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FLASH GENE
Symbol CRKL contributors: mct/npt/pgu - updated : 25-09-2013
HGNC name v-crk sarcoma virus CT10 oncogene homolog (avian)-like
HGNC id 2363
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  moderately
 stomach   highly
Endocrineparathyroid   highly
Hearing/Equilibriumear   moderately
Lymphoid/Immunelymph node   moderately
 thymus   moderately
Nervousnerve   moderately
Reproductivefemale systemuterus  moderately
 male systemprostate  moderately
Urinarybladder   moderately
Visualeye   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  moderately
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one SH2 domain
  • two SH3 domains
  • conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Crkl (96.7 pc)
    homolog to rattus Crkl (96.7 pc)
    intraspecies homolog to CRK
    Homologene
    FAMILY
  • CRK adapter protein family
  • CATEGORY adaptor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text nuclear signaling protein
    basic FUNCTION
  • activating the RAS and JUN kinase signaling pathways
  • transforming fibroblasts in a RAS-dependent fashion
  • adapter protein functioning in signal transduction, best known as a substrate of the BCR-ABL kinase in chronic myelogenous leukemia
  • playing a role in fibroblast transformation by BCR-ABL
  • may mediate the transduction of intracellular signals
  • permits cells to bypass the strict need for adhesion in response to FGF8 through direct interaction with receptor
  • CRK and CRKL adaptor proteins play important roles in numerous signaling pathways, bridging tyrosine kinase substrates to downstream signaling effectors by virtue of their phosphotyrosine-binding SH2 domains and their effector-binding SH3 domains
  • regulates head and neck squamous cell carcinoma-cell growth, motility, and integrin-dependent cell adhesion, suggesting that CRKL plays a principal role in HNSCC tumorigenicity
  • significant role for CRKL in regulating cell motility
  • has the ability to regulate gastric cell proliferation
  • involved in signal transduction from multiple tyrosine kinase receptors
  • cytoskeletal adaptor protein , having crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS development
    text
  • heart development
  • organ morphogenesis
  • parathyroid gland development
  • thymus development
  • PATHWAY
    metabolism
    signaling signal transduction
  • JNK cascade
  • intracellular signaling cascade
  • CRKL-MAPK pathway might be important in human cardiac development and disease
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with INPP5D/SHIP1
  • interacting with DOCK2 and EPOR
  • interacting with phosphorylated CBLB
  • specific interaction between phosphorylated Y463 in FGFR1 with the CRKL SH2 domain
  • Sprouty1 and Sprouty2 bind to the adaptor protein CRKL in a stimulus-dependent manner (Satoh 2010)
  • with CRK have been proposed to interact with tyrosine phosphorylated DAB1 to mediate downstream events in the Reelin pathway
  • interaction with CRK, and DOK7 (critical role for CRK and CRKL downstream from DOK7 in presynaptic and postsynaptic differentiation)(
  • association of ESR1 and CRKL directly enhances the tumorigenic potential of CRKL, thus pointing to its role in cell proliferation
  • CRKL adaptor protein associating with PTPN6 (association is due to CRKL binding to PxxP domains located at AA residues 158-161 within the PTPN6 C-terminal SH2 domain, and AA residues 363-366 within its phosphatase domain)
  • CRKL signaling was associated with SRC family kinase (SFK) signaling, specifically with YES1 kinase
  • promotes CASP8 recruitment to the peripheral spreading edge of cells, and that the catalytic domain of CASP8 directly interacts with the SH2 domain of CRKL
  • DOK1 adaptor is the key effector for the enhancement of CRKL transformation by ABLinhibition
  • cell & other
    REGULATION
    Phosphorylated by BCR-ABL tyrosine kinase in chronic myelogenous leukemia patients
    Other phosphorylated when overexpressed
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    contribute to diverse oncogenic phenotypes in lung cancer, with implications for targeted therapy, and highlight a role of adapter proteins as primary genetic drivers of tumorigenesis
    tumoral     --over  
    correlated with progression and malignant proliferation of breast cancers
    constitutional     --other  
    haploinsufficiency of CRKL could be responsible for the etiology of conotruncal heart defects (CTDs) in individuals with nested distal deletions and might act as a genetic modifier of individuals with the typical 3 Mb deletion
    Susceptibility
    Variant & Polymorphism
    Candidate gene DEL22Q11
    Marker
  • may be a potential molecular target for head and neck squamous cell carcinoma (HNSCC) diagnosis
  • Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    novel therapeutic strategies as well as CRK
    cancerdigestivestomach
    has the potential to serve as a molecular therapy target for gastric cancer
    ANIMAL & CELL MODELS
    mice homozygous for a null mutation exhibit defectsin multiplecranial and cardiac neural crestderivatives, similar to the clinical manifestations of DG/VCFS