myosin-6; unconventional myosin-6 (MYO6, KIAA0389)
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Function
- 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 & cell migration
- required for structural integrity of the Golgi 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 (putative)
- phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles & affects F-actin dynamics
- phosphorylated in vitro by p21- activated kinase (PAK) (putative)
- binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain & the IQ domain appears to contribute to the directionality reversal
- occurs only if the C-terminal lobe of calmodulin is occupied by Ca+2
- interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (putative)
- interacts with DAB2 in vitro, the C-terminal globular tail binds a C-terminal region of DAB2
- interacts with CFTR
- forms a complex with CFTR & DAB2 in the apical membrane of epithelial cells
- interacts with OPTN
Structure
- homodimer
- divided into three regions:
- N-terminal motor (head) domain
- neck domain consisting of a calmodulin-binding linker domain & a single IQ motif
- C-terminal tail region with a coiled-coil & a unique globular domain required for interaction with other proteins
- contains 1 IQ domain
- contains 1 myosin head-like domain
Compartment
- Golgi, trans-Golgi network membrane
- nucleus, cytoplasm, perinuclear region
- membrane, clathrin-coated pit
- cell projection, ruffle membrane
- also present in endocyctic vesicles, & membrane ruffles
- translocates from membrane ruffles, endocytic vesicles & cytoplasm to Golgi, perinuclear membrane & nucleus through induction by p53 & p53-induced DNA damage
- recruited into membrane ruffles from cell surface by EGF- stimulation
- colocalizes with DAB2 in clathrin-coated pits/vesicles
- colocalizes with OPTN at the Golgi complex & in vesicular structures close to the plasma membrane (putative)
- isoform 3:
- cytoplasmic vesicle, clathrin-coated vesicle membrane
- isoform 4:
- cytoplasmic vesicle, clathrin-coated vesicle membrane
Alternative splicing
named isoforms=5
Expression
- expressed in most tissues examined including heart, brain, placenta, pancreas, spleen, thymus, prostate, testis, ovary, small intestine & colon
- highest levels in brain, pancreas, testis & small intestine
- also expressed in fetal brain & cochlea
- isoform 1 & isoform 2, containing the small insert, & isoform 4, containing neither insert, are expressed in unpolarized epithelial cells
Pathology
- defects in MYO6 are the cause of
More general terms
Additional terms
References
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4646
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4646
- OMIM: https://mirror.omim.org/entry/600970
- OMIM: https://mirror.omim.org/entry/606346
- OMIM: https://mirror.omim.org/entry/607821
- UniProt: http://www.uniprot.org/uniprot/Q9UM54.html