InnateDB Protein
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IDBP-154758.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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Sharpin
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Protein Name
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SHANK-associated RH domain interacting protein
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Synonyms
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0610041B22Rik; AW121341; cpdm; RBCKL1; SIPL1;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000023211
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InnateDB Gene
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IDBG-154756 (Sharpin)
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Protein Structure
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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. {ECO:0000269PubMed:17538631, ECO:0000269PubMed:21455173, ECO:0000269PubMed:21455180, ECO:0000269PubMed:21455181}.
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Subcellular Localization |
Cytoplasm, cytosol {ECO:0000250}. Cell junction, synapse {ECO:0000250}. Note=Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. {ECO:0000250}.
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Disease Associations |
Note=Defects in Sharpin are the cause of chronic proliferative dermatitis (cpdm). Cpdm is a spontaneous mutation causing a chronic proliferative dermatitis phenotype, which is characterized histologically by severe inflammation, eosinophilic dermatitis and defects in secondary lymphoid organ development. Mice also display lower total and cortical bone mineral content and bone mineral density, trabecular and cortical bone volume, and trabecular number. TNF-alpha-induced NF-kappa-B activation is attenuated due to inability of the LUBAC complex to mediate linear ubiquitination.
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Tissue Specificity |
Highly expressed in thymus and spleen. Present at high level in splenic B- and T-cells (at protein level). {ECO:0000269PubMed:21455180}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 28 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.
Experimentally validated |
Total |
28
[view]
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Protein-Protein |
28
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
21 [view]
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
MGI:1913331
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InterPro |
IPR001876
Zinc finger, RanBP2-type
IPR029071
Ubiquitin-related domain
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PFAM |
PF00641
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PRINTS |
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PIRSF |
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SMART |
SM00547
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TIGRFAMs |
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Modification |
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SwissProt |
Q91WA6
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PhosphoSite |
PhosphoSite-Q91WA6
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
106025
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UniGene |
Mm.41463
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RefSeq |
NP_079616
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MGI ID |
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MGI Symbol |
Sharpin
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OMIM |
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CCDS |
CCDS37121
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HPRD |
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IMGT |
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EMBL |
AB052763
BC016203
BC055758
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GenPept |
AAH16203
AAH55758
BAC53796
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