TISIDB

Summary
Symbol	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
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=Located to mature stage III and IV melanosomes and apposed endosomal tubular membranes. Transported to pigmented melanosomes by the BLOC-1 complex. Proper trafficking to melanosome is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
Domain	PF00264 Common central domain of tyrosinase
Function	Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid in the presence of bound Cu(2+) ions (PubMed:28661582). May regulate or influence the type of melanin synthesized (PubMed:22556244, PubMed:16704458). Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0006582 melanin metabolic process GO:0006631 fatty acid metabolic process GO:0016050 vesicle organization GO:0018958 phenol-containing compound metabolic process GO:0019748 secondary metabolic process GO:0030318 melanocyte differentiation GO:0032438 melanosome organization GO:0033059 cellular pigmentation GO:0042438 melanin biosynthetic process GO:0042440 pigment metabolic process GO:0043438 acetoacetic acid metabolic process GO:0043455 regulation of secondary metabolic process GO:0043473 pigmentation GO:0044550 secondary metabolite biosynthetic process GO:0046148 pigment biosynthetic process GO:0046189 phenol-containing compound biosynthetic process GO:0046459 short-chain fatty acid metabolic process GO:0048021 regulation of melanin biosynthetic process GO:0048023 positive regulation of melanin biosynthetic process GO:0048066 developmental pigmentation GO:0048753 pigment granule organization GO:0050931 pigment cell differentiation GO:1900376 regulation of secondary metabolite biosynthetic process GO:1900378 positive regulation of secondary metabolite biosynthetic process GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process
Molecular Function	GO:0004497 monooxygenase activity GO:0005507 copper ion binding GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016716 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen GO:0046982 protein heterodimerization activity
Cellular Component	GO:0010008 endosome membrane GO:0030135 coated vesicle GO:0030136 clathrin-coated vesicle GO:0030139 endocytic vesicle GO:0030659 cytoplasmic vesicle membrane GO:0030662 coated vesicle membrane GO:0030665 clathrin-coated vesicle membrane GO:0030666 endocytic vesicle membrane GO:0030669 clathrin-coated endocytic vesicle membrane GO:0033162 melanosome membrane GO:0042470 melanosome GO:0044440 endosomal part GO:0045009 chitosome GO:0045334 clathrin-coated endocytic vesicle 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	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TYRP1 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 TYRP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23633494	B16 Malignant Melanoma	Promote immunity (infiltration); Promote immunity (T cell function); essential for immunotherapy	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.
29602773	melanoma	Promote immunity (T cell function); increase the efficacy of immunotherapy	Previously, we showed that tumor-specific, cytotoxic CD4+ T cells from tyrosinase-related protein 1 transgenic mice could overcome secondary resistance to recurring melanoma when anti-programmed cell death 1 ligand (PD-L1) checkpoint blockade was combined with either anti-lymphocyte-activated gene 3 (LAG-3) Abs or depletion of tumor-specific regulatory T (Treg) cells.
23370329	Melanoma	Promote immunity	In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells.

Summary
Symbol	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
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 TYRP1 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	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
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 TYRP1 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	-0.504	0.749
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.334	0.905
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.683	0.809
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.511	0.541
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.958	0.444
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.06	0.968
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.409	0.77
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.166	0.947
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.198	0.674
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.567	0.469
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	-0.567	0.592
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.068	0.83

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TYRP1 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	0	1.4	-1.4	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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
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	9.1	-9.1	0.458
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	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TYRP1. 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	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TYRP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TYRP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TYRP1. 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	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TYRP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TYRP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TYRP1
Name	tyrosinase-related protein 1
Aliases	GP75; CATB; TRP; b-PROTEIN; OCA3; TYRP; DHICA oxidase; catalase B; glycoprotein 75; melanoma antigen gp75; 5 ......
Chromosomal Location	9p23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TYRP1 collected from DrugBank database.

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

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