Cysteine protease ATG4D (EC 3.4.22.-) (AUT-like 4 cysteine endopeptidase) (Autophagy-related cysteine endopeptidase 4) (Autophagin-4) (Autophagy-related protein 4 homolog D) (HsAPG4D) [Cleaved into: Cysteine protease ATG4D, mitochondrial]
1_MNSVS 6_ PAAAQ 11_ YRSSS 16_ PEDAR 21_ RRPEA 26_ RRPRG 31_ PRGPD 36_ PNGLG 41_ PSGAS 46_ GPALG 51_ SPGAG 56_ PSEPD 61_ EVDKF 66_ KAKFL 71_ TAWNN 76_ VKYGW 81_ VVKSR 86_ TSFSK 91_ ISSIH 96_ LCGRR 101_ YRFEG 106_ EGDIQ 111_ RFQRD 116_ FVSRL 121_ WLTYR 126_ RDFPP 131_ LPGGC 136_ LTSDC 141_ GWGCM 146_ LRSGQ 151_ MMLAQ 156_ GLLLH 161_ FLPRD 166_ WTWAE 171_ GMGLG 176_ PPELS 181_ GSASP 186_ SRYHG 191_ PARWM 196_ PPRWA 201_ QGAPE 206_ LEQER 211_ RHRQI 216_ VSWFA 221_ DHPRA 226_ PFGLH 231_ RLVEL 236_ GQSSG 241_ KKAGD 246_ WYGPS 251_ LVAHI 256_ LRKAV 261_ ESCSD 266_ VTRLV 271_ VYVSQ 276_ DCTVY 281_ KADVA 286_ RLVAR 291_ PDPTA 296_ EWKSV 301_ VILVP 306_ VRLGG 311_ ETLNP 316_ VYVPC 321_ VKELL 326_ RCELC 331_ LGIMG 336_ GKPRH 341_ SLYFI 346_ GYQDD 351_ FLLYL 356_ DPHYC 361_ QPTVD 366_ VSQAD 371_ FPLES 376_ FHCTS 381_ PRKMA 386_ FAKMD 391_ PSCTV 396_ GFYAG 401_ DRKEF 406_ ETLCS 411_ ELTRV 416_ LSSSS 421_ ATERY 426_ PMFTL 431_ AEGHA 436_ QDHSL 441_ DDLCS 446_ QLAQP 451_ TLRLP 456_ RTGRL 461_ LRAKR 466_PSSED
1: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:21177865, PubMed:29458288, PubMed:30661429). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine (PubMed:21177865). 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 (By similarity). 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). 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). ATG4D plays a role in the autophagy-mediated neuronal homeostasis in the central nervous system (By similarity). Compared to other members of the family (ATG4A, ATG4B or ATG4C), constitutes the major protein for the delipidation activity, while it promotes weak proteolytic activation of ATG8 proteins (By similarity). 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)
2: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability