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Protein

Cysteine protease ATG4C

Gene

Atg4c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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 and GABARAPL2, 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 (By similarity). Is not essential for autophagy development under normal conditions but is required for a proper autophagic response under stressful conditions such as prolonged starvation.By similarity1 Publication

Enzyme regulationi

Inhibited by N-ethylmaleimide.By similarity

Kineticsi

  1. KM=47.5 µM for MAP1LC3B
  2. KM=12.4 µM for GABARAPL2

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei111 – 1111NucleophileBy similarity
    Active sitei345 – 3451Sequence analysis
    Active sitei347 – 3471By similarity

    GO - Molecular functioni

    • cysteine-type endopeptidase activity Source: UniProtKB
    • cysteine-type peptidase activity Source: MGI
    • peptidase activity Source: MGI

    GO - Biological processi

    • autophagosome assembly Source: MGI
    • autophagy Source: UniProtKB
    • protein transport Source: UniProtKB-KW
    • proteolysis Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Autophagy, Protein transport, Transport, Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC54.004.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cysteine protease ATG4C (EC:3.4.22.-)
    Alternative name(s):
    AUT-like 3 cysteine endopeptidase
    Autophagin-3
    Autophagy-related cysteine endopeptidase 3
    Autophagy-related protein 4 homolog C
    Gene namesi
    Name:Atg4c
    Synonyms:Apg4c, Autl3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 4

    Organism-specific databases

    MGIiMGI:2651854. Atg4c.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    • extracellular region Source: MGI
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 458458Cysteine protease ATG4CPRO_0000215850Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ811C2.
    PaxDbiQ811C2.
    PRIDEiQ811C2.

    PTM databases

    iPTMnetiQ811C2.
    PhosphoSiteiQ811C2.

    Expressioni

    Gene expression databases

    BgeeiQ811C2.
    CleanExiMM_ATG4C.
    GenevisibleiQ811C2. MM.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000030279.

    Structurei

    3D structure databases

    ProteinModelPortaliQ811C2.
    SMRiQ811C2. Positions 38-426.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C54 family.Curated

    Phylogenomic databases

    eggNOGiKOG2674. Eukaryota.
    ENOG410XPQ0. LUCA.
    GeneTreeiENSGT00530000063000.
    HOGENOMiHOG000294192.
    HOVERGENiHBG050537.
    InParanoidiQ811C2.
    KOiK08342.
    OMAiSWTSNTV.
    OrthoDBiEOG72C4ZV.
    TreeFamiTF314847.

    Family and domain databases

    InterProiIPR032915. ATG4C.
    IPR005078. Peptidase_C54.
    [Graphical view]
    PANTHERiPTHR22624. PTHR22624. 2 hits.
    PTHR22624:SF38. PTHR22624:SF38. 2 hits.
    PfamiPF03416. Peptidase_C54. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q811C2-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEASGTDEVD KLKTKFISAW NNMKYSWVLK TKTYFSRNSP VLLLGKCYHF
    60 70 80 90 100
    KYEDESKMLP ARSGCAIEDH VIAGNVEEFR KDFISRIWLT YREEFPQIEA
    110 120 130 140 150
    SALTTDCGWG CTLRTGQMLL AQGLILHFLG RAWTWPDALH IENADSDSWT
    160 170 180 190 200
    SNTVKKFTAS FEASLSGDRE LRTPAVSLKE TSGKCPDDHA VRNEAYHRKI
    210 220 230 240 250
    ISWFGDSPVA VFGLHRLIEF GKKSGKKAGD WYGPAVVAHI LRKAVEEARH
    260 270 280 290 300
    PDLQGLTIYV AQDCTVYNSD VIDKQTDSVT AGDARDKAVI ILVPVRLGGE
    310 320 330 340 350
    RTNTDYLEFV KGVLSLEYCV GIIGGKPKQS YYFAGFQDDS LIYMDPHYCQ
    360 370 380 390 400
    SFVDVSIKDF PLETFHCPSP KKMSFRKMDP SCTIGFYCRN VQDFERASEE
    410 420 430 440 450
    ITKMLKISSK EKYPLFTFVN GHSKDFDFTS TAASEEDLFS EDERKNFKRF

    STEEFVLL
    Length:458
    Mass (Da):52,056
    Last modified:July 27, 2011 - v2
    Checksum:iE9F1C1A697CA4978
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti87 – 871I → L in AAH58981 (PubMed:15489334).Curated
    Sequence conflicti190 – 1901A → T in CAC85555 (PubMed:12446702).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ312233 Genomic DNA. Translation: CAC85555.1.
    AL627166 Genomic DNA. Translation: CAM26343.1.
    BC058981 mRNA. Translation: AAH58981.1.
    CCDSiCCDS18382.1.
    RefSeqiNP_001139439.1. NM_001145967.1.
    NP_778194.3. NM_175029.3.
    UniGeneiMm.241663.

    Genome annotation databases

    EnsembliENSMUST00000030279; ENSMUSP00000030279; ENSMUSG00000028550.
    ENSMUST00000180278; ENSMUSP00000137035; ENSMUSG00000028550.
    GeneIDi242557.
    KEGGimmu:242557.
    UCSCiuc008tut.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ312233 Genomic DNA. Translation: CAC85555.1.
    AL627166 Genomic DNA. Translation: CAM26343.1.
    BC058981 mRNA. Translation: AAH58981.1.
    CCDSiCCDS18382.1.
    RefSeqiNP_001139439.1. NM_001145967.1.
    NP_778194.3. NM_175029.3.
    UniGeneiMm.241663.

    3D structure databases

    ProteinModelPortaliQ811C2.
    SMRiQ811C2. Positions 38-426.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000030279.

    Protein family/group databases

    MEROPSiC54.004.

    PTM databases

    iPTMnetiQ811C2.
    PhosphoSiteiQ811C2.

    Proteomic databases

    MaxQBiQ811C2.
    PaxDbiQ811C2.
    PRIDEiQ811C2.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000030279; ENSMUSP00000030279; ENSMUSG00000028550.
    ENSMUST00000180278; ENSMUSP00000137035; ENSMUSG00000028550.
    GeneIDi242557.
    KEGGimmu:242557.
    UCSCiuc008tut.1. mouse.

    Organism-specific databases

    CTDi84938.
    MGIiMGI:2651854. Atg4c.

    Phylogenomic databases

    eggNOGiKOG2674. Eukaryota.
    ENOG410XPQ0. LUCA.
    GeneTreeiENSGT00530000063000.
    HOGENOMiHOG000294192.
    HOVERGENiHBG050537.
    InParanoidiQ811C2.
    KOiK08342.
    OMAiSWTSNTV.
    OrthoDBiEOG72C4ZV.
    TreeFamiTF314847.

    Miscellaneous databases

    PROiQ811C2.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ811C2.
    CleanExiMM_ATG4C.
    GenevisibleiQ811C2. MM.

    Family and domain databases

    InterProiIPR032915. ATG4C.
    IPR005078. Peptidase_C54.
    [Graphical view]
    PANTHERiPTHR22624. PTHR22624. 2 hits.
    PTHR22624:SF38. PTHR22624:SF38. 2 hits.
    PfamiPF03416. Peptidase_C54. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy."
      Marino G., Uria J.A., Puente X.S., Quesada V., Bordallo J., Lopez-Otin C.
      J. Biol. Chem. 278:3671-3678(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Brain.
    4. "Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3."
      Marino G., Salvador-Montoliu N., Fueyo A., Knecht E., Mizushima N., Lopez-Otin C.
      J. Biol. Chem. 282:18573-18583(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiATG4C_MOUSE
    AccessioniPrimary (citable) accession number: Q811C2
    Secondary accession number(s): B1ASJ9, Q6PD25
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: July 27, 2011
    Last modified: June 8, 2016
    This is version 106 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. 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.