3h8d

Structural highlights

Disease

[MYO6_MOUSE] Note=Defects in Myo6 are the cause of Snell's waltzer, a condition characterized by circling, head-tossing, deafness and hyperactivity.

Function

[MYO6_MOUSE] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments. Has slow rate of actin-activated ADP release due to weak ATP binding. Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration. Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway. Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells. May act as a regulator of F-actin dynamics. May play a role in transporting DAB2 from the plasma membrane to specific cellular targets. Required for structural integrity of inner ear hair cells. [DAB2_RAT] 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 containg 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.^{[1] [2]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Myosin

References

1. ↑ Zhou J, Scholes J, Hsieh JT. Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer. J Biol Chem. 2003 Feb 28;278(9):6936-41. Epub 2002 Dec 8. PMID:12473651 doi:10.1074/jbc.M210628200
2. ↑ Chetrit D, Ziv N, Ehrlich M. Dab2 regulates clathrin assembly and cell spreading. Biochem J. 2009 Mar 15;418(3):701-15. doi: 10.1042/BJ20081288. PMID:19000037 doi:10.1042/BJ20081288
3. ↑ Yu C, Feng W, Wei Z, Miyanoiri Y, Wen W, Zhao Y, Zhang M. Myosin VI undergoes cargo-mediated dimerization. Cell. 2009 Aug 7;138(3):537-48. PMID:19665975 doi:10.1016/j.cell.2009.05.030