Q29122MYO6_PIGUnconventional myosin-VIUnconventional myosin-6MYO6Sus scrofaPigEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaArtiodactylaSuinaSuidaeSusPorcine myosin-VI: characterization of a new mammalian unconventional myosin.NUCLEOTIDE SEQUENCE [MRNA]FUNCTIONINTERACTION WITH ACTN1SUBCELLULAR LOCATIONTISSUE SPECIFICITYIdentification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types.NUCLEOTIDE SEQUENCE [MRNA]ERRATUM OF PUBMED:8022818Calcium functionally uncouples the heads of myosin VI.PHOSPHORYLATION AT THR-406CALCIUM-BINDINGMUTAGENESIS OF THR-406The unique insert in myosin VI is a structural calcium-calmodulin binding site.CALCIUM-CALMODULIN BINDING SITEDOMAINMyosin VI altered at threonine 406 stabilizes actin filaments in vivo.MUTAGENESIS OF THR-406POSSIBLE FUNCTIONSUBCELLULAR LOCATIONMyosin VI must dimerize and deploy its unusual lever arm in order to perform its cellular roles.SUBUNITDOMAINMUTAGENESIS OF PHE-854; VAL-857; VAL-858 AND LEU-861The structure of the myosin VI motor reveals the mechanism of directionality reversal.X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-859 IN COMPLEX WITH CALMODULINATPASE ACTIVITYMyosin VI dimerization triggers an unfolding of a three-helix bundle in order to extend its reach.X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 771-918SUBUNITDOMAINMyosins 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 (By similarity). Has slow rate of actin-activated ADP release due to weak ATP binding (PubMed:15944696). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (PubMed:16917816). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (By similarity). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (By similarity). Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes (By similarity). Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (By similarity). May act as a regulator of F-actin dynamics (PubMed:7929586). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (By similarity). 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). Modulates RNA polymerase II-dependent transcription (By similarity).Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (PubMed:25159143, PubMed:19664948). Component of the DISP/DOCK7-induced septin displacement complex, at least composed of DOCK7, LRCH3 and MYO6 (By similarity). Able to function as a monomer under specific conditions in vitro (By similarity). Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells (By similarity). 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 (PubMed:15037754). This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium (PubMed:12682054, PubMed:15037754). Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (PubMed:7929586). Interacts with DAB2 (By similarity). In vitro, the C-terminal globular tail binds a C-terminal region of DAB2 (By similarity). Interacts with CFTR (By similarity). Interacts with CABP5 (By similarity). Interacts (via residues 1117-1245) with TOM1 (via residues 392-463) (By similarity). Interacts (via residues 1060-1285) with OPTN (By similarity). Interacts (via residues 1060-1285) with TAX1BP1 and CALCOCO2/NDP52 (By similarity). Interacts with TOM1L2 (By similarity).Q29122P98082-1true2Q29122Q96CV9true3Golgi apparatusTrans-Golgi network membranePeripheral membrane proteinGolgi apparatusNucleusCytoplasmPerinuclear regionMembraneClathrin-coated pitCytoplasmic vesicleClathrin-coated vesicleCell projectionFilopodiumCell projectionRuffle membraneCell projectionMicrovillusCytoplasmCytosolAlso present in endocytic vesicles (PubMed:16917816). Translocates from membrane ruffles, endocytic vesicles and cytoplasm to Golgi apparatus, perinuclear membrane and nucleus through induction by p53 and p53-induced DNA damage (By similarity). Recruited into membrane ruffles from cell surface by EGF-stimulation (By similarity). Colocalizes with DAB2 in clathrin-coated pits/vesicles (By similarity). Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane (By similarity).Expressed in all tissues examined including kidney cortex, intestinal mucosa, liver, lung, heart, jowl muscle, brain cortex and medulla, and in the epithelial cell line, LLC-PK1 (at protein level) (PubMed:7929586). In the kidney, located to the brush border of adult kidney proximal tubule cells (PubMed:7929586).Locates to the apical domain only during the final stages of kidney proximal tubule development.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. Its contribution to the mechanism conferring the myosin movement on actin filaments is debated.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).Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.Represents an unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6).Originally predicted to contain a coiled coil domain but generally accepted to contain a stable SAH domain instead.3D-structureActin-bindingATP-bindingCalmodulin-bindingCell membraneCell projectionCoated pitCytoplasmCytoplasmic vesicleEndocytosisGolgi apparatusHearingMembraneMotor proteinMyosinNucleotide-bindingNucleusPhosphoproteinProtein transportReference proteomeTransportATPTELAFAVAVALAMEDGKPVWAPHPTDGFQVGNIVDIGPDSLTIEPLNQKGKTFLALINQVFPAEEDSKKDVEDNCSLMYLNEATLLHNIKVRYSKDRIYTYVANILIAVNPYFDIPKIYSSETIKSYQGKSLGTMPPHVFAIADKAFRDMKVLKLSQSIIVSGESGAGKTENTKFVLRYLTESYGTGQDIDDRIVEANPLLEAFGNAKTVRNNNSSRFGKFVEIHFNEKSSVVGGFVSHYLLEKSRICVQGKEERNYHIFYRLCAGASEDIRERLHLSSPDNFRYLNRGCTRYFANKETDKQILQNRKSPEYLKAGSLKDPLLDDHGDFIRMCTAMKKIGLDDEEKLDLFRVVAGVLHLGNIDFEEAGSTSGGCNLKNKSTQALEYCAEKLLGLDQDDLRVSLTTRVMLTTAGGAKGTVIKVPLKVEQANNARDALAKTVYSHLFDHVVNRVNQCFPFETSSYFIGVLDIAGFEYFEHNSFEQFCINYCNEKLQQFFNERILKEEQELYQKEGLGVNEVHYVDNQDCIDLIEARLVGILDILDEENRLPQPSDQHFTSAGHQKHKDHFRLSIPRKSKLAIHRNIAYDEGFIIRHFAGAVCYETTQFVEKNNDALHMSLESLICESRDKFIRELFESSTNNNKDTKQKAGKLSFISVGNKFKTQLNLLLDKLRSTGASFIRCIKPNLKMTSHHFEGAQILSQLQCSGMVSVLDLMQGGFPSRASFHEVYNMYKKSLPDKLARLDPRLFCKALFKALGLNEIDYKFGLTKVFFRPGKFAEFDQIMKSDPDHLAELVKRVNHWLICSRWKKVQWCSLSVIKLKNKIKYRAEACIKMQKTIRMWLCKRRHKPRIDGLVKVGTLKKRLDKFNEVVSALKDGKQEMSKQVKDLEISIDALMAKIKSTMMTREQIQKEYDALVKSSAVLLSALQKKKQQEEEAERLRRIQEEMEKERKRREEDEQRRRKEEEERRMKLEMEAKRKQEEEERKKREDDEKRIQAEVEAQLARQREEESQQQAVLEQERRDRELALRIAQSEAELISDEAQADPGLRRGPAVQATKAAAGTKKYDLSKWKYAELRDTINTSCDIELLAACREEFHRRLKVYHAWKSKNKKRNTETEQRAPKSVTDYAQQNPAVQLPARQQEIEMNRQQRFFRIPFIRSADQYKDPQNKKKGWWYAHFDGPWIARQMELHPDKPPILLVAGKDDMEMCELNLEETGLTRKRGAEILPRQFEEIWERCGGIQYLQNAIESRQARPTYATAMLQNLLK
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