TISIDB

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
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	Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus. Melanosome. Endosome, multivesicular body. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Localizes predominantly to intralumenal vesicles (ILVs) within multivesicular bodies. Associates with ILVs found within the lumen of premelanosomes and melanosomes and particularly in compartments that serve as precursors to the striated stage II premelanosomes.; SUBCELLULAR LOCATION: M-alpha: Secreted.
Domain	PF00801 PKD domain
Function	Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.

> Gene Ontology [ TOP ]
Biological Process	GO:0006582 melanin metabolic process GO:0016050 vesicle organization GO:0018958 phenol-containing compound metabolic process GO:0019748 secondary metabolic process GO:0032438 melanosome organization GO:0033059 cellular pigmentation 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:0048753 pigment granule organization GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process
Molecular Function	-
Cellular Component	GO:0005770 late endosome GO:0005771 multivesicular body GO:0010008 endosome membrane GO:0031902 late endosome membrane GO:0032585 multivesicular body membrane GO:0042470 melanosome GO:0044440 endosomal part GO:0048770 pigment granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PMEL 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 PMEL and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
19318471	Melanoma	Promote immunity (T cell function)	Priming immunization with gp100(209-2M) without coadministration of CD4(+) helper T cell-restricted antigens induced the effective expansion of peptide-specific central and effector memory CD8(+) T cells with high proliferation potential in vaccine-draining lymph nodes of stage I to III melanoma patients.
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.
19074859	Melanoma	Promote immunity (T cell function)	In a murine melanoma model, a complex of CA9 and gp100 generated a gp100-specific antitumor response. A soluble form of CA9 shed from tumor cells had the same chaperone-like functions, providing renal tumors and hypoxic cells with a mechanism for stimulating an immune response against extracellular antigens. Interleukin-2 treatment of patient renal tumors in short-term culture increased CA9 shedding, suggesting a strategy for augmenting the immunogenicity of renal tumors.
25038326	melanoma	Promote immunity	Patients with metastatic uveal melanoma received at least 3 vaccinations with autologous dendritic cells, professional antigen-presenting cells loaded with melanoma antigens gp100 and tyrosinase.
29617862	melanoma	Promote immunity	Combining these technologies, we efficiently generated gp100-specific PD-1(-) CD8+ T cells, and demonstrated that the genetically engineered CD8+ T cells have high avidity against melanoma cells both in vitro and in vivo.
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.
16061687	B16 Malignant Melanoma	Promote immunity	Approximately 70% of the animals were cured from existing tumors by treatment with alphaDEC conjugates carrying two different melanoma antigens (TRP-2 and gp100). 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.
24100387	Melanoma	Immunotherapy target	Collectively, these results demonstrate that the TCR-like Ab, GPA7, could redirect NK cells to target the intracellular antigen gp100 and enhance anti-melanoma activity, providing a promising immunotherapeutic strategy to prevent and treat melanoma.
21631324	Melanoma	Promote immunity	In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone. In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone.
17000687	Melanoma	Promote immunity	DNAs encoding cytokines that affect T cells [interleukin (IL)-2, IL-12, IL-15, IL-18, IL-21, and the chemokine CCL21] and antigen-presenting cells [granulocyte macrophage colony-stimulating factor (GM-CSF)] were compared in mouse models as adjuvants to enhance CD8+ T-cell responses and tumor immunity. We found that (a) cytokine DNAs generally increased CD8+ T-cell responses against gp100; (b) ligation to Fc domains further enhanced T-cell responses

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
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 PMEL 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	logFC: 1.53; FDR: 0.000150	Sensitive to T cell-mediated killing
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	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
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 PMEL 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	0.417	0.801
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.886	0.666
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.699	0.86
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.279	0.485
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.238	0.874
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.333	0.862
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.213	0.83
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.041	0.989
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.591	0.86
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.218	0.804
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	-0.753	0.549
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.258	0.0962

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PMEL 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	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	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	2.6	0	2.6	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	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	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PMEL. 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	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PMEL. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PMEL. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PMEL. 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	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PMEL expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PMEL and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PMEL
Name	premelanosome protein
Aliases	D12S53E; Pmel17; gp100; SILV; silver (mouse homolog) like; silver homolog (mouse); ME20; ME20-M; ME20M; P100 ......
Chromosomal Location	12q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PMEL collected from DrugBank database.

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

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