Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cysteine protease ATG4B

Gene

ATG4B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

  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

    Keywordsi

    Molecular functionHydrolase, Protease, Thiol protease
    Biological processAutophagy, Protein transport, Transport, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiR-HSA-1632852 Macroautophagy
    SIGNORiQ9Y4P1

    Protein family/group databases

    MEROPSiC54.003
    TCDBi9.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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000168397.16
    HGNCiHGNC:20790 ATG4B
    MIMi611338 gene
    neXtProtiNX_Q9Y4P1

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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
    ProteomicsDBi86230
    86231 [Q9Y4P1-2]
    86232 [Q9Y4P1-3]
    86233 [Q9Y4P1-4]
    86234 [Q9Y4P1-6]

    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 Expressed in 224 organ(s), highest expression level in left lobe of thyroid gland
    CleanExiHS_ATG4B
    ExpressionAtlasiQ9Y4P1 baseline and differential
    GenevisibleiQ9Y4P1 HS

    Organism-specific databases

    HPAiCAB037195
    HPA069803

    Interactioni

    Binary interactionsi

    Protein-protein interaction databases

    BioGridi116801, 28 interactors
    IntActiQ9Y4P1, 18 interactors
    MINTiQ9Y4P1
    STRINGi9606.ENSP00000384259

    Chemistry databases

    BindingDBiQ9Y4P1

    Structurei

    Secondary structure

    1393
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    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
    OMAiRAPYSIH
    OrthoDBiEOG091G0995
    PhylomeDBiQ9Y4P1
    TreeFamiTF314847

    Family and domain databases

    InterProiView protein in InterPro
    IPR032916 ATG4B_met
    IPR038765 Papain_like_cys_pep_sf
    IPR005078 Peptidase_C54
    PANTHERiPTHR22624 PTHR22624, 1 hit
    PTHR22624:SF39 PTHR22624:SF39, 1 hit
    PfamiView protein in Pfam
    PF03416 Peptidase_C54, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit

    Sequences (5+)i

    Sequence statusi: Complete.

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

    This entry has 5 described isoforms and 8 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 '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

    Computationally mapped potential isoform sequencesi

    There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    C9JQ72C9JQ72_HUMAN
    Cysteine protease
    ATG4B
    266Annotation score:
    H7C2A6H7C2A6_HUMAN
    Cysteine protease
    ATG4B
    193Annotation score:
    C9JIK8C9JIK8_HUMAN
    Cysteine protease
    ATG4B
    219Annotation score:
    C9J3C0C9J3C0_HUMAN
    Cysteine protease
    ATG4B
    147Annotation score:
    C9J1C1C9J1C1_HUMAN
    Cysteine protease
    ATG4B
    66Annotation score:
    C9JVD5C9JVD5_HUMAN
    Cysteine protease
    ATG4B
    105Annotation score:
    H0Y2Y0H0Y2Y0_HUMAN
    Cysteine protease ATG4B
    ATG4B
    76Annotation score:
    F2Z2K8F2Z2K8_HUMAN
    Cysteine protease ATG4B
    ATG4B
    88Annotation score:

    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 → Q5 PublicationsCorresponds to variant dbSNP:rs7601000Ensembl.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

    Similar 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
    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[»]
    5LXHX-ray1.58E/F/G384-393[»]
    5LXIX-ray1.44C/E384-393[»]
    ProteinModelPortaliQ9Y4P1
    SMRiQ9Y4P1
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi116801, 28 interactors
    IntActiQ9Y4P1, 18 interactors
    MINTiQ9Y4P1
    STRINGi9606.ENSP00000384259

    Chemistry databases

    BindingDBiQ9Y4P1
    ChEMBLiCHEMBL1741221

    Protein family/group databases

    MEROPSiC54.003
    TCDBi9.A.15.2.1 the autophagy-related phagophore-formation transporter (apt) family

    PTM databases

    iPTMnetiQ9Y4P1
    PhosphoSitePlusiQ9Y4P1

    Polymorphism and mutation databases

    BioMutaiATG4B
    DMDMi296434400

    Proteomic databases

    EPDiQ9Y4P1
    PaxDbiQ9Y4P1
    PeptideAtlasiQ9Y4P1
    PRIDEiQ9Y4P1
    ProteomicsDBi86230
    86231 [Q9Y4P1-2]
    86232 [Q9Y4P1-3]
    86233 [Q9Y4P1-4]
    86234 [Q9Y4P1-6]

    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
    EuPathDBiHostDB:ENSG00000168397.16
    GeneCardsiATG4B
    H-InvDBiHIX0180188
    HGNCiHGNC:20790 ATG4B
    HPAiCAB037195
    HPA069803
    MIMi611338 gene
    neXtProtiNX_Q9Y4P1
    OpenTargetsiENSG00000168397
    PharmGKBiPA134898340
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2674 Eukaryota
    ENOG410XPQ0 LUCA
    GeneTreeiENSGT00530000063000
    HOVERGENiHBG050536
    InParanoidiQ9Y4P1
    KOiK08342
    OMAiRAPYSIH
    OrthoDBiEOG091G0995
    PhylomeDBiQ9Y4P1
    TreeFamiTF314847

    Enzyme and pathway databases

    ReactomeiR-HSA-1632852 Macroautophagy
    SIGNORiQ9Y4P1

    Miscellaneous databases

    ChiTaRSiATG4B human
    EvolutionaryTraceiQ9Y4P1
    GeneWikiiATG4B
    GenomeRNAii23192
    PROiPR:Q9Y4P1
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000168397 Expressed in 224 organ(s), highest expression level in left lobe of thyroid gland
    CleanExiHS_ATG4B
    ExpressionAtlasiQ9Y4P1 baseline and differential
    GenevisibleiQ9Y4P1 HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR032916 ATG4B_met
    IPR038765 Papain_like_cys_pep_sf
    IPR005078 Peptidase_C54
    PANTHERiPTHR22624 PTHR22624, 1 hit
    PTHR22624:SF39 PTHR22624:SF39, 1 hit
    PfamiView protein in Pfam
    PF03416 Peptidase_C54, 1 hit
    SUPFAMiSSF54001 SSF54001, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiATG4B_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4P1
    Secondary accession number(s): B7WNK2
    , Q53NU4, Q6ZUV8, Q8WYM9, Q96K07, Q96K96, Q96SZ1, Q9Y2F2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: May 18, 2010
    Last modified: November 7, 2018
    This is version 170 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    6. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again