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Protein

MHC class II transactivator

Gene

CIITA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Also mediates enhanced MHC class I transcription; the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes. Exhibits intrinsic GTP-stimulated acetyltransferase activity. Exhibits serine/threonine protein kinase activity: can phosphorylate the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (in vitro).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi420 – 427GTP8

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • ATP binding Source: UniProtKB-KW
  • GTP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB-KW
  • protein complex binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • transcription coactivator activity Source: ProtInc
  • transcription regulatory region DNA binding Source: BHF-UCL
  • transferase activity, transferring acyl groups Source: UniProtKB-KW

GO - Biological processi

  • immune response Source: ProtInc
  • interferon-gamma-mediated signaling pathway Source: Reactome
  • negative regulation of collagen biosynthetic process Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of MHC class I biosynthetic process Source: BHF-UCL
  • positive regulation of MHC class II biosynthetic process Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • response to antibiotic Source: MGI
  • response to interferon-gamma Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Acyltransferase, Kinase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000179583-MONOMER.
ReactomeiR-HSA-877300. Interferon gamma signaling.
SIGNORiP33076.

Names & Taxonomyi

Protein namesi
Recommended name:
MHC class II transactivator (EC:2.3.1.-, EC:2.7.11.1)
Short name:
CIITA
Gene namesi
Name:CIITA
Synonyms:MHC2TA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:7067. CIITA.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • PML body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Bare lymphocyte syndrome 2 (BLS2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:209920
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_005127120K → IE in BLS2. 1
Natural variantiVAR_015551469L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. 1 Publication1
Natural variantiVAR_005129940 – 963Missing in BLS2. 1 PublicationAdd BLAST24
Natural variantiVAR_015553962F → S in BLS2. 1 Publication1
Natural variantiVAR_015554964 – 991Missing in BLS2. Add BLAST28
Natural variantiVAR_0155551027Missing in BLS2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi420 – 421Missing : Strongly reduces GTP-binding and abolishes transactivation at MHC promoters. 1 Publication2
Mutagenesisi561D → A: Strongly reduces GTP-binding and abolishes transactivation at MHC promoters. 1 Publication1

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi4261.
MalaCardsiCIITA.
MIMi209920. phenotype.
OpenTargetsiENSG00000179583.
Orphaneti572. Immunodeficiency by defective expression of HLA class 2.
PharmGKBiPA30795.

Polymorphism and mutation databases

BioMutaiCIITA.
DMDMi317373472.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000892411 – 1130MHC class II transactivatorAdd BLAST1130

Post-translational modificationi

Autophosphorylated, affecting interaction with TAF7.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP33076.
PaxDbiP33076.
PeptideAtlasiP33076.
PRIDEiP33076.

PTM databases

iPTMnetiP33076.
PhosphoSitePlusiP33076.

Expressioni

Gene expression databases

BgeeiENSG00000179583.
CleanExiHS_CIITA.
ExpressionAtlasiP33076. baseline and differential.

Organism-specific databases

HPAiCAB016084.

Interactioni

Subunit structurei

Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SIRT1Q96EB64EBI-1538819,EBI-1802965
ZXDAP981684EBI-1538819,EBI-1538980
ZXDCQ2QGD76EBI-1538819,EBI-1538838

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • protein complex binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110416. 24 interactors.
IntActiP33076. 3 interactors.
STRINGi9606.ENSP00000316328.

Structurei

3D structure databases

ProteinModelPortaliP33076.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini414 – 724NACHTPROSITE-ProRule annotationAdd BLAST311
Repeati985 – 1008LRR 1Add BLAST24
Repeati1016 – 1037LRR 2Add BLAST22
Repeati1045 – 1066LRR 3Add BLAST22
Repeati1073 – 1093LRR 4Add BLAST21

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni94 – 132Required for acetyltransferase activityAdd BLAST39

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi52 – 137Asp/Glu-rich (acidic)Add BLAST86

Domaini

The acetyltransferase domain is necessary for activation of both class I and class II transcription.
The GTP-binding motif doesn't confer GTPase activity but promotes nuclear localization.

Sequence similaritiesi

Contains 4 LRR (leucine-rich) repeats.Curated
Contains 1 NACHT domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000107439.
HOVERGENiHBG000174.
InParanoidiP33076.
KOiK08060.
PhylomeDBiP33076.
TreeFamiTF352118.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR008095. MHC_II_transact.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF13516. LRR_6. 3 hits.
[Graphical view]
PRINTSiPR01719. MHCIIACTVATR.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P33076-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRCLAPRPAG SYLSEPQGSS QCATMELGPL EGGYLELLNS DADPLCLYHF
60 70 80 90 100
YDQMDLAGEE EIELYSEPDT DTINCDQFSR LLCDMEGDEE TREAYANIAE
110 120 130 140 150
LDQYVFQDSQ LEGLSKDIFK HIGPDEVIGE SMEMPAEVGQ KSQKRPFPEE
160 170 180 190 200
LPADLKHWKP AEPPTVVTGS LLVRPVSDCS TLPCLPLPAL FNQEPASGQM
210 220 230 240 250
RLEKTDQIPM PFSSSSLSCL NLPEGPIQFV PTISTLPHGL WQISEAGTGV
260 270 280 290 300
SSIFIYHGEV PQASQVPPPS GFTVHGLPTS PDRPGSTSPF APSATDLPSM
310 320 330 340 350
PEPALTSRAN MTEHKTSPTQ CPAAGEVSNK LPKWPEPVEQ FYRSLQDTYG
360 370 380 390 400
AEPAGPDGIL VEVDLVQARL ERSSSKSLER ELATPDWAER QLAQGGLAEV
410 420 430 440 450
LLAAKEHRRP RETRVIAVLG KAGQGKSYWA GAVSRAWACG RLPQYDFVFS
460 470 480 490 500
VPCHCLNRPG DAYGLQDLLF SLGPQPLVAA DEVFSHILKR PDRVLLILDG
510 520 530 540 550
FEELEAQDGF LHSTCGPAPA EPCSLRGLLA GLFQKKLLRG CTLLLTARPR
560 570 580 590 600
GRLVQSLSKA DALFELSGFS MEQAQAYVMR YFESSGMTEH QDRALTLLRD
610 620 630 640 650
RPLLLSHSHS PTLCRAVCQL SEALLELGED AKLPSTLTGL YVGLLGRAAL
660 670 680 690 700
DSPPGALAEL AKLAWELGRR HQSTLQEDQF PSADVRTWAM AKGLVQHPPR
710 720 730 740 750
AAESELAFPS FLLQCFLGAL WLALSGEIKD KELPQYLALT PRKKRPYDNW
760 770 780 790 800
LEGVPRFLAG LIFQPPARCL GALLGPSAAA SVDRKQKVLA RYLKRLQPGT
810 820 830 840 850
LRARQLLELL HCAHEAEEAG IWQHVVQELP GRLSFLGTRL TPPDAHVLGK
860 870 880 890 900
ALEAAGQDFS LDLRSTGICP SGLGSLVGLS CVTRFRAALS DTVALWESLQ
910 920 930 940 950
QHGETKLLQA AEEKFTIEPF KAKSLKDVED LGKLVQTQRT RSSSEDTAGE
960 970 980 990 1000
LPAVRDLKKL EFALGPVSGP QAFPKLVRIL TAFSSLQHLD LDALSENKIG
1010 1020 1030 1040 1050
DEGVSQLSAT FPQLKSLETL NLSQNNITDL GAYKLAEALP SLAASLLRLS
1060 1070 1080 1090 1100
LYNNCICDVG AESLARVLPD MVSLRVMDVQ YNKFTAAGAQ QLAASLRRCP
1110 1120 1130
HVETLAMWTP TIPFSVQEHL QQQDSRISLR
Length:1,130
Mass (Da):123,514
Last modified:January 11, 2011 - v3
Checksum:i7A61CAA4F3FFECE0
GO
Isoform 2 (identifier: P33076-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-210: AEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPM → V
     887-930: AALSDTVALW...KAKSLKDVED → WGEGLGRDIL...RVGQNGFSPF
     931-1128: Missing.

Show »
Length:883
Mass (Da):96,429
Checksum:iC2D59921C3D5F6C5
GO
Isoform 3 (identifier: P33076-3) [UniParc]FASTAAdd to basket
Also known as: hCIITA'

The sequence of this isoform differs from the canonical sequence as follows:
     161-210: AEPPTVVTGSLLVRPVSDCSTLPCLPLPALFNQEPASGQMRLEKTDQIPM → V
     336-350: EPVEQFYRSLQDTYG → GLAWSPCLGLRPSLH
     351-885: Missing.

Note: Exhibits dominant-negative suppression of MHC class II gene expression.
Show »
Length:546
Mass (Da):59,641
Checksum:i95471F528074C11A
GO
Isoform 4 (identifier: P33076-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     887-930: AALSDTVALW...KAKSLKDVED → WGEGLGRDIL...RVGQNGFSPF
     931-1128: Missing.

Show »
Length:932
Mass (Da):101,661
Checksum:i1C9D9F9BF43DD142
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1020 – 1021LN → RS in ABK41930 (PubMed:12859996).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02927045L → V.Corresponds to variant rs2229317dbSNPEnsembl.1
Natural variantiVAR_005127120K → IE in BLS2. 1
Natural variantiVAR_047907174R → G.4 PublicationsCorresponds to variant rs8046121dbSNPEnsembl.1
Natural variantiVAR_015551469L → P in BLS2; mild immunodeficiency; has residual MHC class II trans activation activity. 1 Publication1
Natural variantiVAR_005128500G → A.3 PublicationsCorresponds to variant rs4774dbSNPEnsembl.1
Natural variantiVAR_015552658A → G.Corresponds to variant rs2229319dbSNPEnsembl.1
Natural variantiVAR_060104781S → L.Corresponds to variant rs13330686dbSNPEnsembl.1
Natural variantiVAR_057711782V → A.Corresponds to variant rs13336804dbSNPEnsembl.1
Natural variantiVAR_047908900Q → R.4 PublicationsCorresponds to variant rs7197779dbSNPEnsembl.1
Natural variantiVAR_005129940 – 963Missing in BLS2. 1 PublicationAdd BLAST24
Natural variantiVAR_015553962F → S in BLS2. 1 Publication1
Natural variantiVAR_015554964 – 991Missing in BLS2. Add BLAST28
Natural variantiVAR_0155551027Missing in BLS2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055099161 – 210AEPPT…DQIPM → V in isoform 2 and isoform 3. 2 PublicationsAdd BLAST50
Alternative sequenceiVSP_055100336 – 350EPVEQ…QDTYG → GLAWSPCLGLRPSLH in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_055101351 – 885Missing in isoform 3. 1 PublicationAdd BLAST535
Alternative sequenceiVSP_055102887 – 930AALSD…KDVED → WGEGLGRDILVLGINCGLGA KPSALWGPFSMQSSRVGQNG FSPF in isoform 2 and isoform 4. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_055103931 – 1128Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74301 mRNA. Translation: CAA52354.1.
U18259 mRNA. Translation: AAA88861.1.
U18288 mRNA. Translation: AAA88862.1.
AY084054 mRNA. Translation: AAM15723.1.
AF410154 mRNA. Translation: AAL04118.1.
EF064747 Genomic DNA. Translation: ABK41930.1.
AC133065 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85169.1.
CH471112 Genomic DNA. Translation: EAW85172.1.
CH471112 Genomic DNA. Translation: EAW85173.1.
CCDSiCCDS10544.1. [P33076-1]
CCDS66943.1. [P33076-3]
PIRiA48843.
RefSeqiNP_000237.2. NM_000246.3.
NP_001273332.1. NM_001286403.1. [P33076-3]
UniGeneiHs.592051.
Hs.701991.

Genome annotation databases

EnsembliENST00000381835; ENSP00000371257; ENSG00000179583. [P33076-3]
GeneIDi4261.
KEGGihsa:4261.
UCSCiuc002dak.5. human. [P33076-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

CIITAbase

CIITA mutation db

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74301 mRNA. Translation: CAA52354.1.
U18259 mRNA. Translation: AAA88861.1.
U18288 mRNA. Translation: AAA88862.1.
AY084054 mRNA. Translation: AAM15723.1.
AF410154 mRNA. Translation: AAL04118.1.
EF064747 Genomic DNA. Translation: ABK41930.1.
AC133065 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85169.1.
CH471112 Genomic DNA. Translation: EAW85172.1.
CH471112 Genomic DNA. Translation: EAW85173.1.
CCDSiCCDS10544.1. [P33076-1]
CCDS66943.1. [P33076-3]
PIRiA48843.
RefSeqiNP_000237.2. NM_000246.3.
NP_001273332.1. NM_001286403.1. [P33076-3]
UniGeneiHs.592051.
Hs.701991.

3D structure databases

ProteinModelPortaliP33076.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110416. 24 interactors.
IntActiP33076. 3 interactors.
STRINGi9606.ENSP00000316328.

PTM databases

iPTMnetiP33076.
PhosphoSitePlusiP33076.

Polymorphism and mutation databases

BioMutaiCIITA.
DMDMi317373472.

Proteomic databases

MaxQBiP33076.
PaxDbiP33076.
PeptideAtlasiP33076.
PRIDEiP33076.

Protocols and materials databases

DNASUi4261.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381835; ENSP00000371257; ENSG00000179583. [P33076-3]
GeneIDi4261.
KEGGihsa:4261.
UCSCiuc002dak.5. human. [P33076-1]

Organism-specific databases

CTDi4261.
DisGeNETi4261.
GeneCardsiCIITA.
HGNCiHGNC:7067. CIITA.
HPAiCAB016084.
MalaCardsiCIITA.
MIMi209920. phenotype.
600005. gene.
neXtProtiNX_P33076.
OpenTargetsiENSG00000179583.
Orphaneti572. Immunodeficiency by defective expression of HLA class 2.
PharmGKBiPA30795.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4308. Eukaryota.
ENOG410ZBX3. LUCA.
GeneTreeiENSGT00860000133673.
HOGENOMiHOG000107439.
HOVERGENiHBG000174.
InParanoidiP33076.
KOiK08060.
PhylomeDBiP33076.
TreeFamiTF352118.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000179583-MONOMER.
ReactomeiR-HSA-877300. Interferon gamma signaling.
SIGNORiP33076.

Miscellaneous databases

GeneWikiiCIITA.
GenomeRNAii4261.
PROiP33076.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179583.
CleanExiHS_CIITA.
ExpressionAtlasiP33076. baseline and differential.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR008095. MHC_II_transact.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF13516. LRR_6. 3 hits.
[Graphical view]
PRINTSiPR01719. MHCIIACTVATR.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiC2TA_HUMAN
AccessioniPrimary (citable) accession number: P33076
Secondary accession number(s): A0N0N9
, D3DUG0, E9PFE0, Q29675, Q8SNB8, Q96KL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 170 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.