Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Required in the presynaptic motoneuron to down-regulate the levels of wnd and restrain synaptic terminal growth at the neuromuscular junction (NMJ) together with Rae1 and Fsn (PubMed:10839352, PubMed:21874015, PubMed:17697379). [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-threonine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-3-O-ubiquitinyl-L-threonine. Protein modification; protein ubiquitination. Component of an E3 ubiquitin ligase complex composed of hiw, Rae1 and Fsn (PubMed:17697379, PubMed:21874015). Interacts with Rae1; the interaction with Rae1 may protect hiw from autophagy-mediated degradation (PubMed:21874015). Express throughout the nervous system (PubMed:10839352, PubMed:21874015). Stage 13 embryos show expression in the central nervous system (CNS) at the longitudinal axon tracts around which the synaptic neuropil forms (PubMed:10839352). Expression outside the CNS starts at stage 16 in presynaptic terminals at the periactive zone which surround the active zone (PubMed:10839352). Expression at neuromuscular junctions (NMJ) and in the CNS is also seen in third instar larvae (at protein level) (PubMed:10839352). The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners (By similarity). The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration. Flies display NMJ synapses that grow exuberantly and are expanded in both the number of boutons and in the extent and length of branches. Belongs to the RING-Cys relay (RCR) family.