ATG4A
entrez
115201
canonical
uniprot
Q8WYN0
canonical
ensembl
ENSG00000101844
resolver
ensp
ENSP00000298131
resolver
ensp
ENSP00000361306
resolver
genesymbol
ATG4A
resolver
genesymbol_syn
APG4A
resolver
genesymbol_syn
AUTL2
resolver
hgnc
HGNC:16489
resolver
uniprot
A6NCH2
resolver
uniprot
B2RAZ7
resolver
uniprot
B4DEA4
resolver
uniprot
D3DUY0
resolver
uniprot
O95534
resolver
uniprot
Q5JYY9
resolver
uniprot
Q5JYZ0
resolver
uniprot
Q86VE5
resolver
uniprot
Q96KQ0
resolver
uniprot
Q96KQ1
resolver
uniprot_entry
ATG4A_HUMAN
resolver
uniprot_entry
B4DEA4_HUMAN
resolver
uniprot_sec
A6NCH2
resolver
uniprot_sec
B2RAZ7
resolver
uniprot_sec
D3DUY0
resolver
uniprot_sec
O95534
resolver
uniprot_sec
Q5JYY9
resolver
uniprot_sec
Q5JYZ0
resolver
uniprot_sec
Q86VE5
resolver
uniprot_sec
Q96KQ0
resolver
uniprot_sec
Q96KQ1
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by N-ethylmaleimide (PubMed:12473658, PubMed:21177865). Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity (PubMed:17347651). {ECO:0000269|PubMed:12473658, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:21177865}.
uniprot
proteins
amino_acid_sequence
MESVLSKYEDQITIFTDYLEEYPDTDELVWILGKQHLLKTEKSKLLSDISARLWFTYRRKFSPIGGTGPSSDAGWGCMLRCGQMMLAQALICRHLGRDWSWEKQKEQPKEYQRILQCFLDRKDCCYSIHQMAQMGVGEGKSIGEWFGPNTVAQVLKKLALFDEWNSLAVYVSMDNTVVIEDIKKMCRVLPLSADTAGDRPPDSLTASNQSKGTSAYCSAWKPLLLIVPLRLGINQINPVYVDAFKECFKMPQSLGALGGKPNNAYYFIGFLGDELIFLDPHTTQTFVDTEENGTVNDQTFHCLQSPQRMNILNLDPSVALGFFCKEEKDFDNWCSLVQKEILKENLRMFELVQKHPSHWPPFVPPAKPEVTTTGAEFIDSTEQLEEFDLEEDFEILSV
uniprot
proteins
ec_number
3.4.22.-
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:12473658, ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:21245471, ECO:0000269|PubMed:22302004, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:31315929, ECO:0000269|PubMed:32732290, ECO:0000269|PubMed:33773106, ECO:0000269|PubMed:33909989}.
uniprot
proteins
mass_dalton
45378
uniprot
proteins
mutagenesis
MUTAGEN 81; /note="C->A: Reduces the redox sensitivity and retains activity in presence of H(2)O(2)."; /evidence="ECO:0000269|PubMed:17347651"; MUTAGEN 390..398; /note="Missing: Decreased ability to mediate proteolytic activation and delipidation of ATG8 proteins."; /evidence="ECO:0000269|PubMed:32732290"; MUTAGEN 397; /note="S->D: Phospho-mimetic mutant; slightly increased delipidation of ATG8 proteins."; /evidence="ECO:0000269|PubMed:28287329
uniprot
proteins
protein_family
Peptidase C54 family
uniprot
proteins
pubmed
12446702
uniprot
proteins
pubmed
12473658
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15169837
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
17347651
uniprot
proteins
pubmed
21177865
uniprot
proteins
pubmed
21245471
uniprot
proteins
pubmed
22302004
uniprot
proteins
pubmed
28287329
uniprot
proteins
pubmed
29458288
uniprot
proteins
pubmed
30808002
uniprot
proteins
pubmed
31315929
uniprot
proteins
pubmed
32732290
uniprot
proteins
pubmed
33773106
uniprot
proteins
pubmed
33909989
uniprot
proteins
sequence_length
398
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BGE6}.
uniprot
proteins