CIITA

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Class II, major histocompatibility complex, transactivator
Identifiers
Symbols CIITA ; C2TA; CIITAIV; MHC2TA; NLRA
External IDs OMIM600005 MGI108445 HomoloGene207 GeneCards: CIITA Gene
EC number 2.7.11.1
RNA expression pattern
PBB GE CIITA 211884 s at tn.png
PBB GE CIITA 210925 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4261 12265
Ensembl ENSG00000179583 ENSMUSG00000022504
UniProt P33076 P79621
RefSeq (mRNA) NM_000246 NM_001243760
RefSeq (protein) NP_000237 NP_001230689
Location (UCSC) Chr 16:
10.97 – 11.03 Mb
Chr 16:
10.49 – 10.53 Mb
PubMed search [1] [2]

CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator.[1] Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection.[1] Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma.[2]

Function[edit]

CIITA mRNA can only be detected in human leukocyte antigen (HLA) system class II-positive cell lines and tissues. This highly restricted tissue distribution suggests that expression of HLA class II genes is to a large extent under the control of CIITA.[3] However CIITA does not appear to directly bind to DNA.[3] Instead CIITA functions through activation of the transcription factor RFX5.[4] Hence CIITA is classified as a transcriptional coactivator.

The CIITA protein contains an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain.[5] The protein uses GTP binding to facilitate its own transport into the nucleus.[6] Once in the nucleus, the protein acts as a positive regulator of class II major histocompatibility complex gene transcription, and is often referred to as the "master control factor" for the expression of these genes.[7][8]

Interactions[edit]

CIITA has been shown to interact with RFX5,[4][9] MAPK1,[10] XPO1,[10][11] Nuclear receptor coactivator 1,[12] RFXANK[9][13] and ZXDC.[14][15]

See also[edit]

References[edit]

  1. ^ a b Steimle V, Otten LA, Zufferey M, Mach B (October 1993). "Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)". Cell 75 (1): 135–46. doi:10.1016/S0092-8674(05)80090-X. PMID 8402893. 
  2. ^ 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 (March 2011). "MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers". Nature 471 (7338): 377–81. doi:10.1038/nature09754. PMID 21368758. 
  3. ^ a b Mach B, Steimle V, Reith W (April 1994). "MHC class II-deficient combined immunodeficiency: a disease of gene regulation". Immunol. Rev. 138 (1): 207–21. doi:10.1111/j.1600-065X.1994.tb00853.x. PMID 8070816. 
  4. ^ a b Scholl T, Mahanta SK, Strominger JL (June 1997). "Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5". Proc. Natl. Acad. Sci. U.S.A. 94 (12): 6330–4. doi:10.1073/pnas.94.12.6330. PMC 21049. PMID 9177217. 
  5. ^ Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS' (January 2001). "Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250". Mol. Cell 7 (1): 105–15. doi:10.1016/S1097-2765(01)00159-9. PMID 11172716. 
  6. ^ Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP (August 1999). "GTP binding by class II transactivator: role in nuclear import". Science 285 (5432): 1402–5. doi:10.1126/science.285.5432.1402. PMID 10464099. 
  7. ^ Harton JA, Ting JP (September 2000). "Class II transactivator: mastering the art of major histocompatibility complex expression". Mol. Cell. Biol. 20 (17): 6185–94. doi:10.1128/MCB.20.17.6185-6194.2000. PMC 86093. PMID 10938095. 
  8. ^ LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W (June 2004). "Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes". Eur. J. Immunol. 34 (6): 1513–25. doi:10.1002/eji.200424964. PMID 15162420. 
  9. ^ a b Hake, S B; Masternak K; Kammerbauer C; Janzen C; Reith W; Steimle V (October 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". Mol. Cell. Biol. (UNITED STATES) 20 (20): 7716–25. doi:10.1128/MCB.20.20.7716-7725.2000. ISSN 0270-7306. PMC 86349. PMID 11003667. 
  10. ^ a b Voong, Lilien N; Slater Allison R; Kratovac Sebila; Cressman Drew E (April 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". J. Biol. Chem. (United States) 283 (14): 9031–9. doi:10.1074/jbc.M706487200. ISSN 0021-9258. PMC 2431044. PMID 18245089. 
  11. ^ Raval, Aparna; Weissman Jocelyn D; Howcroft T Kevin; Singer Dinah S (January 2003). "The GTP-binding domain of class II transactivator regulates its nuclear export". J. Immunol. (United States) 170 (2): 922–30. doi:10.4049/jimmunol.170.2.922. ISSN 0022-1767. PMID 12517958. 
  12. ^ Tzortzakaki, Eleni; Spilianakis Charalambos; Zika Eleni; Kretsovali Androniki; Papamatheakis Joseph (December 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Mol. Endocrinol. (United States) 17 (12): 2509–18. doi:10.1210/me.2002-0439. ISSN 0888-8809. PMID 12933903. 
  13. ^ Nekrep, N; Geyer M; Jabrane-Ferrat N; Peterlin B M (August 2001). "Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome". Mol. Cell. Biol. (United States) 21 (16): 5566–76. doi:10.1128/MCB.21.16.5566-5576.2001. ISSN 0270-7306. PMC 87278. PMID 11463838. 
  14. ^ Al-Kandari, W.; Jambunathan, S.; Navalgund, V.; Koneni, R.; Freer, M.; Parimi, N.; Mudhasani, R.; Fontes, J. D. (2007). "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription". Molecular Immunology 44 (4): 311–321. doi:10.1016/j.molimm.2006.02.029. PMC 1624858. PMID 16600381.  edit
  15. ^ Al-Kandari, W.; Koneni, R.; Navalgund, V.; Aleksandrova, A.; Jambunathan, S.; Fontes, J. D. (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): 1175–1187. doi:10.1016/j.jmb.2007.04.033. PMC 1963517. PMID 17493635.  edit

External links[edit]


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