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Protein

Cysteine protease ATG4B

Gene

ATG4B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme 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

  1. KM=5.1 µM for MAP1LC3B2 Publications
  2. KM=5.8 µM for GABARAP2 Publications
  3. KM=4.4 µM for GABARAPL12 Publications
  4. KM=6.1 µM for GABARAPL22 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei74Nucleophile1
    Active sitei278Sequence analysis1
    Active sitei2801

    GO - Molecular functioni

    • cysteine-type endopeptidase activity Source: GO_Central
    • cysteine-type peptidase activity Source: UniProtKB
    • endopeptidase activity Source: BHF-UCL

    GO - Biological processi

    • autophagosome assembly Source: UniProtKB
    • autophagy Source: UniProtKB
    • C-terminal protein lipidation Source: GO_Central
    • macroautophagy Source: Reactome
    • mitophagy Source: GO_Central
    • nucleophagy Source: GO_Central
    • positive regulation of protein catabolic process Source: Ensembl
    • protein delipidation Source: MGI
    • protein processing Source: GO_Central
    • protein targeting to membrane Source: GO_Central
    • proteolysis Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Autophagy, Protein transport, Transport, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiR-HSA-1632852. Macroautophagy.
    SIGNORiQ9Y4P1.

    Protein family/group databases

    MEROPSiC54.003.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:20790. ATG4B.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • cytosol Source: GO_Central
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi74C → S: Complete loss of protease activity. 4 Publications1
    Mutagenesisi78C → A: Reduces the redox sensitivity and retains activity in presence of H(2)O(2). 1 Publication1
    Mutagenesisi142W → A: Strongly reduced protease activity. 1 Publication1
    Mutagenesisi229R → A: Strongly reduced protease activity. 1 Publication1
    Mutagenesisi278D → A: Complete loss of protease activity. 2 Publications1
    Mutagenesisi280H → A: Complete loss of protease activity. 2 Publications1

    Organism-specific databases

    DisGeNETi23192.
    OpenTargetsiENSG00000168397.
    PharmGKBiPA134898340.

    Chemistry databases

    ChEMBLiCHEMBL1741221.

    Polymorphism and mutation databases

    BioMutaiATG4B.
    DMDMi296434400.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002158441 – 393Cysteine protease ATG4BAdd BLAST393

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1 Publication1
    Modified residuei383PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ9Y4P1.
    PaxDbiQ9Y4P1.
    PeptideAtlasiQ9Y4P1.
    PRIDEiQ9Y4P1.

    PTM databases

    iPTMnetiQ9Y4P1.
    PhosphoSitePlusiQ9Y4P1.

    Expressioni

    Tissue specificityi

    Mainly expressed in the skeletal muscle, followed by brain, heart, liver and pancreas.2 Publications

    Gene expression databases

    BgeeiENSG00000168397.
    CleanExiHS_ATG4B.
    ExpressionAtlasiQ9Y4P1. baseline and differential.
    GenevisibleiQ9Y4P1. HS.

    Organism-specific databases

    HPAiCAB037195.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GABARAPO951668EBI-712014,EBI-712001
    GABARAPL1Q9H0R89EBI-712014,EBI-746969
    GABARAPL2P605209EBI-712014,EBI-720116
    MAP1LC3AQ9H4925EBI-712014,EBI-720768
    MAP1LC3BQ9GZQ813EBI-712014,EBI-373144
    MAP1LC3CQ9BXW43EBI-712014,EBI-2603996

    Protein-protein interaction databases

    BioGridi116801. 25 interactors.
    IntActiQ9Y4P1. 18 interactors.
    MINTiMINT-1414043.
    STRINGi9606.ENSP00000384259.

    Chemistry databases

    BindingDBiQ9Y4P1.

    Structurei

    Secondary structure

    1393
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi5 – 7Combined sources3
    Helixi10 – 13Combined sources4
    Helixi14 – 18Combined sources5
    Beta strandi22 – 24Combined sources3
    Beta strandi26 – 28Combined sources3
    Beta strandi31 – 33Combined sources3
    Turni35 – 37Combined sources3
    Helixi39 – 48Combined sources10
    Beta strandi54 – 57Combined sources4
    Turni61 – 64Combined sources4
    Turni70 – 72Combined sources3
    Helixi74 – 91Combined sources18
    Beta strandi100 – 102Combined sources3
    Helixi106 – 113Combined sources8
    Beta strandi116 – 118Combined sources3
    Helixi125 – 133Combined sources9
    Turni134 – 136Combined sources3
    Helixi145 – 156Combined sources12
    Turni160 – 162Combined sources3
    Beta strandi165 – 168Combined sources4
    Beta strandi173 – 175Combined sources3
    Helixi176 – 183Combined sources8
    Beta strandi184 – 186Combined sources3
    Beta strandi222 – 229Combined sources8
    Beta strandi232 – 234Combined sources3
    Helixi237 – 239Combined sources3
    Helixi240 – 246Combined sources7
    Beta strandi252 – 257Combined sources6
    Beta strandi264 – 270Combined sources7
    Beta strandi273 – 277Combined sources5
    Beta strandi281 – 284Combined sources4
    Beta strandi290 – 292Combined sources3
    Helixi297 – 299Combined sources3
    Beta strandi306 – 309Combined sources4
    Helixi310 – 312Combined sources3
    Beta strandi315 – 325Combined sources11
    Helixi326 – 341Combined sources16
    Beta strandi349 – 353Combined sources5
    Helixi371 – 376Combined sources6

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2CY7X-ray1.90A1-393[»]
    2D1IX-ray2.00A/B1-393[»]
    2Z0DX-ray1.90A1-353[»]
    2Z0EX-ray1.90A1-353[»]
    2ZZPX-ray2.05A1-353[»]
    ProteinModelPortaliQ9Y4P1.
    SMRiQ9Y4P1.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9Y4P1.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C54 family.Curated

    Phylogenomic databases

    eggNOGiKOG2674. Eukaryota.
    ENOG410XPQ0. LUCA.
    GeneTreeiENSGT00530000063000.
    HOVERGENiHBG050536.
    InParanoidiQ9Y4P1.
    KOiK08342.
    OMAiGKEYNAL.
    OrthoDBiEOG091G0995.
    PhylomeDBiQ9Y4P1.
    TreeFamiTF314847.

    Family and domain databases

    InterProiIPR032916. ATG4B_met.
    IPR005078. Peptidase_C54.
    [Graphical view]
    PANTHERiPTHR22624. PTHR22624. 1 hit.
    PTHR22624:SF39. PTHR22624:SF39. 1 hit.
    PfamiPF03416. Peptidase_C54. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9Y4P1-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            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
    Length:393
    Mass (Da):44,294
    Last modified:May 18, 2010 - v2
    Checksum:iF4ADB3192176E0E5
    GO
    Isoform 2 (identifier: Q9Y4P1-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MAHSVPSDSR...GSVGGRTGKM
         370-393: DSSDVERLERFFDSEDEDFEILSL → GESCQVQILLM

    Note: No experimental confirmation available.
    Show »
    Length:468
    Mass (Da):52,529
    Checksum:iF9731E7C406960D6
    GO
    Isoform 3 (identifier: Q9Y4P1-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-74: Missing.
         321-354: FFCKTEDDFNDWCQQVKKLSLLGGALPMFELVEL → KQGRLVRSLIPWAPRPSSWCAAVLGAAVVMCGTP
         355-393: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:280
    Mass (Da):31,042
    Checksum:i0904A795A1B596B3
    GO
    Isoform 4 (identifier: Q9Y4P1-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-74: Missing.
         369-369: L → LGESCQVQVGSLG

    Show »
    Length:331
    Mass (Da):37,037
    Checksum:i97592E25838601B2
    GO
    Isoform 6 (identifier: Q9Y4P1-6) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         370-393: DSSDVERLERFFDSEDEDFEILSL → GESCQVQILLM

    Note: No experimental confirmation available.
    Show »
    Length:380
    Mass (Da):42,622
    Checksum:i48140873BCE7533D
    GO

    Sequence cautioni

    The sequence BAA76787 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence BAC86110 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti136Missing in BAB83890 (PubMed:15169837).Curated1
    Sequence conflicti188P → L in BAB55127 (PubMed:14702039).Curated1
    Sequence conflicti247F → Y in BAB55353 (PubMed:14702039).Curated1
    Sequence conflicti273E → G in BAB55042 (PubMed:14702039).Curated1
    Sequence conflicti312E → N in BAB83890 (PubMed:15169837).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_021486354L → Q.5 PublicationsCorresponds to variant rs7601000dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0130281 – 74Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST74
    Alternative sequenceiVSP_0130291M → MAHSVPSDSRTSRRPTTRPH AARGAPRGSRRPGRTPKWRL PRISARAPYRLRRLRRHTYW PPRRPVAASRCWPVGATPLG SVGGRTGKM in isoform 2. 1 Publication1
    Alternative sequenceiVSP_013031321 – 354FFCKT…ELVEL → KQGRLVRSLIPWAPRPSSWC AAVLGAAVVMCGTP in isoform 3. 1 PublicationAdd BLAST34
    Alternative sequenceiVSP_013032355 – 393Missing in isoform 3. 1 PublicationAdd BLAST39
    Alternative sequenceiVSP_013033369L → LGESCQVQVGSLG in isoform 4. 1 Publication1
    Alternative sequenceiVSP_013034370 – 393DSSDV…EILSL → GESCQVQILLM in isoform 2 and isoform 6. 1 PublicationAdd BLAST24

    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.
    CCDSiCCDS46564.1. [Q9Y4P1-1]
    CCDS46565.1. [Q9Y4P1-6]
    PIRiT12492.
    RefSeqiNP_037457.3. NM_013325.4. [Q9Y4P1-1]
    NP_847896.1. NM_178326.2. [Q9Y4P1-6]
    UniGeneiHs.283610.

    Genome annotation databases

    EnsembliENST00000402096; ENSP00000384661; ENSG00000168397. [Q9Y4P1-4]
    ENST00000404914; ENSP00000384259; ENSG00000168397. [Q9Y4P1-1]
    ENST00000405546; ENSP00000383964; ENSG00000168397. [Q9Y4P1-6]
    GeneIDi23192.
    KEGGihsa:23192.
    UCSCiuc002wbv.4. human. [Q9Y4P1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    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.
    CCDSiCCDS46564.1. [Q9Y4P1-1]
    CCDS46565.1. [Q9Y4P1-6]
    PIRiT12492.
    RefSeqiNP_037457.3. NM_013325.4. [Q9Y4P1-1]
    NP_847896.1. NM_178326.2. [Q9Y4P1-6]
    UniGeneiHs.283610.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2CY7X-ray1.90A1-393[»]
    2D1IX-ray2.00A/B1-393[»]
    2Z0DX-ray1.90A1-353[»]
    2Z0EX-ray1.90A1-353[»]
    2ZZPX-ray2.05A1-353[»]
    ProteinModelPortaliQ9Y4P1.
    SMRiQ9Y4P1.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116801. 25 interactors.
    IntActiQ9Y4P1. 18 interactors.
    MINTiMINT-1414043.
    STRINGi9606.ENSP00000384259.

    Chemistry databases

    BindingDBiQ9Y4P1.
    ChEMBLiCHEMBL1741221.

    Protein family/group databases

    MEROPSiC54.003.

    PTM databases

    iPTMnetiQ9Y4P1.
    PhosphoSitePlusiQ9Y4P1.

    Polymorphism and mutation databases

    BioMutaiATG4B.
    DMDMi296434400.

    Proteomic databases

    EPDiQ9Y4P1.
    PaxDbiQ9Y4P1.
    PeptideAtlasiQ9Y4P1.
    PRIDEiQ9Y4P1.

    Protocols and materials databases

    DNASUi23192.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000402096; ENSP00000384661; ENSG00000168397. [Q9Y4P1-4]
    ENST00000404914; ENSP00000384259; ENSG00000168397. [Q9Y4P1-1]
    ENST00000405546; ENSP00000383964; ENSG00000168397. [Q9Y4P1-6]
    GeneIDi23192.
    KEGGihsa:23192.
    UCSCiuc002wbv.4. human. [Q9Y4P1-1]

    Organism-specific databases

    CTDi23192.
    DisGeNETi23192.
    GeneCardsiATG4B.
    H-InvDBHIX0180188.
    HGNCiHGNC:20790. ATG4B.
    HPAiCAB037195.
    MIMi611338. gene.
    neXtProtiNX_Q9Y4P1.
    OpenTargetsiENSG00000168397.
    PharmGKBiPA134898340.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2674. Eukaryota.
    ENOG410XPQ0. LUCA.
    GeneTreeiENSGT00530000063000.
    HOVERGENiHBG050536.
    InParanoidiQ9Y4P1.
    KOiK08342.
    OMAiGKEYNAL.
    OrthoDBiEOG091G0995.
    PhylomeDBiQ9Y4P1.
    TreeFamiTF314847.

    Enzyme and pathway databases

    ReactomeiR-HSA-1632852. Macroautophagy.
    SIGNORiQ9Y4P1.

    Miscellaneous databases

    ChiTaRSiATG4B. human.
    EvolutionaryTraceiQ9Y4P1.
    GeneWikiiATG4B.
    GenomeRNAii23192.
    PROiQ9Y4P1.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000168397.
    CleanExiHS_ATG4B.
    ExpressionAtlasiQ9Y4P1. baseline and differential.
    GenevisibleiQ9Y4P1. HS.

    Family and domain databases

    InterProiIPR032916. ATG4B_met.
    IPR005078. Peptidase_C54.
    [Graphical view]
    PANTHERiPTHR22624. PTHR22624. 1 hit.
    PTHR22624:SF39. PTHR22624:SF39. 1 hit.
    PfamiPF03416. Peptidase_C54. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiATG4B_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4P1
    Secondary accession number(s): B7WNK2
    , Q53NU4, Q6ZUV8, Q8WYM9, Q96K07, Q96K96, Q96SZ1, Q9Y2F2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: May 18, 2010
    Last modified: November 30, 2016
    This is version 153 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.