ATG4D
entrez
84971
canonical
uniprot
Q86TL0
canonical
ensembl
ENSG00000130734
resolver
ensp
ENSP00000311318
resolver
ensp
ENSP00000578607
resolver
genesymbol
ATG4D
resolver
genesymbol_syn
APG4D
resolver
genesymbol_syn
AUTL4
resolver
hgnc
HGNC:20789
resolver
uniprot
B4DGM8
resolver
uniprot
Q969K0
resolver
uniprot_entry
ATG4D_HUMAN
resolver
uniprot_entry
B4DGM8_HUMAN
resolver
uniprot_sec
Q969K0
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by N-ethylmaleimide. {ECO:0000269|PubMed:21177865}.
uniprot
proteins
amino_acid_sequence
MNSVSPAAAQYRSSSPEDARRRPEARRPRGPRGPDPNGLGPSGASGPALGSPGAGPSEPDEVDKFKAKFLTAWNNVKYGWVVKSRTSFSKISSIHLCGRRYRFEGEGDIQRFQRDFVSRLWLTYRRDFPPLPGGCLTSDCGWGCMLRSGQMMLAQGLLLHFLPRDWTWAEGMGLGPPELSGSASPSRYHGPARWMPPRWAQGAPELEQERRHRQIVSWFADHPRAPFGLHRLVELGQSSGKKAGDWYGPSLVAHILRKAVESCSDVTRLVVYVSQDCTVYKADVARLVARPDPTAEWKSVVILVPVRLGGETLNPVYVPCVKELLRCELCLGIMGGKPRHSLYFIGYQDDFLLYLDPHYCQPTVDVSQADFPLESFHCTSPRKMAFAKMDPSCTVGFYAGDRKEFETLCSELTRVLSSSSATERYPMFTLAEGHAQDHSLDDLCSQLAQPTLRLPRTGRLLRAKRPSSEDFVFL
uniprot
proteins
ec_number
3.4.22.-
uniprot
proteins
function
FUNCTION: [Cysteine protease ATG4D]: 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). {ECO:0000250|UniProtKB:Q8BGV9, ECO:0000250|UniProtKB:Q9Y4P1, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:30661429, ECO:0000269|PubMed:33773106, ECO:0000269|PubMed:33909989}.; FUNCTION: [Cysteine protease ATG4D, mitochondrial]: 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. {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}.
uniprot
proteins
mass_dalton
52922
uniprot
proteins
mutagenesis
MUTAGEN 63; /note="D->A: Abolishes cleavage by CASP3."; /evidence="ECO:0000269|PubMed:19549685
uniprot
proteins
post_translational_modification
PTM: Cleaved by CASP3 during apoptosis which leads to increased activity (PubMed:19549685, PubMed:22441018). The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondrial import of the protein (PubMed:19549685, PubMed:22441018). {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}.
uniprot
proteins
protein_family
Peptidase C54 family
uniprot
proteins
pubmed
12446702
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19549685
uniprot
proteins
pubmed
21177865
uniprot
proteins
pubmed
22441018
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
29458288
uniprot
proteins
pubmed
30661429
uniprot
proteins
pubmed
30808002
uniprot
proteins
pubmed
33773106
uniprot
proteins
pubmed
33909989
uniprot
proteins
pubmed
33988247
uniprot
proteins
sequence_length
474
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Cysteine protease ATG4D]: Cytoplasm {ECO:0000269|PubMed:19549685}.; SUBCELLULAR LOCATION: [Cysteine protease ATG4D, mitochondrial]: Cytoplasm {ECO:0000269|PubMed:19549685}. Mitochondrion matrix {ECO:0000269|PubMed:19549685, ECO:0000269|PubMed:22441018}. Note=Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death. {ECO:0000269|PubMed:22441018}.
uniprot
proteins