TISIDB

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
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	Cytoplasm, cytoskeleton Cell projection, ruffle membrane Note=Associated with microtubules in unstimulated cells but is translocated to the membrane ruffles in cells stimulated ith EGF (epidermal growth factor).
Domain	PF05210 Sprouty protein (Spry)
Function	May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.

> Gene Ontology [ TOP ]
Biological Process	GO:0000132 establishment of mitotic spindle orientation GO:0000226 microtubule cytoskeleton organization GO:0001763 morphogenesis of a branching structure GO:0001933 negative regulation of protein phosphorylation GO:0003401 axis elongation GO:0006469 negative regulation of protein kinase activity GO:0007163 establishment or maintenance of cell polarity GO:0007173 epidermal growth factor receptor signaling pathway GO:0007265 Ras protein signal transduction GO:0007423 sensory organ development GO:0007605 sensory perception of sound GO:0008543 fibroblast growth factor receptor signaling pathway GO:0010799 regulation of peptidyl-threonine phosphorylation GO:0010801 negative regulation of peptidyl-threonine phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0018209 peptidyl-serine modification GO:0018210 peptidyl-threonine modification GO:0030010 establishment of cell polarity GO:0030323 respiratory tube development GO:0030324 lung development GO:0031345 negative regulation of cell projection organization GO:0033135 regulation of peptidyl-serine phosphorylation GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033673 negative regulation of kinase activity GO:0033674 positive regulation of kinase activity GO:0034260 negative regulation of GTPase activity GO:0035239 tube morphogenesis GO:0035265 organ growth GO:0038127 ERBB signaling pathway GO:0038179 neurotrophin signaling pathway GO:0040001 establishment of mitotic spindle localization GO:0040036 regulation of fibroblast growth factor receptor signaling pathway GO:0040037 negative regulation of fibroblast growth factor receptor signaling pathway GO:0042058 regulation of epidermal growth factor receptor signaling pathway GO:0042059 negative regulation of epidermal growth factor receptor signaling pathway GO:0042326 negative regulation of phosphorylation GO:0042471 ear morphogenesis GO:0042472 inner ear morphogenesis GO:0043405 regulation of MAP kinase activity GO:0043407 negative regulation of MAP kinase activity GO:0043409 negative regulation of MAPK cascade GO:0043410 positive regulation of MAPK cascade GO:0043491 protein kinase B signaling GO:0043583 ear development GO:0044344 cellular response to fibroblast growth factor stimulus GO:0045165 cell fate commitment GO:0045860 positive regulation of protein kinase activity GO:0046578 regulation of Ras protein signal transduction GO:0046580 negative regulation of Ras protein signal transduction GO:0048011 neurotrophin TRK receptor signaling pathway GO:0048562 embryonic organ morphogenesis GO:0048568 embryonic organ development GO:0048754 branching morphogenesis of an epithelial tube GO:0048839 inner ear development GO:0050954 sensory perception of mechanical stimulus GO:0051056 regulation of small GTPase mediated signal transduction GO:0051058 negative regulation of small GTPase mediated signal transduction GO:0051293 establishment of spindle localization GO:0051294 establishment of spindle orientation GO:0051346 negative regulation of hydrolase activity GO:0051348 negative regulation of transferase activity GO:0051386 regulation of neurotrophin TRK receptor signaling pathway GO:0051387 negative regulation of neurotrophin TRK receptor signaling pathway GO:0051640 organelle localization GO:0051653 spindle localization GO:0051656 establishment of organelle localization GO:0051896 regulation of protein kinase B signaling GO:0051897 positive regulation of protein kinase B signaling GO:0060425 lung morphogenesis GO:0060437 lung growth GO:0060441 epithelial tube branching involved in lung morphogenesis GO:0060449 bud elongation involved in lung branching GO:0060541 respiratory system development GO:0060560 developmental growth involved in morphogenesis GO:0060562 epithelial tube morphogenesis GO:0060602 branch elongation of an epithelium GO:0061138 morphogenesis of a branching epithelium GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0071774 response to fibroblast growth factor GO:0071900 regulation of protein serine/threonine kinase activity GO:0071901 negative regulation of protein serine/threonine kinase activity GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0090287 regulation of cellular response to growth factor stimulus GO:0090288 negative regulation of cellular response to growth factor stimulus GO:0090596 sensory organ morphogenesis GO:1901184 regulation of ERBB signaling pathway GO:1901185 negative regulation of ERBB signaling pathway GO:1902532 negative regulation of intracellular signal transduction
Molecular Function	GO:0004857 enzyme inhibitor activity GO:0004860 protein kinase inhibitor activity GO:0008047 enzyme activator activity GO:0019207 kinase regulator activity GO:0019209 kinase activator activity GO:0019210 kinase inhibitor activity GO:0019887 protein kinase regulator activity GO:0030291 protein serine/threonine kinase inhibitor activity GO:0030295 protein kinase activator activity GO:0043539 protein serine/threonine kinase activator activity
Cellular Component	GO:0001726 ruffle GO:0005874 microtubule GO:0031252 cell leading edge GO:0031253 cell projection membrane GO:0031256 leading edge membrane GO:0032587 ruffle membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-182971: EGFR downregulation R-HSA-5654726: Negative regulation of FGFR1 signaling R-HSA-5654727: Negative regulation of FGFR2 signaling R-HSA-5654732: Negative regulation of FGFR3 signaling R-HSA-5654733: Negative regulation of FGFR4 signaling R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-190236: Signaling by FGFR R-HSA-5654736: Signaling by FGFR1 R-HSA-5654738: Signaling by FGFR2 R-HSA-5654741: Signaling by FGFR3 R-HSA-5654743: Signaling by FGFR4 R-HSA-1295596: Spry regulation of FGF signaling

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-182971: EGFR downregulation
R-HSA-5654726: Negative regulation of FGFR1 signaling
R-HSA-5654727: Negative regulation of FGFR2 signaling
R-HSA-5654732: Negative regulation of FGFR3 signaling
R-HSA-5654733: Negative regulation of FGFR4 signaling
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-190236: Signaling by FGFR
R-HSA-5654736: Signaling by FGFR1
R-HSA-5654738: Signaling by FGFR2
R-HSA-5654741: Signaling by FGFR3
R-HSA-5654743: Signaling by FGFR4
R-HSA-1295596: Spry regulation of FGF signaling

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SPRY2 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 SPRY2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29635363	glioma	Inhibit immunity	The present study highlights an antitumoral effect of SPRY2 inhibition that is based on excessive activation of ERK signaling and DNA damage response, resulting in reduced cell proliferation and increased cytotoxicity, proposing SPRY2 as a promising pharmacological target in GBM patients.

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
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 SPRY2 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	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
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 SPRY2 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	0.151	0.745
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.359	0.891
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.008	0.996
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.182	0.706
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.209	0.906
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.141	0.944
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.394	0.46
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.427	0.816
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.217	0.906
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.279	0.788
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	0.72	0.629
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.424	0.00209

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of SPRY2 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	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	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPRY2. 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	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPRY2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPRY2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPRY2. 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	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SPRY2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SPRY2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SPRY2
Name	sprouty RTK signaling antagonist 2
Aliases	hSPRY2; sprouty homolog 2 (Drosophila); sprouty 2; sprouty homolog 2; spry-2; Protein sprouty homolog 2
Chromosomal Location	13q31.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SPRY2 collected from DrugBank database.

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

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