TI - UNC-5 function requires phosphorylation of cytoplasmic tyrosine 482 , but its UNC-40-independent functions also require a region between the ZU-5 and death domains . AB - Members of the UNC-5 protein family are transmembrane receptors for UNC-6/netrin guidance cues . To analyze the functional roles of different UNC-5 domains , we sequenced mutations in seven severe and three weak alleles of unc-5 in Caenorhabditis elegans . Four severe alleles contain nonsense mutations . Two weak alleles are truncations of the cytodomain , but one is a missense mutation in an extracellular immunoglobulin domain . To survey the function of different regions of UNC-5 , wild-type and mutant unc-5 : : HA transgenes were tested for their ability to rescue the unc-5 ( e53 ) null mutant . Our data reveal partial functional requirements for the extracellular domains and identify a portion of the cytoplasmic juxtamembrane ( JM ) region as essential for rescue of migrations . When nine cytodomain tyrosines , including seven in the JM region , are mutated to phenylalanine , UNC-5 function and tyrosine phosphorylation are largely compromised . When F482 in the JM region of the mutant protein is reverted to tyrosine , UNC-5 tyrosine phosphorylation and in vivo function are largely recovered , suggesting that Y482 phosphorylation is critical to UNC-5 function in vivo . Our data also show that part of the ZU-5 motif is required for UNC-40-independent signaling of UNC-5 .