MYO6
Domain
Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding.
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (PubMed:18511944). Its contribution to the mechanism conferring the myosin movement on actin filaments is debated (PubMed:18511944).
Function
Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (PubMed:10519557). Has slow rate of actin-activated ADP release due to weak ATP binding (By similarity). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (By similarity). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (PubMed:16507995). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (PubMed:11447109). Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes (PubMed:23023224). Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777). May act as a regulator of F-actin dynamics (By similarity). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (By similarity). May play a role in the extension and network organization of neurites (By similarity). Required for structural integrity of inner ear hair cells (By similarity). Required for the correct localization of CLIC5 and RDX at the stereocilium base (By similarity). Modulates RNA polymerase II-dependent transcription (PubMed:16949370).
Involvement in disease
Deafness, autosomal dominant, 22
DFNA22
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA22 is progressive and postlingual, with onset during childhood. By the age of approximately 50 years, affected individuals invariably have profound sensorineural deafness.
None
The disease is caused by variants affecting the gene represented in this entry.
Deafness, autosomal recessive, 37
DFNB37
A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
None
The disease is caused by variants affecting the gene represented in this entry.
Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy
DFNHCM
An autosomal dominant sensorineural deafness associated with hypertrophic cardiomyopathy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK).
Sequence Similarities
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Tissue Specificity
Expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in brain, pancreas, testis and small intestine. Also expressed in fetal brain and cochlea. Isoform 1 and isoform 2, containing the small insert, and isoform 4, containing neither insert, are expressed in unpolarized epithelial cells.
Cellular localization
- Golgi apparatus
- trans-Golgi network membrane
- Peripheral membrane protein
- Golgi apparatus
- Nucleus
- Cytoplasm
- Perinuclear region
- Membrane
- Clathrin-coated pit
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Cell projection
- Filopodium
- Cell projection
- Ruffle membrane
- Cell projection
- Microvillus
- Cytoplasm
- Cytosol
- Cytoplasmic vesicle
- Autophagosome
- Endosome
- Also present in endocyctic vesicles (PubMed:16507995). Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage (PubMed:16507995). Recruited into membrane ruffles from cell surface by EGF-stimulation (PubMed:9852149). Colocalizes with DAB2 in clathrin-coated pits/vesicles (PubMed:11967127). Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (By similarity). Recruited to endosomes by TOM1 and TOM1L2 (PubMed:23023224).
- Isoform 3
- Cytoplasmic vesicle
- Clathrin-coated vesicle membrane
- Isoform 4
- Cytoplasmic vesicle
- Clathrin-coated vesicle membrane
- Cell projection
- Ruffle membrane
Alternative names
KIAA0389, MYO6, Unconventional myosin-VI, Unconventional myosin-6