HEY2

HEY2
Identificadores
Nomes alternativos	HEY2
IDs externos	OMIM: 604674 HomoloGene: 22705 GeneCards: HEY2
Ontologia genética
Função molecular	• microsatellite binding; • sequence-specific DNA binding; • DNA binding; • protein dimerization activity; • protein homodimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • transcription factor binding; • histone deacetylase binding; • GO:0000983 RNA polymerase II general transcription initiation factor activity; • GO:0001948, GO:0016582 ligação a proteínas plasmáticas; • protein heterodimerization activity; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • GO:0001106 transcription corepressor activity; • sequence-specific double-stranded DNA binding;
Componente celular	• citoplasma; • transcription repressor complex; • Sin3 complex; • cariolinfa; • núcleo celular;
Processo biológico	• 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; • GO:0009373 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; • GO:1901227 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; • regulação genética; • 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; • GO:0045996 negative regulation of transcription, DNA-templated; • cardiac ventricle morphogenesis; • cardiac right ventricle morphogenesis; • ventricular cardiac muscle cell development; • atrioventricular valve development; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 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; • Via de sinalização Notch; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • diferenciação celular; • regulation of neurogenesis; • aortic valve morphogenesis; • epithelial to mesenchymal transition involved in endocardial cushion formation; • GO:1901313 positive regulation of gene expression; • negative regulation of biomineral tissue development; • anterior/posterior pattern specification; • circulatory system development;
	Sources:Amigo / QuickGO
Padrão de expressão RNA
	Mais dados de referência de expressão
Ortólogos
	23493
	n/a
	ENSG00000135547
	n/a
	Q9UBP5; Q5TF93
	n/a
	NM_012259
	n/a
	NP_036391
	n/a
	Wikidata
Ver/Editar Humano

Potenciador cabeludo de divisão relacionado com a proteína 2 (HEY2) do motivo YRPW , também conhecida como fator de hélice-laço-hélice cardiovascular 1 (CHF1), é uma proteína que em humanos é codificada pelo gene HEY2.^[2]^[3]

Mecanismo editar

Esta proteína forma homo ou heterodímeros que se localizam no núcleo e interagem com um complexo de histona desacetilase para reprimir a transcrição. Durante o desenvolvimento embrionário, esse mecanismo é usado para controlar o número de células que se desenvolvem em células progenitoras cardíacas e células do miocárdio.^[4] A relação é inversamente relacionada, portanto, à medida que o número de células que expressam o gene Hey2 aumenta, mais CHF1 está presente para reprimir a transcrição e o número de células que assumem um destino miocárdico diminui.^[4]

Expressão editar

A expressão do gene Hey2 é induzida pela via de sinalização Notch. Nesse mecanismo, as células adjacentes se ligam por meio de receptores notch transmembrana. Dois genes semelhantes e redundantes em camundongos são necessários para o desenvolvimento cardiovascular embrionário e também estão implicados na neurogênese e somitogênese. Variantes de transcritos emendados alternativos foram encontrados, mas sua validade biológica não foi determinada.^[3]

Estudos de nocaute editar

O gene Hey2 está envolvido na formação do sistema cardiovascular e, especialmente, do próprio coração.^[4] Embora estudos não tenham sido conduzidos sobre os efeitos de um mau funcionamento na expressão de Hey2 em humanos, experimentos feitos com ratos sugerem que esse gene pode ser responsável por uma série de defeitos cardíacos. Usando uma técnica de nocaute de gene, os cientistas desativaram os genes Hey1 e Hey2 de camundongos.^[5] Quando apenas o gene Hey1 foi nocauteado, nenhuma mudança fenotípica aparente ocorreu, sugerindo que esses dois genes carregam informações semelhantes e redundantes para o desenvolvimento do coração.^[5]

Significado clínico editar

Variantes comuns de SCN5A, SCN10A e HEY2 (este gene) estão associadas à síndrome de Brugada.^[6]

Interações editar

Foi demonstrado que o HEY2 interage com o Sirtuin 1^[7] e o co-repressor do receptor nuclear 1.^[8]

Referências

↑ «Human PubMed Reference:»
↑ Leimeister C, Externbrink A, Klamt B, Gessler M (julho de 1999). «Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis». Mechanisms of Development. 85 (1–2): 173–7. PMID 10415358. doi:10.1016/S0925-4773(99)00080-5
↑ ^a ^b «Entrez Gene: HEY2 hairy/enhancer-of-split related with YRPW motif 2»
↑ ^a ^b ^c Gibb N, Lazic S, Yuan X, Deshwar AR, Leslie M, Wilson MD, Scott IC (novembro de 2018). «Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development». Development. 145 (22): dev167510. PMID 30355727. doi:10.1242/dev.167510
↑ ^a ^b Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M (abril de 2004). «The Notch target genes Hey1 and Hey2 are required for embryonic vascular development». Genes & Development. 18 (8): 901–11. PMC 395849 . PMID 15107403. doi:10.1101/gad.291004
↑ Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, et al. (setembro de 2013). «Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death». Nature Genetics. 45 (9): 1044–9. PMC 3869788 . PMID 23872634. doi:10.1038/ng.2712
↑ Takata T, Ishikawa F (janeiro de 2003). «Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression». Biochemical and Biophysical Research Communications. 301 (1): 250–7. PMID 12535671. doi:10.1016/S0006-291X(02)03020-6
↑ Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, et al. (setembro de 2001). «HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling». Molecular and Cellular Biology. 21 (17): 6080–9. PMC 87325 . PMID 11486045. doi:10.1128/MCB.21.17.6080-6089.2001

Leitura adicional editar

Iso T, Kedes L, Hamamori Y (março de 2003). «HES and HERP families: multiple effectors of the Notch signaling pathway». Journal of Cellular Physiology. 194 (3): 237–55. PMID 12548545. doi:10.1002/jcp.10208
Kokubo H, Miyagawa-Tomita S, Johnson RL (julho de 2005). «Hesr, a mediator of the Notch signaling, functions in heart and vessel development». Trends in Cardiovascular Medicine. 15 (5): 190–4. PMID 16165016. doi:10.1016/j.tcm.2005.05.005
Chin MT, Maemura K, Fukumoto S, Jain MK, Layne MD, Watanabe M, Hsieh CM, Lee ME (março de 2000). «Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system». The Journal of Biological Chemistry. 275 (9): 6381–7. PMID 10692439. doi:10.1074/jbc.275.9.6381
Zhong TP, Rosenberg M, Mohideen MA, Weinstein B, Fishman MC (março de 2000). «gridlock, an HLH gene required for assembly of the aorta in zebrafish». Science. 287 (5459): 1820–4. Bibcode:2000Sci...287.1820Z. PMID 10710309. doi:10.1126/science.287.5459.1820
Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M, Clarke R, Schmid M, Gessler M (junho de 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. PMID 10860664. doi:10.1006/geno.2000.6200
Firulli BA, Hadzic DB, McDaid JR, Firulli AB (outubro de 2000). «The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function». The Journal of Biological Chemistry. 275 (43): 33567–73. PMC 2561327 . PMID 10924525. doi:10.1074/jbc.M005888200
Nakagawa O, McFadden DG, Nakagawa M, Yanagisawa H, Hu T, Srivastava D, Olson EN (dezembro de 2000). «Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling». Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13655–60. Bibcode:2000PNAS...9713655N. PMC 17631 . PMID 11095750. doi:10.1073/pnas.250485597
Iso T, Sartorelli V, Chung G, Shichinohe T, Kedes L, Hamamori Y (setembro de 2001). «HERP, a new primary target of Notch regulated by ligand binding». Molecular and Cellular Biology. 21 (17): 6071–9. PMC 87324 . PMID 11486044. doi:10.1128/MCB.21.17.6071-6079.2001
Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, Kedes L, Hamamori Y (setembro de 2001). «HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling». Molecular and Cellular Biology. 21 (17): 6080–9. PMC 87325 . PMID 11486045. doi:10.1128/MCB.21.17.6080-6089.2001
Takata T, Ishikawa F (janeiro de 2003). «Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression». Biochemical and Biophysical Research Communications. 301 (1): 250–7. PMID 12535671. doi:10.1016/S0006-291X(02)03020-6
Fischer A, Klamt B, Schumacher N, Glaeser C, Hansmann I, Fenge H, Gessler M (setembro de 2004). «Phenotypic variability in Hey2 -/- mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome». Mammalian Genome. 15 (9): 711–6. PMID 15389319. doi:10.1007/s00335-004-2389-x
Kokubo H, Miyagawa-Tomita S, Nakazawa M, Saga Y, Johnson RL (fevereiro de 2005). «Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system». Developmental Biology. 278 (2): 301–9. PMID 15680351. doi:10.1016/j.ydbio.2004.10.025
Doi H, Iso T, Yamazaki M, Akiyama H, Kanai H, Sato H, et al. (novembro de 2005). «HERP1 inhibits myocardin-induced vascular smooth muscle cell differentiation by interfering with SRF binding to CArG box». Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (11): 2328–34. PMID 16151017. doi:10.1161/01.ATV.0000185829.47163.32
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (outubro de 2005). «Towards a proteome-scale map of the human protein-protein interaction network». Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. PMID 16189514. doi:10.1038/nature04209

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[1] «Human PubMed Reference:»

[pmid10415358-2] Leimeister C, Externbrink A, Klamt B, Gessler M (julho de 1999). «Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis». Mechanisms of Development. 85 (1–2): 173–7. PMID 10415358. doi:10.1016/S0925-4773(99)00080-5

[entrez-3] «Entrez Gene: HEY2 hairy/enhancer-of-split related with YRPW motif 2»

[emily1-4] Gibb N, Lazic S, Yuan X, Deshwar AR, Leslie M, Wilson MD, Scott IC (novembro de 2018). «Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development». Development. 145 (22): dev167510. PMID 30355727. doi:10.1242/dev.167510

[emily2-5] Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M (abril de 2004). «The Notch target genes Hey1 and Hey2 are required for embryonic vascular development». Genes & Development. 18 (8): 901–11. PMC 395849 . PMID 15107403. doi:10.1101/gad.291004

[Bezzina_Barc_2013-6] Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, et al. (setembro de 2013). «Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death». Nature Genetics. 45 (9): 1044–9. PMC 3869788 . PMID 23872634. doi:10.1038/ng.2712

[pmid12535671-7] Takata T, Ishikawa F (janeiro de 2003). «Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression». Biochemical and Biophysical Research Communications. 301 (1): 250–7. PMID 12535671. doi:10.1016/S0006-291X(02)03020-6

[pmid11486045-8] Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, et al. (setembro de 2001). «HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling». Molecular and Cellular Biology. 21 (17): 6080–9. PMC 87325 . PMID 11486045. doi:10.1128/MCB.21.17.6080-6089.2001

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