UNASSIGNED: @entity15439 ( @entity15439 ) is the leading genetic cause of combined @entity1018 . Among the three @entity15439 clinical types, type 2 ( @entity24129 ) occurs most commonly. @entity24129 , @entity38504 , and @entity68399 are three known causative genes of @entity24129 , whereas @entity68400 is a modifier gene found in @entity24129 @entity1 . The proteins encoded by these four @entity15439 genes have been proposed to form a multiprotein complex, the @entity24129 complex, due to interactions found among some of these proteins in vitro, their colocalization in vivo, and mutual dependence of some of these proteins for their normal in vivo localizations. However, evidence showing the formation of the @entity24129 complex is missing, and details on how this complex is formed remain elusive. Here, we systematically investigated interactions among the intracellular regions of the four @entity15439 proteins using colocalization, yeast two-hybrid, and pull-down assays. We show that multiple domains of the four @entity15439 proteins interact among one another. Importantly, both @entity68399 and @entity68400 are required for the complex formation with @entity24129 and @entity38504 . In this @entity24129 quaternary complex, @entity68399 prefers to bind to @entity24129 , whereas @entity68400 prefers to bind to @entity38504 . Interaction between @entity68399 and @entity68400 is the bridge between @entity24129 and @entity38504 . Additionally, the @entity24129 quaternary complex has a variable stoichiometry. These findings suggest that a non-obligate, short term, and dynamic @entity24129 quaternary protein complex may exist in vivo. Our work provides valuable insight into the physiological role of the @entity24129 complex in vivo and informs possible reconstruction of the @entity24129 complex for future therapy.

Whirlin and XXXX ( @entity68400 ) Proteins Are Both Required to Form the Quaternary Protein Complex Associated with @entity15439 .

@entity1018 :: ('MESH:D054062', 'Disease') :: ['hearing and vision loss'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity68400 :: ('79955', 'Gene') :: ['PDZD7'] @entity38504 :: ('84059', 'Gene') :: ['GPR98'] @entity15439 :: ('MESH:D052245', 'Disease') :: ['Usher syndrome', 'USH'] @entity24129 :: ('7399', 'Gene') :: ['USH2A', 'USH2'] @entity68399 :: ('25861', 'Gene') :: ['WHRN']
@entity68400 :: (79955,Gene) :: ['PDZ Domain-containing 7']
