CIITA

CIITA
Identificadores
Nomes alternativos	CIITA
IDs externos	OMIM: 600005 HomoloGene: 207 GeneCards: CIITA
Doenças Geneticamente Relacionadas
	colite ulcerosa, bare lymphocyte syndrome 2
Ontologia genética
Função molecular	• transferase activity; • DNA binding; • nucleotide binding; • GO:0001105 transcription coactivator activity; • GTP binding; • kinase activity; • protein C-terminus binding; • GO:0001948, GO:0016582 ligação a proteínas plasmáticas; • acyltransferase activity; • ATP binding; • GO:0032403 protein-containing complex binding;
Componente celular	• PML body; • cariolinfa; • núcleo celular;
Processo biológico	• positive regulation of MHC class II biosynthetic process; • GO:0009373 regulation of transcription, DNA-templated; • response to interferon-gamma; • fosforilação; • interferon-gamma-mediated signaling pathway; • GO:1904576 response to antibiotic; • GO:1901227 negative regulation of transcription by RNA polymerase II; • transcription, DNA-templated; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 resposta imunitária; • GO:0045996 negative regulation of transcription, DNA-templated; • positive regulation of MHC class I biosynthetic process; • negative regulation of collagen biosynthetic process; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • inflammatory response;
	Sources:Amigo / QuickGO
Padrão de expressão RNA
	; ;
	Mais dados de referência de expressão
Ortólogos
	4261
	n/a
	ENSG00000179583
	n/a
	P33076
	n/a
NM_000246; NM_001286402; NM_001286403; NM_001379330; NM_001379331;
	NM_001379332; NM_001379333; NM_001379334
	n/a
NP_000237; NP_001273331; NP_001273332; NP_001366259; NP_001366260;
	NP_001366261; NP_001366262; NP_001366263
	n/a
	Wikidata
Ver/Editar Humano

O CIITA é um gene humano que codifica uma proteína chamada transativador do principal complexo de histocompatibilidade de classe II.^[3]^[4] Mutações nesse gene são responsáveis pela síndrome dos linfócitos nus, na qual o sistema imunológico está seriamente comprometido e não pode combater efetivamente a infecção.^[3] O rearranjo cromossômico do CIITA está envolvido na patogênese do linfoma de Hodgkin e linfoma primário do mediastino de células B.^[5]

Função

O RNAm do CIITA só pode ser detectado em linhas de células e tecidos positivos para a classe II do sistema de antígeno leucocitário humano (ALH). Esta distribuição de tecido altamente restrita sugere que a expressão dos genes ALH classe II está em grande parte sob o controle de CIITA.^[6] No entanto, o CIITA não parece se ligar diretamente ao DNA.^[6] Em vez disso, o CIITA funciona através da ativação do fator de transcrição RFX5.^[7] Portanto, o CIITA é classificado como um coativador de transcrição.

A proteína CIITA contém um domínio de ativação transcricional ácido, 4 LRRs (repetições ricas em leucina) e um domínio de ligação a GTP.^[8] A proteína usa a ligação GTP para facilitar seu próprio transporte para o núcleo.^[9] Uma vez no núcleo, a proteína atua como um regulador positivo da transcrição de genes do complexo principal de histocompatibilidade classe II e é freqüentemente referida como o "fator de controle principal" para a expressão desses genes.^[10]^[11]

Interações

Foi demonstrado que o CIITA interage com:

MAPK1,^[12]
Coativador de receptores nucleares 1,^[13]
RFX5,^[7]^[14]
RFXANK,^[14]^[15]
XPO1^[12]^[16]
ZXDC.^[17]^[18]

Referências

↑ «Doenças geneticamente associadas a CIITA ver/editar referências no wikidata»
↑ «Human PubMed Reference:»
↑ ^a ^b Steimle V, Otten LA, Zufferey M, Mach B. «Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)». Cell. 75: 135–46. PMID 8402893. doi:10.1016/S0092-8674(05)80090-X
↑ Murphy, Kenneth (1 de junho de 2014). Imunobiologia de Janeway - 8.ed. [S.l.]: Artmed Editora
↑ Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD. «MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers». Nature. 471: 377–81. PMC 3902849. PMID 21368758. doi:10.1038/nature09754
↑ ^a ^b Mach B, Steimle V, Reith W. «MHC class II-deficient combined immunodeficiency: a disease of gene regulation». Immunological Reviews. 138: 207–21. PMID 8070816. doi:10.1111/j.1600-065X.1994.tb00853.x
↑ ^a ^b Scholl T, Mahanta SK, Strominger JL. «Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5». Proceedings of the National Academy of Sciences of the United States of America. 94: 6330–4. PMC 21049. PMID 9177217. doi:10.1073/pnas.94.12.6330
↑ Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS. «Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250». Molecular Cell. 7: 105–15. PMID 11172716. doi:10.1016/S1097-2765(01)00159-9
↑ Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP. «GTP binding by class II transactivator: role in nuclear import». Science. 285: 1402–5. PMID 10464099. doi:10.1126/science.285.5432.1402
↑ Harton JA, Ting JP. «Class II transactivator: mastering the art of major histocompatibility complex expression». Molecular and Cellular Biology. 20: 6185–94. PMC 86093. PMID 10938095. doi:10.1128/MCB.20.17.6185-6194.2000
↑ LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W. «Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes». European Journal of Immunology. 34: 1513–25. PMID 15162420. doi:10.1002/eji.200424964
↑ ^a ^b Voong LN, Slater AR, Kratovac S, Cressman DE (abril de 2008). «Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator». The Journal of Biological Chemistry. 283 (14): 9031–9. PMC 2431044. PMID 18245089. doi:10.1074/jbc.M706487200
↑ Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (dezembro de 2003). «Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways». Molecular Endocrinology. 17 (12): 2509–18. PMID 12933903. doi:10.1210/me.2002-0439
↑ ^a ^b Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V (outubro de 2000). «CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome, and MHC class II gene transactivation». Molecular and Cellular Biology. 20 (20): 7716–25. PMC 86349. PMID 11003667. doi:10.1128/mcb.20.20.7716-7725.2000
↑ Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM (agosto de 2001). «Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome». Molecular and Cellular Biology. 21 (16): 5566–76. PMC 87278. PMID 11463838. doi:10.1128/MCB.21.16.5566-5576.2001
↑ Raval A, Weissman JD, Howcroft TK, Singer DS (janeiro de 2003). «The GTP-binding domain of class II transactivator regulates its nuclear export». Journal of Immunology. 170 (2): 922–30. PMID 12517958. doi:10.4049/jimmunol.170.2.922
↑ Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD (janeiro de 2007). «ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription». Molecular Immunology. 44 (4): 311–21. PMC 1624858. PMID 16600381. doi:10.1016/j.molimm.2006.02.029
↑ Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD (junho de 2007). «The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription». Journal of Molecular Biology. 369 (5): 1175–87. PMC 1963517. PMID 17493635. doi:10.1016/j.jmb.2007.04.033

Ligações externas

MeSH MHC+class+II+transactivator+protein

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

[2] «Human PubMed Reference:»

[pmid8402893-3] Steimle V, Otten LA, Zufferey M, Mach B. «Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)». Cell. 75: 135–46. PMID 8402893. doi:10.1016/S0092-8674(05)80090-X

[4] Murphy, Kenneth (1 de junho de 2014). Imunobiologia de Janeway - 8.ed. [S.l.]: Artmed Editora

[pmid21368758-5] Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, Johnson NA, Zhao Y, Telenius A, Neriah SB, McPherson A, Meissner B, Okoye UC, Diepstra A, van den Berg A, Sun M, Leung G, Jones SJ, Connors JM, Huntsman DG, Savage KJ, Rimsza LM, Horsman DE, Staudt LM, Steidl U, Marra MA, Gascoyne RD. «MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers». Nature. 471: 377–81. PMC 3902849. PMID 21368758. doi:10.1038/nature09754

[pmid8070816-6] Mach B, Steimle V, Reith W. «MHC class II-deficient combined immunodeficiency: a disease of gene regulation». Immunological Reviews. 138: 207–21. PMID 8070816. doi:10.1111/j.1600-065X.1994.tb00853.x

[pmid9177217-7] Scholl T, Mahanta SK, Strominger JL. «Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5». Proceedings of the National Academy of Sciences of the United States of America. 94: 6330–4. PMC 21049. PMID 9177217. doi:10.1073/pnas.94.12.6330

[pmid11172716-8] Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS. «Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250». Molecular Cell. 7: 105–15. PMID 11172716. doi:10.1016/S1097-2765(01)00159-9

[pmid10464099-9] Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP. «GTP binding by class II transactivator: role in nuclear import». Science. 285: 1402–5. PMID 10464099. doi:10.1126/science.285.5432.1402

[pmid10938095-10] Harton JA, Ting JP. «Class II transactivator: mastering the art of major histocompatibility complex expression». Molecular and Cellular Biology. 20: 6185–94. PMC 86093. PMID 10938095. doi:10.1128/MCB.20.17.6185-6194.2000

[pmid15162420-11] LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W. «Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes». European Journal of Immunology. 34: 1513–25. PMID 15162420. doi:10.1002/eji.200424964

[pmid18245089-12] Voong LN, Slater AR, Kratovac S, Cressman DE (abril de 2008). «Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator». The Journal of Biological Chemistry. 283 (14): 9031–9. PMC 2431044. PMID 18245089. doi:10.1074/jbc.M706487200

[pmid12933903-13] Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (dezembro de 2003). «Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways». Molecular Endocrinology. 17 (12): 2509–18. PMID 12933903. doi:10.1210/me.2002-0439

[pmid11003667-14] Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V (outubro de 2000). «CIITA leucine-rich repeats control nuclear localization, in vivo recruitment to the major histocompatibility complex (MHC) class II enhanceosome, and MHC class II gene transactivation». Molecular and Cellular Biology. 20 (20): 7716–25. PMC 86349. PMID 11003667. doi:10.1128/mcb.20.20.7716-7725.2000

[pmid11463838-15] Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM (agosto de 2001). «Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome». Molecular and Cellular Biology. 21 (16): 5566–76. PMC 87278. PMID 11463838. doi:10.1128/MCB.21.16.5566-5576.2001

[pmid12517958-16] Raval A, Weissman JD, Howcroft TK, Singer DS (janeiro de 2003). «The GTP-binding domain of class II transactivator regulates its nuclear export». Journal of Immunology. 170 (2): 922–30. PMID 12517958. doi:10.4049/jimmunol.170.2.922

[17] Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD (janeiro de 2007). «ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription». Molecular Immunology. 44 (4): 311–21. PMC 1624858. PMID 16600381. doi:10.1016/j.molimm.2006.02.029

[18] Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD (junho de 2007). «The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription». Journal of Molecular Biology. 369 (5): 1175–87. PMC 1963517. PMID 17493635. doi:10.1016/j.jmb.2007.04.033

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