Tchem CRK Adapter molecule crk

Protein Summary

Description

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. This gene encodes a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P46108
• A8MWE8
• B0LPE8
• D3DTH6
• Q96GA9
• Q96HJ0

Gene Name

• CRK

Ensembl ID

• ENST00000300574
• ENSP00000300574
• ENSG00000167193
• ENST00000398970
• ENSP00000381942

Symbol

• p38
• CRKII

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	0.99
disease perturbation	0.95
transcription factor perturbation	0.94
kinase perturbation	0.93
pathway	0.85

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 412.2   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 571   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 412.2   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 571   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (2)

Explore Active Ligands

1 – 2 of 2

CHEMBL4281456

CRKTchem

pKd : 8.05

CHEMBL4289336

CRKTchem

pKd : 6.4

Protein-Protein Interactions (360)

Explore Interacting Targets

1 – 10 of 360

• See Interactions on String-DB

RAPGEF1

Tbio

Novelty:  0.00365765

Score:  0.998

Data Source:  Reactome,STRINGDB

DOCK1

Tbio

Novelty:  0.00867391

Score:  0.997

Data Source:  Reactome,STRINGDB

BCAR1

Tbio

Novelty:  0.00329214

Score:  0.996

Data Source:  Reactome,STRINGDB

ABL1

Tclin

Family:  Kinase

Novelty:  0.00023803

Score:  0.996

Data Source:  STRINGDB

PXN

Tbio

Novelty:  0.00082031

Score:  0.996

Data Source:  Reactome,STRINGDB

CBL

Tbio

Family:  Enzyme

Novelty:  0.00114929

Score:  0.995

Data Source:  Reactome,STRINGDB

SRC

Tclin

Family:  Kinase

Novelty:  0.00008479

Score:  0.994

Data Source:  Reactome,STRINGDB

ELMO1

Tbio

Novelty:  0.01598587

Score:  0.985

Data Source:  Reactome,STRINGDB

ELMO2

Tbio

Novelty:  0.04258272

Score:  0.983

Data Source:  Reactome,STRINGDB

MAPK8

Tchem

Family:  Kinase

Novelty:  0.00055723

Score:  0.983

Data Source:  STRINGDB

Nearest Tclin Targets (19)

Explore Nearest Tclin Targets

Upstream (18)

Downstream (1)

1 – 5 of 18

FLT4

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  4

1: Focal adhesion

2: Rap1 signaling pathway

3: MAPK signaling pathway

4: Pathways in cancer

EGFR

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  8

1: Focal adhesion

2: ErbB signaling pathway

3: Regulation of actin cytoskeleton

4: Rap1 signaling pathway

more:  4 more common pathways

PDGFRA

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  7

1: Focal adhesion

2: Regulation of actin cytoskeleton

3: Rap1 signaling pathway

4: MAPK signaling pathway

more:  3 more common pathways

IGF1R

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  4

1: Focal adhesion

2: Rap1 signaling pathway

3: MAPK signaling pathway

4: Pathways in cancer

MET

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  7

1: Focal adhesion

2: Renal cell carcinoma

3: Rap1 signaling pathway

4: MAPK signaling pathway

more:  3 more common pathways

Pathways (103)

Reactome (32)

KEGG (18)

PathwayCommons (35)

WikiPathways (18)

ARMS-mediated activation (R-HSA-170984)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ARMS-mediated activation	7 targets	R-HSA-170984
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Downstream signal transduction	29 targets	R-HSA-186763
Reactome	Fcgamma receptor (FCGR) dependent phagocytosis	163 targets	R-HSA-2029480
Reactome	Hemostasis	666 targets	R-HSA-109582

Name	Explore in Pharos	Explore in Source
ARMS-mediated activation	7 targets	R-HSA-170984
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Downstream signal transduction	29 targets	R-HSA-186763
Fcgamma receptor (FCGR) dependent phagocytosis	163 targets	R-HSA-2029480
Hemostasis	666 targets	R-HSA-109582

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (47)

Functions (11)

Components (8)

Processes (28)

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10

1 – 10 of 11

GO Term	Evidence	Assigned by
protein phosphorylated amino acid binding	Inferred from Direct Assay (IDA)	CAFA
protein self-association	Inferred from Direct Assay (IDA)	CAFA
SH3/SH2 adaptor activity	Inferred from Direct Assay (IDA)	CAFA
ephrin receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
phosphotyrosine residue binding	Inferred from Physical Interaction (IPI)	CAFA
protein tyrosine kinase binding	Inferred from Physical Interaction (IPI)	CAFA
SH2 domain binding	Inferred from Physical Interaction (IPI)	UniProtKB
SH3 domain binding	Inferred from Physical Interaction (IPI)	CAFA
cytoskeletal protein binding	Inferred from Electronic Annotation (IEA)	Ensembl
insulin-like growth factor receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (24)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	3	4	4		94.2
lymphocyte percentage of leukocytes	EFO_0007993	2	3	3		89.6
neutrophil count	EFO_0004833	3	2	3		80.4
myeloid white cell count	EFO_0007988	2	2	2		72.4
C-reactive protein measurement	EFO_0004458	2	2	2		68.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	4		94.2
lymphocyte percentage of leukocytes	EFO_0007993	3		89.6
neutrophil count	EFO_0004833	3		80.4
myeloid white cell count	EFO_0007988	2		72.4
C-reactive protein measurement	EFO_0004458	2		68.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Membrane
Phosphoprotein
Proto-oncogene
Reference proteome

GWAS Trait Find Similar Targets

No Header	No Header
Agents acting on the renin-angiotensin system use measurement
appendicular lean mass
atrial fibrillation
C-reactive protein measurement
granulocyte count
hematocrit
hemoglobin measurement
intraocular pressure measurement
leukocyte count
lymphocyte percentage of leukocytes

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
craniofacial phenotype
digestive/alimentary phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
mortality/aging
muscle phenotype
respiratory system phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	v-crk avian sarcoma virus CT10 oncogene homolog	MGI:88508	12928
Rat	CRK proto-oncogene, adaptor protein	RGD:2405	54245
Dog	CRK proto-oncogene, adaptor protein	VGNC:54290	100684309
Horse	CRK proto-oncogene, adaptor protein	VGNC:51791	100072356
Cow	CRK proto-oncogene, adaptor protein	VGNC:27716	512841

Species	Name	OMA	EggNOG	Inparanoid
Mouse	v-crk avian sarcoma virus CT10 oncogene homolog
Rat	CRK proto-oncogene, adaptor protein
Dog	CRK proto-oncogene, adaptor protein
Horse	CRK proto-oncogene, adaptor protein
Cow	CRK proto-oncogene, adaptor protein

Publication Statistics

PubMed Score 412.20

PubMed score by year

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PubTator Score 244.38

PubTator score by year

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Related Publications

Text Mined References (199)

GeneRif Annotations (74)

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PMID	Year	Title