ATG4B
entrez
23192
canonical
uniprot
Q9Y4P1
canonical
ensembl
ENSG00000168397
resolver
ensp
ENSP00000383964
resolver
ensp
ENSP00000384259
resolver
ensp
ENSP00000384661
resolver
ensp
ENSP00000572667
resolver
ensp
ENSP00000786591
resolver
genesymbol
ATG4B
resolver
genesymbol_syn
APG4B
resolver
genesymbol_syn
AUTL1
resolver
genesymbol_syn
KIAA0943
resolver
hgnc
HGNC:20790
resolver
uniprot
B3KVU2
resolver
uniprot
B7WNK2
resolver
uniprot
B7ZA52
resolver
uniprot
Q53NU4
resolver
uniprot
Q6ZUV8
resolver
uniprot
Q8WYM9
resolver
uniprot
Q96K07
resolver
uniprot
Q96K96
resolver
uniprot
Q96SZ1
resolver
uniprot
Q9Y2F2
resolver
uniprot_entry
ATG4B_HUMAN
resolver
uniprot_entry
B3KVU2_HUMAN
resolver
uniprot_entry
B7ZA52_HUMAN
resolver
uniprot_sec
B7WNK2
resolver
uniprot_sec
Q53NU4
resolver
uniprot_sec
Q6ZUV8
resolver
uniprot_sec
Q8WYM9
resolver
uniprot_sec
Q96K07
resolver
uniprot_sec
Q96K96
resolver
uniprot_sec
Q96SZ1
resolver
uniprot_sec
Q9Y2F2
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by N-ethylmaleimide (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). The cysteine protease activity compounds is inhibited by styrylquinoline compounds 4-28 and LV-320 (PubMed:30076329). {ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:30076329}.
uniprot
proteins
amino_acid_sequence
MDAATLTYDTLRFAEFEDFPETSEPVWILGRKYSIFTEKDEILSDVASRLWFTYRKNFPAIGGTGPTSDTGWGCMLRCGQMIFAQALVCRHLGRDWRWTQRKRQPDSYFSVLNAFIDRKDSYYSIHQIAQMGVGEGKSIGQWYGPNTVAQVLKKLAVFDTWSSLAVHIAMDNTVVMEEIRRLCRTSVPCAGATAFPADSDRHCNGFPAGAEVTNRPSPWRPLVLLIPLRLGLTDINEAYVETLKHCFMMPQSLGVIGGKPNSAHYFIGYVGEELIYLDPHTTQPAVEPTDGCFIPDESFHCQHPPCRMSIAELDPSIAVGFFCKTEDDFNDWCQQVKKLSLLGGALPMFELVELQPSHLACPDVLNLSLDSSDVERLERFFDSEDEDFEILSL
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: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). {ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:15187094, ECO:0000269|PubMed:17347651, ECO:0000269|PubMed:19322194, ECO:0000269|PubMed:20818167, ECO:0000269|PubMed:21177865, ECO:0000269|PubMed:22302004, ECO:0000269|PubMed:26378241, ECO:0000269|PubMed:27527864, ECO:0000269|PubMed:28287329, ECO:0000269|PubMed:28633005, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29232556, ECO:0000269|PubMed:29458288, ECO:0000269|PubMed:30076329, ECO:0000269|PubMed:30443548, ECO:0000269|PubMed:30661429, ECO:0000269|PubMed:31315929, ECO:0000269|PubMed:32686895, ECO:0000269|PubMed:33773106, ECO:0000269|PubMed:33909989}.
uniprot
proteins
mass_dalton
44294
uniprot
proteins
mutagenesis
MUTAGEN 34; /note="S->A: Decreased phosphorylation by AKT2, leading to reduced proteolytic activation of ATG8 family proteins."; /evidence="ECO:0000269|PubMed:30443548"; MUTAGEN 34; /note="S->D: Phospho-mimetic mutant; increased proteolytic activation of ATG8 family proteins."; /evidence="ECO:0000269|PubMed:30443548"; MUTAGEN 74; /note="C->S: Complete loss of protease activity."; /evidence="ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:15187094, ECO:0000269|PubMed:16183633, ECO:0000269|PubMed:16325851, ECO:0000269|PubMed:20818167, ECO:0000269|PubMed:26378241, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:30443548"; MUTAGEN 78; /note="C->A: Reduces the redox sensitivity and retains activity in presence of H(2)O(2)."; /evidence="ECO:0000269|PubMed:17347651"; MUTAGEN 78; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 89; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 121; /note="S->A: Decreased phosphorylation by AKT2; when associated with A-262."; /evidence="ECO:0000269|PubMed:30443548"; MUTAGEN 142; /note="W->A: Strongly reduced protease activity."; /evidence="ECO:0000269|PubMed:16183633"; MUTAGEN 183; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 189; /note="C->S: Does not affect S-nitrosylation. Strongly decreased S-nitrosylation, leading to increased hydrolase activity and autophagic flux; when associated with S-292. Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:28633005, ECO:0000269|PubMed:31880198"; MUTAGEN 203; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 229; /note="R->A: Strongly reduced protease activity."; /evidence="ECO:0000269|PubMed:16183633"; MUTAGEN 246; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 262; /note="S->A: Decreased phosphorylation by AKT2; when associated with A-121."; /evidence="ECO:0000269|PubMed:30443548"; MUTAGEN 278; /note="D->A: Complete loss of protease activity."; /evidence="ECO:0000269|PubMed:16183633, ECO:0000269|PubMed:16325851"; MUTAGEN 280; /note="H->A: Complete loss of protease activity."; /evidence="ECO:0000269|PubMed:16183633, ECO:0000269|PubMed:16325851"; MUTAGEN 292; /note="C->S: Does not affect S-nitrosylation. Strongly decreased S-nitrosylation, leading to increased hydrolase activity and autophagic flux; when associated with S-189. Reduced formation of intrachain and interchain disulfide bonds in response to oxidation. Abolished formation of disulfide bonds, leading to increased autophagy; when associated with S-361."; /evidence="ECO:0000269|PubMed:28633005, ECO:0000269|PubMed:31880198"; MUTAGEN 301; /note="C->S: Does not affect S-nitrosylation. Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:28633005, ECO:0000269|PubMed:31880198"; MUTAGEN 306; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 316; /note="S->A: Abolished phosphorylation by ULK1; promotes hydrolase activity, leading to increased proteolytic activation and delipidation of ATG8 family proteins."; /evidence="ECO:0000269|PubMed:28821708"; MUTAGEN 316; /note="S->D: Phospho-mimetic mutant; reduced hydrolase activity, leading to decreased proteolytic activation and delipidation of ATG8 family proteins."; /evidence="ECO:0000269|PubMed:28821708"; MUTAGEN 323; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 333; /note="C->S: Does not affect formation of disulfide bonds."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 361; /note="C->S: Reduced formation of intrachain and interchain disulfide bonds in response to oxidation. Abolished formation of disulfide bonds, leading to increased autophagy; when associated with S-292."; /evidence="ECO:0000269|PubMed:31880198"; MUTAGEN 383; /note="S->A: Decreased phosphorylation, leading to decreased hydrolase activity and autophagic flux. Does not affect interaction with ATG8 family proteins."; /evidence="ECO:0000269|PubMed:26378241, ECO:0000269|PubMed:28287329, ECO:0000269|PubMed:29232556"; MUTAGEN 383; /note="S->E: Phospho-mimetic mutant; does not affect interaction with ATG8 family proteins."; /evidence="ECO:0000269|PubMed:28287329"; MUTAGEN 388..391; /note="FEIL->AEIA: In 2mLIR; decreased interaction with ATG8 family proteins MAP1LC3A, MAP1LC3B and MAP1LC3C. Decreased ability to mediate delipidation of ATG8 proteins conjugated to phosphatidylethanolamine (PE)."; /evidence="ECO:0000269|PubMed:28287329, ECO:0000269|PubMed:29458288"; MUTAGEN 392; /note="S->A: Decreased phosphorylation, leading to decreased hydrolase activity and autophagic flux. Does not affect interaction with ATG8 family proteins."; /evidence="ECO:0000269|PubMed:26378241, ECO:0000269|PubMed:28287329"; MUTAGEN 392; /note="S->E: Phospho-mimetic mutant; slightly increased interaction with ATG8 family proteins."; /evidence="ECO:0000269|PubMed:28287329
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-383 and Ser-392 promotes autophagy by increasing protein delipidation activity without affecting proteolytic activation of ATG8 proteins (PubMed:26378241). Phosphorylation at Ser-316 by ULK1 inhibits autophagy by decreasing both proteolytic activation and delipidation activities (PubMed:28821708). Phosphorylation at Ser-316 is dephosphorylated by protein phosphatase 2A (PP2A) (PubMed:28821708). Phosphorylation at Ser-34 by AKT2 promotes its hydrolase activity, leading to increased proteolytic activation and delipidation of ATG8 family proteins (PubMed:30443548). Phosphorylation at Ser-34 by AKT1 promotes mitochondrial localization and inhibition of the F1F0-ATP synthase activity, leading to elevation of mitochondrial reactive oxygen species (ROS) (PubMed:29165041). {ECO:0000269|PubMed:26378241, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29165041, ECO:0000269|PubMed:30443548}.; PTM: Ubiquitinated by RNF5, leading to its degradation by the proteasome. {ECO:0000269|PubMed:23093945}.; PTM: S-nitrosylation at Cys-189 and Cys-292 in response to high glucose decreases both proteolytic activation and delipidation activities. {ECO:0000269|PubMed:28633005}.; PTM: O-glycosylated by OGT, leading to increase protease activity, thereby promoting the proteolytic activation of ATG8 family proteins. {ECO:0000269|PubMed:27527864}.; PTM: Forms reversible intrachain disulfide bonds in response to oxidative stress (PubMed:31880198). Forms interchain disulfide bonds, leading to formation of homooligomers in response to oxidation (PubMed:31880198). {ECO:0000269|PubMed:31880198}.
uniprot
proteins
protein_family
Peptidase C54 family
uniprot
proteins
pubmed
10231032
uniprot
proteins
pubmed
12446702
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15169837
uniprot
proteins
pubmed
15187094
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16183633
uniprot
proteins
pubmed
16325851
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17347651
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19322194
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20818167
uniprot
proteins
pubmed
21177865
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22302004
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23093945
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26378241
uniprot
proteins
pubmed
27527864
uniprot
proteins
pubmed
28287329
uniprot
proteins
pubmed
28633005
uniprot
proteins
pubmed
28821708
uniprot
proteins
pubmed
29165041
uniprot
proteins
pubmed
29232556
uniprot
proteins
pubmed
29458288
uniprot
proteins
pubmed
30076329
uniprot
proteins
pubmed
30443548
uniprot
proteins
pubmed
30661429
uniprot
proteins
pubmed
30808002
uniprot
proteins
pubmed
31315929
uniprot
proteins
pubmed
31880198
uniprot
proteins
pubmed
32686895
uniprot
proteins
pubmed
33607258
uniprot
proteins
pubmed
33773106
uniprot
proteins
pubmed
33909989
uniprot
proteins
sequence_length
393
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:29165041}. Cytoplasm, cytosol {ECO:0000269|PubMed:29165041}. Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:29165041}. Endoplasmic reticulum {ECO:0000269|PubMed:29165041}. Mitochondrion {ECO:0000269|PubMed:29165041}. Note=Mainly localizes to the cytoplasm, including cytosol (PubMed:29165041). A samll potion localizes to mitochondria; phosphorylation at Ser-34 promotes localization to mitochondria (PubMed:29165041). {ECO:0000269|PubMed:29165041}.
uniprot
proteins