Cysteine protease ATG4B (EC 3.4.22.-) (AUT-like 1 cysteine endopeptidase) (Autophagy-related cysteine endopeptidase 1) (Autophagin-1) (Autophagy-related protein 4 homolog B) (HsAPG4B) (hAPG4B)
1_MDAAT 6_ LTYDT 11_ LRFAE 16_ FEDFP 21_ ETSEP 26_ VWILG 31_ RKYSI 36_ FTEKD 41_ EILSD 46_ VASRL 51_ WFTYR 56_ KNFPA 61_ IGGTG 66_ PTSDT 71_ GWGCM 76_ LRCGQ 81_ MIFAQ 86_ ALVCR 91_ HLGRD 96_ WRWTQ 101_ RKRQP 106_ DSYFS 111_ VLNAF 116_ IDRKD 121_ SYYSI 126_ HQIAQ 131_ MGVGE 136_ GKSIG 141_ QWYGP 146_ NTVAQ 151_ VLKKL 156_ AVFDT 161_ WSSLA 166_ VHIAM 171_ DNTVV 176_ MEEIR 181_ RLCRT 186_ SVPCA 191_ GATAF 196_ PADSD 201_ RHCNG 206_ FPAGA 211_ EVTNR 216_ PSPWR 221_ PLVLL 226_ IPLRL 231_ GLTDI 236_ NEAYV 241_ ETLKH 246_ CFMMP 251_ QSLGV 256_ IGGKP 261_ NSAHY 266_ FIGYV 271_ GEELI 276_ YLDPH 281_ TTQPA 286_ VEPTD 291_ GCFIP 296_ DESFH 301_ CQHPP 306_ CRMSI 311_ AELDP 316_ SIAVG 321_ FFCKT 326_ EDDFN 331_ DWCQQ 336_ VKKLS 341_ LLGGA 346_ LPMFE 351_ LVELQ 356_ PSHLA 361_ CPDVL 366_ NLSLD 371_ SSDVE 376_ RLERF 381_ FDSED 386_EDFEI
1: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:15169837, PubMed:15187094, PubMed:17347651, PubMed:19322194, PubMed:21177865, PubMed:22302004, PubMed:26378241, PubMed:27527864, PubMed:28633005, PubMed:28821708, PubMed:29232556, PubMed:30076329, PubMed:30443548, PubMed:30661429). Required for canonical autophagy (macroautophagy), non-canonical autophagy as well as for mitophagy (PubMed:33773106, PubMed:33909989). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine (PubMed:15169837, PubMed:15187094, PubMed:17347651, PubMed:19322194, PubMed:20818167, PubMed:21177865, PubMed:22302004, PubMed:27527864, PubMed:28287329, PubMed:28633005, PubMed:29458288, PubMed:30661429). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (PubMed:15169837, PubMed:15187094, PubMed:17347651, PubMed:19322194, PubMed:21177865, PubMed:22302004). Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3 (PubMed:31315929, PubMed:33773106). In addition to the protease activity, also mediates delipidation of ATG8 family proteins (PubMed:15187094, PubMed:19322194, PubMed:28633005, PubMed:29458288, PubMed:32686895, PubMed:33909989). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (PubMed:15187094, PubMed:19322194, PubMed:29458288, PubMed:32686895, PubMed:33909989). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (PubMed:33909989). Compared to other members of the family (ATG4A, ATG4C or ATG4C), constitutes the major protein for proteolytic activation of ATG8 proteins, while it displays weaker delipidation activity than other ATG4 paralogs (PubMed:29458288, PubMed:30661429). Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy (PubMed:33773106)