TISIDB

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
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	Melanosome membrane Single-pass type I membrane protein Melanosome Note=Proper trafficking to melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
Domain	PF00264 Common central domain of tyrosinase
Function	Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA) (PubMed:8306979). Involved in regulating eumelanin and phaeomelanin levels.

> Gene Ontology [ TOP ]
Biological Process	GO:0002052 positive regulation of neuroblast proliferation GO:0006570 tyrosine metabolic process GO:0006582 melanin metabolic process GO:0006583 melanin biosynthetic process from tyrosine GO:0007405 neuroblast proliferation GO:0008544 epidermis development GO:0009072 aromatic amino acid family metabolic process GO:0010720 positive regulation of cell development GO:0017145 stem cell division GO:0018958 phenol-containing compound metabolic process GO:0019748 secondary metabolic process GO:0021846 cell proliferation in forebrain GO:0021847 ventricular zone neuroblast division GO:0021869 forebrain ventricular zone progenitor cell division GO:0021872 forebrain generation of neurons GO:0021873 forebrain neuroblast division GO:0030900 forebrain development GO:0036445 neuronal stem cell division GO:0042438 melanin biosynthetic process GO:0042440 pigment metabolic process GO:0043473 pigmentation GO:0044550 secondary metabolite biosynthetic process GO:0046148 pigment biosynthetic process GO:0046189 phenol-containing compound biosynthetic process GO:0048066 developmental pigmentation GO:0048103 somatic stem cell division GO:0050769 positive regulation of neurogenesis GO:0051962 positive regulation of nervous system development GO:0055057 neuroblast division GO:0061351 neural precursor cell proliferation GO:0072089 stem cell proliferation GO:0072091 regulation of stem cell proliferation GO:1901605 alpha-amino acid metabolic process GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process GO:1902692 regulation of neuroblast proliferation GO:2000177 regulation of neural precursor cell proliferation GO:2000179 positive regulation of neural precursor cell proliferation GO:2000648 positive regulation of stem cell proliferation
Molecular Function	GO:0004167 dopachrome isomerase activity GO:0005507 copper ion binding GO:0016853 isomerase activity GO:0016860 intramolecular oxidoreductase activity GO:0016863 intramolecular oxidoreductase activity, transposing C=C bonds
Cellular Component	GO:0030659 cytoplasmic vesicle membrane GO:0033162 melanosome membrane GO:0042470 melanosome GO:0045009 chitosome GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04916 Melanogenesis hsa00350 Tyrosine metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-5662702: Melanin biosynthesis R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DCT 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 DCT and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
10667570	Melanoma	Promote immunity	To further explore the linkage between immunotherapy and autoimmunity, we studied the response to vaccination with a related antigen, TRP-2. i.m. inoculation of plasmid DNA encoding murine trp-2 elicited antigen-specific CTLs that recognized the B16 mouse melanoma and protected the mice from challenge with tumor cells.
29249397	Melanoma	Promote immunity (T cell function); essential for immunotherapy	LCP mRNA vaccine encoding TRP2 elicited a robust antigen-specific cytotoxic T cell response and a humoral immune response in a C57BL/6 mouse model of B16F10 melanoma.
23633494	B16 Malignant Melanoma	Promote immunity	Simultaneous transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the VEGF receptor-2 (VEGFR2; KDR) that is overexpressed on tumor vasculature and T-cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared with treatment with either cell type alone or T cells coexpressing these two targeting molecules. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their antitumor potency.
24004885	Melanoma	Promote immunity (T cell function)	Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis. Compared with free Trp2 peptide/CpG, vaccination with LCP encapsulating p-Trp2 and CpG resulted in superior inhibition of tumor growth in both B16F10 subcutaneous and lung metastasis models. An IFN-γ production assay and in vivo CTL response study revealed that the improved efficacy was a result of a Trp2-specific immune response.
16061687	B16 Malignant Melanoma	Promote immunity	To exploit these properties for immunization purposes, we conjugated the melanoma antigen tyrosinase-related protein (TRP)-2 to alphaDEC-205 antibodies and immunized mice with these conjugates together with dendritic cell-activating oligonucleotides (CpG). Thus, these data show that targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity.
16112911	Melanoma	Promote immunity	Enhancement of immunity by a DNA melanoma vaccine against TRP2 with CCL21 as an adjuvant. Induction of anti-TRP2 immunity depended mainly on cell-mediated immunity, which was regulated by timing and route of CCL21 administration with DNA vaccine.

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
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 DCT 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	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
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 DCT 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	0.59	0.674
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	2.826	0.321
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.062	0.671
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.206	0.679
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.489	0.585
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.086	0.296
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.254	0.827
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-1.056	0.659
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.65	0.802
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.022	0.957
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	0.242	0.699
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.155	0.547

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DCT 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	2.7	1	1
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	3.4	0.3	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
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	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
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	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DCT. 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	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DCT. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DCT. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DCT. 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	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DCT expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DCT and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DCT
Name	dopachrome tautomerase
Aliases	dopachrome delta-isomerase; TYRP2; tyrosine-related protein 2; TRP-2; L-dopachrome Delta-isomerase; dopachro ......
Chromosomal Location	13q32
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DCT collected from DrugBank database.

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

Browse DCT