HEY2

Hairy/enhancer-of-split related with YRPW motif 2
Identifiers
Symbols	HEY2; CHF1; GRIDLOCK; GRL; HERP1; HESR2; HRT2; MGC10720; bHLHb32
External IDs	OMIM: 604674 MGI: 1341884 HomoloGene: 22705 GeneCards: HEY2 Gene
Gene Ontology Molecular function • DNA binding • protein binding • histone deacetylase binding Cellular component • nucleus Biological process • negative regulation of transcription from RNA polymerase II promoter • vasculogenesis • Notch signaling pathway • multicellular organismal development • negative regulation of transcription, DNA-dependent • smooth muscle cell differentiation • positive regulation of cardiac muscle cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23493	15214
Ensembl	ENSG00000135547	ENSMUSG00000019789
UniProt	Q9UBP5	Q0VGJ1
RefSeq (mRNA)	NM_012259	NM_013904.1
RefSeq (protein)	NP_036391	NP_038932.1
Location (UCSC)	Chr 6: 126.07 – 126.08 Mb	Chr 10: 30.55 – 30.56 Mb
PubMed search	[1]	[2]

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.

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 (2006). "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, et al. (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. 
• Zhong TP, Rosenberg M, Mohideen MA, et al. (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, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2561327. 
• Nakagawa O, McFadden DG, Nakagawa M, et al. (2001). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17631. 
• Iso T, Sartorelli V, Chung G, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87324. 
• Iso T, Sartorelli V, Poizat C, et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87325. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• 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. 
• Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404. 
• Fischer A, Klamt B, Schumacher N, et al. (2005). "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. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Kokubo H, Miyagawa-Tomita S, Nakazawa M, et al. (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, et al. (2006). "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, et al. (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

• MeSH HEY2+protein,+human

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