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FLASH GENE
Symbol DOCK2 contributors: mct/pgu - updated : 06-09-2017
HGNC name dedicator of cyto-kinesis 2
HGNC id 2988
Corresponding disease
IMD40 Immunodeficiency 40
Location 5q35.1      Physical location : 169.064.250 - 169.510.384
Synonym name dedicator of cyto-kinesis 2
Synonym symbol(s) KIAA0209, FLJ46592
DNA
TYPE functioning gene
STRUCTURE 446.13 kb     52 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif Viral sequence   long terminal repeat
text structure specific HERV-K LTR within intron 30
MAPPING cloned Y linked N status provisional
Physical map
LOC134541 5q35.1 similar to Ten-m2 ODZ2 5q35.1 odd Oz/ten-m homolog 2 KIBRA 5q35.1 KIBRA protein RARS 5pter-q11 arginyl-tRNA synthetase LOC345630 5q35.1 similar to fibrillarin PANK3 5q35 pantothenate kinase 3 LOC389342 5 similar to 60S ribosomal protein L10 (QM protein homolog) SLIT3 5q35 slit homolog 3 (Drosophila) FLJ20364 5q35.1 hypothetical protein FLJ20364 DOCK2 5q35.1 dedicator of cyto-kinesis 2 FOXI1 5q34 forkhead box I1 LOC345430 5q35.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC133874 5q35.1 hypothetical gene LOC133874 LCP2 5q34 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) KCNMB1 5q34 potassium large conductance calcium-activated channel, subfamily M, beta member 1 KCNIP1 5q35.2 Kv channel interacting protein 1 LOC389343 5 LOC389343 GABRP 5q33-q34 gamma-aminobutyric acid (GABA) A receptor, pi RANBP17 5q31 RAN binding protein 17 USP12P1 5q33-q34 ubiquitin specific protease 12 pseudogene 1 TLX3 5q35.1 T-cell leukemia, homeobox 3 LOC391847 5 similar to hypothetical protein LOC391848 5 similar to 60S ribosomal protein L10 (QM protein homolog) NPM1 5q35 nucleophosmin (nucleolar phosphoprotein B23, numatrin) FGF18 5q34 fibroblast growth factor 18 FBXW1B 5q35.1 F-box and WD-40 domain protein 1B STK10 5q35.1 serine/threonine kinase 10 LOC285588 5q35.2 similar to RIKEN cDNA 1700007I06 DC-UbP 5q35.2 dendritic cell-derived ubiquitin-like protein KIAA1295 5q35.2 KIAA1295 protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
52 - 6117 211.8 1830 - 2010 20350533
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunespleen   highly Homo sapiens
 thymus   highly Homo sapiens
Nervousbrain     Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoietic   predominantly Homo sapiens
Blood / hematopoieticplasma    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte Homo sapiens
Blood/Hematopoieticmature hematopoietic Homo sapiens
Blood/Hematopoieticprogenitor cell Homo sapiens
Lymphoid/Immunemacrophage Homo sapiens
Nervousglia Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • SH3 domain at the N terminus
  • a DHR-1 domain for binding to PIP3 and mediating the GTP-GDP exchange reaction for Rac
  • a DOCK homology region (DHR)-2 (CZH2 or Docker domain)
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Dock2 (95.2pc)
    homolog to rattus Dock2 (93.8pc)
    intraspecies homolog to DOCK180, CED5
    Homologene
    FAMILY
  • CDM protein family
  • DOCK family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • upon stimulation, translocates to the plasma membrane in a phosphatidylinositol 3,4,5 triphosphate-dependent manner
  • basic FUNCTION
  • being indispensable for lymphocyte chemotaxis
  • activating RAC1 in non-adherent cells
  • playing a critical role in lymphocyte migration by regulating actin cytoskeleton through Rac activation
  • playing a significant role in bone marrow lymphopoiesis, but is dispensable for hematopoietic stem/progenitor cell engraftment
  • major Rac GEF that controls motility and polarity during neutrophil chemotaxis
  • regulates microglial innate immunity independent of PTGS2 induction and DOCK2+ microglia are associated with human AD pathology
  • regulating the cell proliferation in B cell lymphoma through RAC1 and MAPK activation thus having a prominent role in hematopoietic malignancy regulates cell motility and cytokine production through the activation of RAC1 in hematopoietic cells and plays a pivotal role in the modulation of the immune system
  • role for DOCK2 in proliferation of hormone-refractory CXCR5-positive psostate carcinoma cells
  • activate the Rho-family GTPases RAC1 and CDC42 to control cell migration, morphogenesis, and phagocytosis
  • hematopoietic cell-specific, atypical guanine nucleotide exchange factor, controls lymphocyte migration through ras-related C3 botulinum toxin substrate (Rac) activation
  • mediates the GTP-GDP exchange reaction for RAC1 via its DOCK homology region (DHR)-2
  • modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity
  • DOCK2 contributes to APP plaque burden via regulation of microglial innate immune function
  • DOCK5 acts with DOCK2 in neutrophils to regulate multiple cellular functions
  • DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation
  • is a novel regulator for vascular smooth muscle cell (SMC) phenotypic modulation and vascular lesion formation after vascular injury
  • is involved in cell motility, polarity, adhesion, proliferation, and apoptosis, and is essential for lymphocyte migration and activation as well as neutrophil chemotaxis
  • key molecule for lymphocyte activation and migration
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and RAC1 are localized to the plasma membrane
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to RAC1 in non adherent cells
  • associating with engulfment and cell motility (ELMO1) through its Src-homology 3 (SH3) domain (critical for DOCK2-mediated Rac activation)
  • links T cell receptor signals to downregulation of IL4R to control the lineage commitment of CD4+ T cells
  • interacting with Rac2 and Cdc42 (specifically recognize Rac2 and Cdc42 through its switch 1 as well as 2-3regions)
  • the entire regions of both DOCK2 and ELMO1 assemble to create a rigid structure, which is required for the DOCK2/ELMO1 binding, that is structural basis by which DOCK2 and ELMO1 mutually relieve their autoinhibition for the activation of RAC1 for lymphocyte chemotaxis
  • role for ELMO1 in controlling DOCK2 levels and DOCK2-dependent T cell migration in primary lymphocytes
  • cell & other
    REGULATION
    Other DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize to Rac activation during neutrophils chemotaxis
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD40
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    DOCK2 is a COX2 expression-independent therapeutic target for neurodegenerative diseases such as AD
    immunology  
    therapeutic target for immunologic disorders caused by lymphocyte infiltration
    cancerhemopathy 
    is a potential therapeutic target for novel AML treatments, as this protein regulates the survival of leukemia cells with elevated FLT3 activity and sensitizes FLT3/ITD leukemic cells to conventional antileukemic agents
    ANIMAL & CELL MODELS
  • T-lymphoid progenitor cells in fetal mice express two closely related CDM family molecules, Dock2 and Dock1, and 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