TISIDB

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
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 Cell membrane Note=Translocated to the plasma membrane upon cell adhesion.
Domain	PF00017 SH2 domain PF00018 SH3 domain PF07653 Variant SH3 domain
Function	Isoform Crk-II: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.

> Gene Ontology [ TOP ]
Biological Process	GO:0000186 activation of MAPKK activity GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002433 immune response-regulating cell surface receptor signaling pathway involved in phagocytosis GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006909 phagocytosis GO:0007265 Ras protein signal transduction GO:0010720 positive regulation of cell development GO:0010769 regulation of cell morphogenesis involved in differentiation GO:0010770 positive regulation of cell morphogenesis involved in differentiation GO:0010810 regulation of cell-substrate adhesion GO:0010811 positive regulation of cell-substrate adhesion GO:0016601 Rac protein signal transduction GO:0022604 regulation of cell morphogenesis GO:0031589 cell-substrate adhesion GO:0032147 activation of protein kinase activity GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0033674 positive regulation of kinase activity GO:0034446 substrate adhesion-dependent cell spreading GO:0035020 regulation of Rac protein signal transduction GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0043405 regulation of MAP kinase activity GO:0043410 positive regulation of MAPK cascade GO:0045785 positive regulation of cell adhesion GO:0045860 positive regulation of protein kinase activity GO:0046578 regulation of Ras protein signal transduction GO:0048010 vascular endothelial growth factor receptor signaling pathway GO:0048013 ephrin receptor signaling pathway GO:0051056 regulation of small GTPase mediated signal transduction GO:0051493 regulation of cytoskeleton organization GO:0071900 regulation of protein serine/threonine kinase activity GO:1900024 regulation of substrate adhesion-dependent cell spreading GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
Molecular Function	GO:0005070 SH3/SH2 adaptor activity GO:0030674 protein binding, bridging GO:0035591 signaling adaptor activity GO:0042169 SH2 domain binding GO:0045309 protein phosphorylated amino acid binding GO:0046875 ephrin receptor binding GO:0051219 phosphoprotein binding GO:0060090 binding, bridging
Cellular Component	GO:0015629 actin cytoskeleton

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04012 ErbB signaling pathway hsa04015 Rap1 signaling pathway hsa04062 Chemokine signaling pathway hsa04510 Focal adhesion hsa04666 Fc gamma R-mediated phagocytosis hsa04722 Neurotrophin signaling pathway hsa04810 Regulation of actin cytoskeleton hsa04910 Insulin signaling pathway
Reactome	R-HSA-170984: ARMS-mediated activation R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-186763: Downstream signal transduction R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-354192: Integrin alphaIIb beta3 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-8875555: MET activates RAP1 and RAC1 R-HSA-8875878: MET promotes cell motility R-HSA-8875656: MET receptor recycling R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-8849471: PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases R-HSA-76009: Platelet Aggregation (Plug Formation) R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-169893: Prolonged ERK activation events R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation R-HSA-912631: Regulation of signaling by CBL R-HSA-162582: Signal Transduction R-HSA-449147: Signaling by Interleukins R-HSA-6806834: Signaling by MET R-HSA-186797: Signaling by PDGF R-HSA-8848021: Signaling by PTK6 R-HSA-194138: Signaling by VEGF R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-372708: p130Cas linkage to MAPK signaling for integrins

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04010 MAPK signaling pathway
hsa04012 ErbB signaling pathway
hsa04015 Rap1 signaling pathway
hsa04062 Chemokine signaling pathway
hsa04510 Focal adhesion
hsa04666 Fc gamma R-mediated phagocytosis
hsa04722 Neurotrophin signaling pathway
hsa04810 Regulation of actin cytoskeleton
hsa04910 Insulin signaling pathway

Reactome

R-HSA-170984: ARMS-mediated activation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-186763: Downstream signal transduction
R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-354192: Integrin alphaIIb beta3 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-8875555: MET activates RAP1 and RAC1
R-HSA-8875878: MET promotes cell motility
R-HSA-8875656: MET receptor recycling
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-8849471: PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-76009: Platelet Aggregation (Plug Formation)
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-169893: Prolonged ERK activation events
R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation
R-HSA-912631: Regulation of signaling by CBL
R-HSA-162582: Signal Transduction
R-HSA-449147: Signaling by Interleukins
R-HSA-6806834: Signaling by MET
R-HSA-186797: Signaling by PDGF
R-HSA-8848021: Signaling by PTK6
R-HSA-194138: Signaling by VEGF
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-372708: p130Cas linkage to MAPK signaling for integrins

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CRK 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 CRK and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29618525	Melanoma	Promote immunity (Nk cell function); increase the efficacy of immunotherapy	The diminished function of Crk x CrkL-double-deficient NK cells correlated with decreased phosphorylation of STAT4 and STAT1 in response to IL-12 and IFN-α stimulation, respectively.

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
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 CRK 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	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
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 CRK 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	-0.183	0.358
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.288	0.888
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.109	0.943
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.52	0.155
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.496	0.788
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.559	0.828
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.028	0.94
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.099	0.955
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.179	0.927
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.205	0.887
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	0.823	0.699
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.016	0.771

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of CRK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	7.4	0.0709
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	7.4	0.096
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CRK. 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	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CRK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CRK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CRK. 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	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CRK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CRK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CRK
Name	v-crk avian sarcoma virus CT10 oncogene homolog
Aliases	CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location	17p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CRK collected from DrugBank database.

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

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