TISIDB

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus Nucleus, PML body Note=Recruited to PML body by PML.
Domain	PF13516 Leucine Rich repeat
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. 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).

> Gene Ontology [ TOP ]
Biological Process	GO:0010712 regulation of collagen metabolic process GO:0010713 negative regulation of collagen metabolic process GO:0032963 collagen metabolic process GO:0032964 collagen biosynthetic process GO:0032965 regulation of collagen biosynthetic process GO:0032966 negative regulation of collagen biosynthetic process GO:0034341 response to interferon-gamma GO:0044236 multicellular organism metabolic process GO:0044246 regulation of multicellular organismal metabolic process GO:0044252 negative regulation of multicellular organismal metabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0045341 MHC class I biosynthetic process GO:0045342 MHC class II biosynthetic process GO:0045343 regulation of MHC class I biosynthetic process GO:0045345 positive regulation of MHC class I biosynthetic process GO:0045346 regulation of MHC class II biosynthetic process GO:0045348 positive regulation of MHC class II biosynthetic process GO:0046677 response to antibiotic GO:0060333 interferon-gamma-mediated signaling pathway GO:0071346 cellular response to interferon-gamma
Molecular Function	GO:0003713 transcription coactivator activity GO:0005525 GTP binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor binding GO:0016746 transferase activity, transferring acyl groups GO:0019001 guanyl nucleotide binding GO:0032561 guanyl ribonucleotide binding GO:0033613 activating transcription factor binding
Cellular Component	GO:0016604 nuclear body GO:0016605 PML body

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04612 Antigen processing and presentation
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-877300: Interferon gamma signaling

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CIITA and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between CIITA and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16424052	Breast carcinoma	Promote immunity (T cell function); essential for immunotherapy	Tumor cells transduced with the MHC class II Transactivator and CD80 activate tumor-specific CD4+ T cells whether or not they are silenced for invariant chain. To determine if Ii expression affects presentation of MHC class II-restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii.

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CIITA in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CIITA in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.485	0.365
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.627	0.617
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.383	0.692
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.639	0.175
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.63	0.801
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.661	0.847
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.023	0.054
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.412	0.226
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.536	0.694
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.596	0.292
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.643	0.454
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.208	0.275

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CIITA in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CIITA. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CIITA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CIITA. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CIITA. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CIITA expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CIITA and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CIITA
Name	class II, major histocompatibility complex, transactivator
Aliases	NLRA; NLR family, acid domain containing; nucleotide-binding oligomerization domain, leucine rich repeat and ......
Chromosomal Location	16p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CIITA collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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