Ubiquitin thioesterase otulin (EC 3.4.19.12) (Deubiquitinating enzyme otulin) (OTU domain-containing deubiquitinase with linear linkage specificity) (Ubiquitin thioesterase Gumby)
1_MSRGT 6_ MPQPE 11_ AWPGA 16_ SCAET 21_ PAREA 26_ AATAR 31_ DGGKA 36_ AASGQ 41_ PRPEM 46_ QCPAE 51_ HEEDM 56_ YRAAD 61_ EIEKE 66_ KELLI 71_ HERGA 76_ SEPRL 81_ SVAPE 86_ MDIMD 91_ YCKKE 96_ WRGNT 101_ QKATC 106_ MKMGY 111_ EEVSQ 116_ KFTSI 121_ RRVRG 126_ DNYCA 131_ LRATL 136_ FQAMS 141_ QAVGL 146_ PPWLQ 151_ DPELM 156_ LLPEK 161_ LISKY 166_ NWIKQ 171_ WKLGL 176_ KFDGK 181_ NEDLV 186_ DKIKE 191_ SLTLL 196_ RKKWA 201_ GLAEM 206_ RTAEA 211_ RQIAC 216_ DELFT 221_ NEAEE 226_ YSLYE 231_ AVKFL 236_ MLNRA 241_ IELYN 246_ DKEKG 251_ KEVPF 256_ FSVLL 261_ FARDT 266_ SNDPG 271_ QLLRN 276_ HLNQV 281_ GHTGG 286_ LEQVE 291_ MFLLA 296_ YAVRH 301_ TIQVY 306_ RLSKY 311_ NTEEF 316_ ITVYP 321_ TDPPK 326_ DWPVV 331_ TLIAE 336_ DDRHY 341_ NIPVR 346_VCEET
1: Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327, PubMed:26997266, PubMed:27523608, PubMed:27559085, PubMed:28919039, PubMed:30804083, PubMed:35170849, PubMed:35587511, PubMed:38630025, PubMed:38652464). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by regulating the activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met-1'-linked autoubiquitination of the LUBAC complex, thereby preventing inactivation of the LUBAC complex (PubMed:26670046). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a role in innate immune response by restricting linear polyubiquitin formation on LUBAC complex in response to NOD2 stimulation, probably to limit NOD2-dependent pro-inflammatory signaling (PubMed:23806334)