Browse CRK

Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
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
 
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
 
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
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
  Literatures describing the relation between CRK and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29618525MelanomaPromote immunity (Nk cell function); increase the efficacy of immunotherapyThe 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
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1830.358
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2880.888
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1090.943
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.520.155
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.4960.788
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5590.828
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0280.94
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0990.955
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1790.927
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2050.887
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8230.699
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0160.771
> Mutation difference between responders and non-responders
 
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 % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.407.40.0709
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.407.40.096
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
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
 
> Receptor
 
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CRK expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CRK and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCRK
Namev-crk avian sarcoma virus CT10 oncogene homolog
Aliases CRKII; proto-oncogene c-Crk; Adapter molecule crk
Chromosomal Location17p13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CRK collected from DrugBank database.
> Drugs from DrugBank database
 

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