| Tbio | 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. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis.
Comments
Property Summary
| NCBI Gene PubMed Count | 29 |
| Grant Count | 18 |
| R01 Count | 15 |
| Funding | $5,540,810.26 |
| PubMed Score | 20.05 |
| PubTator Score | 19.09 |
| Disease | Z-score | Confidence |
|---|---|---|
| Branchiootic syndrome 10 | 3.288 | 1.6 |
| Dermatitis 107 | ||
| Eosinophilia 65 | ||
| non primary Sjogren syndrome sicca 840 |
| PMID | Text |
|---|---|
| 26600301 | the roles of SHARPIN in inhibiting integrin activity and supporting linear ubiquitination are (molecularly) distinct. |
| 26506596 | Data show that SHANK-associated RH domain interacting protein (SHARPIN) gene expression in breast cancer patients predicts clinical outcomes. |
| 25992689 | progesterone significantly reduced SIPL1 mRNA and protein expression in MCF7 cells. As progesterone enhances breast cancer tumorigenesis in context dependent manner, inhibition of SIPL1 expression may contribute to progesterone's non-tumorigenic function |
| 25443631 | Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis. |
| 25152374 | SIPL1 binds PTEN and enhances PTEN polyubiquitination. |
| 25018115 | SIPL1 promotes AKT activation by decreasing the amount of PTEN protein in CHO-K1 cells. |
| 24210817 | SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells. |
| 22750873 | crystals of SHARPIN belonged to the primitive tetragonal space group P4(3)2(1)2, with unit-cell parameters a = b = 61.55, c = 222.81 A |
| 22549881 | the crystal structure of the N-terminal portion of SHARPIN, which adopts the highly conserved pleckstrin homology superfold that is often used as a scaffold to create protein interaction modules |
| 21947080 | SHARPIN inhibits the critical switching of beta1-integrins from inactive to active conformations. |
| More... |
MAPPAGGAAAAASDLGSAAVLLAVHAAVRPLGAGPDAEAQLRRLQLSADPERPGRFRLELLGAGPGAVNL 1 - 70 EWPLESVSYTIRGPTQHELQPPPGGPGTLSLHFLNPQEAQRWAVLVRGATVEGQNGSKSNSPPALGPEAC 71 - 140 PVSLPSPPEASTLKGPPPEADLPRSPGNLTEREELAGSLARAIAGGDEKGAAQVAAVLAQHRVALSVQLQ 141 - 210 EACFPPGPIRLQVTLEDAASAASAASSAHVALQVHPHCTVAALQEQVFSELGFPPAVQRWVIGRCLCVPE 211 - 280 RSLASYGVRQDGDPAFLYLLSAPREAPATGPSPQHPQKMDGELGRLFPPSLGLPPGPQPAASSLPSPLQP 281 - 350 SWSCPSCTFINAPDRPGCEMCSTQRPCTWDPLAAAST 351 - 387 //
| PMID | Year | Title |
|---|---|---|
| 27523608 | 2016 | The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity. |
| 27070702 | 2016 | Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma. |
| 26600301 | 2015 | Mutually Exclusive Roles of SHARPIN in Integrin Inactivation and NF-?B Signaling. |
| 26506596 | 2015 | A novel gammaretroviral shuttle vector insertional mutagenesis screen identifies SHARPIN as a breast cancer metastasis gene and prognostic biomarker. |
| 25992689 | 2015 | Elevation of SIPL1 (SHARPIN) Increases Breast Cancer Risk. |
| 25443631 | 2014 | Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. |
| 25152374 | 2014 | SIPL1-facilitated PTEN ubiquitination contributes to its association with PTEN. |
| 25018115 | 2014 | SIPL1 enhances the proliferation, attachment, and migration of CHO cells by inhibiting PTEN function. |
| 24816252 | 2014 | An atlas of genetic influences on human blood metabolites. |
| 24726323 | 2014 | Molecular basis and regulation of OTULIN-LUBAC interaction. |
| More... |
