Sharpin
entrez
106025
canonical
uniprot
Q91WA6
canonical
ensembl
ENSMUSG00000022552
resolver
ensp
ENSMUSP00000023211
resolver
ensp
ENSMUSP00000218689
resolver
genesymbol
Sharpin
resolver
genesymbol_syn
Cpdm
resolver
genesymbol_syn
Sipl1
resolver
uniprot
Q7TNT3
resolver
uniprot
Q8CHL3
resolver
uniprot_entry
SHRPN_MOUSE
resolver
uniprot_sec
Q7TNT3
resolver
uniprot_sec
Q8CHL3
resolver
amino_acid_sequence
MSPPAGGAAVAADPASPVVLLAVHAAVRPLGAGQDAEAQPRKLQLIADPERPGRFRLGLLGTEPGAVSLEWPLEAICYTVRGPNQHELQPPPGGPGTFSVHFLDPEEAQQWAALVRDATAEGQNGSGSPAPAPAPAMCPISPPCSSMAQIPKATQPEVDLPQSSGNFKKEELATRLSQAIAGGDEKAAAQVAAVLAQHHVALNVQLMEAWFPPGPIRLQVTVEDATSVLSSSSSAHVSLKIHPHCSIAALQDQVFSEFGFPPAVQRWVIGRCLCMPERSLASYGVSQDGDPAFLYLLSAPREVSGQSLQNSKMDRKLGLFPQSLGLPHDLQPSSSSLPSPSQPGWSCPSCTFINASNRPGCEMCSTQRPCAWDPLAAAST
uniprot
proteins
disease_involvement
DISEASE: 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-induced NF-kappa-B activation is attenuated due to inability of the LUBAC complex to mediate linear ubiquitination. {ECO:0000269|PubMed:17538631, ECO:0000269|PubMed:19650867, ECO:0000269|PubMed:20811394, ECO:0000269|PubMed:21069580, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181}.
uniprot
proteins
function
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 (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is 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. The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria. LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (By similarity). {ECO:0000250|UniProtKB:Q9H0F6, ECO:0000269|PubMed:17538631, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181}.
uniprot
proteins
mass_dalton
39852
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q9H0F6}.
uniprot
proteins
pubmed
12753155
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17538631
uniprot
proteins
pubmed
19650867
uniprot
proteins
pubmed
20811394
uniprot
proteins
pubmed
20956555
uniprot
proteins
pubmed
21069580
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21455173
uniprot
proteins
pubmed
21455180
uniprot
proteins
pubmed
21455181
uniprot
proteins
sequence_length
380
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9H0F6}. Synapse {ECO:0000250|UniProtKB:Q9EQL9}. Note=Enriched at synaptic sites in mature neurons where it colocalizes with SHANK1. {ECO:0000250|UniProtKB:Q9EQL9}.
uniprot
proteins