SHARPIN Lysate – Tissue Lysate

Function: 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. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Ref.10 Ref.11 Ref.12

Subunit structure: Monomer and homodimer. Interacts with SHANK1, EYA1 and EYA2

By similarity. 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. Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location: Cytoplasm › cytosol Ref.2.

Tissue specificity: 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. Ref.2

Domain: The Ubiquitin-like domain is required for the interaction with RNF31. Ref.10 Ref.11 Ref.12The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin. Ref.10 Ref.11 Ref.12

Sequence similarities: Contains 1 RanBP2-type zinc finger.Contains 1 ubiquitin-like domain.

Sequence caution: The sequence BAC11666.1 differs from that shown. Reason: Frameshift at position 334. The sequence BAC53797.1 differs from that shown. Reason: Frameshift at position 218. The sequence BAC53798.1 differs from that shown. Reason: Aberrant splicing.