TISIDB

Summary
Symbol	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
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	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	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine. In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone.

> Gene Ontology [ TOP ]
Biological Process	GO:0006570 tyrosine metabolic process GO:0006582 melanin metabolic process GO:0006583 melanin biosynthetic process from tyrosine GO:0006726 eye pigment biosynthetic process GO:0007584 response to nutrient GO:0007601 visual perception GO:0009072 aromatic amino acid family metabolic process GO:0009314 response to radiation GO:0009411 response to UV GO:0009416 response to light stimulus GO:0009991 response to extracellular stimulus GO:0014074 response to purine-containing compound GO:0018958 phenol-containing compound metabolic process GO:0019748 secondary metabolic process GO:0031667 response to nutrient levels GO:0033273 response to vitamin GO:0033280 response to vitamin D GO:0042438 melanin biosynthetic process GO:0042440 pigment metabolic process GO:0042441 eye pigment metabolic process GO:0043324 pigment metabolic process involved in developmental pigmentation GO:0043473 pigmentation GO:0043474 pigment metabolic process involved in pigmentation GO:0044550 secondary metabolite biosynthetic process GO:0046148 pigment biosynthetic process GO:0046189 phenol-containing compound biosynthetic process GO:0046683 response to organophosphorus GO:0048066 developmental pigmentation GO:0048069 eye pigmentation GO:0048538 thymus development GO:0048732 gland development GO:0050953 sensory perception of light stimulus GO:0051591 response to cAMP GO:1901605 alpha-amino acid metabolic process GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process
Molecular Function	GO:0004497 monooxygenase activity GO:0004503 monophenol 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:0005798 Golgi-associated vesicle 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	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TYR 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 TYR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24647571	Melanoma	Promote immunity (infiltration)	Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8(+) and CD4(+) T-cell infiltrates.
19417017	Melanoma	Promote immunity	TriMix DCs coelectroporated with tyrosinase are able to stimulate tyrosinase-specific CD8(+) T cells in vitro from the blood of nonvaccinated melanoma patients.
23904461	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic.

Summary
Symbol	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
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

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Statistical results of TYR 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	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
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

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Points in the above scatter plot represent the expression difference of TYR 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	1.501	0.194
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	2.394	0.532
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.855	0.763
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.897	0.327
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.53	0.238
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.113	0.94
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.499	0.63
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.33	0.894
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.36	0.627
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.091	0.482

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TYR 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	4.1	-0.4	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	3.7	5.1	-1.4	1
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	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TYR. 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	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TYR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TYR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TYR. 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	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TYR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TYR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TYR
Name	tyrosinase
Aliases	OCAIA; OCA1A; OCA1; oculocutaneous albinism IA; ATN; SHEP3; LB24-AB; SK29-AB; monophenol monooxygenase; tumo ......
Chromosomal Location	11q14.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TYR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TYR.

ID	Name	Drug Type	Targets	#Targets
DB00157	NADH	Small Molecule	AASS, ACADS, ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH7, AKR1B1, AKR1C1 ......	144
DB00548	Azelaic Acid	Small Molecule	AKR1D1, SRD5A2, TYR	3
DB00600	Monobenzone	Small Molecule	TYR	1
DB01055	Mimosine	Small Molecule	CCL2, SHMT1, TYR	3
DB09526	Hydroquinone	Small Molecule	TYR	1

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