TISIDB

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
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	Cytoplasm.
Domain	PF00168 C2 domain PF12763 Cytoskeletal-regulatory complex EF hand PF16652 Pleckstrin homology domain PF00621 RhoGEF domain PF00018 SH3 domain PF07653 Variant SH3 domain PF14604 Variant SH3 domain
Function	Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003).

> Gene Ontology [ TOP ]
Biological Process	GO:0001558 regulation of cell growth GO:0007265 Ras protein signal transduction GO:0007266 Rho protein signal transduction GO:0010720 positive regulation of cell development GO:0010975 regulation of neuron projection development GO:0010976 positive regulation of neuron projection development GO:0016049 cell growth GO:0022604 regulation of cell morphogenesis GO:0030307 positive regulation of cell growth GO:0031346 positive regulation of cell projection organization GO:0035023 regulation of Rho protein signal transduction GO:0045666 positive regulation of neuron differentiation GO:0045927 positive regulation of growth GO:0046578 regulation of Ras protein signal transduction GO:0048588 developmental cell growth GO:0048638 regulation of developmental growth GO:0048639 positive regulation of developmental growth GO:0050769 positive regulation of neurogenesis GO:0051056 regulation of small GTPase mediated signal transduction GO:0051962 positive regulation of nervous system development GO:0060560 developmental growth involved in morphogenesis GO:0097484 dendrite extension GO:1903859 regulation of dendrite extension GO:1903861 positive regulation of dendrite extension GO:1990138 neuron projection extension
Molecular Function	GO:0005070 SH3/SH2 adaptor activity GO:0005085 guanyl-nucleotide exchange factor activity GO:0005088 Ras guanyl-nucleotide exchange factor activity GO:0005089 Rho guanyl-nucleotide exchange factor activity GO:0030674 protein binding, bridging GO:0035591 signaling adaptor activity GO:0060090 binding, bridging
Cellular Component	GO:0005813 centrosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-199991: Membrane Trafficking R-HSA-5653656: Vesicle-mediated transport

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ITSN2 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 ITSN2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29337666	Wiskott-Aldrich Syndrome	Promote immunity (B cell)	Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination. In vivo, ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL that correlates with a diminished ability to form long term conjugates with T cells, to proliferate in vivo, and to differentiate into germinal centre cells.

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
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 ITSN2 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	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
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 ITSN2 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	0.19	0.506
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.504	0.689
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.042	0.966
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.232	0.47
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.463	0.843
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.058	0.984
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.229	0.563
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.454	0.788
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.015	0.993
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.368	0.782
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	0.854	0.663
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.055	0.525

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ITSN2 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	14.8	2.7	12.1	0.0439
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	14.8	3.4	11.4	0.0746
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	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	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	14.3	10.7	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	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ITSN2. 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	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ITSN2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ITSN2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ITSN2. 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	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ITSN2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ITSN2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ITSN2
Name	intersectin 2
Aliases	KIAA1256; SH3P18; SWA; PRO2015; SH3 domain protein 1B; SH3P18-like WASP associated protein; SH3D1B; SH3 doma ......
Chromosomal Location	2p23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ITSN2 collected from DrugBank database.

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

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