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P33076 (C2TA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
MHC class II transactivator

Short name=CIITA
Gene names
Name:CIITA
Synonyms:MHC2TA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1130 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. No DNA binding of in vitro translated CIITA was detected. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both. Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter. Ref.5 Ref.6

Subunit structure

Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2) Ref.5 Ref.6 Ref.7

Subcellular location

Nucleus. NucleusPML body. Note: Recruited to PML body by PML. Ref.7

Involvement in disease

Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.8 Ref.9 Ref.11

Sequence similarities

Contains 4 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
SCID
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionActivator
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

cellular response to electrical stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

immune response

Traceable author statement Ref.1. Source: ProtInc

inflammatory response

Inferred from electronic annotation. Source: Ensembl

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

negative regulation of collagen biosynthetic process

Inferred by curator PubMed 19041327. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19041327. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19041327. Source: BHF-UCL

positive regulation of MHC class I biosynthetic process

Inferred from direct assay PubMed 20639463. Source: BHF-UCL

positive regulation of MHC class II biosynthetic process

Inferred by curator PubMed 9171108. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20639463. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 19041327. Source: BHF-UCL

response to antibiotic

Inferred from direct assay PubMed 107465. Source: MGI

response to interferon-gamma

Inferred from direct assay PubMed 19041327. Source: BHF-UCL

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from direct assay Ref.7. Source: UniProtKB

cell surface

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

activating transcription factor binding

Inferred from physical interaction PubMed 9171108. Source: BHF-UCL

protein C-terminus binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein complex binding

Inferred from direct assay Ref.5. Source: UniProtKB

transcription coactivator activity

Traceable author statement Ref.2. Source: ProtInc

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19041327. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11301130MHC class II transactivator
PRO_0000089241

Regions

Domain414 – 724311NACHT
Repeat985 – 100824LRR 1
Repeat1016 – 103722LRR 2
Repeat1045 – 106622LRR 3
Repeat1073 – 109321LRR 4
Nucleotide binding420 – 4278ATP Potential
Compositional bias52 – 13786Asp/Glu-rich (acidic)

Natural variations

Natural variant451L → V.
Corresponds to variant rs2229317 [ dbSNP | Ensembl ].
VAR_029270
Natural variant1201K → IE in BLS2.
VAR_005127
Natural variant1741R → G. Ref.1 Ref.2
Corresponds to variant rs8046121 [ dbSNP | Ensembl ].
VAR_047907
Natural variant4691L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. Ref.9
VAR_015551
Natural variant5001G → A. Ref.1 Ref.2
Corresponds to variant rs4774 [ dbSNP | Ensembl ].
VAR_005128
Natural variant6581A → G.
Corresponds to variant rs2229319 [ dbSNP | Ensembl ].
VAR_015552
Natural variant7811S → L.
Corresponds to variant rs13330686 [ dbSNP | Ensembl ].
VAR_060104
Natural variant7821V → A.
Corresponds to variant rs13336804 [ dbSNP | Ensembl ].
VAR_057711
Natural variant9001Q → R. Ref.1 Ref.2
Corresponds to variant rs7197779 [ dbSNP | Ensembl ].
VAR_047908
Natural variant940 – 96324Missing in BLS2.
VAR_005129
Natural variant9621F → S in BLS2. Ref.8
VAR_015553
Natural variant964 – 99128Missing in BLS2.
VAR_015554
Natural variant10271Missing in BLS2. Ref.11
VAR_015555

Sequences

Sequence LengthMass (Da)Tools
P33076 [UniParc].

Last modified January 11, 2011. Version 3.
Checksum: 7A61CAA4F3FFECE0

FASTA1,130123,514
        10         20         30         40         50         60 
MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF YDQMDLAGEE 

        70         80         90        100        110        120 
EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE LDQYVFQDSQ LEGLSKDIFK 

       130        140        150        160        170        180 
HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE LPADLKHWKP AEPPTVVTGS LLVRPVSDCS 

       190        200        210        220        230        240 
TLPCLPLPAL FNQEPASGQM RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL 

       250        260        270        280        290        300 
WQISEAGTGV SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM 

       310        320        330        340        350        360 
PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG AEPAGPDGIL 

       370        380        390        400        410        420 
VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV LLAAKEHRRP RETRVIAVLG 

       430        440        450        460        470        480 
KAGQGKSYWA GAVSRAWACG RLPQYDFVFS VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA 

       490        500        510        520        530        540 
DEVFSHILKR PDRVLLILDG FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG 

       550        560        570        580        590        600 
CTLLLTARPR GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD 

       610        620        630        640        650        660 
RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL DSPPGALAEL 

       670        680        690        700        710        720 
AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR AAESELAFPS FLLQCFLGAL 

       730        740        750        760        770        780 
WLALSGEIKD KELPQYLALT PRKKRPYDNW LEGVPRFLAG LIFQPPARCL GALLGPSAAA 

       790        800        810        820        830        840 
SVDRKQKVLA RYLKRLQPGT LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL 

       850        860        870        880        890        900 
TPPDAHVLGK ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ 

       910        920        930        940        950        960 
QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE LPAVRDLKKL 

       970        980        990       1000       1010       1020 
EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG DEGVSQLSAT FPQLKSLETL 

      1030       1040       1050       1060       1070       1080 
NLSQNNITDL GAYKLAEALP SLAASLLRLS LYNNCICDVG AESLARVLPD MVSLRVMDVQ 

      1090       1100       1110       1120       1130 
YNKFTAAGAQ QLAASLRRCP HVETLAMWTP TIPFSVQEHL QQQDSRISLR 

« Hide

References

« Hide 'large scale' references
[1]"Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or bare lymphocyte syndrome)."
Steimle V., Otten L.A., Zufferey M., Mach B.
Cell 75:135-146(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS BLS2 LYS-120 DEL ILE-GLU INS AND 940-THR--ALA-963 DEL, VARIANTS GLY-174; ALA-500 AND ARG-900.
[2]"Activation of class II MHC genes requires both the X box region and the class II transactivator (CIITA)."
Riley J.L., Westerheide S.D., Price J.A., Brown J.A., Boss J.M.
Immunity 2:533-543(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLY-174; ALA-500 AND ARG-900.
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription."
Al-Kandari W., Koneni R., Navalgund V., Aleksandrova A., Jambunathan S., Fontes J.D.
J. Mol. Biol. 369:1175-1187(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZXDA AND ZXDC.
[6]"ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene transcription."
Al-Kandari W., Jambunathan S., Navalgund V., Koneni R., Freer M., Parimi N., Mudhasani R., Fontes J.D.
Mol. Immunol. 44:311-321(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZXDC.
[7]"PML promotes MHC class II gene expression by stabilizing the class II transactivator."
Ulbricht T., Alzrigat M., Horch A., Reuter N., von Mikecz A., Steimle V., Schmitt E., Kraemer O.H., Stamminger T., Hemmerich P.
J. Cell Biol. 199:49-63(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PML.
[8]"Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA."
Quan V., Towey M., Sacks S., Kelly A.P.
Immunogenetics 49:957-963(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BLS2 GROUP A SER-962.
[9]"Mutation in the class II trans-activator leading to a mild immunodeficiency."
Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., Fischer A., Lisowska-Grospierre B.
J. Immunol. 167:1787-1794(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BLS2 GROUP A PRO-469.
[10]Erratum
Wiszniewski W., Fondaneche M.-C., Le Deist F., Kanariou M., Selz F., Brousse N., Steimle V., Barbieri G., Alcaide-Loridan C., Charron D., Fischer A., Lisowska-Grospierre B.
J. Immunol. 169:607-607(2002)
[11]"Three novel mutations of the CIITA gene in MHC class II-deficient patients with a severe immunodeficiency."
Dziembowska M., Fondaneche M.-C., Vedrenne J., Barbieri G., Wiszniewski W., Picard C., Cant A.J., Steimle V., Charron D., Alcaide-Loridan C., Fischer A., Lisowska-Grospierre B.
Immunogenetics 53:821-829(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BLS2 GROUP A 964-LEU--ASP-991 DEL AND ILE-1027 DEL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X74301 mRNA. Translation: CAA52354.1.
U18259 mRNA. Translation: AAA88861.1.
AC133065 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85169.1.
CH471112 Genomic DNA. Translation: EAW85172.1.
PIRA48843.
RefSeqNP_000237.2. NM_000246.3.
UniGeneHs.701991.

3D structure databases

ProteinModelPortalP33076.
SMRP33076. Positions 944-1120.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110416. 19 interactions.
IntActP33076. 3 interactions.
STRING9606.ENSP00000316328.

PTM databases

PhosphoSiteP33076.

Polymorphism databases

DMDM317373472.

Proteomic databases

PaxDbP33076.
PRIDEP33076.

Protocols and materials databases

DNASU4261.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324288; ENSP00000316328; ENSG00000179583.
GeneID4261.
KEGGhsa:4261.
UCSCuc002dag.2. human.

Organism-specific databases

CTD4261.
GeneCardsGC16P010879.
HGNCHGNC:7067. CIITA.
HPACAB016084.
MIM209920. phenotype.
600005. gene.
neXtProtNX_P33076.
Orphanet572. Immunodeficiency by defective expression of HLA class 2.
PharmGKBPA30795.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG269671.
HOGENOMHOG000107439.
HOVERGENHBG000174.
KOK08060.
OMAQKRPFPE.
OrthoDBEOG7P5T07.
PhylomeDBP33076.
TreeFamTF352118.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP33076.
BgeeP33076.
CleanExHS_CIITA.
GenevestigatorP33076.

Family and domain databases

InterProIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR008095. MHC_II_transact.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF12799. LRR_4. 1 hit.
[Graphical view]
PRINTSPR01719. MHCIIACTVATR.
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCIITA.
GenomeRNAi4261.
NextBio16805.
PROP33076.
SOURCESearch...

Entry information

Entry nameC2TA_HUMAN
AccessionPrimary (citable) accession number: P33076
Secondary accession number(s): D3DUG0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM