UniProtKB - Q9Y4P1 (ATG4B_HUMAN)
Protein
Cysteine protease ATG4B
Gene
ATG4B
Organism
Homo sapiens (Human)
Status
Functioni
Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins MAP1LC3, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine. 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. Has also an activity of delipidating enzyme for the PE-conjugated forms.6 Publications
Activity regulationi
Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H2O2 inhibits its activity.1 Publication
Kineticsi
- KM=5.1 µM for MAP1LC3B2 Publications
- KM=5.8 µM for GABARAP2 Publications
- KM=4.4 µM for GABARAPL12 Publications
- KM=6.1 µM for GABARAPL22 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 74 | Nucleophile4 Publications | 1 | |
Active sitei | 278 | Sequence analysis2 Publications | 1 | |
Active sitei | 280 | 2 Publications | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: InterPro
- cysteine-type peptidase activity Source: UniProtKB
- endopeptidase activity Source: BHF-UCL
GO - Biological processi
- autophagy Source: BHF-UCL
- macroautophagy Source: Reactome
- positive regulation of protein catabolic process Source: Ensembl
- protein delipidation Source: MGI
- protein transport Source: UniProtKB-KW
- proteolysis Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Autophagy, Protein transport, Transport, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9Y4P1 |
Reactomei | R-HSA-1632852, Macroautophagy |
SIGNORi | Q9Y4P1 |
Protein family/group databases
MEROPSi | C54.003 |
TCDBi | 9.A.15.2.1, the autophagy-related phagophore-formation transporter (apt) family |
Names & Taxonomyi
Protein namesi | Recommended name: Cysteine protease ATG4B (EC:3.4.22.-)Alternative name(s): AUT-like 1 cysteine endopeptidase Autophagin-1 Autophagy-related cysteine endopeptidase 1 Autophagy-related protein 4 homolog B Short name: hAPG4B |
Gene namesi | Name:ATG4B Synonyms:APG4B, AUTL1, KIAA0943 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20790, ATG4B |
MIMi | 611338, gene |
neXtProti | NX_Q9Y4P1 |
VEuPathDBi | HostDB:ENSG00000168397.16 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: Reactome
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 74 | C → S: Complete loss of protease activity. 4 Publications | 1 | |
Mutagenesisi | 78 | C → A: Reduces the redox sensitivity and retains activity in presence of H(2)O(2). 1 Publication | 1 | |
Mutagenesisi | 142 | W → A: Strongly reduced protease activity. 1 Publication | 1 | |
Mutagenesisi | 229 | R → A: Strongly reduced protease activity. 1 Publication | 1 | |
Mutagenesisi | 278 | D → A: Complete loss of protease activity. 2 Publications | 1 | |
Mutagenesisi | 280 | H → A: Complete loss of protease activity. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 23192 |
OpenTargetsi | ENSG00000168397 |
PharmGKBi | PA134898340 |
Miscellaneous databases
Pharosi | Q9Y4P1, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1741221 |
Genetic variation databases
BioMutai | ATG4B |
DMDMi | 296434400 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000215844 | 1 – 393 | Cysteine protease ATG4BAdd BLAST | 393 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources1 Publication | 1 | |
Modified residuei | 383 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q9Y4P1 |
jPOSTi | Q9Y4P1 |
MassIVEi | Q9Y4P1 |
PaxDbi | Q9Y4P1 |
PeptideAtlasi | Q9Y4P1 |
PRIDEi | Q9Y4P1 |
ProteomicsDBi | 86230 [Q9Y4P1-1] 86231 [Q9Y4P1-2] 86232 [Q9Y4P1-3] 86233 [Q9Y4P1-4] 86234 [Q9Y4P1-6] |
PTM databases
iPTMneti | Q9Y4P1 |
PhosphoSitePlusi | Q9Y4P1 |
Expressioni
Tissue specificityi
Mainly expressed in the skeletal muscle, followed by brain, heart, liver and pancreas.2 Publications
Gene expression databases
Bgeei | ENSG00000168397, Expressed in left lobe of thyroid gland and 236 other tissues |
ExpressionAtlasi | Q9Y4P1, baseline and differential |
Genevisiblei | Q9Y4P1, HS |
Organism-specific databases
HPAi | ENSG00000168397, Low tissue specificity |
Interactioni
Binary interactionsi
Hide detailsQ9Y4P1
Protein-protein interaction databases
BioGRIDi | 116801, 36 interactors |
IntActi | Q9Y4P1, 23 interactors |
MINTi | Q9Y4P1 |
STRINGi | 9606.ENSP00000384259 |
Chemistry databases
BindingDBi | Q9Y4P1 |
Miscellaneous databases
RNActi | Q9Y4P1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9Y4P1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9Y4P1 |
Family & Domainsi
Sequence similaritiesi
Belongs to the peptidase C54 family.Curated
Phylogenomic databases
eggNOGi | KOG2674, Eukaryota |
GeneTreei | ENSGT00530000063000 |
HOGENOMi | CLU_021259_0_1_1 |
InParanoidi | Q9Y4P1 |
OMAi | RAPYSIH |
OrthoDBi | 431748at2759 |
PhylomeDBi | Q9Y4P1 |
TreeFami | TF314847 |
Family and domain databases
DisProti | DP01326 |
IDEALi | IID00347 |
InterProi | View protein in InterPro IPR032916, ATG4B_met IPR038765, Papain-like_cys_pep_sf IPR005078, Peptidase_C54 |
PANTHERi | PTHR22624, PTHR22624, 1 hit PTHR22624:SF39, PTHR22624:SF39, 1 hit |
Pfami | View protein in Pfam PF03416, Peptidase_C54, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
s (5+)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 5 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9Y4P1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDAATLTYDT LRFAEFEDFP ETSEPVWILG RKYSIFTEKD EILSDVASRL
60 70 80 90 100
WFTYRKNFPA IGGTGPTSDT GWGCMLRCGQ MIFAQALVCR HLGRDWRWTQ
110 120 130 140 150
RKRQPDSYFS VLNAFIDRKD SYYSIHQIAQ MGVGEGKSIG QWYGPNTVAQ
160 170 180 190 200
VLKKLAVFDT WSSLAVHIAM DNTVVMEEIR RLCRTSVPCA GATAFPADSD
210 220 230 240 250
RHCNGFPAGA EVTNRPSPWR PLVLLIPLRL GLTDINEAYV ETLKHCFMMP
260 270 280 290 300
QSLGVIGGKP NSAHYFIGYV GEELIYLDPH TTQPAVEPTD GCFIPDESFH
310 320 330 340 350
CQHPPCRMSI AELDPSIAVG FFCKTEDDFN DWCQQVKKLS LLGGALPMFE
360 370 380 390
LVELQPSHLA CPDVLNLSLD SSDVERLERF FDSEDEDFEI LSL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JIK8 | C9JIK8_HUMAN | Cysteine protease | ATG4B | 219 | Annotation score: | ||
C9J1C1 | C9J1C1_HUMAN | Cysteine protease | ATG4B | 66 | Annotation score: | ||
H0Y2Y0 | H0Y2Y0_HUMAN | Autophagy-related protein 4 homolog... | ATG4B | 76 | Annotation score: | ||
F2Z2K8 | F2Z2K8_HUMAN | Autophagy-related protein 4 homolog... | ATG4B | 88 | Annotation score: |
Sequence cautioni
The sequence BAA76787 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence BAC86110 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 136 | Missing in BAB83890 (PubMed:15169837).Curated | 1 | |
Sequence conflicti | 188 | P → L in BAB55127 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 247 | F → Y in BAB55353 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 273 | E → G in BAB55042 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 312 | E → N in BAB83890 (PubMed:15169837).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021486 | 354 | L → Q5 PublicationsCorresponds to variant dbSNP:rs7601000Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013028 | 1 – 74 | Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST | 74 | |
Alternative sequenceiVSP_013029 | 1 | M → MAHSVPSDSRTSRRPTTRPH AARGAPRGSRRPGRTPKWRL PRISARAPYRLRRLRRHTYW PPRRPVAASRCWPVGATPLG SVGGRTGKM in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_013031 | 321 – 354 | FFCKT…ELVEL → KQGRLVRSLIPWAPRPSSWC AAVLGAAVVMCGTP in isoform 3. 1 PublicationAdd BLAST | 34 | |
Alternative sequenceiVSP_013032 | 355 – 393 | Missing in isoform 3. 1 PublicationAdd BLAST | 39 | |
Alternative sequenceiVSP_013033 | 369 | L → LGESCQVQVGSLG in isoform 4. 1 Publication | 1 | |
Alternative sequenceiVSP_013034 | 370 – 393 | DSSDV…EILSL → GESCQVQILLM in isoform 2 and isoform 6. 1 PublicationAdd BLAST | 24 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ504652 mRNA Translation: CAD43219.1 AB066215 mRNA Translation: BAB83890.1 AB023160 mRNA Translation: BAA76787.2 Different initiation. AK027332 mRNA Translation: BAB55042.1 AK027462 mRNA Translation: BAB55127.1 AK027763 mRNA Translation: BAB55353.1 AK125277 mRNA Translation: BAC86110.1 Different initiation. AL080168 mRNA Translation: CAB45756.1 AC133528 Genomic DNA Translation: AAY14919.1 BC000719 mRNA Translation: AAH00719.1 |
CCDSi | CCDS46564.1 [Q9Y4P1-1] CCDS46565.1 [Q9Y4P1-6] |
PIRi | T12492 |
RefSeqi | NP_037457.3, NM_013325.4 [Q9Y4P1-1] NP_847896.1, NM_178326.2 [Q9Y4P1-6] |
Genome annotation databases
Ensembli | ENST00000402096; ENSP00000384661; ENSG00000168397 [Q9Y4P1-4] ENST00000404914; ENSP00000384259; ENSG00000168397 [Q9Y4P1-1] ENST00000405546; ENSP00000383964; ENSG00000168397 [Q9Y4P1-6] |
GeneIDi | 23192 |
KEGGi | hsa:23192 |
UCSCi | uc002wbv.4, human [Q9Y4P1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ504652 mRNA Translation: CAD43219.1 AB066215 mRNA Translation: BAB83890.1 AB023160 mRNA Translation: BAA76787.2 Different initiation. AK027332 mRNA Translation: BAB55042.1 AK027462 mRNA Translation: BAB55127.1 AK027763 mRNA Translation: BAB55353.1 AK125277 mRNA Translation: BAC86110.1 Different initiation. AL080168 mRNA Translation: CAB45756.1 AC133528 Genomic DNA Translation: AAY14919.1 BC000719 mRNA Translation: AAH00719.1 |
CCDSi | CCDS46564.1 [Q9Y4P1-1] CCDS46565.1 [Q9Y4P1-6] |
PIRi | T12492 |
RefSeqi | NP_037457.3, NM_013325.4 [Q9Y4P1-1] NP_847896.1, NM_178326.2 [Q9Y4P1-6] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2CY7 | X-ray | 1.90 | A | 1-393 | [»] | |
2D1I | X-ray | 2.00 | A/B | 1-393 | [»] | |
2Z0D | X-ray | 1.90 | A | 1-353 | [»] | |
2Z0E | X-ray | 1.90 | A | 1-353 | [»] | |
2ZZP | X-ray | 2.05 | A | 1-353 | [»] | |
5LXH | X-ray | 1.58 | E/F/G | 384-393 | [»] | |
5LXI | X-ray | 1.44 | C/E | 384-393 | [»] | |
SMRi | Q9Y4P1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116801, 36 interactors |
IntActi | Q9Y4P1, 23 interactors |
MINTi | Q9Y4P1 |
STRINGi | 9606.ENSP00000384259 |
Chemistry databases
BindingDBi | Q9Y4P1 |
ChEMBLi | CHEMBL1741221 |
Protein family/group databases
MEROPSi | C54.003 |
TCDBi | 9.A.15.2.1, the autophagy-related phagophore-formation transporter (apt) family |
PTM databases
iPTMneti | Q9Y4P1 |
PhosphoSitePlusi | Q9Y4P1 |
Genetic variation databases
BioMutai | ATG4B |
DMDMi | 296434400 |
Proteomic databases
EPDi | Q9Y4P1 |
jPOSTi | Q9Y4P1 |
MassIVEi | Q9Y4P1 |
PaxDbi | Q9Y4P1 |
PeptideAtlasi | Q9Y4P1 |
PRIDEi | Q9Y4P1 |
ProteomicsDBi | 86230 [Q9Y4P1-1] 86231 [Q9Y4P1-2] 86232 [Q9Y4P1-3] 86233 [Q9Y4P1-4] 86234 [Q9Y4P1-6] |
Protocols and materials databases
Antibodypediai | 12105, 700 antibodies |
DNASUi | 23192 |
Genome annotation databases
Ensembli | ENST00000402096; ENSP00000384661; ENSG00000168397 [Q9Y4P1-4] ENST00000404914; ENSP00000384259; ENSG00000168397 [Q9Y4P1-1] ENST00000405546; ENSP00000383964; ENSG00000168397 [Q9Y4P1-6] |
GeneIDi | 23192 |
KEGGi | hsa:23192 |
UCSCi | uc002wbv.4, human [Q9Y4P1-1] |
Organism-specific databases
CTDi | 23192 |
DisGeNETi | 23192 |
GeneCardsi | ATG4B |
HGNCi | HGNC:20790, ATG4B |
HPAi | ENSG00000168397, Low tissue specificity |
MIMi | 611338, gene |
neXtProti | NX_Q9Y4P1 |
OpenTargetsi | ENSG00000168397 |
PharmGKBi | PA134898340 |
VEuPathDBi | HostDB:ENSG00000168397.16 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2674, Eukaryota |
GeneTreei | ENSGT00530000063000 |
HOGENOMi | CLU_021259_0_1_1 |
InParanoidi | Q9Y4P1 |
OMAi | RAPYSIH |
OrthoDBi | 431748at2759 |
PhylomeDBi | Q9Y4P1 |
TreeFami | TF314847 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y4P1 |
Reactomei | R-HSA-1632852, Macroautophagy |
SIGNORi | Q9Y4P1 |
Miscellaneous databases
BioGRID-ORCSi | 23192, 9 hits in 1005 CRISPR screens |
ChiTaRSi | ATG4B, human |
EvolutionaryTracei | Q9Y4P1 |
GeneWikii | ATG4B |
GenomeRNAii | 23192 |
Pharosi | Q9Y4P1, Tbio |
PROi | PR:Q9Y4P1 |
RNActi | Q9Y4P1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000168397, Expressed in left lobe of thyroid gland and 236 other tissues |
ExpressionAtlasi | Q9Y4P1, baseline and differential |
Genevisiblei | Q9Y4P1, HS |
Family and domain databases
DisProti | DP01326 |
IDEALi | IID00347 |
InterProi | View protein in InterPro IPR032916, ATG4B_met IPR038765, Papain-like_cys_pep_sf IPR005078, Peptidase_C54 |
PANTHERi | PTHR22624, PTHR22624, 1 hit PTHR22624:SF39, PTHR22624:SF39, 1 hit |
Pfami | View protein in Pfam PF03416, Peptidase_C54, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ATG4B_HUMAN | |
Accessioni | Q9Y4P1Primary (citable) accession number: Q9Y4P1 Secondary accession number(s): B7WNK2 Q9Y2F2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2005 |
Last sequence update: | May 18, 2010 | |
Last modified: | April 7, 2021 | |
This is version 187 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families