InterPro domain: IPR036114

Myosin VI is a monomeric myosin, which moves towards the minus-end of actin filaments, in contrast to most other myosins which moves towards the plus-end of actin filaments. It is thought that myosin VI, unlike plus-end directed myosins, does not use a pure lever arm mechanism, but instead steps with a mechanism analogous to the kinesin neck-linker uncoupling model [ 1 , 2 ]. Myosin VI mediates cargo transport and also serves as an anchor that supports cellular architectures by physically connecting cytoskeletons with its binding targets, such as membranes. It has being implicated in a myriad of functions: the transport of cytoplasmic organelles, maintenance of normal Golgi morphology, endocytosis, secretion, cell migration, border cell migration during development, and in cancer metastasis, playing roles in deafness and retinal development among others [ 3 , 4 , 5 , 6 ]. While how this is accomplished is largely unknown there are several interacting proteins that have been identified such as disabled homologue 2 (DAB2), GIPC1, synapse-associated protein 97 (SAP97; also known as DLG1) and optineurin, which have been found to target myosin VI to different cellular compartments [ 7 ].

Myosin VI contains an N-terminal motor domain followed by a short neck (also called the lever arm), a hypothetical coiled-coil domain in the middle, and a C-terminal globular cargo-binding domain (CBD) [ 7 ]. The catalytic (head) domain has ATPase activity and belongs to the larger group of P-loop NTPases.

1. Processive Steps in the Reverse Direction Require Uncoupling of the Lead Head Lever Arm of Myosin VI. Mol. Cell 48, 75-86
2. Myosin VI: an innovative motor that challenged the swinging lever arm hypothesis. Nat. Rev. Mol. Cell Biol. 11, 128-37
3. Myosin VI targeting to clathrin-coated structures and dimerization is mediated by binding to Disabled-2 and PtdIns(4,5)P2. Nat. Cell Biol. 9, 176-83
4. Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer. Proc. Natl. Acad. Sci. U.S.A. 101, 8144-9
5. Progressive hereditary hearing impairment caused by a MYO6 mutation resembles presbyacusis. Hear. Res. 299, 88-98
6. Myosin 6 is required for iris development and normal function of the outer retina. Invest. Ophthalmol. Vis. Sci. 54, 7223-33
7. Myosin VI undergoes cargo-mediated dimerization. Cell 138, 537-48