SHARPIN
SHARPIN (SHANK associated RH domain interactor, also known as SIPL1 and DKFZP434N1923) is a component of the linear ubiquitin chain assembly complex, LUBAC. Within LUBAC it supports the conjugation of linear polyubiquitin chains, a modification central to NF-kappa-B activation and the regulation of inflammation. Browse Assay Genie's current range of SHARPIN research reagents below, or read on for the biology behind the target.
SHARPIN is part of the LUBAC complex, which conjugates linear polyubiquitin chains in a head-to-tail manner to its substrates. LUBAC attaches linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and JNK signalling pathways. Linear ubiquitination by LUBAC interferes with TNF-induced cell death and so helps prevent inflammation. LUBAC is recruited to the TNF-R1 signalling complex after its components have been polyubiquitinated by BIRC2 and/or BIRC3, and it then adds linear polyubiquitin to IKBKG and possibly other components that contribute to the stability of the complex.
LUBAC also contributes to innate immunity. It conjugates linear polyubiquitin chains at the surface of bacteria that invade the cytosol, building the ubiquitin coat around them. LUBAC cannot start this coat; it can only extend linear chains on pre-existing ubiquitin. The coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation. Together with OTULIN, LUBAC also regulates canonical Wnt signalling during angiogenesis. NCBI describes the protein as enabling polyubiquitin modification-dependent protein binding and as involved in defence response to bacteria, protein linear polyubiquitination and regulation of signal transduction.
The SHARPIN gene is on chromosome 8q24.3 and encodes a protein localised to the cytosol and the synapse. HGNC places it in the RANBP2-type zinc finger group and in the linear ubiquitin chain assembly complex group. The official name reflects its association with SHANK, and SIPL1 and DKFZP434N1923 are alternative designations. Mouse and rat both have a Sharpin ortholog, which allows comparative work on SHARPIN across model systems.
SHARPIN is a LUBAC component involved in activating the canonical NF-kappa-B pathway through linear ubiquitination of IKBKG and RIPK1.
Linear ubiquitination by LUBAC interferes with TNF-induced cell death, making SHARPIN relevant to studies of how inflammation is restrained.
LUBAC builds linear polyubiquitin on the ubiquitin coat of cytosolic bacteria, an eat-me signal for xenophagy and NF-kappa-B activation.
Together with OTULIN, the LUBAC complex regulates canonical Wnt signalling during angiogenesis.
SHARPIN is a component of the LUBAC complex, which conjugates linear polyubiquitin chains to substrates such as IKBKG and RIPK1. This drives canonical NF-kappa-B and JNK signalling, limits TNF-induced cell death and helps prevent inflammation. Check the datasheet of any product for its validated reactivity.
The HGNC full name is SHANK associated RH domain interactor. Aliases include SIPL1 and DKFZP434N1923, and UniProt lists the protein as Sharpin. HGNC classifies it with the RANBP2-type zinc fingers and the linear ubiquitin chain assembly complex group.
Yes. Both mouse and rat have an ortholog named Sharpin, so the protein can be studied in common rodent models. The human protein is annotated as part of the LUBAC complex and is found in the cytosol and at the synapse.
Other LUBAC components, TNF-receptor signalling partners and NF-kappa-B pathway proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9H0F6; product specifications from Assay Genie datasheets.