ID:SHRPN_HUMAN DESCRIPTION: RecName: Full=Sharpin; AltName: Full=Shank-associated RH domain-interacting protein; AltName: Full=Shank-interacting protein-like 1; Short=hSIPL1; 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. SUBUNIT: Self-associates (By similarity). 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. INTERACTION: P17301:ITGA2; NbExp=5; IntAct=EBI-3942966, EBI-702960; P08648:ITGA5; NbExp=4; IntAct=EBI-3942966, EBI-1382311; SUBCELLULAR LOCATION: Cytoplasm, cytosol. 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. DOMAIN: The Ubiquitin-like domain is required for the interaction with RNF31. DOMAIN: The 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. SIMILARITY: Contains 1 RanBP2-type zinc finger. SIMILARITY: Contains 1 ubiquitin-like domain. SEQUENCE CAUTION: Sequence=BAC11666.1; Type=Frameshift; Positions=334; Sequence=BAC53797.1; Type=Frameshift; Positions=218; Sequence=BAC53798.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9H0F6
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
