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Protein

Cysteine protease ATG4D

Gene

Atg4d

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Cysteine protease ATG4D: Cysteine protease required for the cytoplasm to vacuole transport (Cvt) and autophagy. 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 similarity
Cysteine protease ATG4D, mitochondrial: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability (By similarity).By similarity

Enzyme regulationi

Inhibited by N-ethylmaleimide.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei144 – 1441NucleophileBy similarity
Active sitei356 – 3561Sequence analysis
Active sitei358 – 3581By similarity

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • autophagy Source: UniProtKB
  • protein transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis, Autophagy, Protein transport, Transport, Ubl conjugation pathway

Protein family/group databases

MEROPSiC54.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Cysteine protease ATG4D (EC:3.4.22.-)
Alternative name(s):
AUT-like 4 cysteine endopeptidase
Autophagin-4
Autophagy-related cysteine endopeptidase 4
Autophagy-related protein 4 homolog D
Cleaved into the following chain:
Gene namesi
Name:Atg4d
Synonyms:Apg4d, Autl4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2444308. Atg4d.

Subcellular locationi

Cysteine protease ATG4D :
  • Cytoplasm By similarity
Cysteine protease ATG4D, mitochondrial :
  • Cytoplasm By similarity
  • Mitochondrion matrix By similarity

  • Note: Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 474474Cysteine protease ATG4DPRO_0000215854Add
BLAST
Chaini64 – 474411Cysteine protease ATG4D, mitochondrialPRO_0000423409Add
BLAST

Post-translational modificationi

Cleaved by CASP3 during apoptosis which leads to increased activity. The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondroal import of the protein.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei63 – 642Cleavage; by CASP3By similarity

Proteomic databases

MaxQBiQ8BGV9.
PaxDbiQ8BGV9.
PRIDEiQ8BGV9.

PTM databases

iPTMnetiQ8BGV9.
PhosphoSiteiQ8BGV9.

Expressioni

Gene expression databases

BgeeiQ8BGV9.
CleanExiMM_ATG4D.
GenevisibleiQ8BGV9. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000068450.

Structurei

3D structure databases

ProteinModelPortaliQ8BGV9.
SMRiQ8BGV9. Positions 115-434.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni64 – 10340Cryptic mitochondrial signal peptideBy similarityAdd
BLAST

Domaini

Residues 64 to 103 constitute a cryptic mitochondrial transit peptide which is revealed after cleavage by caspase of residues 1 to 63 upon oxidative stress and cell death. It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria (By similarity).By similarity

Sequence similaritiesi

Belongs to the peptidase C54 family.Curated

Phylogenomic databases

eggNOGiKOG2674. Eukaryota.
ENOG410XPQ0. LUCA.
GeneTreeiENSGT00530000063000.
HOGENOMiHOG000294192.
HOVERGENiHBG050537.
InParanoidiQ8BGV9.
KOiK08342.
OMAiKYGWAVK.
OrthoDBiEOG72C4ZV.
PhylomeDBiQ8BGV9.
TreeFamiTF314847.

Family and domain databases

InterProiIPR005078. Peptidase_C54.
[Graphical view]
PANTHERiPTHR22624. PTHR22624. 2 hits.
PfamiPF03416. Peptidase_C54. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8BGV9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSVSPAAAQ YRSGSSEDAR RADCRRPRGQ TRIPDPSNLG PSGSGVAALG
60 70 80 90 100
SSGTDPAEPD EVDKFKAKFL TAWNNVKYGW AVKSRTSFSK ISTVHLCGRC
110 120 130 140 150
YHFEGEGDIQ RFQRDFVSRL WLTYRRDFPP LAGGSLTSDC GWGCMLRSGQ
160 170 180 190 200
MMLAQGLLLH FLPRDWRWVE GTGLASSEMP GPASPSRCRG PGRRGPPRWT
210 220 230 240 250
QGALEMEQDR WHRRIVSWFA DHPRAPFGLH RLVELGRSSG KKAGDWYGPS
260 270 280 290 300
VVAHILRKAV ESCSEVSRLV VYVSQDCTVY KADVARLLSW PDPTAEWKSV
310 320 330 340 350
VILVPVRLGG ETLNPVYVPC VKELLRSELC LGIMGGKPRH SLYFIGYQDD
360 370 380 390 400
FLLYLDPHYC QPTVDVSQPS FPLESFHCTS PRKMAFAKMD PSCTVGFYAG
410 420 430 440 450
NRKEFETLCS ELMRILSSSS VTERYPMFTV AEGHAQDHSL DALCTQLSQP
460 470
TLRLPCTGRL LKAKRPSSED FVFL
Length:474
Mass (Da):52,910
Last modified:March 1, 2003 - v1
Checksum:i699C1472A562FB20
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261R → Q in BAC38269 (PubMed:16141072).Curated
Sequence conflicti111 – 1111R → Q in AAH30861 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ312333 Genomic DNA. Translation: CAC85952.1.
AK036571 mRNA. Translation: BAC29484.1.
AK081605 mRNA. Translation: BAC38269.1.
AK081002 mRNA. Translation: BAC38110.1.
BC030861 mRNA. Translation: AAH30861.1.
BC069851 mRNA. Translation: AAH69851.1.
CCDSiCCDS22899.1.
RefSeqiNP_705811.8. NM_153583.10.
UniGeneiMm.440165.

Genome annotation databases

EnsembliENSMUST00000065005; ENSMUSP00000068450; ENSMUSG00000002820.
GeneIDi235040.
KEGGimmu:235040.
UCSCiuc009okt.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ312333 Genomic DNA. Translation: CAC85952.1.
AK036571 mRNA. Translation: BAC29484.1.
AK081605 mRNA. Translation: BAC38269.1.
AK081002 mRNA. Translation: BAC38110.1.
BC030861 mRNA. Translation: AAH30861.1.
BC069851 mRNA. Translation: AAH69851.1.
CCDSiCCDS22899.1.
RefSeqiNP_705811.8. NM_153583.10.
UniGeneiMm.440165.

3D structure databases

ProteinModelPortaliQ8BGV9.
SMRiQ8BGV9. Positions 115-434.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000068450.

Protein family/group databases

MEROPSiC54.005.

PTM databases

iPTMnetiQ8BGV9.
PhosphoSiteiQ8BGV9.

Proteomic databases

MaxQBiQ8BGV9.
PaxDbiQ8BGV9.
PRIDEiQ8BGV9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000065005; ENSMUSP00000068450; ENSMUSG00000002820.
GeneIDi235040.
KEGGimmu:235040.
UCSCiuc009okt.2. mouse.

Organism-specific databases

CTDi84971.
MGIiMGI:2444308. Atg4d.

Phylogenomic databases

eggNOGiKOG2674. Eukaryota.
ENOG410XPQ0. LUCA.
GeneTreeiENSGT00530000063000.
HOGENOMiHOG000294192.
HOVERGENiHBG050537.
InParanoidiQ8BGV9.
KOiK08342.
OMAiKYGWAVK.
OrthoDBiEOG72C4ZV.
PhylomeDBiQ8BGV9.
TreeFamiTF314847.

Miscellaneous databases

PROiQ8BGV9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BGV9.
CleanExiMM_ATG4D.
GenevisibleiQ8BGV9. MM.

Family and domain databases

InterProiIPR005078. Peptidase_C54.
[Graphical view]
PANTHERiPTHR22624. PTHR22624. 2 hits.
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].
  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: Bone, Cerebellum and Head.
  3. "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: Colon and Eye.
  4. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 13-25, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.

Entry informationi

Entry nameiATG4D_MOUSE
AccessioniPrimary (citable) accession number: Q8BGV9
Secondary accession number(s): Q8C4N9, Q8K0Q2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 1, 2003
Last modified: June 8, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, 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.