Izvorni kôd stranice CIITA

{{Infokutija gen}}
'''CIITA''' je ljudski [[gen]] sa p kraka [[hromosom 16|hromosoma 16]],  koji kodira [[protein]] zvani '''transaktivator klase II [[glavni kompleks histokompatibilnosti|glavog kompleksa histokompatibilnosti]]'''.<ref name="pmid8402893">{{cite journal | vauthors = Steimle V, Otten LA, Zufferey M, Mach B | title = Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome) | journal = Cell | volume = 75 | issue = 1 | pages = 135–46 | date = Oct 1993 | pmid = 8402893 | doi = 10.1016/S0092-8674(05)80090-X | s2cid = 30276144 }}</ref>  Mutacije ovog gena su odgovorne za [[sindrom golih limfocita]] u kojem je [[imunski sistem]] ozbiljno ugrožen i ne može se efikasno boriti protiv [[infekcije]].<ref name="pmid8402893"/> Hromosomskim preuređenjem CIITA-e uključeno je u patogenezu [[Hodgkinov limfom|Hodgkinovog limfoma]] i [[primarni medijastinski B-ćelijski limfom|primarnog medijastinskog B-ćelijskog limfoma]].<ref name="pmid21368758">{{cite journal | vauthors = 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 | title = MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers | journal = Nature | volume = 471 | issue = 7338 | pages = 377–81 | date = Mar 2011 | pmid = 21368758 | pmc = 3902849 | doi = 10.1038/nature09754 | bibcode = 2011Natur.471..377S }}</ref>
 
==Aminokiselinska sekvenca== 
Dužina [[polipeptid]]nog lanca je  1.130  [[aminokiselina]], a [[dalton (jedinica)|molekulska težina]]  123.514 [[dalton (jedinica)|Da]].
{{legenda aminokiselina}} 
<table style="font-family:monospace;">
<tr style="text-align:right;"><th>10</th><th></th><th>20</th><th></th><th>30</th><th></th><th>40</th><th></th><th>50</th></tr>
<tr style="background-color: #eee;"><td>MRCLAPRPAG</td><td style="background-color: #f9f9f9;"></td><td>SYLSEPQGSS</td><td style="background-color: #f9f9f9;"></td><td>QCATMELGPL</td><td style="background-color: #f9f9f9;"></td><td>EGGYLELLNS</td><td style="background-color: #f9f9f9;"></td><td>DADPLCLYHF</td></tr>
<tr style="background-color: #eee;"><td>YDQMDLAGEE</td><td style="background-color: #f9f9f9;"></td><td>EIELYSEPDT</td><td style="background-color: #f9f9f9;"></td><td>DTINCDQFSR</td><td style="background-color: #f9f9f9;"></td><td>LLCDMEGDEE</td><td style="background-color: #f9f9f9;"></td><td>TREAYANIAE</td></tr>
<tr style="background-color: #eee;"><td>LDQYVFQDSQ</td><td style="background-color: #f9f9f9;"></td><td>LEGLSKDIFK</td><td style="background-color: #f9f9f9;"></td><td>HIGPDEVIGE</td><td style="background-color: #f9f9f9;"></td><td>SMEMPAEVGQ</td><td style="background-color: #f9f9f9;"></td><td>KSQKRPFPEE</td></tr>
<tr style="background-color: #eee;"><td>LPADLKHWKP</td><td style="background-color: #f9f9f9;"></td><td>AEPPTVVTGS</td><td style="background-color: #f9f9f9;"></td><td>LLVRPVSDCS</td><td style="background-color: #f9f9f9;"></td><td>TLPCLPLPAL</td><td style="background-color: #f9f9f9;"></td><td>FNQEPASGQM</td></tr>
<tr style="background-color: #eee;"><td>RLEKTDQIPM</td><td style="background-color: #f9f9f9;"></td><td>PFSSSSLSCL</td><td style="background-color: #f9f9f9;"></td><td>NLPEGPIQFV</td><td style="background-color: #f9f9f9;"></td><td>PTISTLPHGL</td><td style="background-color: #f9f9f9;"></td><td>WQISEAGTGV</td></tr>
<tr style="background-color: #eee;"><td>SSIFIYHGEV</td><td style="background-color: #f9f9f9;"></td><td>PQASQVPPPS</td><td style="background-color: #f9f9f9;"></td><td>GFTVHGLPTS</td><td style="background-color: #f9f9f9;"></td><td>PDRPGSTSPF</td><td style="background-color: #f9f9f9;"></td><td>APSATDLPSM</td></tr>
<tr style="background-color: #eee;"><td>PEPALTSRAN</td><td style="background-color: #f9f9f9;"></td><td>MTEHKTSPTQ</td><td style="background-color: #f9f9f9;"></td><td>CPAAGEVSNK</td><td style="background-color: #f9f9f9;"></td><td>LPKWPEPVEQ</td><td style="background-color: #f9f9f9;"></td><td>FYRSLQDTYG</td></tr>
<tr style="background-color: #eee;"><td>AEPAGPDGIL</td><td style="background-color: #f9f9f9;"></td><td>VEVDLVQARL</td><td style="background-color: #f9f9f9;"></td><td>ERSSSKSLER</td><td style="background-color: #f9f9f9;"></td><td>ELATPDWAER</td><td style="background-color: #f9f9f9;"></td><td>QLAQGGLAEV</td></tr>
<tr style="background-color: #eee;"><td>LLAAKEHRRP</td><td style="background-color: #f9f9f9;"></td><td>RETRVIAVLG</td><td style="background-color: #f9f9f9;"></td><td>KAGQGKSYWA</td><td style="background-color: #f9f9f9;"></td><td>GAVSRAWACG</td><td style="background-color: #f9f9f9;"></td><td>RLPQYDFVFS</td></tr>
<tr style="background-color: #eee;"><td>VPCHCLNRPG</td><td style="background-color: #f9f9f9;"></td><td>DAYGLQDLLF</td><td style="background-color: #f9f9f9;"></td><td>SLGPQPLVAA</td><td style="background-color: #f9f9f9;"></td><td>DEVFSHILKR</td><td style="background-color: #f9f9f9;"></td><td>PDRVLLILDG</td></tr>
<tr style="background-color: #eee;"><td>FEELEAQDGF</td><td style="background-color: #f9f9f9;"></td><td>LHSTCGPAPA</td><td style="background-color: #f9f9f9;"></td><td>EPCSLRGLLA</td><td style="background-color: #f9f9f9;"></td><td>GLFQKKLLRG</td><td style="background-color: #f9f9f9;"></td><td>CTLLLTARPR</td></tr>
<tr style="background-color: #eee;"><td>GRLVQSLSKA</td><td style="background-color: #f9f9f9;"></td><td>DALFELSGFS</td><td style="background-color: #f9f9f9;"></td><td>MEQAQAYVMR</td><td style="background-color: #f9f9f9;"></td><td>YFESSGMTEH</td><td style="background-color: #f9f9f9;"></td><td>QDRALTLLRD</td></tr>
<tr style="background-color: #eee;"><td>RPLLLSHSHS</td><td style="background-color: #f9f9f9;"></td><td>PTLCRAVCQL</td><td style="background-color: #f9f9f9;"></td><td>SEALLELGED</td><td style="background-color: #f9f9f9;"></td><td>AKLPSTLTGL</td><td style="background-color: #f9f9f9;"></td><td>YVGLLGRAAL</td></tr>
<tr style="background-color: #eee;"><td>DSPPGALAEL</td><td style="background-color: #f9f9f9;"></td><td>AKLAWELGRR</td><td style="background-color: #f9f9f9;"></td><td>HQSTLQEDQF</td><td style="background-color: #f9f9f9;"></td><td>PSADVRTWAM</td><td style="background-color: #f9f9f9;"></td><td>AKGLVQHPPR</td></tr>
<tr style="background-color: #eee;"><td>AAESELAFPS</td><td style="background-color: #f9f9f9;"></td><td>FLLQCFLGAL</td><td style="background-color: #f9f9f9;"></td><td>WLALSGEIKD</td><td style="background-color: #f9f9f9;"></td><td>KELPQYLALT</td><td style="background-color: #f9f9f9;"></td><td>PRKKRPYDNW</td></tr>
<tr style="background-color: #eee;"><td>LEGVPRFLAG</td><td style="background-color: #f9f9f9;"></td><td>LIFQPPARCL</td><td style="background-color: #f9f9f9;"></td><td>GALLGPSAAA</td><td style="background-color: #f9f9f9;"></td><td>SVDRKQKVLA</td><td style="background-color: #f9f9f9;"></td><td>RYLKRLQPGT</td></tr>
<tr style="background-color: #eee;"><td>LRARQLLELL</td><td style="background-color: #f9f9f9;"></td><td>HCAHEAEEAG</td><td style="background-color: #f9f9f9;"></td><td>IWQHVVQELP</td><td style="background-color: #f9f9f9;"></td><td>GRLSFLGTRL</td><td style="background-color: #f9f9f9;"></td><td>TPPDAHVLGK</td></tr>
<tr style="background-color: #eee;"><td>ALEAAGQDFS</td><td style="background-color: #f9f9f9;"></td><td>LDLRSTGICP</td><td style="background-color: #f9f9f9;"></td><td>SGLGSLVGLS</td><td style="background-color: #f9f9f9;"></td><td>CVTRFRAALS</td><td style="background-color: #f9f9f9;"></td><td>DTVALWESLQ</td></tr>
<tr style="background-color: #eee;"><td>QHGETKLLQA</td><td style="background-color: #f9f9f9;"></td><td>AEEKFTIEPF</td><td style="background-color: #f9f9f9;"></td><td>KAKSLKDVED</td><td style="background-color: #f9f9f9;"></td><td>LGKLVQTQRT</td><td style="background-color: #f9f9f9;"></td><td>RSSSEDTAGE</td></tr>
<tr style="background-color: #eee;"><td>LPAVRDLKKL</td><td style="background-color: #f9f9f9;"></td><td>EFALGPVSGP</td><td style="background-color: #f9f9f9;"></td><td>QAFPKLVRIL</td><td style="background-color: #f9f9f9;"></td><td>TAFSSLQHLD</td><td style="background-color: #f9f9f9;"></td><td>LDALSENKIG</td></tr>
<tr style="background-color: #eee;"><td>DEGVSQLSAT</td><td style="background-color: #f9f9f9;"></td><td>FPQLKSLETL</td><td style="background-color: #f9f9f9;"></td><td>NLSQNNITDL</td><td style="background-color: #f9f9f9;"></td><td>GAYKLAEALP</td><td style="background-color: #f9f9f9;"></td><td>SLAASLLRLS</td></tr>
<tr style="background-color: #eee;"><td>LYNNCICDVG</td><td style="background-color: #f9f9f9;"></td><td>AESLARVLPD</td><td style="background-color: #f9f9f9;"></td><td>MVSLRVMDVQ</td><td style="background-color: #f9f9f9;"></td><td>YNKFTAAGAQ</td><td style="background-color: #f9f9f9;"></td><td>QLAASLRRCP</td></tr>
<tr style="background-color: #eee;"><td>HVETLAMWTP</td><td style="background-color: #f9f9f9;"></td><td>TIPFSVQEHL</td><td style="background-color: #f9f9f9;"></td><td>QQQDSRISLR</td></tr>
</table>

== Funkcija ==
CIITA [[informacijska RNK|iRNK]] može se detektovati samo u [[ljudski leukocitni antigen|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.<ref name="pmid8070816">{{cite journal | vauthors = Mach B, Steimle V, Reith W | title = MHC class II-deficient combined immunodeficiency: a disease of gene regulation | journal = Immunological Reviews | volume = 138 | issue = 1 | pages = 207–21 | date = Apr 1994 | pmid = 8070816 | doi = 10.1111/j.1600-065X.1994.tb00853.x | s2cid = 28869787 }}</ref>  Međutim, izgleda da se CIITA ne vezuje direktno za DNK.<ref name="pmid8070816"/> Umjesto toga CIITA funkcionira kroz aktivaciju [[transkripcijski faktor|transkripcijskog faktora]] [[RFX5]].<ref name="pmid9177217">{{cite journal | vauthors = Scholl T, Mahanta SK, Strominger JL | title = Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 12 | pages = 6330–4 | date = Jun 1997 | pmid = 9177217 | pmc = 21049 | doi = 10.1073/pnas.94.12.6330 | bibcode = 1997PNAS...94.6330S | doi-access = free }}</ref> Stoga je CIITA klasifikovan kao transkripcijski [[koaktivator (genetika)|koaktivator]].
 
CIITA protein sadrži kiseli domenski [[aktivator (genetika)|aktivator transkripcije]], 4 LRRs ([[ponavljanje bogato leucinom|leucinom bogatih ponavljanja]]) i [[guanozin-trifosfat|GTP]] vezujući domen.<ref name="pmid11172716">{{cite journal | vauthors = Raval A, Howcroft TK, Weissman JD, Kirshner S, Zhu XS, Yokoyama K, Ting J, Singer DS | title = Transcriptional coactivator, CIITA, is an acetyltransferase that bypasses a promoter requirement for TAF(II)250 | journal = Molecular Cell | volume = 7 | issue = 1 | pages = 105–15 | date = Jan 2001 | pmid = 11172716 | doi = 10.1016/S1097-2765(01)00159-9 | doi-access = free }}</ref> Protein koristi GTP vezivanje kako bi olakšao vlastiti transport u jedro.<ref name="pmid10464099">{{cite journal | vauthors = Harton JA, Cressman DE, Chin KC, Der CJ, Ting JP | title = GTP binding by class II transactivator: role in nuclear import | journal = Science | volume = 285 | issue = 5432 | pages = 1402–5 | date = Aug 1999 | pmid = 10464099 | doi = 10.1126/science.285.5432.1402 }}</ref> Jednom u jedru, protein djeluje kao pozitivan regulator [[transkripcija (genetika)|transkripcija gena]], [[MHC|glavnog kompleksa histokompatibilnosti]] klase II i često se naziva "master kontrolni faktor" za ekspresiju ovih gena.<ref name="pmid10938095">{{cite journal | vauthors = Harton JA, Ting JP | title = Class II transactivator: mastering the art of major histocompatibility complex expression | journal = Molecular and Cellular Biology | volume = 20 | issue = 17 | pages = 6185–94 | date = Sep 2000 | pmid = 10938095 | pmc = 86093 | doi = 10.1128/MCB.20.17.6185-6194.2000 }}</ref><ref name="pmid15162420">{{cite journal | vauthors = LeibundGut-Landmann S, Waldburger JM, Krawczyk M, Otten LA, Suter T, Fontana A, Acha-Orbea H, Reith W | title = Mini-review: Specificity and expression of CIITA, the master regulator of MHC class II genes | journal = European Journal of Immunology | volume = 34 | issue = 6 | pages = 1513–25 | date = Jun 2004 | pmid = 15162420 | doi = 10.1002/eji.200424964 | s2cid = 21226976 }}</ref>
 
Ekspresiju CIITA inducira [[interferon gama]], možda potpomognut drugim signalima.<ref name="pmid32966619">{{cite journal | vauthors = Heuberger C, Pott J, Maloy KJ | title = Why do intestinal epithelial cells express MHC class II? | journal = Immunology | volume = 162 | issue=4 | pages = 357–367 |date=2021 | doi = 10.1111/imm.13270 | pmc =7968399 | pmid = 32966619}}</ref> [[MHC klasa II|MHC&nbsp;II]] ekspresija u ćelijama [[Crijevo|crijevnog epitela]] je pojačana pod [[upala|upalom]].<ref name="pmid32966619" />

== Interakcije ==
Pokazalo se da CIITA [[interakcija protein-protein|interraguje]] sa:
{{div col|colwidth=20em}}
* [[MAPK1]],<ref name = pmid18245089>{{cite journal | vauthors = Voong LN, Slater AR, Kratovac S, Cressman DE | title = Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator | journal = The Journal of Biological Chemistry | volume = 283 | issue = 14 | pages = 9031–9 | date = Apr 2008 | pmid = 18245089 | pmc = 2431044 | doi = 10.1074/jbc.M706487200 | doi-access = free }}</ref>
* [[Koaktivator 1 jedearnog receptora]],<ref name = pmid12933903>{{cite journal | vauthors = Tzortzakaki E, Spilianakis C, Zika E, Kretsovali A, Papamatheakis J | title = Steroid receptor coactivator 1 links the steroid and interferon gamma response pathways | journal = Molecular Endocrinology | volume = 17 | issue = 12 | pages = 2509–18 | date = Dec 2003 | pmid = 12933903 | doi = 10.1210/me.2002-0439 | doi-access = free }}</ref>
* [[RFX5]],<ref name = pmid9177217 /><ref name = pmid11003667>{{cite journal | vauthors = Hake SB, Masternak K, Kammerbauer C, Janzen C, Reith W, Steimle V | title = 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 | journal = Molecular and Cellular Biology | volume = 20 | issue = 20 | pages = 7716–25 | date = Oct 2000 | pmid = 11003667 | pmc = 86349 | doi =  10.1128/mcb.20.20.7716-7725.2000}}</ref>
* [[RFXANK]],<ref name = pmid11003667/><ref name = pmid11463838>{{cite journal | vauthors = Nekrep N, Geyer M, Jabrane-Ferrat N, Peterlin BM | title = Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome | journal = Molecular and Cellular Biology | volume = 21 | issue = 16 | pages = 5566–76 | date = Aug 2001 | pmid = 11463838 | pmc = 87278 | doi = 10.1128/MCB.21.16.5566-5576.2001 }}</ref>
* [[XPO1]],<ref name = pmid18245089/><ref name = pmid12517958>{{cite journal | vauthors = Raval A, Weissman JD, Howcroft TK, Singer DS | title = The GTP-binding domain of class II transactivator regulates its nuclear export | journal = Journal of Immunology | volume = 170 | issue = 2 | pages = 922–30 | date = Jan 2003 | pmid = 12517958 | doi =  10.4049/jimmunol.170.2.922| doi-access = free }}</ref>  i
* [[ZXDC]].<ref>{{cite journal | vauthors = Al-Kandari W, Jambunathan S, Navalgund V, Koneni R, Freer M, Parimi N, Mudhasani R, Fontes JD | title = ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription | journal = Molecular Immunology | volume = 44 | issue = 4 | pages = 311–21 | date = Jan 2007 | pmid = 16600381 | pmc = 1624858 | doi = 10.1016/j.molimm.2006.02.029 }}</ref><ref>{{cite journal | vauthors = Al-Kandari W, Koneni R, Navalgund V, Aleksandrova A, Jambunathan S, Fontes JD | title = The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription | journal = Journal of Molecular Biology | volume = 369 | issue = 5 | pages = 1175–87 | date = Jun 2007 | pmid = 17493635 | pmc = 1963517 | doi = 10.1016/j.jmb.2007.04.033 }}</ref>
{{Div col end}}
 
== Također pogledajte ==
* [[MHC klasa II]]
{{-}}
 
== Reference ==
{{Reflist|33em}}
 
== Vanjski linkovi ==
* {{MeshName|MHC+class+II+transactivator+protein}}
* {{UCSC gene info|CIITA}}
 
{{NLM content}}

[[Kategorija:LRR proteini]]
[[Kategorija:NOD receptori]]
[[Kategorija:Geni na hromosomu 16]]
[[Kategorija:Ljudski proteini]]
[[Kategorija:Proteomika]]