TISIDB

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
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	Membrane Peripheral membrane protein Cell membrane Peripheral membrane protein Cytoplasmic vesicle, secretory vesicle membrane Peripheral membrane protein Note=Detected close to the plasma membrane and on secretory granules. In pancreas, interacts with insulin-containing vesicles (By similarity).
Domain	PF00168 C2 domain
Function	Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001505 regulation of neurotransmitter levels GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0002792 negative regulation of peptide secretion GO:0006836 neurotransmitter transport GO:0006887 exocytosis GO:0006906 vesicle fusion GO:0007269 neurotransmitter secretion GO:0009306 protein secretion GO:0009914 hormone transport GO:0010817 regulation of hormone levels GO:0015833 peptide transport GO:0016050 vesicle organization GO:0016079 synaptic vesicle exocytosis GO:0017156 calcium ion regulated exocytosis GO:0017157 regulation of exocytosis GO:0017158 regulation of calcium ion-dependent exocytosis GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0042886 amide transport GO:0044801 single-organism membrane fusion GO:0045055 regulated exocytosis GO:0045921 positive regulation of exocytosis GO:0046676 negative regulation of insulin secretion GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0046888 negative regulation of hormone secretion GO:0048284 organelle fusion GO:0048489 synaptic vesicle transport GO:0048791 calcium ion-regulated exocytosis of neurotransmitter GO:0050708 regulation of protein secretion GO:0050709 negative regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050796 regulation of insulin secretion GO:0051047 positive regulation of secretion GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051222 positive regulation of protein transport GO:0051224 negative regulation of protein transport GO:0051640 organelle localization GO:0051648 vesicle localization GO:0051650 establishment of vesicle localization GO:0051656 establishment of organelle localization GO:0060627 regulation of vesicle-mediated transport GO:0061025 membrane fusion GO:0071985 multivesicular body sorting pathway GO:0090087 regulation of peptide transport GO:0090174 organelle membrane fusion GO:0090276 regulation of peptide hormone secretion GO:0090278 negative regulation of peptide hormone secretion GO:0097479 synaptic vesicle localization GO:0097480 establishment of synaptic vesicle localization GO:0099003 vesicle-mediated transport in synapse GO:0099504 synaptic vesicle cycle GO:0099531 presynaptic process involved in chemical synaptic transmission GO:0099643 signal release from synapse GO:1903305 regulation of regulated secretory pathway GO:1903531 negative regulation of secretion by cell GO:1903532 positive regulation of secretion by cell GO:1904950 negative regulation of establishment of protein localization GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0000149 SNARE binding GO:0005543 phospholipid binding GO:0005544 calcium-dependent phospholipid binding GO:0017016 Ras GTPase binding GO:0017137 Rab GTPase binding GO:0019905 syntaxin binding GO:0030276 clathrin binding GO:0031267 small GTPase binding GO:0042043 neurexin family protein binding GO:0051020 GTPase binding
Cellular Component	GO:0005813 centrosome GO:0019898 extrinsic component of membrane GO:0030133 transport vesicle GO:0030141 secretory granule GO:0030658 transport vesicle membrane GO:0030659 cytoplasmic vesicle membrane GO:0070382 exocytic vesicle GO:0098793 presynapse GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-109582: Hemostasis R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-76005: Response to elevated platelet cytosolic Ca2+

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SYTL4 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 ]
There is no record.

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
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

[ TOP ]

Statistical results of SYTL4 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	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
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

[ TOP ]

Points in the above scatter plot represent the expression difference of SYTL4 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	-0.552	0.169
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.124	0.16
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.127	0.836
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.108	0.716
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.307	0.882
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.138	0.956
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.988	0.0756
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.967	0.311
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.054	0.295
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.787	0.0249
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	2.627	0.0338
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.02	0.884

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SYTL4 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	2.6	3.7	-1.1	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	7.1	-7.1	0.467
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	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SYTL4. 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	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SYTL4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SYTL4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SYTL4. 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	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SYTL4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SYTL4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SYTL4
Name	synaptotagmin-like 4
Aliases	granuphilin-a; exophilin-2; Granuphilin; Synaptotagmin-like protein 4
Chromosomal Location	Xq21.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SYTL4 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting SYTL4.

ID	Name	Drug Type	Targets	#Targets
DB00030	Insulin Human	Biotech	CPE, CTSD, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV, PCSK1, PCSK2, RB1, ......	12
DB00071	Insulin Pork	Biotech	CPE, CTSD, HLA-DQA2, HLA-DQB1, IDE, IGF1R, IGFBP7, INSR, LRP2, NOV ......	14

Browse SYTL4