ID:MYO6_HUMAN DESCRIPTION: RecName: Full=Unconventional myosin-VI; AltName: Full=Unconventional myosin-6; 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 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). SUBUNIT: Homodimer. 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). SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein. Golgi apparatus (By similarity). 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). SUBCELLULAR LOCATION: Isoform 3: Cytoplasmic vesicle, clathrin- coated vesicle membrane. SUBCELLULAR LOCATION: Isoform 4: Cytoplasmic vesicle, clathrin- coated vesicle membrane. Cell projection, ruffle membrane. 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. 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 coiled-coil and a unique globular domain required for interaction with other proteins. PTM: 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) (By similarity). DISEASE: Defects in MYO6 are the cause of deafness autosomal dominant type 22 (DFNA22) [MIM:606346]. DFNA22 is a form of 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. DISEASE: Defects in MYO6 are the cause of deafness autosomal recessive type 37 (DFNB37) [MIM:607821]. DISEASE: Defects in MYO6 are the cause of deafness sensorineural with hypertrophic cardiomyopathy (DFNHCM) [MIM:606346]. SIMILARITY: Contains 1 IQ domain. SIMILARITY: Contains 1 myosin head-like domain. CAUTION: Represents a unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6). SEQUENCE CAUTION: Sequence=BAA20843.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UM54
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006886 intracellular protein transport GO:0006897 endocytosis GO:0007018 microtubule-based movement GO:0007605 sensory perception of sound GO:0015031 protein transport GO:0030048 actin filament-based movement GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0042493 response to drug GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0051046 regulation of secretion
BX647397 - Homo sapiens mRNA; cDNA DKFZp686L10144 (from clone DKFZp686L10144). BC012598 - Homo sapiens myosin VI, mRNA (cDNA clone IMAGE:4295486), with apparent retained intron. AB002387 - Homo sapiens mRNA for KIAA0389 gene. BC146764 - Homo sapiens myosin VI, mRNA (cDNA clone MGC:166836 IMAGE:9007206), complete cds. U90236 - Homo sapiens myosin VI (MYO6) mRNA, complete cds. AB385322 - Synthetic construct DNA, clone: pF1KA0389, Homo sapiens MYO6 gene for myosin-VI, complete cds, without stop codon, in Flexi system. KJ891664 - Synthetic construct Homo sapiens clone ccsbBroadEn_01058 MYO6 gene, encodes complete protein. KY781827 - Homo sapiens myosin VI transcript variant 007 (Myo6-007) mRNA, complete cds, alternatively spliced. KY781828 - Homo sapiens myosin VI transcript variant 008 (Myo6-008) mRNA, complete cds, alternatively spliced. L29145 - Homo sapiens myosin mRNA, partial cds. JD368568 - Sequence 349592 from Patent EP1572962. JD126088 - Sequence 107112 from Patent EP1572962. LF208563 - JP 2014500723-A/16066: Polycomb-Associated Non-Coding RNAs. AK095294 - Homo sapiens cDNA FLJ37975 fis, clone CTONG2010133, highly similar to Homo sapiens myosin VI (MYO6) gene. JD292192 - Sequence 273216 from Patent EP1572962. JD244877 - Sequence 225901 from Patent EP1572962. JD502596 - Sequence 483620 from Patent EP1572962. JD504012 - Sequence 485036 from Patent EP1572962. JD376752 - Sequence 357776 from Patent EP1572962. JD537352 - Sequence 518376 from Patent EP1572962. JD194754 - Sequence 175778 from Patent EP1572962. JD185482 - Sequence 166506 from Patent EP1572962. MA444140 - JP 2018138019-A/16066: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9UM54 (Reactome details) participates in the following event(s):
R-HSA-190519 Internalization of gap junction plaques R-HSA-416320 Trafficking of GluR1-containing AMPA receptors R-HSA-190873 Gap junction degradation R-HSA-399719 Trafficking of AMPA receptors R-HSA-190828 Gap junction trafficking R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity R-HSA-157858 Gap junction trafficking and regulation R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission R-HSA-199991 Membrane Trafficking R-HSA-112315 Transmission across Chemical Synapses R-HSA-5653656 Vesicle-mediated transport R-HSA-112316 Neuronal System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
