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Q96DT6

- ATG4C_HUMAN

UniProt

Q96DT6 - ATG4C_HUMAN

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Protein

Cysteine protease ATG4C

Gene

ATG4C

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

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
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, 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
Complete GO annotation...

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

BgeeiQ96DT6.
CleanExiHS_ATG4C.
ExpressionAtlasiQ96DT6. baseline and differential.
GenevestigatoriQ96DT6.

Organism-specific databases

HPAiHPA007049.

Interactioni

Protein-protein interaction databases

BioGridi124372. 11 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.
GeneTreeiENSGT00530000063000.
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

        10         20         30         40         50
MEATGTDEVD KLKTKFISAW NNMKYSWVLK TKTYFSRNSP VLLLGKCYHF
60 70 80 90 100
KYEDEDKTLP AESGCTIEDH VIAGNVEEFR KDFISRIWLT YREEFPQIEG
110 120 130 140 150
SALTTDCGWG CTLRTGQMLL AQGLILHFLG RAWTWPDALN IENSDSESWT
160 170 180 190 200
SHTVKKFTAS FEASLSGERE FKTPTISLKE TIGKYSDDHE MRNEVYHRKI
210 220 230 240 250
ISWFGDSPLA LFGLHQLIEY GKKSGKKAGD WYGPAVVAHI LRKAVEEARH
260 270 280 290 300
PDLQGITIYV AQDCTVYNSD VIDKQSASMT SDNADDKAVI ILVPVRLGGE
310 320 330 340 350
RTNTDYLEFV KGILSLEYCV GIIGGKPKQS YYFAGFQDDS LIYMDPHYCQ
360 370 380 390 400
SFVDVSIKDF PLETFHCPSP KKMSFRKMDP SCTIGFYCRN VQDFKRASEE
410 420 430 440 450
ITKMLKFSSK EKYPLFTFVN GHSRDYDFTS TTTNEEDLFS EDEKKQLKRF

STEEFVLL
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. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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. 11 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.
GeneTreei ENSGT00530000063000.
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

Bgeei Q96DT6.
CleanExi HS_ATG4C.
ExpressionAtlasi Q96DT6. baseline and differential.
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

« 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 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 29, 2014
This is version 103 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