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FLASH GENE
Symbol DOK1 contributors: mct/npt - updated : 07-04-2015
HGNC name docking protein 1, 62kDa (downstream of tyrosine kinase 1)
HGNC id 2990
Location 2p12      Physical location : 74.781.859 - 74.784.662
Synonym name
  • docking protein 1, 62kD (downstream of tyrosine kinase 1)
  • downstream of tyrosine kinase 1
  • Synonym symbol(s) MGC117395, MGC138860, P62DOK, pp62
    DNA
    TYPE functioning gene
    STRUCTURE 9.35 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D2S145 - DOK1 - D2S169 - cen
    Authors Nelms (98)
    regionally located in the PARK3 region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2269 52.4 481 - 2007 17092301
    also called isoform p62DOK1
    3 splicing 1992 - 342 - 2007 17092301
  • also called variant p22DOK1
  • a class II proline-rich C terminal motif
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet
    Lymphoid/ImmuneB cell
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines chronic myeloid leukemia progenitor cells
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal insulin receptor substrate motif (IRS1),
  • potential tyrosine-phosphorylation binding sites (PTB)
  • a putative pleckstrin homology (PH) domain at the N terminus, necessary for the tyrosine phosphorylation of Dok proteins and their negative functions in T cells (Guittard 2009)
  • ten PXXP SH3 recognition motifs
  • HOMOLOGY
    Homologene
    FAMILY
  • Dok family of adaptors
  • type A subfamily
  • CATEGORY adaptor , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text activation of PI3 kinase by KIT ligand promotes DOK1 binding to the membrane where DOK1 is phosphorylated by Src and Tec family kinases;recruited to membrane by KILG or PI3K
    basic FUNCTION
  • protein-protein interaction
  • promoting adipocyte hypertrophy by counteracting the inhibitory effect of ERK on PPAR-gamma and may thus confer predisposition to diet-induced obesity
  • negatively regulates mitogen-activated protein kinase Erk downstream of protein-tyrosine kinases (PTKs) (Honma 2006)
  • major tyrosine-phosphorylated protein associated to TEC, a protein tyrosine kinase expressed in T cells (Gerard 2004)
  • involved in a negative feedback regulation of TEC via a downregulation of its tyrosine phosphorylation and downstream signalling pathways including the Ras pathway (Gerard 2004)
  • adaptor protein that function in feedback loops to modulate tyrosine kinase signaling (Berger 2010)
  • function in negative-feedback signaling loops that tightly modulate the duration and intensity of growth factor signaling (Berger 2010)
  • represents a true TSG in epithelial ovarian cancer
  • INPP5D, DOK1 and DOK2 play central roles in CD4-mediated inhibitory signaling
  • novel role for DOK1 in the regulation of thymic differentiation and in particular, in the development of PLZF(+) gammadelta T cells
  • acts as a key mediator of cellular stress-induced cell death
  • DOK1, DOK2, and DOK3 cooperatively play critical anti-inflammatory roles in lung homeostasis
  • DOK1 and DOK2 differentially regulate TLR2-induced pro-inflammatory signaling in astrocytes and microglia
  • DOK1 and DOK2 proteins are involved in an intrinsic negative feedback loop downstream of NK-cell-activating receptors
  • DOK1 adaptor is the key effector for the enhancement of CRKL transformation by ABLinhibition
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text negative regulator of proliferation when bound to membrane
    PATHWAY
    metabolism
    signaling signal transduction
    mitogenic signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • linking activin receptors with Smad (MADH3) proteins and leading to B cells apoptosis
  • associating to RASA1 (GAP-RAS)
  • associating to SH2D1A and activating NF kappa B
  • associating with LCK
  • links the activated insulin receptor to adipocyte hypertrophy, thereby contributing to the pathogenesis of diet-induced obesity
  • novel mechanism of action of PTK6 in the promotion of tumor formation, which involves the targeting of tumor suppressor DOK1 for degradation through the ubiquitin proteasomal pathway
  • cell & other
    REGULATION
    activated by phosphorylated by BCR-ABL and other tyrosine protein kinase
    KIT ligand (KITLG)
    upregulated by LCK
    phosphorylated and recruited to membrane by PI3K and SRC family kinases
    Other substrate for BCR-ABL and other tyrosine-kinases
    regulated mainly by the transcription factor E2F1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    constitutively tyrosine phosphorylated in chronic myelogenic leukemia progenitor cells
    constitutional       loss of function
    DOK1 and DOK2 deficiency induces osteopenia by activation of osteoclasts
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • hypermethylation of DOK1 is a potentially critical event in human carcinogenesis, and may be a potential cancer biomarker
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    hypermethylation of DOK1 is and an attractive target for epigenetic-based therapy
    ANIMAL & CELL MODELS