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Q96DT6 (ATG4C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ATG4C
Synonyms:APG4C, AUTL1, AUTL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length458 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Enzyme regulation

Inhibited by N-ethylmaleimide.

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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

Sequence similarities

Belongs to the peptidase C54 family.

Biophysicochemical properties

Kinetic parameters:

KM=47.5 µM for MAP1LC3B Ref.8

KM=12.4 µM for GABARAPL2

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 458458Cysteine protease ATG4C
PRO_0000215849

Sites

Active site1111Nucleophile By similarity
Active site3451 Potential
Active site3471 By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q96DT6 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 6A23A05E7F20AF27

FASTA45852,497
        10         20         30         40         50         60 
MEATGTDEVD KLKTKFISAW NNMKYSWVLK TKTYFSRNSP VLLLGKCYHF KYEDEDKTLP 

        70         80         90        100        110        120 
AESGCTIEDH VIAGNVEEFR KDFISRIWLT YREEFPQIEG SALTTDCGWG CTLRTGQMLL 

       130        140        150        160        170        180 
AQGLILHFLG RAWTWPDALN IENSDSESWT SHTVKKFTAS FEASLSGERE FKTPTISLKE 

       190        200        210        220        230        240 
TIGKYSDDHE MRNEVYHRKI ISWFGDSPLA LFGLHQLIEY GKKSGKKAGD WYGPAVVAHI 

       250        260        270        280        290        300 
LRKAVEEARH PDLQGITIYV AQDCTVYNSD VIDKQSASMT SDNADDKAVI ILVPVRLGGE 

       310        320        330        340        350        360 
RTNTDYLEFV KGILSLEYCV GIIGGKPKQS YYFAGFQDDS LIYMDPHYCQ SFVDVSIKDF 

       370        380        390        400        410        420 
PLETFHCPSP KKMSFRKMDP SCTIGFYCRN VQDFKRASEE ITKMLKFSSK EKYPLFTFVN 

       430        440        450 
GHSRDYDFTS TTTNEEDLFS EDEKKQLKRF STEEFVLL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS623.1.
RefSeqNP_116241.2. NM_032852.3.
NP_835739.1. NM_178221.2.
XP_005271345.1. XM_005271288.1.
UniGeneHs.7353.

3D structure databases

ProteinModelPortalQ96DT6.
SMRQ96DT6. Positions 38-426.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124372. 10 interactions.
IntActQ96DT6. 9 interactions.
STRING9606.ENSP00000322159.

Protein family/group databases

MEROPSC54.004.

PTM databases

PhosphoSiteQ96DT6.

Polymorphism databases

DMDM61211867.

Proteomic databases

MaxQBQ96DT6.
PaxDbQ96DT6.
PRIDEQ96DT6.

Protocols and materials databases

DNASU84938.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317868; ENSP00000322159; ENSG00000125703.
ENST00000371120; ENSP00000360161; ENSG00000125703.
GeneID84938.
KEGGhsa:84938.
UCSCuc001dat.3. human.

Organism-specific databases

CTD84938.
GeneCardsGC01P063249.
HGNCHGNC:16040. ATG4C.
HPAHPA007049.
MIM611339. gene.
neXtProtNX_Q96DT6.
PharmGKBPA25183.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG239662.
HOGENOMHOG000294192.
HOVERGENHBG050537.
InParanoidQ96DT6.
KOK08342.
OMAARSGCTI.
PhylomeDBQ96DT6.
TreeFamTF314847.

Gene expression databases

ArrayExpressQ96DT6.
BgeeQ96DT6.
CleanExHS_ATG4C.
GenevestigatorQ96DT6.

Family and domain databases

InterProIPR005078. Peptidase_C54.
[Graphical view]
PANTHERPTHR22624. PTHR22624. 1 hit.
PfamPF03416. Peptidase_C54. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATG4C. human.
GenomeRNAi84938.
NextBio75392.
PROQ96DT6.
SOURCESearch...

Entry information

Entry nameATG4C_HUMAN
AccessionPrimary (citable) accession number: Q96DT6
Secondary accession number(s): A6NLR8, D3DQ58, Q96K04
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM