TCF4

TCF4
Estruturas disponíveis
PDB	Pesquisa Human UniProt: PDBe RCSB
Lista de códigos id do PDB
	2KWF
Identificadores
Nomes alternativos	TCF4
IDs externos	OMIM: 602272 HomoloGene: 2407 GeneCards: TCF4
Doenças Geneticamente Relacionadas
	morbid obesity, esquizofrenia, colite ulcerosa, sclerosing cholangitis, Distrofia de Fuchs, Pitt-Hopkins syndrome, Distrofia de Fuchs
Ontologia genética
Função molecular	• protein dimerization activity; • protein homodimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • bHLH transcription factor binding; • E-box binding; • protein C-terminus binding; • GO:0001948, GO:0016582 ligação a proteínas plasmáticas; • identical protein binding; • TFIIB-class transcription factor binding; • protein heterodimerization activity; • DNA binding; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Componente celular	• transcription regulator complex; • núcleo celular; • beta-catenin-TCF complex; • beta-catenin-TCF7L2 complex;
Processo biológico	• diferenciação celular; • GO:0009373 regulation of transcription, DNA-templated; • protein-DNA complex assembly; • transcription, DNA-templated; • nervous system development; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • DNA-templated transcription, initiation; • transcription initiation from RNA polymerase II promoter; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • positive regulation of neuron differentiation;
	Sources:Amigo / QuickGO
Ortólogos
	6925
	n/a
	ENSG00000196628
	n/a
	P15884
	n/a
NM_001083962; NM_001243226; NM_001243227; NM_001243228; NM_001243230;
	NM_001243231; NM_001243232; NM_001243233; NM_001243234; NM_001243235; NM_001243236; NM_001306207; NM_001306208; NM_003199; NM_001330604; NM_001330605; NM_001348211; NM_001348212; NM_001348213; NM_001348214; NM_001348215; NM_001348216; NM_001348217; NM_001348218; NM_001348219; NM_001348220; NM_001369572; NM_001369573; NM_001369574; NM_001369575; NM_001369576; NM_001369577; NM_001369578; NM_001369579; NM_001369580; NM_001369581; NM_001369582; NM_001369583; NM_001369584; NM_001369585; NM_001369586; NM_001369567; NM_001369568; NM_001369569; NM_001369570; NM_001369571
	n/a
NP_001077431; NP_001230155; NP_001230156; NP_001230157; NP_001230159;
	NP_001230160; NP_001230161; NP_001230162; NP_001230163; NP_001230164; NP_001230165; NP_001293136; NP_001293137; NP_001317533; NP_001317534; NP_003190; NP_001335140; NP_001335141; NP_001335142; NP_001335143; NP_001335144; NP_001335145; NP_001335146; NP_001335147; NP_001335148; NP_001335149; NP_001356501; NP_001356502; NP_001356503; NP_001356504; NP_001356505; NP_001356506; NP_001356507; NP_001356508; NP_001356509; NP_001356510; NP_001356511; NP_001356512; NP_001356513; NP_001356514; NP_001356515; NP_001356496; NP_001356497; NP_001356498; NP_001356499; NP_001356500
	n/a
	Wikidata
Ver/Editar Humano

Fator de transcrição 4 (TCF-4) também conhecido como fator de transcrição de imunoglobulina 2 (ITF-2) é uma proteína que em humanos é codificada pelo gene TCF4 localizado no cromossomo 18q21.2.^[3]

Funções

As proteínas TCF4 atuam como fatores de transcrição que se ligam ao motivo mu-E5 / kappa-E2, que aumenta a imunoglobulina. TCF4 ativa a transcrição ligando-se à sequência E-box (5’-CANNTG-3 ’) encontrada geralmente no elemento iniciador do SSTR2-INR ou receptor 2 da somatostatina. Posteriormente, ele será encontrado na tireóide, no timo e nos rins, enquanto na idade adulta o TCF4 é encontrado nos linfócitos, músculos e sistema gastrointestinal.^[4]^[5]

Importância clínica

Mutações no TCF4 causam a síndrome de Pitt-Hopkins (PTHS). Essas mutações fazem com que as proteínas TCF4 não se liguem ao DNA adequadamente e controlem a diferenciação do sistema nervoso. Na maioria dos casos estudados, as mutações foram de novo, o que significa que foi uma nova mutação não encontrada em outros membros da família do paciente. Os sintomas comuns da síndrome de Pitt-Hopkins incluem boca larga, problemas gastrointestinais, atraso no desenvolvimento de habilidades motoras finas, problemas de fala e respiração, epilepsia e outros defeitos cerebrais.^[6]^[7]

Um estudo identificou o gene TCF4 como um regulador principal da esquizofrenia.^[8]

Referências

↑ «Doenças geneticamente associadas a TCF4 ver/editar referências no wikidata»
↑ «Human PubMed Reference:»
↑ Henthorn P, McCarrick-Walmsley R, Kadesch T (fevereiro de 1990). «Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor». Nucleic Acids Research. 18 (3). 678 páginas. PMC 333500 . PMID 2308860. doi:10.1093/nar/18.3.678
↑ de Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. (abril de 2009). «Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome». Human Mutation. 30 (4): 669–76. PMID 19235238. doi:10.1002/humu.20935
↑ Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R (dezembro de 1996). «The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene». The EMBO Journal. 15 (23): 6680–90. PMC 452492 . PMID 8978694
↑ Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, et al. (maio de 2007). «Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction». American Journal of Human Genetics. 80 (5): 988–93. PMC 1852736 . PMID 17436254. doi:10.1086/515582
↑ Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, et al. (maio de 2007). «Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)». American Journal of Human Genetics. 80 (5): 994–1001. PMC 1852727 . PMID 17436255. doi:10.1086/515583
↑ «Scientists recognize genes as master regulators in schizophrenia». Tech Explorist (em inglês). 16 de setembro de 2019. Consultado em 16 de setembro de 2019

Leitura adicional

Herbst A, Helferich S, Behrens A, Göke B, Kolligs FT (outubro de 2009). «The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1)». Biochemical and Biophysical Research Communications. 387 (4): 736–40. PMID 19635457. doi:10.1016/j.bbrc.2009.07.102
Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, Holter W, Rauch A, Zhuang Y, Reizis B (outubro de 2008). «Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development». Cell. 135 (1): 37–48. PMC 2631034 . PMID 18854153. doi:10.1016/j.cell.2008.09.016
Bain G, Murre C (abril de 1998). «The role of E-proteins in B- and T-lymphocyte development». Seminars in Immunology. 10 (2): 143–53. PMID 9618760. doi:10.1006/smim.1998.0116
Yerges LM, Klei L, Cauley JA, Roeder K, Kammerer CM, Moffett SP, et al. (dezembro de 2009). «High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men». Journal of Bone and Mineral Research. 24 (12): 2039–49. PMC 2791518 . PMID 19453261. doi:10.1359/jbmr.090524
Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (agosto de 2009). «Common polygenic variation contributes to risk of schizophrenia and bipolar disorder». Nature. 460 (7256): 748–52. PMC 3912837 . PMID 19571811. doi:10.1038/nature08185
Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, Ullmann R, Musante L, Ropers HH (agosto de 2008). «Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome». American Journal of Medical Genetics Part A. 146A (16): 2053–9. PMID 18627065. doi:10.1002/ajmg.a.32419
Herbst A, Bommer GT, Kriegl L, Jung A, Behrens A, Csanadi E, et al. (agosto de 2009). «ITF-2 is disrupted via allelic loss of chromosome 18q21, and ITF-2B expression is lost at the adenoma-carcinoma transition». Gastroenterology. 137 (2): 639–48, 648.e1-9. PMID 19394332. doi:10.1053/j.gastro.2009.04.049
Nagasawa M, Schmidlin H, Hazekamp MG, Schotte R, Blom B (setembro de 2008). «Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B». European Journal of Immunology. 38 (9): 2389–400. PMID 18792017. doi:10.1002/eji.200838470
Rosenfeld JA, Leppig K, Ballif BC, Thiese H, Erdie-Lalena C, Bawle E, Sastry S, Spence JE, Bandholz A, Surti U, Zonana J, Keller K, Meschino W, Bejjani BA, Torchia BS, Shaffer LG (novembro de 2009). «Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations». Genetics in Medicine. 11 (11): 797–805. PMID 19938247. doi:10.1097/GIM.0b013e3181bd38a9
Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. (agosto de 2009). «Common variants conferring risk of schizophrenia». Nature. 460 (7256): 744–7. PMC 3077530 . PMID 19571808. doi:10.1038/nature08186

Este artigo sobre Genética é um esboço. Você pode ajudar a Wikipédia expandindo-o.

[1] «Doenças geneticamente associadas a TCF4 ver/editar referências no wikidata»

[2] «Human PubMed Reference:»

[pmid2308860-3] Henthorn P, McCarrick-Walmsley R, Kadesch T (fevereiro de 1990). «Sequence of the cDNA encoding ITF-2, a positive-acting transcription factor». Nucleic Acids Research. 18 (3). 678 páginas. PMC 333500 . PMID 2308860. doi:10.1093/nar/18.3.678

[pmid19235238-4] Pontual L, Mathieu Y, Golzio C, Rio M, Malan V, Boddaert N, et al. (abril de 2009). «Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome». Human Mutation. 30 (4): 669–76. PMID 19235238. doi:10.1002/humu.20935

[pmid8978694-5] Pscherer A, Dörflinger U, Kirfel J, Gawlas K, Rüschoff J, Buettner R, Schüle R (dezembro de 1996). «The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene». The EMBO Journal. 15 (23): 6680–90. PMC 452492 . PMID 8978694

[pmid17436254-6] Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N, et al. (maio de 2007). «Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction». American Journal of Human Genetics. 80 (5): 988–93. PMC 1852736 . PMID 17436254. doi:10.1086/515582

[pmid17436255-7] Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, et al. (maio de 2007). «Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)». American Journal of Human Genetics. 80 (5): 994–1001. PMC 1852727 . PMID 17436255. doi:10.1086/515583

[8] «Scientists recognize genes as master regulators in schizophrenia». Tech Explorist (em inglês). 16 de setembro de 2019. Consultado em 16 de setembro de 2019

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