HEY2

HEY2
Identifiers
Aliases	HEY2, CHF1, GRIDLOCK, GRL, HERP1, HESR2, HRT2, bHLHb32, hes related family bHLH transcription factor with YRPW motif 2
External IDs	OMIM: 604674; MGI: 1341884; HomoloGene: 22705; GeneCards: HEY2; OMA:HEY2 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6q22.31 Start 125,747,664 bp End 125,761,269 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10|10 A4 Start 30,708,355 bp End 30,718,797 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in popliteal artery tibial arteries right ventricle myocardium of left ventricle right coronary artery oocyte Descending thoracic aorta secondary oocyte right uterine tube corpus epididymis Top expressed in trigeminal ganglion ascending aorta inner enamel epithelium left ventricle tunica media of zone of aorta cumulus cell primordial ventricle semi-lunar valve aortic valve lumbar spinal ganglion More reference expression data BioGPS More reference expression data
Gene ontology Molecular function microsatellite binding sequence-specific DNA binding DNA binding protein dimerization activity protein homodimerization activity DNA-binding transcription factor activity transcription factor binding histone deacetylase binding RNA polymerase II general transcription initiation factor activity protein binding protein heterodimerization activity DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription repressor activity, RNA polymerase II-specific transcription corepressor activity sequence-specific double-stranded DNA binding Cellular component cytoplasm transcription repressor complex Sin3 complex nucleoplasm nucleus Biological process dorsal aorta morphogenesis cardiac vascular smooth muscle cell development cochlea development pattern specification process cell fate commitment pulmonary valve morphogenesis regulation of inner ear auditory receptor cell differentiation negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation regulation of transcription, DNA-templated heart trabecula formation tricuspid valve morphogenesis regulation of vasculogenesis pulmonary artery morphogenesis cardiac septum morphogenesis negative regulation of cardiac vascular smooth muscle cell differentiation muscular septum morphogenesis ventricular septum morphogenesis protein-DNA complex assembly cardiac muscle hypertrophy outflow tract morphogenesis ascending aorta morphogenesis cardiac left ventricle morphogenesis labyrinthine layer blood vessel development negative regulation of transcription by RNA polymerase II coronary vasculature morphogenesis smooth muscle cell differentiation negative regulation of gene expression endocardial cushion to mesenchymal transition involved in heart valve formation transcription, DNA-templated ventricular trabecula myocardium morphogenesis positive regulation of heart rate vasculogenesis multicellular organism development atrial septum morphogenesis negative regulation of cardiac muscle cell apoptotic process heart development arterial endothelial cell differentiation positive regulation of cardiac muscle cell proliferation blood vessel development cardiac muscle hypertrophy in response to stress umbilical cord morphogenesis negative regulation of transcription regulatory region DNA binding mesenchymal cell development artery development regulation of gene expression negative regulation of transcription by transcription factor localization negative regulation of transcription initiation from RNA polymerase II promoter vascular associated smooth muscle cell development anterior/posterior axis specification tricuspid valve formation negative regulation of transcription, DNA-templated cardiac ventricle morphogenesis cardiac right ventricle morphogenesis ventricular cardiac muscle cell development atrioventricular valve development positive regulation of transcription by RNA polymerase II negative regulation of Notch signaling pathway cardiac epithelial to mesenchymal transition Notch signaling involved in heart development Notch signaling pathway positive regulation of transcription, DNA-templated cell differentiation regulation of neurogenesis aortic valve morphogenesis epithelial to mesenchymal transition involved in endocardial cushion formation positive regulation of gene expression negative regulation of biomineral tissue development anterior/posterior pattern specification circulatory system development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23493 15214 Ensembl ENSG00000135547 ENSMUSG00000019789 UniProt Q9UBP5 Q5TF93 Q9QUS4 RefSeq (mRNA) NM_012259 NM_013904 RefSeq (protein) NP_036391 NP_038932 Location (UCSC) Chr 6: 125.75 – 125.76 Mb Chr 10: 30.71 – 30.72 Mb PubMed search
Wikidata
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Hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) also known as cardiovascular helix-loop-helix factor 1 (CHF1) is a protein that in humans is encoded by the HEY2 gene.

Function

CHF1 is a member of the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (bHLH)-type transcription factors. The encoded protein forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress transcription. Expression of this gene is induced by the Notch signaling pathway. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in neurogenesis and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.

Clinical significance

Common variants of SCN5A, SCN10A, and HEY2 (this gene) are associated with Brugada syndrome.

Interactions

HEY2 has been shown to interact with Sirtuin 1 and Nuclear receptor co-repressor 1.

Further reading

• Iso T, Kedes L, Hamamori Y (2003). "HES and HERP families: multiple effectors of the Notch signaling pathway". J. Cell. Physiol. 194 (3): 237–55. doi:10.1002/jcp.10208. PMID 12548545.
• Kokubo H, Miyagawa-Tomita S, Johnson RL (2005). "Hesr, a mediator of the Notch signaling, functions in heart and vessel development". Trends Cardiovasc. Med. 15 (5): 190–4. doi:10.1016/j.tcm.2005.05.005. PMID 16165016.
• Chin MT, Maemura K, Fukumoto S, Jain MK, Layne MD, Watanabe M, Hsieh CM, Lee ME (2000). "Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system". J. Biol. Chem. 275 (9): 6381–7. doi:10.1074/jbc.275.9.6381. PMID 10692439.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Zhong TP, Rosenberg M, Mohideen MA, Weinstein B, Fishman MC (2000). "gridlock, an HLH gene required for assembly of the aorta in zebrafish". Science. 287 (5459): 1820–4. doi:10.1126/science.287.5459.1820. PMID 10710309.
• Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M, Clarke R, Schmid M, Gessler M (2000). "Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family". Genomics. 66 (2): 195–203. doi:10.1006/geno.2000.6200. PMID 10860664.
• Firulli BA, Hadzic DB, McDaid JR, Firulli AB (2000). "The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function". J. Biol. Chem. 275 (43): 33567–73. doi:10.1074/jbc.M005888200. PMC 2561327. PMID 10924525.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Nakagawa O, McFadden DG, Nakagawa M, Yanagisawa H, Hu T, Srivastava D, Olson EN (2000). "Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling". Proc. Natl. Acad. Sci. U.S.A. 97 (25): 13655–60. doi:10.1073/pnas.250485597. PMC 17631. PMID 11095750.
• Iso T, Sartorelli V, Chung G, Shichinohe T, Kedes L, Hamamori Y (2001). "HERP, a new primary target of Notch regulated by ligand binding". Mol. Cell. Biol. 21 (17): 6071–9. doi:10.1128/MCB.21.17.6071-6079.2001. PMC 87324. PMID 11486044.
• Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, Kedes L, Hamamori Y (2001). "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling". Mol. Cell. Biol. 21 (17): 6080–9. doi:10.1128/MCB.21.17.6080-6089.2001. PMC 87325. PMID 11486045.
• Takata T, Ishikawa F (2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochem. Biophys. Res. Commun. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID 12535671.
• Fischer A, Klamt B, Schumacher N, Glaeser C, Hansmann I, Fenge H, Gessler M (2004). "Phenotypic variability in Hey2 -/- mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome". Mamm. Genome. 15 (9): 711–6. doi:10.1007/s00335-004-2389-x. PMID 15389319.
• Kokubo H, Miyagawa-Tomita S, Nakazawa M, Saga Y, Johnson RL (2005). "Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system". Dev. Biol. 278 (2): 301–9. doi:10.1016/j.ydbio.2004.10.025. PMID 15680351.
• Doi H, Iso T, Yamazaki M, Akiyama H, Kanai H, Sato H, Kawai-Kowase K, Tanaka T, Maeno T, Okamoto E, Arai M, Kedes L, Kurabayashi M (2005). "HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box". Arterioscler. Thromb. Vasc. Biol. 25 (11): 2328–34. doi:10.1161/01.ATV.0000185829.47163.32. PMID 16151017.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

External links

• HEY2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.