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FLASH GENE
Symbol DAB2 contributors: mct/ - updated : 26-08-2015
HGNC name disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila)
HGNC id 2662
PROTEIN
PHYSICAL PROPERTIES Hydrophobic
STRUCTURE
motifs/domains
  • an N-terminal phosphotyrosine-binding (PTB) domain
  • a phosphotyrosine interaction domain PBD/PID
  • multiple SH3 binding motifs
  • a C-terminal proline-rich domain (PRD), which have been shown to associate with the low-density lipoprotein receptor
  • HOMOLOGY
    interspecies homolog to Drosophila disabled- 2
    homolog to murine mitogen responsive-phosphoprotein p96
    Homologene
    FAMILY
    CATEGORY adaptor , signaling , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • putatively involved in cellular transduction
  • implicated in clathrin-mediated internalization of LDL-receptor family members
  • can modulate androgen receptor-mediated cell growth in both normal and malignant prostatic epithelial cells (this could evolve into a new therapeutic strategy of prostate cancer)
  • playing a role in ARH fibroblasts (hypercholesterolemia, severe), where it is apparently required to allow normal translation of LDL receptor mRNA
  • implicated in signal transduction pathways and in protein traffic regulation
  • via SRC and focal adhesion signaling, plays a role in endothelial cell function
  • controls migration and capillary-like tube formation by modulating FAK activity via SRC
  • could attenuate Wnt/beta-catenin signaling by stabilizing AXIN1 and preventing its translocation to the membrane
  • stabilizes AXIN1 and attenuates Wnt/beta-catenin signaling by preventing PPP1CC from binding AXIN1
  • intracellular adaptor protein proposed to function in endocytosis
  • multidomain cargo-specific endocytic adaptor and a mediator of signal transduction, is a potential integrator of trafficking and signaling
  • is pivotal for endothelial cell migration by affecting VEGFA expression
  • tumour suppressor functions of DAB2 involve modulation of canonical Wnt signalling by regulating the endocytic fate of the LRP6 receptor
  • is the key adaptor in the clathrin-associated endocytic complexes to mediate fibrinogen internalization
  • endocytic adaptor protein involved in clathrin-mediated endocytosis and cargo trafficking
  • has a physiological role in the endocytosis of lipoproteins and cholesterol metabolism
  • negatively regulates TGFB1-induced c-Jun N-terminal kinase (JNK) activation, whereas activation of the Smad pathway is unaffected
  • plays a role in modulating TGF-beta signaling to enhance apoptotic clearance of mammary epithelial cells during involution
  • is required for migration and invasion of prostate cancer cells
  • in the absence of LDLRAP1, DAB2 in liver endothelial cells regulates cholesterol synthesis in hepatocytes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS endocytosis transport
    text participating in the clathrin-mediated endocytosis process
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MYH9 is functionally linked to megalin by interaction with DAB2 and is likely involved in megalin-mediated endocytosis in proximal tubule cells
  • significant role for DAB2 both in the endocytosis and post-endocytic fate of CFTR
  • FCHO2 is a major DAB2-interacting protein
  • selectively recruits LRP6 to the clathrin-dependent endocytic route, thereby sequestering it from caveolin-mediated endocytosis
  • MYO6 functions in endocytosis in conjunction with binding partners including adaptor protein (TFAP2A, DAB2, and GIPC1)
  • DAB2 interacts with TGFBR1 to restrict its lateral diffusion at the plasma membrane and enhance its clathrin-mediated endocytosis
  • both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule
  • loss of traction force on ligand-bound ITGB3 causes recruitment of DAB2/clathrin, resulting in endocytosis of integrins
  • combination of LDLRAP1 and DAB2 is responsible for the majority of adaptor function in LDLR endocytosis and LDLR-mediated cholesterol homeostasis
  • cell & other
    REGULATION
    induced by GATA6 in the visceral endoderm
    Other phosphorylated in mitosis and is thus regulated in the cell cycle
    negative regulation is part of an accommodation of the cell to the altered physicochemical conditions prevalent in mitosis, aimed at allowing endocytic activity throughout the cell cycle
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in 80-90p100 ovarian tumors and ovarian/breast cancer cell lines
    tumoral     --low  
    occurs in early pre-neoplastic stages of development of esophageal cancer
    tumoral        
    loss of its expression, commonly observed in breast cancer, may facilitate TGFb-stimulated EMT, and therefore increase the propensity for metastasis
    tumoral       loss of function
    in myelodysplastic syndrome (MDS) in part by DNA methylation, and the suppression of DAB2 expression by DNA methylation may play a role in the development of MDS
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • elimination of both Arh and Dab2 genes in mice resulted in profound hypercholesterolemia similar to that resulting from Ldlr homozygous deletion