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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
DNA
TYPE functioning gene
STRUCTURE 36.32 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
LOC391298 22 similar to KIAA0649 gene product LOC388854 22 similar to Gamma-glutamyltranspeptidase 1 precursor (Gamma-glutamyltransferase 1) (CD224 antigen) LOC388855 22 hypothetical gene supported by BC039313 LOC388856 22 hypothetical gene supported by BC039313 LOC388857 22 similar to KIAA0649 gene product LOC391299 22 similar to Collagen alpha 1(II) chain precursor USP41 22q11.22 ubiquitin specific protease 41 ZNF74 22q11.21 zinc finger protein 74 (Cos52) SCARF2 22q11.21 scavenger receptor class F, member 2 FLJ14360 22q11.21 hypothetical protein FLJ14360 PCQAP 22q11.21 PC2 (positive cofactor 2, multiprotein complex) glutamine/Q-rich-associated protein LOC391300 22 similar to hypothetical protein FLJ20297 LOC343839 22q11.21 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) LOC150207 22q11.21 hypothetical gene LOC150207 POM121L4P 22 POM121 membrane glycoprotein-like 4 pseudogene (rat) DKFZp434N035 22q11.21 hypothetical protein DKFZp434N035 PIK4CA 22q11.21 phosphatidylinositol 4-kinase, catalytic, alpha polypeptide SERPIND1 22q11.21 serine (or cysteine) proteinase inhibitor, clade D (heparin cofactor), member 1 SNAP29 22q11.21 synaptosomal-associated protein, 29kDa CRKL 22q11.21 v-crk sarcoma virus CT10 oncogene homolog (avian)-like FLJ30473 22q11.21-q11.22 hypothetical protein FLJ30473 LZTR1 22q11.1-q11.2 leucine-zipper-like transcriptional regulator, 1 THAP7 22q11.2 THAP domain containing 7 FLJ39582 22q11.2 hypothetical protein FLJ39582 MGC16703 22q11.22 alpha tubulin-like P2RXL1 22q11.21 purinergic receptor P2X-like 1, orphan receptor SLC7A4 22q11.21 solute carrier family 7 (cationic amino acid transporter, y+ system), member 4 LOC391301 22 similar to Tubulin alpha-3/alpha-7 chain (Alpha-tubulin 3/7) LOC388858 22 similar to Bcr protein LOC391302 22 hypothetical gene supported by AY358961; NM_014549 LOC376818 22q11.22 E2F transcription factor 6 pseudogene LOC388859 22 similar to Nucleosome binding protein 1 (Nucleosome binding protein 45) (NBP-45) (GARP45 protein) LOC388860 22 similar to Gamma-glutamyltranspeptidase 1 precursor (Gamma-glutamyltransferase 1) (CD224 antigen) LOC388861 22 similar to E2F transcription factor 6 isoform a LOC388862 22 LOC388862 LOC388863 22 similar to dJ831C21.3 (novel protein similar to DKFZP434P211 protein) LOC388864 22 similar to breakpoint cluster region isoform 1 LOC391303 22 similar to Nucleosome binding protein 1 (Nucleosome binding protein 45) (NBP-45) (GARP45 protein) LOC391304 22 similar to KIAA0649 gene product LOC391305 22 similar to Sushi domain (SCR repeat) containing KIAA1666  KIAA1666 protein HIC2 22q11.21 hypermethylated in cancer 2
regionally located centromeric of the chronic myelogenous leukemia breakpoint region
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 5336 33 303 - 2009 1930730
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