TISIDB

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
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
Domain	PF11851 Domain of unknown function (DUF3371) PF00010 Helix-loop-helix DNA-binding domain PF15951 MITF/TFEB/TFEC/TFE3 N-terminus
Function	Transcription factor that regulates the expression of genes with essential roles in cell differentiation, proliferation and survival. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoters of target genes, such as BCL2 and tyrosinase (TYR). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium.

> Gene Ontology [ TOP ]
Biological Process	GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002761 regulation of myeloid leukocyte differentiation GO:0006352 DNA-templated transcription, initiation GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0030099 myeloid cell differentiation GO:0030316 osteoclast differentiation GO:0030318 melanocyte differentiation GO:0031334 positive regulation of protein complex assembly GO:0043254 regulation of protein complex assembly GO:0043473 pigmentation GO:0044089 positive regulation of cellular component biogenesis GO:0045637 regulation of myeloid cell differentiation GO:0045670 regulation of osteoclast differentiation GO:0048066 developmental pigmentation GO:0050900 leukocyte migration GO:0050931 pigment cell differentiation GO:0097529 myeloid leukocyte migration GO:0097531 mast cell migration GO:1902105 regulation of leukocyte differentiation GO:1903706 regulation of hemopoiesis GO:2000142 regulation of DNA-templated transcription, initiation GO:2000144 positive regulation of DNA-templated transcription, initiation
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04380 Osteoclast differentiation hsa04916 Melanogenesis
Reactome	R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-3232118: SUMOylation of transcription factors

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MITF 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

[ TOP ]

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

PMID	Cancer type	Relation to immunity	Evidence sentences
20099279	Melanoma	Promote immunity	MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes.
28096186	Melanoma	Inhibit immunity	In melanoma, low expression of the lineage survival oncogene microphthalmia-associated transcription factor (MITF) correlates with invasion, senescence, and drug resistance. Here we show that microenvironmental cues, including inflammation-mediated resistance to adoptive T-cell immunotherapy, transcriptionally repress MITF via ATF4 in response to inhibition of translation initiation factor eIF2B.

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
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

[ TOP ]

Statistical results of MITF 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	Second most enriched score: 0.54	Sensitive to T cell-mediated killing
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	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
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

[ TOP ]

Points in the above scatter plot represent the expression difference of MITF 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	0.631	0.345
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.328	0.597
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.113	0.955
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.421	0.308
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.497	0.774
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.33	0.873
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.248	0.602
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.454	0.839
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.07	0.978
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.44	0.714
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	-0.12	0.944
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.483	0.00151

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of MITF 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	0	0	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	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	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	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MITF. 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	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MITF. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MITF. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MITF. 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	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MITF expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MITF and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MITF
Name	microphthalmia-associated transcription factor
Aliases	MI; bHLHe32; homolog of mouse microphthalmia; WS2A; WS2; Waardenburg syndrome, type 2A; class E basic helix- ......
Chromosomal Location	3p14.1-p12.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MITF collected from DrugBank database.

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

Browse MITF