CIITA

CIITA
Identifiers
Aliases	CIITA, C2TA, CIITAIV, MHC2TA, NLRA, class II, major histocompatibility complex, transactivator, class II major histocompatibility complex transactivator
External IDs	OMIM: 600005; MGI: 108445; HomoloGene: 207; GeneCards: CIITA; OMA:CIITA - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.13 Start 10,866,222 bp[1] End 10,943,021 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 A1 Start 10,297,923 bp[2] End 10,346,282 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte appendix spleen lymph node sural nerve gallbladder upper lobe of left lung blood apex of heart Top expressed in mesenteric lymph nodes spleen blood thymus lumbar subsegment of spinal cord subcutaneous adipose tissue duodenum morula right kidney lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity DNA binding nucleotide binding transcription coactivator activity GTP binding kinase activity protein C-terminus binding protein binding acyltransferase activity ATP binding protein-containing complex binding Cellular component PML body nucleoplasm nucleus Biological process positive regulation of MHC class II biosynthetic process regulation of transcription, DNA-templated response to interferon-gamma phosphorylation interferon-gamma-mediated signaling pathway response to antibiotic negative regulation of transcription by RNA polymerase II transcription, DNA-templated positive regulation of transcription, DNA-templated immune response negative regulation of transcription, DNA-templated positive regulation of MHC class I biosynthetic process negative regulation of collagen biosynthetic process positive regulation of transcription by RNA polymerase II inflammatory response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4261 12265 Ensembl ENSG00000179583 ENSMUSG00000022504 UniProt P33076 P79621 RefSeq (mRNA) NM_000246 NM_001286402 NM_001286403 NM_001379330 NM_001379331 NM_001379332 NM_001379333 NM_001379334 NM_001243760 NM_001243761 NM_007575 NM_001302618 NM_001302619 RefSeq (protein) NP_000237 NP_001273331 NP_001273332 NP_001366259 NP_001366260 NP_001366261 NP_001366262 NP_001366263 NP_001230689 NP_001230690 NP_001289547 NP_001289548 NP_031601 Location (UCSC) Chr 16: 10.87 – 10.94 Mb Chr 16: 10.3 – 10.35 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator.[5] Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and cannot effectively fight infection.[5] Chromosomal rearrangement of CIITA is involved in the pathogenesis of Hodgkin lymphoma and primary mediastinal B cell lymphoma.[6]

Function

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.[7] However, CIITA does not appear to directly bind to DNA.[7] Instead CIITA functions through activation of the transcription factor RFX5.[8] 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.[9] The protein uses GTP binding to facilitate its own transport into the nucleus.[10] 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.[11][12]

CIITA expression is induced by interferon gamma, possibly assisted by other signals.[13] MHC II expression in intestinal epithelial cells is upregulated under inflammation.[13]

Interactions

CIITA has been shown to interact with:

• MAPK1,[14]
• Nuclear receptor coactivator 1,[15]
• RFX5,[8][16]
• RFXANK,[16][17]
• XPO1,[14][18] and
• ZXDC.[19][20]

See also

• MHC class II

References

1. GRCh38: Ensembl release 89: ENSG00000179583 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022504 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Steimle V, Otten LA, Zufferey M, Mach B (Oct 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. S2CID 30276144.
6. 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 (Mar 2011). "MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers". Nature. 471 (7338): 377–81. Bibcode:2011Natur.471..377S. doi:10.1038/nature09754. PMC 3902849. PMID 21368758.
7. Mach B, Steimle V, Reith W (Apr 1994). "MHC class II-deficient combined immunodeficiency: a disease of gene regulation". Immunological Reviews. 138 (1): 207–21. doi:10.1111/j.1600-065X.1994.tb00853.x. PMID 8070816. S2CID 28869787.
8. Scholl T, Mahanta SK, Strominger JL (Jun 1997). "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 (12): 6330–4. Bibcode:1997PNAS...94.6330S. doi:10.1073/pnas.94.12.6330. PMC 21049. PMID 9177217.
9. Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS (Jan 2001). "Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250". Molecular Cell. 7 (1): 105–15. doi:10.1016/S1097-2765(01)00159-9. PMID 11172716.
10. Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP (Aug 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.
11. Harton JA, Ting JP (Sep 2000). "Class II transactivator: mastering the art of major histocompatibility complex expression". Molecular and Cellular Biology. 20 (17): 6185–94. doi:10.1128/MCB.20.17.6185-6194.2000. PMC 86093. PMID 10938095.
12. LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W (Jun 2004). "Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes". European Journal of Immunology. 34 (6): 1513–25. doi:10.1002/eji.200424964. PMID 15162420. S2CID 21226976.
13. Heuberger C, Pott J, Maloy KJ (2021). "Why do intestinal epithelial cells express MHC class II?". Immunology. 162 (4): 357–367. doi:10.1111/imm.13270. PMC 7968399. PMID 32966619.
14. Voong LN, Slater AR, Kratovac S, Cressman DE (Apr 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". The Journal of Biological Chemistry. 283 (14): 9031–9. doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089.
15. Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J (Dec 2003). "Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways". Molecular Endocrinology. 17 (12): 2509–18. doi:10.1210/me.2002-0439. PMID 12933903.
16. Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V (Oct 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. doi:10.1128/mcb.20.20.7716-7725.2000. PMC 86349. PMID 11003667.
17. Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM (Aug 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. doi:10.1128/MCB.21.16.5566-5576.2001. PMC 87278. PMID 11463838.
18. Raval A, Weissman JD, Howcroft TK, Singer DS (Jan 2003). "The GTP-binding domain of class II transactivator regulates its nuclear export". Journal of Immunology. 170 (2): 922–30. doi:10.4049/jimmunol.170.2.922. PMID 12517958.
19. Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD (Jan 2007). "ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription". Molecular Immunology. 44 (4): 311–21. doi:10.1016/j.molimm.2006.02.029. PMC 1624858. PMID 16600381.
20. Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD (Jun 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. doi:10.1016/j.jmb.2007.04.033. PMC 1963517. PMID 17493635.

External links

• MHC+class+II+transactivator+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CIITA genome location and CIITA gene details page in the UCSC Genome Browser.

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