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CIITA

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CIITA
Identifikatori
AliasiCIITA
Vanjski ID-jeviOMIM: 600005 MGI: 108445 HomoloGene: 207 GeneCards: CIITA
Lokacija gena (čovjek)
Hromosom 16 (čovjek)
Hrom.Hromosom 16 (čovjek)[1]
Hromosom 16 (čovjek)
Genomska lokacija za CIITA
Genomska lokacija za CIITA
Bend16p13.13Početak10,866,222 bp[1]
Kraj10,943,021 bp[1]
Lokacija gena (miš)
Hromosom 16 (miš)
Hrom.Hromosom 16 (miš)[2]
Hromosom 16 (miš)
Genomska lokacija za CIITA
Genomska lokacija za CIITA
Bend16|16 A1Početak10,297,923 bp[2]
Kraj10,346,282 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• aktivnost sa transferazom
• vezivanje sa DNK
• nucleotide binding
• GO:0001105 transcription coactivator activity
• GTP binding
• kinase activity
• protein C-terminus binding
• GO:0001948, GO:0016582 vezivanje za proteine
• acyltransferase activity
• ATP binding
• GO:0032403 protein-containing complex binding
Ćelijska komponenta• PML body
• nukleoplazma
• jedro
Biološki proces• positive regulation of MHC class II biosynthetic process
• GO:0009373 regulation of transcription, DNA-templated
• response to interferon-gamma
• Fosforilacija
• 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 Imuni odgovor
• 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
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

4261

12265

Ensembl

ENSG00000179583

ENSMUSG00000022504

UniProt

P33076

P79621

RefSeq (mRNK)
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 (bjelančevina)
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

Lokacija (UCSC)Chr 16: 10.87 – 10.94 MbChr 16: 10.3 – 10.35 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

CIITA je ljudski gen sa p kraka hromosoma 16, koji kodira protein zvani transaktivator klase II glavog kompleksa histokompatibilnosti.[5] Mutacije ovog gena su odgovorne za sindrom golih limfocita u kojem je imunski sistem ozbiljno ugrožen i ne može se efikasno boriti protiv infekcije.[5] Hromosomskim preuređenjem CIITA-e uključeno je u patogenezu Hodgkinovog limfoma i primarnog medijastinskog B-ćelijskog limfoma.[6]

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 1.130 aminokiselina, a molekulska težina 123.514 Da.

1020304050
MRCLAPRPAGSYLSEPQGSSQCATMELGPLEGGYLELLNSDADPLCLYHF
YDQMDLAGEEEIELYSEPDTDTINCDQFSRLLCDMEGDEETREAYANIAE
LDQYVFQDSQLEGLSKDIFKHIGPDEVIGESMEMPAEVGQKSQKRPFPEE
LPADLKHWKPAEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQM
RLEKTDQIPMPFSSSSLSCLNLPEGPIQFVPTISTLPHGLWQISEAGTGV
SSIFIYHGEVPQASQVPPPSGFTVHGLPTSPDRPGSTSPFAPSATDLPSM
PEPALTSRANMTEHKTSPTQCPAAGEVSNKLPKWPEPVEQFYRSLQDTYG
AEPAGPDGILVEVDLVQARLERSSSKSLERELATPDWAERQLAQGGLAEV
LLAAKEHRRPRETRVIAVLGKAGQGKSYWAGAVSRAWACGRLPQYDFVFS
VPCHCLNRPGDAYGLQDLLFSLGPQPLVAADEVFSHILKRPDRVLLILDG
FEELEAQDGFLHSTCGPAPAEPCSLRGLLAGLFQKKLLRGCTLLLTARPR
GRLVQSLSKADALFELSGFSMEQAQAYVMRYFESSGMTEHQDRALTLLRD
RPLLLSHSHSPTLCRAVCQLSEALLELGEDAKLPSTLTGLYVGLLGRAAL
DSPPGALAELAKLAWELGRRHQSTLQEDQFPSADVRTWAMAKGLVQHPPR
AAESELAFPSFLLQCFLGALWLALSGEIKDKELPQYLALTPRKKRPYDNW
LEGVPRFLAGLIFQPPARCLGALLGPSAAASVDRKQKVLARYLKRLQPGT
LRARQLLELLHCAHEAEEAGIWQHVVQELPGRLSFLGTRLTPPDAHVLGK
ALEAAGQDFSLDLRSTGICPSGLGSLVGLSCVTRFRAALSDTVALWESLQ
QHGETKLLQAAEEKFTIEPFKAKSLKDVEDLGKLVQTQRTRSSSEDTAGE
LPAVRDLKKLEFALGPVSGPQAFPKLVRILTAFSSLQHLDLDALSENKIG
DEGVSQLSATFPQLKSLETLNLSQNNITDLGAYKLAEALPSLAASLLRLS
LYNNCICDVGAESLARVLPDMVSLRVMDVQYNKFTAAGAQQLAASLRRCP
HVETLAMWTPTIPFSVQEHLQQQDSRISLR

Funkcija

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CIITA iRNK može se detektovati samo u ljudskom leukocitnzm antigenima (HLA) sistema klase II-pozitivne ćelijske linije i tkiva. Ova vrlo ograničena distribucija tkiva sugerira da je ekspresija gena HLA klase II u velikoj mjeri pod kontrolom CIITA-e.[7] Međutim, izgleda da se CIITA ne vezuje direktno za DNK.[7] Umjesto toga CIITA funkcionira kroz aktivaciju transkripcijskog faktora RFX5.[8] Stoga je CIITA klasifikovan kao transkripcijski koaktivator.

CIITA protein sadrži kiseli domenski aktivator transkripcije, 4 LRRs (leucinom bogatih ponavljanja) i GTP vezujući domen.[9] Protein koristi GTP vezivanje kako bi olakšao vlastiti transport u jedro.[10] Jednom u jedru, protein djeluje kao pozitivan regulator transkripcija gena, glavnog kompleksa histokompatibilnosti klase II i često se naziva "master kontrolni faktor" za ekspresiju ovih gena.[11][12]

Ekspresiju CIITA inducira interferon gama, možda potpomognut drugim signalima.[13] MHC II ekspresija u ćelijama crijevnog epitela je pojačana pod upalom.[13]

Interakcije

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Pokazalo se da CIITA interraguje sa:

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000179583 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022504 - Ensembl, maj 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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.

Vanjski linkovi

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Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

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