Sharpin (Shank-associated RH domain-interacting protein) (Shank-interacting protein-like 1) (hSIPL1)
1_MAPPA 6_ GGAAA 11_ AASDL 16_ GSAAV 21_ LLAVH 26_ AAVRP 31_ LGAGP 36_ DAEAQ 41_ LRRLQ 46_ LSADP 51_ ERPGR 56_ FRLEL 61_ LGAGP 66_ GAVNL 71_ EWPLE 76_ SVSYT 81_ IRGPT 86_ QHELQ 91_ PPPGG 96_ PGTLS 101_ LHFLN 106_ PQEAQ 111_ RWAVL 116_ VRGAT 121_ VEGQN 126_ GSKSN 131_ SPPAL 136_ GPEAC 141_ PVSLP 146_ SPPEA 151_ STLKG 156_ PPPEA 161_ DLPRS 166_ PGNLT 171_ EREEL 176_ AGSLA 181_ RAIAG 186_ GDEKG 191_ AAQVA 196_ AVLAQ 201_ HRVAL 206_ SVQLQ 211_ EACFP 216_ PGPIR 221_ LQVTL 226_ EDAAS 231_ AASAA 236_ SSAHV 241_ ALQVH 246_ PHCTV 251_ AALQE 256_ QVFSE 261_ LGFPP 266_ AVQRW 271_ VIGRC 276_ LCVPE 281_ RSLAS 286_ YGVRQ 291_ DGDPA 296_ FLYLL 301_ SAPRE 306_ APATG 311_ PSPQH 316_ PQKMD 321_ GELGR 326_ LFPPS 331_ LGLPP 336_ GPQPA 341_ ASSLP 346_ SPLQP 351_ SWSCP 356_ SCTFI 361_ NAPDR 366_ PGCEM 371_ CSTQR 376_ PCTWD 381_PLAAA
1: 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: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:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (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 (PubMed:21455173, PubMed:21455180, PubMed:21455181). 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 (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998)