH GATA4, AND MUTAGENESIS OF 33-SER--SER-37.
RX PubMed=15485867; DOI=10.1074/jbc.m409879200;
RA Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M.,
RA Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O.;
RT "Hairy-related transcription factors inhibit GATA-dependent cardiac gene
RT expression through a signal-responsive mechanism.";
RL J. Biol. Chem. 279:54937-54943(2004).
RN [22]
RP FUNCTION.
RX PubMed=15680351; DOI=10.1016/j.ydbio.2004.10.025;
RA Kokubo H., Miyagawa-Tomita S., Nakazawa M., Saga Y., Johnson R.L.;
RT "Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch
RT signaling in the developing cardiovascular system.";
RL Dev. Biol. 278:301-309(2005).
RN [23]
RP FUNCTION, INTERACTION WITH GATA4 AND GATA6, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16199874; DOI=10.1128/mcb.25.20.8960-8970.2005;
RA Fischer A., Klattig J., Kneitz B., Diez H., Maier M., Holtmann B.,
RA Englert C., Gessler M.;
RT "Hey basic helix-loop-helix transcription factors are repressors of GATA4
RT and GATA6 and restrict expression of the GATA target gene ANF in fetal
RT hearts.";
RL Mol. Cell. Biol. 25:8960-8970(2005).
RN [24]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=17332425; DOI=10.1161/01.res.0000261693.13269.bf;
RA Koibuchi N., Chin M.T.;
RT "CHF1/Hey2 plays a pivotal role in left ventricular maturation through
RT suppression of ectopic atrial gene expression.";
RL Circ. Res. 100:850-855(2007).
RN [25]
RP FUNCTION, INTERACTION WITH HEYL, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17303760; DOI=10.1161/01.res.0000260913.95642.3b;
RA Fischer A., Steidl C., Wagner T.U., Lang E., Jakob P.M., Friedl P.,
RA Knobeloch K.-P., Gessler M.;
RT "Combined loss of Hey1 and HeyL causes congenital heart defects because of
RT impaired epithelial to mesenchymal transition.";
RL Circ. Res. 100:856-863(2007).
RN [26]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17259303; DOI=10.1242/dev.02777;
RA Kokubo H., Tomita-Miyagawa S., Hamada Y., Saga Y.;
RT "Hesr1 and Hesr2 regulate atrioventricular boundary formation in the
RT developing heart through the repression of Tbx2.";
RL Development 134:747-755(2007).
CC -!- FUNCTION: Transcriptional repressor which functions as a downstream
CC effector of Notch signaling in cardiovascular development. Specifically
CC required for the Notch-induced endocardial epithelial to mesenchymal
CC transition, which is itself criticial for cardiac valve and septum
CC development. May be required in conjunction with HEY1 to specify
CC arterial cell fate or identity. Promotes maintenance of neuronal
CC precursor cells and glial versus neuronal fate specification. Binds
CC preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses
CC transcription by the cardiac transcriptional activators GATA4 and GATA6
CC and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3.
CC {ECO:0000269|PubMed:10692439, ECO:0000269|PubMed:11095750,
CC ECO:0000269|PubMed:11160397, ECO:0000269|PubMed:11486045,
CC ECO:0000269|PubMed:12372253, ECO:0000269|PubMed:12372254,
CC ECO:0000269|PubMed:12454287, ECO:0000269|PubMed:12947105,
CC ECO:0000269|PubMed:15107403, ECO:0000269|PubMed:15297376,
CC ECO:0000269|PubMed:15345511, ECO:0000269|PubMed:15485867,
CC ECO:0000269|PubMed:15680351, ECO:0000269|PubMed:16199874,
CC ECO:0000269|PubMed:17259303, ECO:0000269|PubMed:17303760,
CC ECO:0000269|PubMed:17332425}.
CC -!- SUBUNIT: May self-associate (By similarity). Interacts with ARNT (By
CC similarity). Interacts with GATA4, GATA6, HES1 and HEYL. Interacts with
CC HDAC1, NCOR1 and SIN3A. {ECO:0000250, ECO:0000269|PubMed:11486045,
CC ECO:0000269|PubMed:15485867, ECO:0000269|PubMed:16199874,
CC ECO:0000269|PubMed:17303760}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-ProRule:PRU00981, ECO:0000269|PubMed:11741889}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the aorta, lower expression
CC detected in the heart, brain, kidney, lung, muscle, ovary and testis.
CC {ECO:0000269|PubMed:10588864, ECO:0000269|PubMed:10692439,
CC ECO:0000269|PubMed:10860664, ECO:0000269|PubMed:12947105}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing somites and the
CC ventricles of the heart. Expressed in the otic vesicles between 8.5 dpc
CC and 10.5 dpc. Expressed in the myocardium of the ventricles at 9.5 dpc
CC and in the atrioventricular cushions from 9.5 to 12.5 dpc. At 10.5 dpc,
CC strongly expressed in the spinal nerves, the cranial ganglia and the
CC telencephalon. At 11.5 dpc, expressed in the craniofacial region of the
CC distal part of the maxillary arch, along the rostral mandibular arch
CC and surrounding the lateral nasal processes. Expressed in the midbrain-
CC hindbrain boundary and the posterior edge of the hand- and foot-paddle.
CC Expressed in the mediodorsal region of the telencephalon and the
CC ventricular zone of the ventral spinal cord at 12 dpc, then in the
CC ventral region of the telencephalon and the cortical plate at 15 dpc.
CC Expression in the heart is limited to the compact myocardial layer at
CC 17.5 dpc. Also expressed in the developing retina up to P5, at which
CC point expression decreases. {ECO:0000269|PubMed:10415358,
CC ECO:0000269|PubMed:10588864, ECO:0000269|PubMed:10692439,
CC ECO:0000269|PubMed:10860664, ECO:0000269|PubMed:11160397,
CC ECO:0000269|PubMed:12947105, ECO:0000269|PubMed:16199874,
CC ECO:0000269|PubMed:17259303, ECO:0000269|PubMed:17303760,
CC ECO:0000269|PubMed:17332425}.
CC -!- INDUCTION: By activation of the Notch signaling pathway.
CC {ECO:0000269|PubMed:10964718, ECO:0000269|PubMed:11095750,
CC ECO:0000269|PubMed:11741889}.
CC -!- DISRUPTION PHENOTYPE: Mice display a spectrum of cardiac malformations
CC including ventricular septal defects, tetralogy of Fallot and tricuspid
CC atresia. The penetrance of the cardiac malformation phenotype varies
CC according to the strain, suggesting the presence of modifier genes.
CC {ECO:0000269|PubMed:12372253, ECO:0000269|PubMed:12372254,
CC ECO:0000269|PubMed:12454287, ECO:0000269|PubMed:15297376,
CC ECO:0000269|PubMed:16199874, ECO:0000269|PubMed:17303760,
CC ECO:0000269|PubMed:17332425}.
CC -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR EMBL; AF172287; AAF14546.1; -; mRNA.
DR EMBL; AJ271867; CAB71346.1; -; mRNA.
DR EMBL; AF173902; AAF20174.1; -; mRNA.
DR EMBL; AF232240; AAF37298.1; -; mRNA.
DR EMBL; AB093589; BAC55066.1; -; mRNA.
DR EMBL; AK031506; BAC27428.1; -; mRNA.
DR EMBL; AK158000; BAE34310.1; -; mRNA.
DR EMBL; BC103575; AAI03576.1; -; mRNA.
DR EMBL; BC103576; AAI03577.1; -; mRNA.
DR CCDS; CCDS23766.1; -.
DR RefSeq; NP_038932.1; NM_013904.1.
DR AlphaFoldDB; Q9QUS4; -.
DR SMR; Q9QUS4; -.
DR BioGRID; 200283; 1.
DR IntAct; Q9QUS4; 2.
DR STRING; 10090.ENSMUSP00000019924; -.
DR PhosphoSitePlus; Q9QUS4; -.
DR PaxDb; Q9QUS4; -.
DR PRIDE; Q9QUS4; -.
DR Antibodypedia; 32702; 238 antibodies from 33 providers.
DR DNASU; 15214; -.
DR Ensembl; ENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789.
DR GeneID; 15214; -.
DR KEGG; mmu:15214; -.
DR UCSC; uc007etp.1; mouse.
DR CTD; 23493; -.
DR MGI; MGI:1341884; Hey2.
DR VEuPathDB; HostDB:ENSMUSG00000019789; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000160636; -.
DR HOGENOM; CLU_048294_1_0_1; -.
DR InParanoid; Q9QUS4; -.
DR OMA; HWTAAFH; -.
DR OrthoDB; 1201152at2759; -.
DR PhylomeDB; Q9QUS4; -.
DR TreeFam; TF323617; -.
DR BioGRID-ORCS; 15214; 0 hits in 74 CRISPR screens.
DR PRO; PR:Q9QUS4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9QUS4; protein.
DR Bgee; ENSMUSG00000019789; Expressed in trigeminal ganglion and 252 other tissues.
DR ExpressionAtlas; Q9QUS4; baseline and differential.
DR Genevisible; Q9QUS4; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISS:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0009948; P:anterior/posterior axis specification; IGI:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0003180; P:aortic valve morphogenesis; IDA:BHF-UCL.
DR GO; GO:0060842; P:arterial endothelial cell differentiation; IGI:BHF-UCL.
DR GO; GO:0060840; P:artery development; IGI:MGI.
DR GO; GO:0035910; P:ascending aorta morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003171; P:atrioventricular valve development; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IGI:MGI.
DR GO; GO:0060837; P:blood vessel endothelial cell differentiation; IGI:MGI.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; IMP:MGI.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IDA:MGI.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060948; P:cardiac vascular smooth muscle cell development; IMP:MGI.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0072359; P:circulatory system development; IBA:GO_Central.
DR GO; GO:0090102; P:cochlea development; IMP:MGI.
DR GO; GO:0060977; P:coronary vasculature morphogenesis; IMP:MGI.
DR GO; GO:0035912; P:dorsal aorta morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003199; P:endocardial cushion to mesenchymal transition involved in heart valve formation; IGI:MGI.
DR GO; GO:0060347; P:heart trabecula formation; IMP:BHF-UCL.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IGI:BHF-UCL.
DR GO; GO:0014031; P:mesenchymal cell development; IMP:BHF-UCL.
DR GO; GO:0003150; P:muscular septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:BHF-UCL.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000820; P:negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0060633; P:negative regulation of transcription initiation from RNA polymerase II promoter; ISO:MGI.
DR GO; GO:2000678; P:negative regulation of transcription regulatory region DNA binding; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0061314; P:Notch signaling involved in heart development; IC:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0065004; P:protein-DNA complex assembly; IDA:MGI.
DR GO; GO:0061156; P:pulmonary artery morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0045607; P:regulation of inner ear auditory receptor cell differentiation; IGI:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:MGI.
DR GO; GO:2001212; P:regulation of vasculogenesis; IGI:BHF-UCL.
DR GO; GO:0003195; P:tricuspid valve formation; IMP:MGI.
DR GO; GO:0003186; P:tricuspid valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0036304; P:umbilical cord morphogenesis; IGI:BHF-UCL.
DR GO; GO:0001570; P:vasculogenesis; IGI:MGI.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IMP:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IGI:MGI.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Notch signaling pathway; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..339
FT /note="Hairy/enhancer-of-split related with YRPW motif
FT protein 2"
FT /id="PRO_0000245516"
FT DOMAIN 48..103
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 122..157
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..116
FT /note="Transcriptional repression and interaction with
FT NCOR1 and SIN3A"
FT /evidence="ECO:0000269|PubMed:11486045"
FT REGION 310..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 329..332
FT /note="YQPW motif"
FT COMPBIAS 24..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 33..37
FT /note="Missing: Abrogates interaction with GATA4 and
FT repression of GATA4-mediated transcription."
FT /evidence="ECO:0000269|PubMed:15485867"
FT MUTAGEN 49..61
FT /note="RKKRRGIIEKRRR->LE: Abrogates DNA-binding and
FT transcriptional repression."
FT /evidence="ECO:0000269|PubMed:11095750"
FT CONFLICT 7
FT /note="E -> K (in Ref. 6; BAC27428)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="G -> E (in Ref. 6; BAE34310)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 339 AA; 35873 MW; 105BEEA06DE50444 CRC64;
MKRPCEETTS ESDLDETIDV GSENNYPGHA TSSVMRSNSP TTTSQIMARK KRRGIIEKRR
RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL KMLQATGGKG YFDAHALATD
FMSIGFRECL TEVARYLSSV EGLDPSDPLR VRLVSHLSTC ASQREAAVMT SSMAHHHHPL
HPHHWAAAFH HLPTALLQPN GLHTSESTPC RLSTSSEVPS AHGSALLTAT FAHADSALRM
PSGGTVAPCV PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA
AATAISPPLS VSAASSPQQT STGTNNKPYQ PWGTEVGAF
