ATG4D autophagy related 4D cysteine peptidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATG4Dprovided by HGNC
Official Full Name: autophagy related 4D cysteine peptidaseprovided by HGNC
Primary source: HGNC:HGNC:20789
See related: Ensembl:ENSG00000130734 MIM:611340; AllianceGenome:HGNC:20789
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APG4D; AUTL4; APG4-D; HsAPG4D
Summary: 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]
Expression: Broad expression in testis (RPKM 21.1), duodenum (RPKM 13.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (10543904..10553418)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (10664918..10679876)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (10654580..10664094)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.
Title: Silencing of ATG4D suppressed proliferation and enhanced cisplatin-induced apoptosis in hepatocellular carcinoma through Akt/Caspase-3 pathway.
Pathogenic variants of ATG4D in infertile men with non-obstructive azoospermia identified using whole-exome sequencing.
Title: Pathogenic variants of ATG4D in infertile men with non-obstructive azoospermia identified using whole-exome sequencing.
ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system.
Title: ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system.
Human HAP1 and HeLa cells lacking ATG4B exhibit a severe but incomplete defect in LC3/GABARAP processing and autophagy. By further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to residual priming activity, which is sufficient to enable lipidation of endogenous GABARAPL1 on autophagic structures.
Title: Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells.
High ATG4D expression is associated with Colorectal Cancer.
Title: The Influence of Tumor Microenvironment on ATG4D Gene Expression in Colorectal Cancer Patients.
study elucidated a novel Malat1-miR-101-STMN1/RAB5A/ATG4D regulatory network that Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma cells
Title: Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma.
This study highlights the transcriptional inactivation mechanisms of ATG2B, ATG4D, ATG9A and ATG9B promoter methylation status and the possible origin of autophagy signal pathway repression in invasive ductal carcinomas.
Title: Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma.
The actions of ATG4 family members (particularly ATG4B) are required for the control of autophagosome fusion with late, degradative compartments in differentiating human erythroblasts.
Title: Autophagy facilitates organelle clearance during differentiation of human erythroblasts: evidence for a role for ATG4 paralogs during autophagosome maturation.
the import of Atg4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, reactive oxygen species, mitophagy and cell viability.
Title: A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress.
Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis.
Title: Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif binds more strongly to autophagy-related protein 4 (ATG4)-cleaved form I (LC3-I) than to ATG4-cleaved form II (LC3-II) in an A3G-independent manner	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type exopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-phosphatidylethanolamide deconjugating activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in aggrephagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in autophagosome assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in autophagosome assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in mitophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in piecemeal microautophagy of the nucleus	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein delipidation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to phagophore assembly site	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: cysteine protease ATG4D

Names: APG4 autophagy 4 homolog D; ATG4 autophagy related 4 homolog D; AUT-like 4 cysteine endopeptidase; autophagin-4; autophagy-related cysteine endopeptidase 4; autophagy-related protein 4 homolog D; cysteine protease involved in autophagy

NP_001268433.1

EC 3.4.22.-

NP_116274.3

EC 3.4.22.-

XP_006722990.1

EC 3.4.22.-

XP_054178417.1

EC 3.4.22.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001281504.2 → NP_001268433.1 cysteine protease ATG4D isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 2, which has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AK294676, BC068992

UniProtKB/TrEMBL

B4DGM8

Conserved Domains (1) summary

pfam03416
Location:47 → 348

Peptidase_C54; Peptidase family C54
NM_032885.6 → NP_116274.3 cysteine protease ATG4D isoform 1 precursor

See identical proteins and their annotated locations for NP_116274.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC068992, HY063028

Consensus CDS

CCDS12241.1

UniProtKB/Swiss-Prot

Q86TL0, Q969K0

UniProtKB/TrEMBL

Q53FA6

Related

ENSP00000311318.3, ENST00000309469.9

Conserved Domains (1) summary

pfam03416
Location:110 → 411

Peptidase_C54; Peptidase family C54

RNA

NR_104024.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK056210, AK314712, BC007639, HY063028

Related

ENST00000588857.5
NR_104025.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC007639, HY063028

Related

ENST00000588667.5