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FLASH GENE
Symbol CRK contributors: mct - updated : 21-05-2017
HGNC name v-crk sarcoma virus CT10 oncogene homolog (avian)
HGNC id 2362
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal SH2 domain functioning as a positive regulator of transformation
  • C-terminal SH3 domain functioning as a negative regulator of transformation
  • HOMOLOGY
    interspecies homolog to avian sarcoma virus CT10 (v-crk)
    Homologene
    FAMILY
  • adapter protein family
  • CATEGORY adaptor , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • colocolizing with DOCK1 and ELMO1 to membrane ruffles
  • significant percentage of the total endogenous CRK partitions in the nucleus in mammalian cells, where it forms distinct complexes with DOCK1, WEE1, and ABL1
  • basic FUNCTION
  • adaptor protein, involved in cell growth and motility
  • involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4
  • playing a crucial role in the aggressiveness of human synovial sarcoma
  • play a critical role in the breakdown of adherens junctions and the spreading of sheets of epithelial cells
  • have both cytosolic and nuclear functions
  • its nuclear compartmentalization antagonizes its cytoskeletal functions and assign a proapoptotic role to the nuclear pool of CRK
  • effector molecule for Rac1 activation that regulates cell motility
  • regulates cell migration, morphogenesis, invasion, phagocytosis, and survival
  • 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
  • CRK-MYO1C interaction, which modulates membrane dynamics by regulating RAC1 activity, is crucial for cell adhesion and spreading
  • CRK and CRKL have overlapping functions that are critical for maintaining cell structure and have critical roles in cell structure and motility by maintaining cytoskeletal integrity 0)
  • CRK, CRKL were required for effector T cell trafficking into sites of inflammation, but not for migration to lymphoid organs
  • CRK and CRKL play essential overlapping roles in fibroblast growth
  • CRK and CRKL play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription
    cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text cytoskeletal rearrangements during phagocytosis and cell motility,in the late steps of apoptotic process (complementation group 2 in C elegans)
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to GRB2, ELMO1
  • activating RAC1
  • interacting with PAFAH1B1
  • SH2-SH3 adaptor protein CRK is an essential target of GIT2 inhibition
  • with CRKL have been proposed to interact with tyrosine phosphorylated DAB1 to mediate downstream events in the Reelin pathway
  • interaction with DOK7, and CRKL (critical role for CRK and CRKL downstream from DOK7 in presynaptic and postsynaptic differentiation)(
  • interaction with SOS1 (have a surprising negative role for ABL kinases in CRK transformation)
  • cell & other
    REGULATION
    Other regulated by GRF2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in oral squamous cell carcinomas, tightly associated with an aggressive phenotype
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma
    ANIMAL & CELL MODELS