CIITA class II, major histocompatibility complex, transactivator [Homo sapiens (human)] - Gene

Summary

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Official Symbol: CIITAprovided by HGNC
Official Full Name: class II, major histocompatibility complex, transactivatorprovided by HGNC
Primary source: HGNC:7067
See related: HPRD:02475; MIM:600005
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: C2TA; NLRA; MHC2TA; CIITAIV
Summary: This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the "master control factor" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 16p13

Sequence :: Chromosome: 16; NC_000016.9 (10971055..11018840)

See CIITA in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

A significant correlation has been found in the genotype distribution for markers in CIITA (rs11074932 and rs3087456) and the development of type 1 diabetes in the Swedish cohort.
Title: Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes.
Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women
Title: Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women.
The genotypes and allele frequencies distribution of CIITA G-944C were different in the Jinuo, Dai and Aini minority populations. Polymorphism was closely associated with HBsAg carriage.
Title: [Study on the relationship between HBV infection and polymorphism of CIITA G-944C gene among Jinuo, Dai and Aini minority populations in Yunnan province].
PML is required for efficient IFN-gamma-induced MHC II gene transcription through regulation of the class II transactivator (CIITA)
Title: PML promotes MHC class II gene expression by stabilizing the class II transactivator.
The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement
Title: The MHC2TA gene polymorphisms are not associated with restenosis after coronary stenting in Mexican patients.
Our results support involvement of CIITA in RA, but imply that this is population dependent and that the aetiological variant is yet to be discovered.
Title: CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations.
The expressions of CTA and HLA-DR in Jurkat cells remarkably increase after heat shock.
Title: [Heat shock induced the expression of major histocompatibility complex class transactivator and human leukocyte antigen-DR in Jurkat cells].
ESAT6 could inhibit the expression of type I and type IV CIITA through different pathways
Title: ESAT6 differentially inhibits IFN-γ-inducible class II transactivator isoforms in both a TLR2-dependent and -independent manner.
The silencing of MHC II molecules in highly metastatic breast cancer cells is associated with distinct epigenetic modifications targeted specifically to the chromatin of CIITApIV.
Title: Dysregulated recruitment of the histone methyltransferase EZH2 to the class II transactivator (CIITA) promoter IV in breast cancer cells.
CIITA overexpression can also activate the expression of these genes, indicating that the immunoproteasome genes LMP2 and LMP7 can be activated by both CIITA dependent and CIITA independent pathways
Title: CIITA is silenced by epigenetic mechanisms that prevent the recruitment of transactivating factors in rhabdomyosarcoma cells.

Submit: New GeneRIF Correction See all (112)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

SCID due to absent class II HLA antigens

MIM: 209920

Genetic Testing Registry

NHGRI GWAS Catalog

Genome-wide association identifies multiple ulcerative colitis susceptibility loci.

Multiple common variants for celiac disease influencing immune gene expression.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle	PubMed
Envelope transmembrane glycoprotein gp41	env	CIITA-mediated enhancement of HIV-1 infection is gp120/gp41/CD4-dependent and occurs at the early steps in the infection cycle	PubMed
Gag, Pr55	gag	CIITA enhancement of HIV-1 Gag processing is through the viral protease activity	PubMed
	gag	Gag production is significantly increased by fusing HIV-1-infected CD4- and CXCR4-expressing rat fibroblasts with uninfected human T-, B-, and macrophage cell lines. This process is regulated by HP68 and MHC class II transactivator (CIITA)	PubMed
Tat, p14	tat	HIV-1 Tat inhibits CIITA by competing with CIITA for binding to P-TEFb	PubMed
	tat	The HLA class II transcriptional activator, CIITA, inhibits HIV-1 Tat and virus replication	PubMed
	tat	HIV-1 Tat downregulates expression of MHC class II genes in antigen-presenting cells (APC) by inhibiting the transactivator of MHC class II genes, CIITA	PubMed
capsid	gag	p24 production is significantly increased by fusing HIV-1-infected CD4- and CXCR4-expressing rat fibroblasts with uninfected human T-, B-, and macrophage cell lines. This process is regulated by HP68 and MHC class II transactivator (CIITA)	PubMed
pol	gag-pol	CIITA enhancement of HIV-1 Gag processing is through the viral protease activity, which results from increased levels of HIV-1 Gag-Pol by CIITA	PubMed
	gag-pol	CIITA increases the viral protease activity through increased HIV-1 Gag-Pol levels	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
AC133065.3	NP_001092.1	ACTB	BIND	PubMed	Beta-actin interacts with p-MHC2TA.
AC133065.3	NP_778224.1	HIST4H4	BIND	PubMed	H4 interacts with p-MHC2TA.
AC133065.3	NP_000928.1	POLR2A	BIND	PubMed	Pol II interacts with p-MHC2TA.
P33076	P56524	HDAC4	HPRD	PubMed
P33076	Q9UQL6	HDAC5	HPRD	PubMed
P33076	Q92831	KAT2B	HPRD	PubMed
P33076	Q15788	NCOA1	HPRD	PubMed
P33076	P25208	NFYB	HPRD	PubMed
P33076	P17612	PRKACA	HPRD	PubMed
P33076	P48382	RFX5	HPRD	PubMed
P33076	O14593	RFXANK	HPRD	PubMed
P33076	P49848	TAF6	HPRD	PubMed
P33076	O14980	XPO1	HPRD	PubMed
P33076	ZXD family zinc finger C	ZXDC	HPRD	PubMed
BioGRID:110416	BioGRID:107420	CDK1	BioGRID	PubMed	Biochemical Activity
BioGRID:110416	BioGRID:109187	GSK3B	BioGRID	PubMed	Biochemical Activity
BioGRID:110416	BioGRID:109214	GTF2B	BioGRID	PubMed	Reconstituted Complex
BioGRID:110416	BioGRID:109315	HDAC1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110416	BioGRID:109316	HDAC2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:110416	BioGRID:115106	HDAC4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:115331	HDAC5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:111580	MAPK1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:110416	BioGRID:111581	MAPK3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:114200	NCOA1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110416	BioGRID:111674	PSMC2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:111675	PSMC3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:111678	PSMC5	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110416	BioGRID:111925	RFX5	BioGRID	PubMed	Affinity Capture-Western; Far Western; Reconstituted Complex; Two-hybrid
BioGRID:110416	BioGRID:114180	RFXANK	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110416	BioGRID:116901	SIN3B	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110416	BioGRID:112481	SMARCA4	BioGRID	PubMed	Reconstituted Complex
BioGRID:110416	BioGRID:112743	TAF9	BioGRID	PubMed	Reconstituted Complex
BioGRID:110416	BioGRID:113348	XPO1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Pathways from BioSystems

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Antigen processing and presentation, organism-specific biosystem (from KEGG)
Antigen processing and presentation, organism-specific biosystem
Antigen processing and presentation
Antigen processing and presentation, conserved biosystem (from KEGG)
Antigen processing and presentation, conserved biosystem
Antigen processing and presentation
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Influenza A, organism-specific biosystem (from KEGG)
Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Influenza A, conserved biosystem (from KEGG)
Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Interferon Signaling, organism-specific biosystem (from REACTOME)
Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
Interferon gamma signaling, organism-specific biosystem (from REACTOME)
Interferon gamma signaling, organism-specific biosystemInterferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by ...
Primary immunodeficiency, organism-specific biosystem (from KEGG)
Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
Primary immunodeficiency, conserved biosystem (from KEGG)
Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
Toxoplasmosis, organism-specific biosystem (from KEGG)
Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
Toxoplasmosis, conserved biosystem (from KEGG)
Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
Tuberculosis, organism-specific biosystem (from KEGG)
Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
Tuberculosis, conserved biosystem (from KEGG)
Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
Type II interferon signaling (IFNG), organism-specific biosystem (from WikiPathways)
Type II interferon signaling (IFNG), organism-specific biosystemAdapted from Raza et al. (2008). This pathway is initiated by IFNG binding to its receptor and a subsequent phosphorylation cascade involving a number of the JAK and STAT family of proteins. Several ...

General gene information

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Markers

RH65129 (e-PCR)
- UniSTS:92434

GDB:434012 (e-PCR)
- UniSTS:157204

PMC83901P1 (e-PCR)
- UniSTS:273434

RH79123 (e-PCR)
- UniSTS:15185

PMC133907P1 (e-PCR)
- UniSTS:270680

PMC133907P2 (e-PCR)
- UniSTS:270681

PMC133907P3 (e-PCR)
- UniSTS:270682

PMC133907P4 (e-PCR)
- UniSTS:270683

PMC133916P2 (e-PCR)
- UniSTS:270687

D1S1423 (e-PCR)
- UniSTS:149619

PMC316580P8 (e-PCR)
- UniSTS:273015

SHGC-67307 (e-PCR)
- UniSTS:89991

SHGC-60649 (e-PCR)
- UniSTS:37017

PMC125964P1 (e-PCR)
- UniSTS:270517

STS-U18288 (e-PCR)
- UniSTS:29661

Genotypes

See CIITA SNP Geneview Report
See CIITA SNP Genotype Report
See CIITA SNP Variation Viewer Report

Homology

Homologs of the CIITA gene: The CIITA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
NOT DNA binding	TAS Traceable Author Statement more info	PubMed
activating transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein complex binding	IDA Inferred from Direct Assay more info	PubMed
transcription coactivator activity	TAS Traceable Author Statement more info	PubMed
transcription regulatory region DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cytokine-mediated signaling pathway	TAS Traceable Author Statement more info
immune response	TAS Traceable Author Statement more info	PubMed
interferon-gamma-mediated signaling pathway	TAS Traceable Author Statement more info
negative regulation of collagen biosynthetic process	IC Inferred by Curator more info	PubMed
negative regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of MHC class I biosynthetic process	IDA Inferred from Direct Assay more info
positive regulation of MHC class II biosynthetic process	IC Inferred by Curator more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info
positive regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
response to antibiotic	IDA Inferred from Direct Assay more info	PubMed
response to interferon-gamma	IDA Inferred from Direct Assay more info	PubMed
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
PML body	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: MHC class II transactivator

Names: MHC class II transactivator; NLR family, acid domain containing; MHC class II transactivator type III; nucleotide-binding oligomerization domain, leucine rich repeat and acid domain containing

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009628.1 RefSeqGene

Range

5001..52786

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_49

mRNA and Protein(s)

NM_000246.3 → NP_000237.2 MHC class II transactivator

Status: REVIEWED

Source sequence(s)

AC133065, AY699071, BE247223, X74301

Consensus CDS

CCDS10544.1

UniProtKB/Swiss-Prot

P33076

UniProtKB/TrEMBL

Q66X48

Conserved Domains (3) summary

cd00116
Location:789 – 1114
Blast Score: 540

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

pfam05729
Location:414 – 583
Blast Score: 434

NACHT; NACHT domain

pfam12799
Location:985 – 1030
Blast Score: 101

LRR_4; Leucine Rich repeats (2 copies)

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

10971055..11018840

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

10888898..10936424

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

10866960..10914751

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01006803.1 (17504..53658)	None
genomic	ABBA01006804.1	None
genomic	AC133065.3 (57114..104898)	None
genomic	AF000003.1	AAB92363.1
genomic	AMYH01007152.1 (305284..353075)	None
genomic	CH471112.2	EAW85168.1
		EAW85169.1
		EAW85170.1
		EAW85171.1
		EAW85172.1
		EAW85173.1
		EAW85174.1
genomic	U94773.1	AAC39714.1
mRNA	AF410154.1	AAL04118.1
mRNA	AY084054.1	AAM15723.1
mRNA	AY084055.1	AAM15724.1
mRNA	AY699071.1	AAU06586.1
mRNA	BE247223.1	None
mRNA	BM193016.1	None
mRNA	U18259.1	AAA88861.1
mRNA	U18288.1	AAA88862.1
mRNA	U31931.1	AAA92364.1
mRNA	X74301.1	CAA52354.1
other-genetic	BC172348.1	AAI72348.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P33076.3	GenPept	UniProtKB/Swiss-Prot:P33076

Additional links

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Additional Links

Epigenomics
MIM 600005
CIITAbase: Mutation registry for MHCII transactivating protein deficiency (previously known as MHC2TAbase) CIITAbase/
GeneTests for MIM: 600005
CIITA homepage - Mendelian genes CIITA
Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_46
UCSC UCSC
UniGene Hs.701991