This PH domain is found at the N terminus of sharpin and is involved in dimerisation. Sharpin is part of the LUBAC complex, a large multi-protein E3 ubiquitin ligase complex that catalyses the formation of linear ubiquitin chains and regulates immune and apoptopic signalling pathways [].
This entry consists of RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1, also known as HOIL-1) and SHARPIN. Both are components of the E3 ligase complex LUBAC (linear ubiquitin chain assembly complex). LUBAC is composed of HOIP, RBCK1/HOIL-1, and SHARPIN. HOIP is the catalytic subunit and its E3 activity can be effectively activated by HOIL-1 or SHARPIN []. The LUBAC complex catalyses the formation of linear ubiquitin chains and regulates immune and apoptopic signaling pathways [, , ].RBCK1/HOIL-1 contains an ubiquitin-like (UBL) domain followed by a Npl4 zinc finger (NZF) domain and a RBR (RING-between-RING) domain in the C-terminal portion of the protein. RBCK1 is a RING-between-RING E3 ligase, and it has also been shown to act as a transcriptional activator []. SHARPIN also contains a UBL domain and a Ub-binding NZF domain, but lacks the RBR domain and has a additional N-terminal pleckstrin homology (PH) domain [, ].
