Fig. 1. (A) Predicted domain structures of the USH1 proteins. Myosin VIIa consists of a spectrin-like SH3 subdomain followed by the motor head, a neck region composed of five IQ (isoleucine-glutamine) motifs and a large tail. The tail starts with an -helical domain, followed by two large repeats, each containing a myosin tail homology 4 (MyTH4) and a 4.1, Ezrin, Radixin, Moesin (FERM)-like domain. These are separated by a poorly conserved Src homology 3 (SH3) domain. Positions of the spliced exon 25 (ex 25) and 34 (ex 34) are indicated. There are three classes of harmonin isoform, depending on the presence of two or three PDZ domains and the presence or absence of a second coiled-coil (CC) domain associated with a proline-, serine- and threonine-rich (PST) domain. The largest cadherin 23 and protocadherin 15 isoforms have 27 extracellular cadherin (EC) repeats and 11 EC repeats, respectively. Sans is composed of three ankyrin (ANK)-like repeats and a sterile alpha motif (SAM) domain. (B) Summary of the direct interactions between USH1 proteins. The domains involved in each interaction are indicated by arrows. Harmonin is able to bind to any of the other USH1 proteins. The cytoplasmic regions of cadherin 23a isoforms containing or lacking the exon 68-encoded peptide (ex 68 in A) preferentially bind to the harmonin PDZ1 or PDZ2 domain, respectively. Harmonin can bind to the cytoplasmic region of protocadherin 15 through its first two PDZ domains. It can also bind to the myosin VIIa tail through a PDZ1–C-terminal-MyTH4-FERM domain interaction. Harmonin can also bind to Sans through a PDZ1-SAM region interaction. Finally, the Sans central region can bind to the myosin VIIa N-terminal MyTH4-FERM domain. Harmonin (not shown) and Sans can also form homodimers.