Cysteine protease ATG4A (EC 3.4.22.-) (AUT-like 2 cysteine endopeptidase) (Autophagy-related cysteine endopeptidase 2) (Autophagin-2) (Autophagy-related protein 4 homolog A) (HsAPG4A) (hAPG4A)
1_MESVL 6_ SKYED 11_ QITIF 16_ TDYLE 21_ EYPDT 26_ DELVW 31_ ILGKQ 36_ HLLKT 41_ EKSKL 46_ LSDIS 51_ ARLWF 56_ TYRRK 61_ FSPIG 66_ GTGPS 71_ SDAGW 76_ GCMLR 81_ CGQMM 86_ LAQAL 91_ ICRHL 96_ GRDWS 101_ WEKQK 106_ EQPKE 111_ YQRIL 116_ QCFLD 121_ RKDCC 126_ YSIHQ 131_ MAQMG 136_ VGEGK 141_ SIGEW 146_ FGPNT 151_ VAQVL 156_ KKLAL 161_ FDEWN 166_ SLAVY 171_ VSMDN 176_ TVVIE 181_ DIKKM 186_ CRVLP 191_ LSADT 196_ AGDRP 201_ PDSLT 206_ ASNQS 211_ KGTSA 216_ YCSAW 221_ KPLLL 226_ IVPLR 231_ LGINQ 236_ INPVY 241_ VDAFK 246_ ECFKM 251_ PQSLG 256_ ALGGK 261_ PNNAY 266_ YFIGF 271_ LGDEL 276_ IFLDP 281_ HTTQT 286_ FVDTE 291_ ENGTV 296_ NDQTF 301_ HCLQS 306_ PQRMN 311_ ILNLD 316_ PSVAL 321_ GFFCK 326_ EEKDF 331_ DNWCS 336_ LVQKE 341_ ILKEN 346_ LRMFE 351_ LVQKH 356_ PSHWP 361_ PFVPP 366_ AKPEV 371_ TTTGA 376_ EFIDS 381_ TEQLE 386_ EFDLE 391_EDFEI
1: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:12473658, PubMed:15169837, PubMed:17347651, PubMed:21177865, PubMed:21245471, PubMed:22302004, PubMed:32732290). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine (PubMed:12473658, PubMed:15169837, PubMed:17347651, PubMed:21177865, PubMed:21245471, PubMed:22302004). 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:12473658, PubMed:15169837, PubMed:17347651, PubMed:21177865, PubMed:21245471, PubMed:22302004). Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP (PubMed:12473658, PubMed:15169837, PubMed:17347651, PubMed:21177865, PubMed:21245471, 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:29458288, PubMed:33909989). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (PubMed:29458288, PubMed:33909989). Compared to ATG4B, the major protein for proteolytic activation of ATG8 proteins, shows weaker ability to cleave the C-terminal amino acid of ATG8 proteins, while it displays stronger delipidation activity (PubMed:29458288). 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)