Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q86TL0

- ATG4D_HUMAN

UniProt

Q86TL0 - ATG4D_HUMAN

Protein

Cysteine protease ATG4D

Gene

ATG4D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 1 (01 Jun 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Cysteine protease ATG4D: 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.
    Cysteine protease ATG4D, mitochondrial: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.

    Enzyme regulationi

    Inhibited by N-ethylmaleimide.

    Kineticsi

    1. KM=13.1 µM for MAP1LC3B1 Publication
    2. KM=7.2 µM for GABARAPL21 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei63 – 642Cleavage; by CASP3
    Active sitei144 – 1441NucleophileBy similarity
    Active sitei356 – 3561Sequence Analysis
    Active sitei358 – 3581By similarity

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. autophagy Source: UniProtKB-KW
    3. protein transport Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis, Autophagy, Protein transport, Transport, Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC54.005.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cysteine protease ATG4D (EC:3.4.22.-)
    Alternative name(s):
    AUT-like 4 cysteine endopeptidase
    Autophagin-4
    Autophagy-related cysteine endopeptidase 4
    Autophagy-related protein 4 homolog D
    Cleaved into the following chain:
    Gene namesi
    Name:ATG4D
    Synonyms:APG4D, AUTL4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:20789. ATG4D.

    Subcellular locationi

    Chain Cysteine protease ATG4D, mitochondrial : Cytoplasm. Mitochondrion matrix
    Note: Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. mitochondrial matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi63 – 631D → A: Abolishes cleavage by CASP3. 1 Publication

    Organism-specific databases

    PharmGKBiPA134907475.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 474474Cysteine protease ATG4DPRO_0000215853Add
    BLAST
    Chaini64 – 474411Cysteine protease ATG4D, mitochondrialPRO_0000423408Add
    BLAST

    Post-translational modificationi

    Cleaved by CASP3 during apoptosis which leads to increased activity. The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondroal import of the protein.2 Publications

    Proteomic databases

    PaxDbiQ86TL0.
    PRIDEiQ86TL0.

    PTM databases

    PhosphoSiteiQ86TL0.

    Expressioni

    Tissue specificityi

    Mainly expressed in skeletal muscle and, to a lower extent, in testis.1 Publication

    Gene expression databases

    ArrayExpressiQ86TL0.
    BgeeiQ86TL0.
    CleanExiHS_ATG4D.
    GenevestigatoriQ86TL0.

    Interactioni

    Protein-protein interaction databases

    BioGridi124401. 1 interaction.
    STRINGi9606.ENSP00000311318.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86TL0.
    SMRiQ86TL0. Positions 115-434.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni64 – 10340Cryptic mitochondrial signal peptideAdd
    BLAST

    Domaini

    Residues 64 to 103 constitute a cryptic mitochondrial transit peptide which is revealed after cleavage by caspase of residues 1 to 63 upon oxidative stress and cell death. It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria (PubMed:22441018).1 Publication

    Sequence similaritiesi

    Belongs to the peptidase C54 family.Curated

    Phylogenomic databases

    eggNOGiNOG239662.
    HOGENOMiHOG000294192.
    HOVERGENiHBG050537.
    InParanoidiQ86TL0.
    KOiK08342.
    OMAiKYGWAVK.
    PhylomeDBiQ86TL0.
    TreeFamiTF314847.

    Family and domain databases

    InterProiIPR005078. Peptidase_C54.
    [Graphical view]
    PANTHERiPTHR22624. PTHR22624. 1 hit.
    PfamiPF03416. Peptidase_C54. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q86TL0-1) [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

    MNSVSPAAAQ YRSSSPEDAR RRPEARRPRG PRGPDPNGLG PSGASGPALG    50
    SPGAGPSEPD EVDKFKAKFL TAWNNVKYGW VVKSRTSFSK ISSIHLCGRR 100
    YRFEGEGDIQ RFQRDFVSRL WLTYRRDFPP LPGGCLTSDC GWGCMLRSGQ 150
    MMLAQGLLLH FLPRDWTWAE GMGLGPPELS GSASPSRYHG PARWMPPRWA 200
    QGAPELEQER RHRQIVSWFA DHPRAPFGLH RLVELGQSSG KKAGDWYGPS 250
    LVAHILRKAV ESCSDVTRLV VYVSQDCTVY KADVARLVAR PDPTAEWKSV 300
    VILVPVRLGG ETLNPVYVPC VKELLRCELC LGIMGGKPRH SLYFIGYQDD 350
    FLLYLDPHYC QPTVDVSQAD FPLESFHCTS PRKMAFAKMD PSCTVGFYAG 400
    DRKEFETLCS ELTRVLSSSS ATERYPMFTL AEGHAQDHSL DDLCSQLAQP 450
    TLRLPRTGRL LRAKRPSSED FVFL 474
    Length:474
    Mass (Da):52,922
    Last modified:June 1, 2003 - v1
    Checksum:iDBD91A3F1F80D2B8
    GO
    Isoform 2 (identifier: Q86TL0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-333: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:141
    Mass (Da):16,008
    Checksum:iC30E0A97CBB1E2D2
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 333333Missing in isoform 2. 1 PublicationVSP_056671Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ312332 mRNA. Translation: CAC85951.1.
    AC011461 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84116.1.
    BC007639 mRNA. Translation: AAH07639.1.
    BC016845 mRNA. Translation: AAH16845.1.
    BC068992 mRNA. Translation: AAH68992.1.
    CCDSiCCDS12241.1.
    RefSeqiNP_001268433.1. NM_001281504.1.
    NP_116274.3. NM_032885.5.
    UniGeneiHs.512799.

    Genome annotation databases

    EnsembliENST00000309469; ENSP00000311318; ENSG00000130734.
    ENST00000540862; ENSP00000441375; ENSG00000130734.
    GeneIDi84971.
    KEGGihsa:84971.
    UCSCiuc002mov.3. human.

    Polymorphism databases

    DMDMi61211809.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ312332 mRNA. Translation: CAC85951.1 .
    AC011461 Genomic DNA. No translation available.
    CH471106 Genomic DNA. Translation: EAW84116.1 .
    BC007639 mRNA. Translation: AAH07639.1 .
    BC016845 mRNA. Translation: AAH16845.1 .
    BC068992 mRNA. Translation: AAH68992.1 .
    CCDSi CCDS12241.1.
    RefSeqi NP_001268433.1. NM_001281504.1.
    NP_116274.3. NM_032885.5.
    UniGenei Hs.512799.

    3D structure databases

    ProteinModelPortali Q86TL0.
    SMRi Q86TL0. Positions 115-434.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124401. 1 interaction.
    STRINGi 9606.ENSP00000311318.

    Protein family/group databases

    MEROPSi C54.005.

    PTM databases

    PhosphoSitei Q86TL0.

    Polymorphism databases

    DMDMi 61211809.

    Proteomic databases

    PaxDbi Q86TL0.
    PRIDEi Q86TL0.

    Protocols and materials databases

    DNASUi 84971.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000309469 ; ENSP00000311318 ; ENSG00000130734 .
    ENST00000540862 ; ENSP00000441375 ; ENSG00000130734 .
    GeneIDi 84971.
    KEGGi hsa:84971.
    UCSCi uc002mov.3. human.

    Organism-specific databases

    CTDi 84971.
    GeneCardsi GC19P010654.
    HGNCi HGNC:20789. ATG4D.
    MIMi 611340. gene.
    neXtProti NX_Q86TL0.
    PharmGKBi PA134907475.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG239662.
    HOGENOMi HOG000294192.
    HOVERGENi HBG050537.
    InParanoidi Q86TL0.
    KOi K08342.
    OMAi KYGWAVK.
    PhylomeDBi Q86TL0.
    TreeFami TF314847.

    Miscellaneous databases

    GenomeRNAii 84971.
    NextBioi 75518.
    PROi Q86TL0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q86TL0.
    Bgeei Q86TL0.
    CleanExi HS_ATG4D.
    Genevestigatori Q86TL0.

    Family and domain databases

    InterProi IPR005078. Peptidase_C54.
    [Graphical view ]
    PANTHERi PTHR22624. PTHR22624. 1 hit.
    Pfami PF03416. Peptidase_C54. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] (ISOFORM 1), TISSUE SPECIFICITY.
      Tissue: Fetal liver.
    2. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "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] (ISOFORMS 1 AND 2).
      Tissue: Lung, Ovary and Uterus.
    5. "Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis."
      Betin V.M., Lane J.D.
      J. Cell Sci. 122:2554-2566(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CLEAVAGE BY CASP3, MUTAGENESIS OF ASP-63, SUBCELLULAR LOCATION.
    6. "Kinetics comparisons of mammalian Atg4 homologues indicate selective preferences toward diverse Atg8 substrates."
      Li M., Hou Y., Wang J., Chen X., Shao Z.M., Yin X.M.
      J. Biol. Chem. 286:7327-7338(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress."
      Betin V.M., MacVicar T.D., Parsons S.F., Anstee D.J., Lane J.D.
      Autophagy 8:664-676(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION (CYSTEINE PROTEASE ATG4D, MITOCHONDRIAL), CLEAVAGE BY CASP3, SUBCELLULAR LOCATION, DOMAIN, CRYPTIC SIGNAL PEPTIDE.

    Entry informationi

    Entry nameiATG4D_HUMAN
    AccessioniPrimary (citable) accession number: Q86TL0
    Secondary accession number(s): Q969K0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: June 1, 2003
    Last modified: October 1, 2014
    This is version 94 of the entry and version 1 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3