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Protein

Cysteine protease ATG4A

Gene

Atg4a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript leveli

Functioni

Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. Cleaves the C-terminal amino acid of ATG8 family proteins 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. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP. Has also an activity of delipidating enzyme for the PE-conjugated forms (By similarity).By similarity

Enzyme regulationi

Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H2O2 inhibits its activity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei77 – 771NucleophileBy similarity
Active sitei276 – 2761Sequence analysis
Active sitei278 – 2781By similarity

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • cysteine-type peptidase activity Source: MGI

GO - Biological processi

  • autophagy Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • proteolysis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Autophagy, Protein transport, Transport, Ubl conjugation pathway

Protein family/group databases

MEROPSiC54.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Cysteine protease ATG4A (EC:3.4.22.-)
Alternative name(s):
AUT-like 2 cysteine endopeptidase
Autophagin-2
Autophagy-related cysteine endopeptidase 2
Autophagy-related protein 4 homolog A
Gene namesi
Name:Atg4a
Synonyms:Apg4a, Autl2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:2147903. Atg4a.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 396396Cysteine protease ATG4APRO_0000215839Add
BLAST

Proteomic databases

EPDiQ8C9S8.
MaxQBiQ8C9S8.
PaxDbiQ8C9S8.
PRIDEiQ8C9S8.

Expressioni

Gene expression databases

BgeeiQ8C9S8.
ExpressionAtlasiQ8C9S8. baseline and differential.
GenevisibleiQ8C9S8. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000108595.

Structurei

3D structure databases

ProteinModelPortaliQ8C9S8.
SMRiQ8C9S8. Positions 25-356.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C54 family.Curated

Phylogenomic databases

eggNOGiKOG2674. Eukaryota.
ENOG410XPQ0. LUCA.
GeneTreeiENSGT00530000063000.
HOGENOMiHOG000007008.
HOVERGENiHBG050536.
InParanoidiQ8C9S8.
KOiK08342.
OMAiRMKIMNL.
OrthoDBiEOG73V6KD.
PhylomeDBiQ8C9S8.
TreeFamiTF314847.

Family and domain databases

InterProiIPR033474. ATG4A.
IPR005078. Peptidase_C54.
[Graphical view]
PANTHERiPTHR22624. PTHR22624. 1 hit.
PTHR22624:SF35. PTHR22624:SF35. 1 hit.
PfamiPF03416. Peptidase_C54. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8C9S8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESVMSKYEN QILIFPDYLE EFPDTDELVW ILGKQHPLKT EKSKLLSDIS
60 70 80 90 100
ARLWFTYRRK FSPIGGTGPS SDAGWGCMLR CGQMMLAQAL ICRHLGRDWN
110 120 130 140 150
WERQKEQPKE YQRILQCFLD RKDCCYSIHQ MAQMGVGEGK SIGEWFGPNT
160 170 180 190 200
VAQVIKKLAL FDEWNSLAVY VSMDNTVVIE DIKKMCCVLP VGAADPAGDF
210 220 230 240 250
LTASNQSRDT SVPCSAWKPL LLIVPLRLGI NQINPVYVEA FKECFKMPQS
260 270 280 290 300
LGALGGKPNN AYYFIGFLGD ELIFLDPHTT QTFVDIEESG LVDDQTFHCL
310 320 330 340 350
QSPQRMSILN LDPSVALGFF CKEEKDFDNW CSLVQKEILK ENLRMFELVQ
360 370 380 390
KHPSHWPPFV PPAKPEVTTT GAEFIESTEQ LEDFELEEDF EILSVG
Length:396
Mass (Da):45,095
Last modified:March 15, 2005 - v2
Checksum:i99196D35E6856594
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381L → F in CAD43221 (PubMed:12446702).Curated
Sequence conflicti159 – 1591A → T in CAD43221 (PubMed:12446702).Curated
Sequence conflicti171 – 1711V → D in BAC30924 (PubMed:16141072).Curated
Sequence conflicti203 – 2031A → V in CAD43221 (PubMed:12446702).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ504654 mRNA. Translation: CAD43221.1.
AK041379 mRNA. Translation: BAC30924.1.
RefSeqiNP_777364.3. NM_174875.3.
UniGeneiMm.102230.
Mm.393320.

Genome annotation databases

EnsembliENSMUST00000112971; ENSMUSP00000108595; ENSMUSG00000079418.
GeneIDi666468.
KEGGimmu:666468.
UCSCiuc029unx.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ504654 mRNA. Translation: CAD43221.1.
AK041379 mRNA. Translation: BAC30924.1.
RefSeqiNP_777364.3. NM_174875.3.
UniGeneiMm.102230.
Mm.393320.

3D structure databases

ProteinModelPortaliQ8C9S8.
SMRiQ8C9S8. Positions 25-356.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000108595.

Protein family/group databases

MEROPSiC54.002.

Proteomic databases

EPDiQ8C9S8.
MaxQBiQ8C9S8.
PaxDbiQ8C9S8.
PRIDEiQ8C9S8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000112971; ENSMUSP00000108595; ENSMUSG00000079418.
GeneIDi666468.
KEGGimmu:666468.
UCSCiuc029unx.1. mouse.

Organism-specific databases

CTDi115201.
MGIiMGI:2147903. Atg4a.

Phylogenomic databases

eggNOGiKOG2674. Eukaryota.
ENOG410XPQ0. LUCA.
GeneTreeiENSGT00530000063000.
HOGENOMiHOG000007008.
HOVERGENiHBG050536.
InParanoidiQ8C9S8.
KOiK08342.
OMAiRMKIMNL.
OrthoDBiEOG73V6KD.
PhylomeDBiQ8C9S8.
TreeFamiTF314847.

Miscellaneous databases

PROiQ8C9S8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8C9S8.
ExpressionAtlasiQ8C9S8. baseline and differential.
GenevisibleiQ8C9S8. MM.

Family and domain databases

InterProiIPR033474. ATG4A.
IPR005078. Peptidase_C54.
[Graphical view]
PANTHERiPTHR22624. PTHR22624. 1 hit.
PTHR22624:SF35. PTHR22624:SF35. 1 hit.
PfamiPF03416. Peptidase_C54. 1 hit.
[Graphical view]
ProtoNetiSearch...

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].
    Strain: C57BL/6J.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Thymus.

Entry informationi

Entry nameiATG4A_MOUSE
AccessioniPrimary (citable) accession number: Q8C9S8
Secondary accession number(s): Q811B8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 15, 2005
Last modified: June 8, 2016
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.