Ubl carboxyl-terminal hydrolase 18 (EC 3.4.19.-) (43 kDa ISG15-specific protease) (hUBP43) (ISG15-specific-processing protease) (Ubl thioesterase 18)
1_MSKAF 6_ GLLRQ 11_ ICQSI 16_ LAESS 21_ QSPAD 26_ LEEKK 31_ EEDSN 36_ MKREQ 41_ PRERP 46_ RAWDY 51_ PHGLV 56_ GLHNI 61_ GQTCC 66_ LNSLI 71_ QVFVM 76_ NVDFT 81_ RILKR 86_ ITVPR 91_ GADEQ 96_ RRSVP 101_ FQMLL 106_ LLEKM 111_ QDSRQ 116_ KAVRP 121_ LELAY 126_ CLQKC 131_ NVPLF 136_ VQHDA 141_ AQLYL 146_ KLWNL 151_ IKDQI 156_ TDVHL 161_ VERLQ 166_ ALYTI 171_ RVKDS 176_ LICVD 181_ CAMES 186_ SRNSS 191_ MLTLP 196_ LSLFD 201_ VDSKP 206_ LKTLE 211_ DALHC 216_ FFQPR 221_ ELSSK 226_ SKCFC 231_ ENCGK 236_ KTRGK 241_ QVLKL 246_ THLPQ 251_ TLTIH 256_ LMRFS 261_ IRNSQ 266_ TRKIC 271_ HSLYF 276_ PQSLD 281_ FSQIL 286_ PMKRE 291_ SCDAE 296_ EQSGG 301_ QYELF 306_ AVIAH 311_ VGMAD 316_ SGHYC 321_ VYIRN 326_ AVDGK 331_ WFCFN 336_ DSNIC 341_ LVSWE 346_ DIQCT 351_ YGNPN 356_ YHWQE 361_ TAYLL 366_VYMKM
1: Interferon-induced ISG15-specific protease that plays a crucial role for maintaining a proper balance of ISG15-conjugated proteins in cells (PubMed:11788588). Regulates protein ISGylation by efficiently cleaving ISG15 conjugates linked via isopeptide bonds. Regulates T-cell activation and T-helper 17 (Th17) cell differentiation by deubiquitinating TAK1, likely to keep TAK1-TAB complexes in steady conditions (PubMed:23825189). In turn, restricts activation of NF-kappa-B, NFAT, and JNK as well as expression of IL2 in T-cells after TCR activation (PubMed:23825189). Acts as a molecular adapter with USP20 to promote innate antiviral response through deubiquitinating STING1 (PubMed:27801882). Involved also in the negative regulation of the inflammatory response triggered by type I interferon (PubMed:27325888, PubMed:28165510). Upon recruitment by STAT2 to the type I interferon receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I interferon signaling pathway (PubMed:28165510)
2: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling. Major deISGylation enzyme for nuclear proteins (PubMed:22170061)