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Q96DT6

- ATG4C_HUMAN

UniProt

Q96DT6 - ATG4C_HUMAN

Protein

Cysteine protease ATG4C

Gene

ATG4C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. 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 similarity. 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 similarity1 Publication

    Enzyme regulationi

    Inhibited by N-ethylmaleimide.

    Kineticsi

    1. KM=47.5 µM for MAP1LC3B1 Publication
    2. KM=12.4 µM for GABARAPL21 Publication

    Sites

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

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: UniProtKB
    2. peptidase activity Source: UniProtKB

    GO - Biological processi

    1. autophagic vacuole assembly Source: UniProtKB
    2. autophagy Source: UniProtKB
    3. protein targeting to membrane Source: UniProtKB
    4. proteolysis Source: UniProtKB

    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, AUTL1, AUTL3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:16040. ATG4C.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB
    3. extracellular region Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA25183.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 458458Cysteine protease ATG4CPRO_0000215849Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ96DT6.
    PaxDbiQ96DT6.
    PRIDEiQ96DT6.

    PTM databases

    PhosphoSiteiQ96DT6.

    Expressioni

    Tissue specificityi

    Highly expressed in skeletal muscle, heart, liver and testis.1 Publication

    Gene expression databases

    ArrayExpressiQ96DT6.
    BgeeiQ96DT6.
    CleanExiHS_ATG4C.
    GenevestigatoriQ96DT6.

    Organism-specific databases

    HPAiHPA007049.

    Interactioni

    Protein-protein interaction databases

    BioGridi124372. 10 interactions.
    IntActiQ96DT6. 9 interactions.
    STRINGi9606.ENSP00000322159.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96DT6.
    SMRiQ96DT6. Positions 38-426.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the peptidase C54 family.Curated

    Phylogenomic databases

    eggNOGiNOG239662.
    HOGENOMiHOG000294192.
    HOVERGENiHBG050537.
    InParanoidiQ96DT6.
    KOiK08342.
    OMAiARSGCTI.
    PhylomeDBiQ96DT6.
    TreeFamiTF314847.

    Family and domain databases

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

    Sequencei

    Sequence statusi: Complete.

    Q96DT6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEATGTDEVD KLKTKFISAW NNMKYSWVLK TKTYFSRNSP VLLLGKCYHF    50
    KYEDEDKTLP AESGCTIEDH VIAGNVEEFR KDFISRIWLT YREEFPQIEG 100
    SALTTDCGWG CTLRTGQMLL AQGLILHFLG RAWTWPDALN IENSDSESWT 150
    SHTVKKFTAS FEASLSGERE FKTPTISLKE TIGKYSDDHE MRNEVYHRKI 200
    ISWFGDSPLA LFGLHQLIEY GKKSGKKAGD WYGPAVVAHI LRKAVEEARH 250
    PDLQGITIYV AQDCTVYNSD VIDKQSASMT SDNADDKAVI ILVPVRLGGE 300
    RTNTDYLEFV KGILSLEYCV GIIGGKPKQS YYFAGFQDDS LIYMDPHYCQ 350
    SFVDVSIKDF PLETFHCPSP KKMSFRKMDP SCTIGFYCRN VQDFKRASEE 400
    ITKMLKFSSK EKYPLFTFVN GHSRDYDFTS TTTNEEDLFS EDEKKQLKRF 450
    STEEFVLL 458
    Length:458
    Mass (Da):52,497
    Last modified:December 1, 2001 - v1
    Checksum:i6A23A05E7F20AF27
    GO

    Sequence cautioni

    The sequence BAB55356.1 differs from that shown. Reason: Frameshift at position 420.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ312234 mRNA. Translation: CAC85556.1.
    AJ320169 mRNA. Translation: CAC43939.1.
    AK027773 mRNA. Translation: BAB55356.1. Frameshift.
    AC103923 Genomic DNA. No translation available.
    CH471059 Genomic DNA. Translation: EAX06579.1.
    CH471059 Genomic DNA. Translation: EAX06580.1.
    BC033024 mRNA. Translation: AAH33024.1.
    CCDSiCCDS623.1.
    RefSeqiNP_116241.2. NM_032852.3.
    NP_835739.1. NM_178221.2.
    XP_005271345.1. XM_005271288.1.
    UniGeneiHs.7353.

    Genome annotation databases

    EnsembliENST00000317868; ENSP00000322159; ENSG00000125703.
    ENST00000371120; ENSP00000360161; ENSG00000125703.
    GeneIDi84938.
    KEGGihsa:84938.
    UCSCiuc001dat.3. human.

    Polymorphism databases

    DMDMi61211867.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ312234 mRNA. Translation: CAC85556.1 .
    AJ320169 mRNA. Translation: CAC43939.1 .
    AK027773 mRNA. Translation: BAB55356.1 . Frameshift.
    AC103923 Genomic DNA. No translation available.
    CH471059 Genomic DNA. Translation: EAX06579.1 .
    CH471059 Genomic DNA. Translation: EAX06580.1 .
    BC033024 mRNA. Translation: AAH33024.1 .
    CCDSi CCDS623.1.
    RefSeqi NP_116241.2. NM_032852.3.
    NP_835739.1. NM_178221.2.
    XP_005271345.1. XM_005271288.1.
    UniGenei Hs.7353.

    3D structure databases

    ProteinModelPortali Q96DT6.
    SMRi Q96DT6. Positions 38-426.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124372. 10 interactions.
    IntActi Q96DT6. 9 interactions.
    STRINGi 9606.ENSP00000322159.

    Protein family/group databases

    MEROPSi C54.004.

    PTM databases

    PhosphoSitei Q96DT6.

    Polymorphism databases

    DMDMi 61211867.

    Proteomic databases

    MaxQBi Q96DT6.
    PaxDbi Q96DT6.
    PRIDEi Q96DT6.

    Protocols and materials databases

    DNASUi 84938.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000317868 ; ENSP00000322159 ; ENSG00000125703 .
    ENST00000371120 ; ENSP00000360161 ; ENSG00000125703 .
    GeneIDi 84938.
    KEGGi hsa:84938.
    UCSCi uc001dat.3. human.

    Organism-specific databases

    CTDi 84938.
    GeneCardsi GC01P063249.
    HGNCi HGNC:16040. ATG4C.
    HPAi HPA007049.
    MIMi 611339. gene.
    neXtProti NX_Q96DT6.
    PharmGKBi PA25183.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG239662.
    HOGENOMi HOG000294192.
    HOVERGENi HBG050537.
    InParanoidi Q96DT6.
    KOi K08342.
    OMAi ARSGCTI.
    PhylomeDBi Q96DT6.
    TreeFami TF314847.

    Miscellaneous databases

    ChiTaRSi ATG4C. human.
    GenomeRNAii 84938.
    NextBioi 75392.
    PROi Q96DT6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96DT6.
    Bgeei Q96DT6.
    CleanExi HS_ATG4C.
    Genevestigatori Q96DT6.

    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], TISSUE SPECIFICITY.
      Tissue: Brain.
    2. "Cloning and sequencing of a human homologue of the yeast Apg4 cysteine endopeptidase involved in autophagy."
      Chen J.M., Barrett A.J.
      Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Heart.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    4. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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].
      Tissue: Testis.
    7. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    8. "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.

    Entry informationi

    Entry nameiATG4C_HUMAN
    AccessioniPrimary (citable) accession number: Q96DT6
    Secondary accession number(s): A6NLR8, D3DQ58, Q96K04
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 15, 2005
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 102 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 1
      Human chromosome 1: 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