Protein: DAB2_MOUSE
Sequence: MSNEVETSTTNGQPDQQAAPKAPSKKEKKKGSEKTDEYLLARFKGDGVKYKAKLIGIDDVPDARGDKMSQDSMMKLKGMAAAGRSQGQHKQRIWVNISLSGIKIIDEKTGVIEHEHPVNKISFIARDVTDNRAFGYVCGGEGQHQFFAIKTGQQAEPLVVDLKDLFQVIYNVKKKEEDKKKVEEANKAEENGSEALMTLDDQANKLKLGVDQMDLFGDMSTPPDLNSPTESKDILLVDLNSEIDTNQNSLRENPFLTNGVTSCSLPRPKPQASFLPENAFSANLNFFPTPNPDPFRDDPFAQPDQSAPSSFDSLTSPDQKKASLSSSSTPQSKGPLNGDTDYFGQQFDQLSNRTGKPEAQGGPWPYPSSQTQQAVRTQNGVSEREQNGFHIKSSPNPFVGSPPKGLSVPNGVKQDLESSVQSSAHDSIAIIPPPQSTKPGRGRRTAKSSANDLLASDIFASEPPGQMSPTGQPAVPQSNFLDLFKGNAPAPVGPLVGLGTVPVTPPQAGPWTPVVYSPSTTVVPGAIISGQPPSFRQPLVFGTTPAVQVWNQSPSFATPASPPPPTVWCPTTSVAPNAWSSTSPLGNPFQSNNIFPPPTMSTQSSPQPMMSSVLATPPQPPPRNGPLKDIPSDAFTGLDPLGDKEVKEVKEMFKDFQLRQPPLVPSRKGETPPSGTSSAFSSYFNNKVGIPQEHVDHDDFDANQLLNKINEPPKPAPRQGVLLGTKSADNSLENPFSKGFSSSNPSVVSQPASSDPHRSPFGNPFA
What is the function of this 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.  Isoform p96 is involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development.  Required for recycling of the TGF-beta receptor.  Isoform p67 is not involved in LDL receptor endocytosis.  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.  Isoform p67 may be involved in transcriptional regulation.  May act as a tumor suppressor.
What are the official names of this protein?
Disabled homolog 2, Adaptor molecule disabled-2, Differentially expressed in ovarian carcinoma 2, DOC-2, Mitogen-responsive phosphoprotein.
What are the subcellular locations of this protein?
Cytoplasmic vesicle, clathrin-coated vesicle membrane. Membrane, clathrin-coated pit. Note=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 (By similarity). SUBCELLULAR LOCATION: [Isoform p96]: Membrane, clathrin-coated pit. Note=Colocalizes with LDLR at clathrin-coated pits. SUBCELLULAR LOCATION: [Isoform p67]: Cytoplasm. Nucleus. Note=Diffuse localization in the cytoplasm; does not localize to clathrin-coated pits.