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MGP002019

UniProt Annotations

Entry Information
Gene Namemyosin VI
Protein EntryMYO6_HUMAN
UniProt IDQ9UM54
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=6; Name=3; IsoId=Q9UM54-3; Sequence=Displayed; Name=1; IsoId=Q9UM54-1; Sequence=VSP_022332; Name=2; IsoId=Q9UM54-2; Sequence=VSP_007985; Name=4; IsoId=Q9UM54-4; Sequence=VSP_022333; Name=5; IsoId=Q9UM54-5; Sequence=VSP_007985, VSP_022333; Name=6; IsoId=Q9UM54-6; Sequence=VSP_042208;
CautionRepresents an unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6). {ECO:0000305}.
DiseaseDeafness, autosomal dominant, 22 (DFNA22) [MIM:606346]: 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. {ECO:0000269|PubMed:11468689}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDeafness, autosomal recessive, 37 (DFNB37) [MIM:607821]: 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. {ECO:0000269|PubMed:12687499}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseDeafness, sensorineural, with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346]: An autosomal dominant sensorineural deafness associated with hypertrophic cardiomyopathy. {ECO:0000269|PubMed:15060111}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainDivided 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 coiled-coil and a unique globular domain required for interaction with other proteins.
FunctionMyosins 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 (By similarity). {ECO:0000250}.
InteractionP98082:DAB2; NbExp=3; IntAct=EBI-350606, EBI-1171238; P98078:Dab2 (xeno); NbExp=4; IntAct=EBI-350606, EBI-1391846;
PtmPhosphorylation 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) (By similarity). {ECO:0000250}.
Sequence CautionSequence=BAA20843.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. {ECO:0000305}.
SimilarityContains 1 IQ domain. {ECO:0000305}.
SimilarityContains 1 myosin motor domain. {ECO:0000305}.
Subcellular LocationGolgi apparatus, trans-Golgi network membrane; Peripheral membrane protein. Golgi apparatus {ECO:0000250}. Nucleus. Cytoplasm, perinuclear region. Membrane, clathrin-coated pit. Cell projection, ruffle membrane; Peripheral membrane protein. Note=Also present in endocyctic vesicles, and membrane ruffles. Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and 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 and in vesicular structures close to the plasma membrane (By similarity). {ECO:0000250}.
Subcellular LocationIsoform 3: Cytoplasmic vesicle, clathrin- coated vesicle membrane.
Subcellular LocationIsoform 4: Cytoplasmic vesicle, clathrin- coated vesicle membrane. Cell projection, ruffle membrane.
SubunitHomodimer. Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal. This interaction occurs only if the C- terminal lobe of calmodulin is occupied by calcium. Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (By similarity). 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 and DAB2 in the apical membrane of epithelial cells. Interacts with OPTN (By similarity). {ECO:0000250}.
Tissue SpecificityExpressed 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. {ECO:0000269|PubMed:9259267}.
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