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SHARPIN Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to 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 to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Self-associates. Interacts with SHANK1, EYA1 and EYA2. Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximative 600 kDa suggesting a heteromultimeric assembly of its subunits. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation- dependent manner. Highly expressed in skeletal muscle and placenta and at lower levels in brain, heart, colon without mucosa, thymus, spleen, kidney, liver, small intestine, lung and peripheral blood leukocytes. Up-regulated in various tumor tissues such as kidney, liver, ovary and pancreas tumors. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Apoptosis
Chromosomal Location of Human Ortholog: 8q24.3
Cellular Component: cytosol
Molecular Function: polyubiquitin binding; protein binding; ubiquitin-protein ligase activity
Biological Process: I-kappaB kinase/NF-kappaB cascade; negative regulation of inflammatory response; positive regulation of I-kappaB kinase/NF-kappaB cascade; proteasomal ubiquitin-dependent protein catabolic process
Reference #:  Q9H0F6 (UniProtKB)
Alt. Names/Synonyms: DKFZp434N1923; hSIPL1; SHANK-associated RH domain interactor; Shank-associated RH domain-interacting protein; Shank-interacting protein-like 1; SHARPIN; SHRPN; SIPL1
Gene Symbols: SHARPIN
Molecular weight: 39,949 Da
Basal Isoelectric point: 5.53  Predict pI for various phosphorylation states
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