Reviewed, UniProtKB/Swiss-Prot Q96DT6 (ATG4C_HUMAN)

Names and origin

Protein names

Recommended name:
    Cysteine protease ATG4C
    EC=3.4.22.-
Alternative name(s):
    Autophagy-related protein 4 homolog C
    Autophagin-3
    Autophagy-related cysteine endopeptidase 3
    AUT-like 3 cysteine endopeptidase

Gene names

Name:	ATG4C
Synonyms:	APG4C, AUTL1, AUTL3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	458 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Cysteine protease required for autophagy, which cleaves the C-terminal part of either MAP1LC3, GABARAPL2 or GABARAP, allowing the liberation of form I. A subpopulation of form I is subsequently converted to a smaller form (form II). Form II, with a revealed C-terminal glycine, is considered to be the phosphatidylethanolamine (PE)-conjugated form, and has the capacity for the binding to autophagosomes.
Enzyme regulation	Inhibited by N-ethylmaleimide.
Subcellular location	CytoplasmProbable.
Tissue specificity	Highly expressed in skeletal muscle, heart, liver and testis.
Sequence similarities	Belongs to the peptidase C54 family.
Sequence caution	The sequence BAB55356.1 differs from that shown. Reason: Frameshift at position 420.

Ontologies

Keywords
Biological process	Autophagy Protein transport Transport Ubl conjugation pathway
Cellular component	Cytoplasm
Molecular function	Hydrolase Protease Thiol protease
Gene Ontology (GO)
Biological process	autophagosome formation Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to membrane Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to vacuole Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB extracellular region Ref.1 Inferred from direct assay. Source: UniProtKB microtubule associated complex Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	cysteine-type endopeptidase activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB microtubule binding Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 458	458	Cysteine protease ATG4C
Sites
	Active site	111	1	Nucleophile By similarity
	Active site	345	1	Potential
	Active site	347	1	By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q96DT6-1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 6A23A05E7F20AF27	FASTA	458	52,497
	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

References

	« Hide 'large scale' referencesShow '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: 12446702] [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: 14702039] [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: 16710414] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. BC033024 mRNA. Translation: AAH33024.1.
RefSeq	NP_116241.2. NP_835739.1.
UniGene	Hs.7353
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	C54.004.
PTM databases
PhosphoSite	Q96DT6.
Genome annotation databases
Ensembl	ENSG00000125703. Homo sapiens. [Contig view]
GeneID	84938.
KEGG	hsa:84938.
Organism-specific databases
H-InvDB	HIX0000660.
HGNC	HGNC:16040. ATG4C.
HPA	HPA007049.
MIM	611339. gene.
PharmGKB	PA25183.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q96DT6.
HOVERGEN	Q96DT6.
Gene expression databases
ArrayExpress	Q96DT6.
CleanEx	HS_ATG4C.
GermOnline	ENSG00000125703. Homo sapiens.
Family and domain databases
InterPro	IPR005078. Peptidase_C54. [Graphical view]
PANTHER	PTHR22624. Peptidase_C54. 1 hit.
Pfam	PF03416. Peptidase_C54. 1 hit. [Graphical view]
ProDom	Q96DT6. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ATG4C_HUMAN

Accession

Primary (citable) accession number: Q96DT6
Secondary accession number(s): A6NLR8, Q96K04

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	December 1, 2001
Last modified:	September 2, 2008
This is version 46 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)