The microtubule-based kinesin motors and actin-based myosin motors generate movements required for intracellular trafficking, cell division, and muscle contraction. In general, these proteins consist of a motor domain that generates movement and a tail region that varies widely from class to class and is thought to mediate many of the regulatory or cargo binding functions specific to each class of motor [ (PUBMED:11212352) ]. The Myosin Tail Homology 4 (MyTH4) domain has been identified as a conserved domain in the tail domains of several different unconventional myosins [ (PUBMED:11401444) ] and a plant kinesin-like protein [ (PUBMED:1074599) ], but has more recently been found in several non-motor proteins [ (PUBMED:12062040) ]. Although the function is not yet fully understood, there is an evidence that the MyTH4 domain of Myosin-X (Myo10) binds to microtubules and thus could provide a link between an actin-based motor protein and the microtubule cytoskeleton [ (PUBMED:15372037) ].
The MyTH4 domain is found in one or two copies associated with other domains, such as myosin head, kinesin motor, FERM, PH, SH3 and IQ. The domain is predicted to be largely alpha-helical, interrupted by three or four turns. The MyTH4 domain contains four highly conserved regions designated MGD (consensus sequence L(K/R)(F/Y)MGDhP, LRDE (consensus LRDEhYCQhhKQHxxxN), RGW (consensus RGWxLh), and ELEA (RxxPPSxhELEA), where h indicates a hydrophobic residue and x is any residue [ (PUBMED:11401444) ].
Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B.
Genomics. 1996; 36: 440-8
Display abstract
Myosin-VIIa is an unconventional myosin with relatively restricted expression. Cloned first from an intestinal epithelium cell line, it occurs most notably in the testis, in the receptor cells of the inner ear, and in the pigment epithelium of the retina. Defects in myosin-VIIa cause the shaker-1 phenotype in mice and Usher syndrome 1B in human, which are characterized by deafness, lack of vestibular function, and (in human) progressive retinal degeneration. Because the described cDNAs encode less than half of the protein predicted from immunoblots, we have cloned cDNAs encoding the rest of human myosin-VIIa. Two transcripts were found, one encoding the predicted 250-kDa protein and another encoding a shorter form. Both transcripts were found in highest abundance in testis, although the shorter transcript was much less abundant. Both could be detected in lymphocytes by RT-PCR. The myosin tail encoded by the long transcript includes a long repeat of approximately 460 amino acids. Each repeat contains a novel "MyTH4" domain similar to domains in three other myosins, and a domain similar to the membrane-associated portion of talin and other members of the band-4.1 family.
Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the MyTH4 domain.
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with MyTH4 domain which could be assigned to a KEGG orthologous group, and not all proteins containing MyTH4 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
