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Aliases for ATG4D Gene

Aliases for ATG4D Gene

  • Autophagy Related 4D Cysteine Peptidase 2 3 5
  • Autophagy-Related Cysteine Endopeptidase 4 3 4
  • Autophagy-Related Protein 4 Homolog D 3 4
  • AUT-Like 4 Cysteine Endopeptidase 3 4
  • Autophagin-4 3 4
  • APG4D 3 4
  • AUTL4 3 4
  • AUT-Like 4, Cysteine Endopeptidase (S. Cerevisiae) 2
  • ATG4 Autophagy Related 4 Homolog D (S. Cerevisiae) 2
  • APG4 Autophagy 4 Homolog D (S. Cerevisiae) 2
  • Autophagy Related 4D, Cysteine Peptidase 2
  • Cysteine Protease Involved In Autophagy 3
  • ATG4 Autophagy Related 4 Homolog D 3
  • APG4 Autophagy 4 Homolog D 3
  • Cysteine Protease ATG4D 3
  • EC 3.4.22.- 4
  • EC 3.4.22 61
  • APG4-D 3

External Ids for ATG4D Gene

Previous HGNC Symbols for ATG4D Gene

  • AUTL4
  • APG4D

Previous GeneCards Identifiers for ATG4D Gene

  • GC19P010654
  • GC19P010232

Summaries for ATG4D Gene

Entrez Gene Summary for ATG4D Gene

  • Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene belongs to the autophagy-related protein 4 (Atg4) family of C54 endopeptidases. Members of this family encode proteins that play a role in the biogenesis of autophagosomes, which sequester the cytosol and organelles for degradation by lysosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneCards Summary for ATG4D Gene

ATG4D (Autophagy Related 4D Cysteine Peptidase) is a Protein Coding gene. Among its related pathways are Cellular Senescence and Autophagy Pathway. GO annotations related to this gene include cysteine-type endopeptidase activity and cysteine-type peptidase activity. An important paralog of this gene is ATG4C.

UniProtKB/Swiss-Prot for ATG4D Gene

  • 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.

  • 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.

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ATG4D Gene

Genomics for ATG4D Gene

Regulatory Elements for ATG4D Gene

Enhancers for ATG4D Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19G010514 1.6 FANTOM5 ENCODE dbSUPER 15.7 -26.7 -26678 5.2 PKNOX1 FOXA2 SIN3A ZNF2 ZNF48 ZNF121 GLIS2 KLF7 ZNF263 SP3 S1PR5 KRI1 ATG4D ZNF846 LOC100419831 CDKN2D SLC44A2 MIR1238 RNU7-140P ILF3
GH19G010595 1.6 FANTOM5 Ensembl ENCODE dbSUPER 12.9 +52.3 52307 2.0 USF1 ZSCAN4 MAX EBF1 EGR1 ADNP RELB ETV6 IKZF2 MTA2 KRI1 CDKN2D SLC44A2 ICAM3 ATG4D ILF3 TYK2 DNM2 C19orf38 S1PR5
GH19G010509 1.3 Ensembl ENCODE dbSUPER 12.6 -33.5 -33466 1.0 CTCF NFIB RAD21 RARA ZNF664 ZFHX2 GLIS2 ZBTB48 PATZ1 ZNF143 ATG4D CDKN2D KRI1 SLC44A2 KEAP1 S1PR5
GH19G010593 1.2 Ensembl ENCODE dbSUPER 11.5 +50.2 50223 1.6 HDGF KLF1 USF1 EBF1 EED RELB IKZF2 MTA2 BHLHE40 NR2F1 CDKN2D KRI1 ILF3 ATG4D LOC100820734 AP1M2
GH19G010612 1.1 Ensembl ENCODE dbSUPER 11.9 +68.8 68752 1.3 ELK4 GTF2F1 TBP STAT1 MAX ZNF121 HNRNPL CHD2 TCF7L2 SLC44A2 ILF3 ATG4D CDKN2D KRI1 PIR56383
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around ATG4D on UCSC Golden Path with GeneCards custom track

Promoters for ATG4D Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000107034 106 1201 CREB3L1 MLX DMAP1 FEZF1 YY1 SLC30A9 ZNF143 ZNF263 SP3 NFYC

Transcription factor binding sites by QIAGEN in the ATG4D gene promoter:

Genomic Location for ATG4D Gene

Chromosome:
19
Start:
10,543,894 bp from pter
End:
10,553,423 bp from pter
Size:
9,530 bases
Orientation:
Plus strand

Genomic View for ATG4D Gene

Genes around ATG4D on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ATG4D Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ATG4D Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ATG4D Gene

Proteins for ATG4D Gene

  • Protein details for ATG4D Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q86TL0-ATG4D_HUMAN
    Recommended name:
    Cysteine protease ATG4D
    Protein Accession:
    Q86TL0
    Secondary Accessions:
    • Q969K0

    Protein attributes for ATG4D Gene

    Size:
    474 amino acids
    Molecular mass:
    52922 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for ATG4D Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ATG4D Gene

Selected DME Specific Peptides for ATG4D Gene

Q86TL0:
  • ILVPVRLGGE
  • AGDWYGP
  • WGCMLRSGQM
  • FPLESFHC
  • VYVSQDCTVYKAD
  • HSLYFIGYQD
  • AWNNVKYGW
  • KMDPSCT
  • WLTYRRDFP

Post-translational modifications for ATG4D Gene

  • 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.
  • Ubiquitination at Lys281, Lys298, and Lys322
  • Modification sites at PhosphoSitePlus

Domains & Families for ATG4D Gene

Gene Families for ATG4D Gene

Protein Domains for ATG4D Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for ATG4D Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q86TL0

UniProtKB/Swiss-Prot:

ATG4D_HUMAN :
  • 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 (PubMed:22441018).
  • Belongs to the peptidase C54 family.
Domain:
  • 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 (PubMed:22441018).
Family:
  • Belongs to the peptidase C54 family.
genes like me logo Genes that share domains with ATG4D: view

Function for ATG4D Gene

Molecular function for ATG4D Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=13.1 uM for MAP1LC3B {ECO:0000269 PubMed:21177865}; KM=7.2 uM for GABARAPL2 {ECO:0000269 PubMed:21177865};
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by N-ethylmaleimide.
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Function:
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.

Enzyme Numbers (IUBMB) for ATG4D Gene

Gene Ontology (GO) - Molecular Function for ATG4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity ISS 12446702
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with ATG4D: view
genes like me logo Genes that share phenotypes with ATG4D: view

Animal Model Products

  • Taconic Biosciences Mouse Models for ATG4D

CRISPR Products

miRNA for ATG4D Gene

miRTarBase miRNAs that target ATG4D

Inhibitory RNA Products

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ATG4D Gene

Localization for ATG4D Gene

Subcellular locations from UniProtKB/Swiss-Prot for ATG4D Gene

Cysteine protease ATG4D: Cytoplasm.
Cysteine protease ATG4D, mitochondrial: Cytoplasm. Mitochondrion matrix. Note=Imported into mitochondrial matrix after cleavage by CASP3 during oxidative stress and cell death. {ECO:0000269 PubMed:22441018}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ATG4D gene
Compartment Confidence
cytosol 4
mitochondrion 3
nucleus 2
lysosome 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for ATG4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,ISS 12446702
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix IEA --
GO:0005829 cytosol IBA --
genes like me logo Genes that share ontologies with ATG4D: view

Pathways & Interactions for ATG4D Gene

genes like me logo Genes that share pathways with ATG4D: view

Pathways by source for ATG4D Gene

1 GeneTex pathway for ATG4D Gene
2 Reactome pathways for ATG4D Gene
2 KEGG pathways for ATG4D Gene

Gene Ontology (GO) - Biological Process for ATG4D Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000045 autophagosome assembly IBA --
GO:0000422 mitophagy IBA --
GO:0006501 C-terminal protein lipidation IBA --
GO:0006508 proteolysis IEA --
GO:0006612 protein targeting to membrane IBA --
genes like me logo Genes that share ontologies with ATG4D: view

No data available for SIGNOR curated interactions for ATG4D Gene

Drugs & Compounds for ATG4D Gene

(8) Drugs for ATG4D Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nimodipine Approved Pharma Potentiation, Activator 25
Omeprazole Approved, Investigational, Vet_approved Pharma Activator H+,K+-ATPase inhibitor 348
Nocodazole Experimental Pharma Tubulin production inhibitor,anti-neoplastic agent 0
Chloroquine diphosphate Pharma Antimalarial drug 149
Dexamethasone (DHAP) Pharma Glucocorticoidan;ti-inflammatory 0

(8) ApexBio Compounds for ATG4D Gene

Compound Action Cas Number
Chloroquine diphosphate Antimalarial drug 50-63-5
Dexamethasone (DHAP) Glucocorticoidan;ti-inflammatory 1950-02-2
Divalproex Sodium Epilepsy/migraines/bipolar disorder medicine 76584-70-8
Nimodipine 66085-59-4
Nocodazole Tubulin production inhibitor,anti-neoplastic agent 31430-18-9
Omeprazole H+,K+-ATPase inhibitor 73590-58-6
Sulfacetamide Sodium Sulfonamide antibiotic 127-56-0
Trifluoperazine 2HCl 440-17-5
genes like me logo Genes that share compounds with ATG4D: view

Drug Products

Transcripts for ATG4D Gene

Unigene Clusters for ATG4D Gene

Autophagy related 4D, cysteine peptidase:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ATG4D Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b · 2c ^ 3a · 3b · 3c ^ 4a · 4b · 4c · 4d · 4e · 4f ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9 ^ 10
SP1:
SP2: - - -
SP3:
SP4: - - - -
SP5: - - -
SP6: -
SP7:
SP8:
SP9:

Relevant External Links for ATG4D Gene

GeneLoc Exon Structure for
ATG4D
ECgene alternative splicing isoforms for
ATG4D

Expression for ATG4D Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ATG4D Gene

Protein differential expression in normal tissues from HIPED for ATG4D Gene

This gene is overexpressed in Placenta (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for ATG4D Gene



Protein tissue co-expression partners for ATG4D Gene

NURSA nuclear receptor signaling pathways regulating expression of ATG4D Gene:

ATG4D

SOURCE GeneReport for Unigene cluster for ATG4D Gene:

Hs.512799

mRNA Expression by UniProt/SwissProt for ATG4D Gene:

Q86TL0-ATG4D_HUMAN
Tissue specificity: Mainly expressed in skeletal muscle and, to a lower extent, in testis.

Evidence on tissue expression from TISSUES for ATG4D Gene

  • Lung(4.2)
  • Pancreas(3.2)
genes like me logo Genes that share expression patterns with ATG4D: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ATG4D Gene

Orthologs for ATG4D Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ATG4D Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ATG4D 34 35
  • 99.08 (n)
dog
(Canis familiaris)
Mammalia ATG4D 34 35
  • 89.92 (n)
cow
(Bos Taurus)
Mammalia ATG4D 34 35
  • 88.91 (n)
rat
(Rattus norvegicus)
Mammalia Atg4d 34
  • 83.51 (n)
mouse
(Mus musculus)
Mammalia Atg4d 34 16 35
  • 83.33 (n)
oppossum
(Monodelphis domestica)
Mammalia ATG4D 35
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ATG4D 35
  • 72 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia ATG4D 35
  • 57 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia atg4d 34
  • 59.93 (n)
zebrafish
(Danio rerio)
Actinopterygii atg4da 35
  • 51 (a)
OneToMany
atg4db 35
  • 41 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004023 34
  • 56.96 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG6194 34 35
  • 53.43 (n)
worm
(Caenorhabditis elegans)
Secernentea atg-4.2 34 35
  • 46.18 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ATG4 35
  • 21 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.753 35
  • 30 (a)
OneToMany
Species where no ortholog for ATG4D was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ATG4D Gene

ENSEMBL:
Gene Tree for ATG4D (if available)
TreeFam:
Gene Tree for ATG4D (if available)

Paralogs for ATG4D Gene

Paralogs for ATG4D Gene

genes like me logo Genes that share paralogs with ATG4D: view

Variants for ATG4D Gene

Sequence variations from dbSNP and Humsavar for ATG4D Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs1000024901 -- 10,548,634(+) GAACA(A/G)TCTCT intron-variant
rs1000179148 -- 10,542,729(+) GGCCT(C/T)GCAAG upstream-variant-2KB
rs1000543180 -- 10,544,124(+) AGTAC(C/T)GGAGC nc-transcript-variant, reference, missense, utr-variant-5-prime
rs1000613152 -- 10,543,077(+) CTCAC(A/G)CCTGT upstream-variant-2KB
rs1000916464 -- 10,544,006(+) CGGGC(C/T)CCGTG nc-transcript-variant, utr-variant-5-prime

Structural Variations from Database of Genomic Variants (DGV) for ATG4D Gene

Variant ID Type Subtype PubMed ID
nsv833744 CNV loss 17160897
nsv833745 CNV loss 17160897

Variation tolerance for ATG4D Gene

Residual Variation Intolerance Score: 65.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.97; 36.50% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ATG4D Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ATG4D

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ATG4D Gene

Disorders for ATG4D Gene

Relevant External Links for ATG4D

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ATG4D

No disorders were found for ATG4D Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ATG4D Gene

Publications for ATG4D Gene

  1. Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis. (PMID: 19549685) Betin V.M. … Lane J.D. (J. Cell. Sci. 2009) 3 4 22 64
  2. Human autophagins, a family of cysteine proteinases potentially implicated in cell degradation by autophagy. (PMID: 12446702) Marino G. … Lopez-Otin C. (J. Biol. Chem. 2003) 2 3 4 64
  3. A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress. (PMID: 22441018) Betin V.M. … Lane J.D. (Autophagy 2012) 3 4 64
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4 64
  5. Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma. (PMID: 27265029) Zhang X. … Li H.J. (Gene 2016) 3 64

Products for ATG4D Gene

Sources for ATG4D Gene

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