TISIDB

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
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	Cell membrane Multi-pass membrane protein Lysosome membrane Multi-pass membrane protein Late endosome membrane Multi-pass membrane protein Endosome, multivesicular body Melanosome Secreted, exosome Cell surface Note=Also found in Weibel-Palade bodies of endothelial cells (PubMed:10793155). Located in platelet dense granules (PubMed:7682577). Detected in a subset of pre-melanosomes. Detected on intralumenal vesicles (ILVs) within multivesicular bodies (PubMed:21962903).
Domain	PF00335 Tetraspanin family
Function	Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.

> Gene Ontology [ TOP ]
Biological Process	GO:0002090 regulation of receptor internalization GO:0002092 positive regulation of receptor internalization GO:0002576 platelet degranulation GO:0006887 exocytosis GO:0006898 receptor-mediated endocytosis GO:0007034 vacuolar transport GO:0007160 cell-matrix adhesion GO:0007229 integrin-mediated signaling pathway GO:0010959 regulation of metal ion transport GO:0015672 monovalent inorganic cation transport GO:0016197 endosomal transport GO:0021700 developmental maturation GO:0030100 regulation of endocytosis GO:0031589 cell-substrate adhesion GO:0031623 receptor internalization GO:0033059 cellular pigmentation GO:0035646 endosome to melanosome transport GO:0035826 rubidium ion transport GO:0035924 cellular response to vascular endothelial growth factor stimulus GO:0038084 vascular endothelial growth factor signaling pathway GO:0043112 receptor metabolic process GO:0043473 pigmentation GO:0043476 pigment accumulation GO:0043482 cellular pigment accumulation GO:0043485 endosome to pigment granule transport GO:0045055 regulated exocytosis GO:0045807 positive regulation of endocytosis GO:0048066 developmental pigmentation GO:0048259 regulation of receptor-mediated endocytosis GO:0048260 positive regulation of receptor-mediated endocytosis GO:0048757 pigment granule maturation GO:0050931 pigment cell differentiation GO:0060627 regulation of vesicle-mediated transport GO:0090287 regulation of cellular response to growth factor stimulus GO:1900746 regulation of vascular endothelial growth factor signaling pathway GO:1902547 regulation of cellular response to vascular endothelial growth factor stimulus GO:2000680 regulation of rubidium ion transport GO:2001044 regulation of integrin-mediated signaling pathway GO:2001046 positive regulation of integrin-mediated signaling pathway
Molecular Function	-
Cellular Component	GO:0005765 lysosomal membrane GO:0005770 late endosome GO:0005771 multivesicular body GO:0005775 vacuolar lumen GO:0010008 endosome membrane GO:0030141 secretory granule GO:0030659 cytoplasmic vesicle membrane GO:0030667 secretory granule membrane GO:0031088 platelet dense granule membrane GO:0031902 late endosome membrane GO:0031904 endosome lumen GO:0032585 multivesicular body membrane GO:0042470 melanosome GO:0042827 platelet dense granule GO:0044440 endosomal part GO:0048770 pigment granule GO:0097487 multivesicular body, internal vesicle GO:0098852 lytic vacuole membrane GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04142 Lysosome
Reactome	R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-76005: Response to elevated platelet cytosolic Ca2+

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD63 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 CD63 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28507029	Cervical Carcinoma	Promote immunity (T cell function)	CD63-Mediated Antigen Delivery into Extracellular Vesicles via DNA Vaccination Results in Robust CD8+T Cell Responses. CD63 delivery into EVs led to better CD8+T cell responses than calnexin delivery into the endoplasmic reticulum.

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
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 CD63 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	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
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 CD63 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	-0.062	0.847
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.087	0.987
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.169	0.964
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.103	0.807
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.009	0.997
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.223	0.947
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.264	0.676
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.388	0.892
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.13	0.967
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.03	0.993
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	0.098	0.985
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.041	0.562

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD63 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	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	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	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD63. 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	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD63. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD63. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD63. 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	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD63 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD63 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD63
Name	CD63 molecule
Aliases	ME491; TSPAN30; MLA1; CD63 antigen (melanoma 1 antigen); OMA81H; granulophysin; melanoma-associated antigen ......
Chromosomal Location	12q12-q13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD63 collected from DrugBank database.

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

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