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FLASH GENE
Symbol DOCK1 contributors: mct - updated : 31-12-2018
HGNC name dedicator of cytokinesis 1
HGNC id 2987
Location 10q26.2      Physical location : 128.594.022 - 129.250.779
Synonym name
  • 180 kDa protein downstream of CRK
  • downstream of CrK
    • Synonym symbol(s) RP11-82L9.1, DOCK180, CED-5
    DNA
    TYPE functioning gene
    SPECIAL FEATURE escaping inactivation
    STRUCTURE 481.82 kb     51 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    51 - 6751 215 1865 - 1996 8661160
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Endocrinepancreas   highly
     parathyroid   highly
    Reproductivefemale systemplacenta  highly
     female systemovary  highly
     male systemtestis    Homo sapiens
    Respiratorylung   highly
     respiratory tractlarynx  highly
    Urinarykidney   highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    ReproductiveSertoli cell Homo sapiens
    Urinarypodocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a SH3 domain (signal transduction)
  • two conserved domains, called DOCK homology region (DHR)-1 and -2 , DHR1 is required for binding to phosphoinositides
    • and DHR2 (CZH-2) is necessary and sufficient for the GEF activity
    conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Dock1 (96.5pc)
    Homologene
    FAMILY
  • DOCK180-family proteins
  • CZH proteins family
    • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endosome
    text
  • associating with cell membrane when farnesylated
  • colocalizing with CRK-II and ELMO1 in membrane ruffles
  • colocalized with DOCK1 at endosomes
    • basic FUNCTION
  • engulfment and removal of cells undergoing apoptosis
  • involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility
  • implicated in cell migration, phagocytosis of apoptotic cells, T-cell activation and neurite outgrowth, and probably arose relatively early in eukaryotic evolution
  • functionning as a GRF, which activates Rac Rho small GTPases
  • essential role in mediating attractive resposnes by neurons to netrin 1
  • plays an essential role in a wide variety of biological functions including cell migration, phagocytosis of apoptotic cells, and myoblast fusion
  • regulates cation-independent mannose 6-phosphate receptor (CI-MPR) trafficking via SNX5 and this function is independent of its guanine nucleotide exchange factor activity toward RAC1
  • has an essential role in embryonic development
  • DOCK1 and DOCK5 are critical regulators of the fusion step during primary myogenesis
  • ELMO1 and DOCK1 function through the RAC1 GTPase in hippocampal neurons
  • DOCK1 and DOCK5 are not the important exchange factors regulating RAC1 activity during the establishment and maintenance of the glomerular barrier
    • CELLULAR PROCESS cell life, cell death/apoptosis
    cell organization/biogenesis
    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
    a component
  • RHOG-ELMO-DOCK1 pathway is required for activation of RAC1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor
  • forms a trimeric complex with ELMO1 and BAI1
  • ELMO1/DOCK1 complex functions through Rac1 in various cellular contexts including migration and phagocytosis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to CRK and ELMO1
  • activating RAC1
  • DOCK1-ELMO1 interaction is necessary to modulate actin cytoskeleton for phagocytosis and cell migration
  • GRASP and IPCEF1 promote ARF-to-RAC1 signaling and cell migration by coordinating the association of CYTH2 with DOCK1
  • ELMO1 is necessary for functions of DOCK1, functioning in a complex with DOCK1 in spine morphogenesis through activating the RAC1 GTPase
  • DOCK1 is required for signaling by ELMO1-MACF1
  • GRASP binds directly both CYTH2 and DOCK1 to coordinate their activities, and by doing so promotes crosstalk between ARF and RAC1
  • unlike DOCK5, DOCK1 bound to phosphatidic acid (PA) through the C-terminal polybasic amino acid cluster and was localized to dorsal ruffles
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in acute myeloid leukemia with increased mortality
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, Dock2 and Dock1, and the impaired fetal thymus colonization in mice deficient for Dock2 and Dock1 was not as severe as that in mice doubly deficient for Ccr7 and Ccr9