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 [, ].
This entry represents the FAM105 family, including FAM105A (OTULINL) and FAM105B (OTULIN). Otulin is an ubiquitin thioesterase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response []. FAM105A shares a high degree of similarity with protein otulin; however, FAM105A lacks the conserved active site at position 139 which is replaced by an Asp residue, and does not show deubiquitinase activity [].
