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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
Location 5p13.1      Physical location : 39.371.779 - 39.425.335
Synonym name
  • differentially expressed in ovarian cancer 2
  • differentially-expressed protein 2
  • Synonym symbol(s) DOC2, DOC-2, FLJ26626, p96
    DNA
    TYPE functioning gene
    STRUCTURE 53.56 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box) (TATA box)
    Binding site
    text structure TFIIB recognition elements, NFKB, AP2 and other sites
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC345513 5p13.2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) IDN3 5p13.2 IDN3 protein LOC391777 5 similar to ribosomal protein S4, X-linked FLJ13231 5p13.2 hypothetical protein FLJ13231 LOC389283 5 LOC389283 OFD1P1 5p13 oral-facial-digital syndrome 1, pseudogene 1 NUP155 5p13 nucleoporin 155kDa FLJ10233 5p13.2 hypothetical protein FLJ10233 GDNF 5p13-p12 glial cell derived neurotrophic factor FLJ39155 5p13.2 hypothetical protein FLJ39155 LIFR 5p13-p12 leukemia inhibitory factor receptor LOC253254 5p13.2 hypothetical LOC253254 OSMR 5p13.2 oncostatin M receptor KIAA1999 MGC39830 5p13.2 hypothetical protein MGC39830 FYB 5p13.1 FYN binding protein (FYB-120/130) C9 5p13 complement component 9 DAB2 5p13-p12.1 disabled homolog 2, mitogen-responsive phosphoprotein (Drosophila) LOC285634 5p13.2 similar to DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26; RNA helicase HDB; deleted in cancer 1; RNA helicase HDB/DICE1; DEAD box protein LOC389285 5 LOC389285 PTGER4 5p13.1 prostaglandin E receptor 4 (subtype EP4) OSRF 5p15.2-p12 osmosis responsive factor PRKAA1 5p14-p11 protein kinase, AMP-activated, alpha 1 catalytic subunit LOC389286 5 similar to FKSG62 RPL37 5p13-p12 ribosomal protein L37 CARD6 5p12 caspase recruitment domain family, member 6 C7 5p13 complement component 7 FLJ40243 5p13.1 hypothetical protein FLJ40243 C6 5p13 complement component 6 LOC345557 5p13.1 similar to RIKEN cDNA B130016O10 gene TCP1L2 5pter-p15.32 t-complex 1-like 2 OXCT 5p13 3-oxoacid CoA transferase LOC285636 5p13.1 hypothetical protein LOC285636 FBXO4 5p12 F-box only protein 4 LOC391779 5 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 4597 96 770 epithelial ovarian cells 2014 25360623
  • also called FL, p96
  • decreased expression in breast carcinoma
  • involved in MAPK signal transduction
  • 14 splicing 4554 - 749 brain stem retina -
    also called DAB2P93
    - - - 67 - - 2010 21063401
  • decreased expression in breast carcinoma
  • EXPRESSION
    Rna function
  • mRNA levels are greater in the small than in the large intestine
  • Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestineileum   Rattus norvegicusAdult
     intestinesmall intestinejejunum   Rattus norvegicusAdult
    Reproductivefemale systemplacenta  highly
    Skin/Tegumentskin   highly
    Urinarykidney     Rattus norvegicusAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Reproductiveepithelial cell
    cell lineage
    cell lines ovarian cancer cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text visceral endoderm
    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
  • 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
  • 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