This entry represents a binding domain found in E3 ubiquitin-protein ligase RNF31 like proteins. RNF31 is also known as HOIL-1L binding partner (HOIP). The interaction of HOIL-1L and HOIP is via the UBL-UBA interaction. This interaction is important in E3 complex formation and the subsequent activation of NF-kappaB [].
RNF31 is a component of the linear ubiquitin chain assembly complex (LUBAC) [, , ]. RNF31 is also known as HOIL-1L interacting protein (HOIP). It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice [].LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptopic signaling pathways [, , ]. LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and HOIP [, ].This family also includes the fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates. Ithas been shown to play a role in heat-stress response [], as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila [].
This is the C-terminal domain of RNF31 (also known as HOIP) from humans. HOIP is a component of the linear ubiquitin chain assembly complex (LUBAC), which synthesizes the linear ubiquitin chains that help control innate immunity and inflammation [, , ]. This region has an RBR domain which catalyzes the transfer of ubiquitin onto a substrate [].
Otulin (also known as FAM105B) belongs to the ovarian tumour (OTU) deubiquitinases (DUBs) family []. It specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response []. It associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates [].
This is a PUB domain (PNGase/UBA- or UBX-containing domain), found in E3 ubiquitin-protein ligase RNF31, also known as Ring finger protein 31 and HOIL-1-interacting protein (HOIP) []. RNF31/HOIP has been shown to contribute to inborn human immunity disorders, in which RNF31/HOIP missense mutation at PUB domain gives rise to the de-stabilized LUBAC complex (linear ubiquitin chain assembly complex) and subsequently causes the auto-inflammation and immunodeficiency. In addition, RNF31 is reported to modify ERK and JNK pathways leading to cisplatin resistance []. Functional studies indicate that HOIP and OTULIN interact and act as a bimolecular editing pair for linear ubiquitin signals where the HOIP-PUB domain binds to the PUB interacting motif (PIM) of OTULIN and the chaperone VCP/p9. This interaction plays an important role where the HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP-dependent activation of the NF-KB pathway [, ].
