DAB2

This gene encodes a mitogen-responsive phosphoprotein. It is expressed in normal ovarian epithelial cells, but is down-regulated or absent from ovarian carcinoma cell lines, suggesting its role as a tumor suppressor. This protein binds to the SH3 domains of GRB2, an adaptor protein that couples tyrosine kinase receptors to SOS (a guanine nucleotide exchange factor for Ras), via its C-terminal proline-rich sequences, and may thus modulate growth factor/Ras pathways by competing with SOS for binding to GRB2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

DAB2, Clathrin Adaptor Protein

Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. May act as a tumor suppressor.

Apoptotic process Source: UniProtKB-KW
Leading edge cell differentiation Source: UniProtKB
Membrane organization Source: Reactome
Multicellular organism development Source: UniProtKB-KW
Negative regulation of androgen receptor signaling pathway Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
Negative regulation of protein binding Source: BHF-UCL
Negative regulation of protein localization to plasma membrane Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of cell migration Source: UniProtKB
Positive regulation of clathrin-dependent endocytosis Source: UniProtKB
Positive regulation of early endosome to late endosome transport Source: UniProtKB
Positive regulation of endocytosis Source: UniProtKB
Positive regulation of epithelial to mesenchymal transition Source: UniProtKB
Positive regulation of pathway-restricted SMAD protein phosphorylation Source: UniProtKB
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
Positive regulation of protein phosphorylation Source: BHF-UCL
Positive regulation of SMAD protein signal transduction Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
Positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: BHF-UCL
Protein transport Source: UniProtKB-KW
Receptor-mediated endocytosis Source: GO_Central
Wnt signaling pathway Source: UniProtKB-KW

Cytoplasm; Clathrin-coated vesicle membrane; Clathrin-coated pit. Colocalizes with large insert-containing isoforms of MYO6 at clathrin-coated pits/vesicles. During mitosis is progressively displaced from the membrane and translocated to the cytoplasm.

Phosphorylated. Phosphorylation during mitosis is leading to membrane displacement (By similarity).