Sharpin (SHARPIN)

Component of the LUBAC complex which conjugates linear polyubiquitin chains at a head-to-tail way to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin into IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways.

Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited into the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC parts by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin into IKBKG and possibly other components contributing to the stability of the complex.