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ATG4A autophagy related 4A cysteine peptidase [ Homo sapiens (human) ]

Gene ID: 115201, updated on 11-Apr-2024

Summary

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Official Symbol
ATG4Aprovided by HGNC
Official Full Name
autophagy related 4A cysteine peptidaseprovided by HGNC
Primary source
HGNC:HGNC:16489
See related
Ensembl:ENSG00000101844 MIM:300663; AllianceGenome:HGNC:16489
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
APG4A; AUTL2; HsAPG4A
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 encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. [provided by RefSeq, Mar 2016]
Expression
Ubiquitous expression in thyroid (RPKM 5.4), colon (RPKM 5.0) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
Xq22.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (108088829..108154671)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (106526530..106592262)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (107335008..107397901)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene NACHT, LRR and PYD domains-containing protein 10-like Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:107234349-107235548 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107239283-107239988 Neighboring gene NLR family pyrin domain containing 3 pseudogene 1 Neighboring gene testis expressed 13B Neighboring gene V-set and immunoglobulin domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29838 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29839 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:107370111-107370674 Neighboring gene proteasome 26S subunit, non-ATPase 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:107399852-107400352 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107419738-107420424 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107420425-107421109 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107421110-107421795 Neighboring gene collagen type IV alpha 6 chain Neighboring gene uncharacterized LOC124905205 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chrX:107513459-107514658 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:107596629-107597181 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:107609798-107610337 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:107634248-107634889 Neighboring gene collagen type IV alpha 5 chain Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:107843610-107844540 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:107884720-107885919

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. ATG4A regulates human erythroid maturation and mitochondrial clearance. Stolla MC, et al. Blood Adv, 2022 Jun 28. PMID 35443024, Free PMC Article
  2. Knockdown of ATG4A inhibits breast cancer progression and promotes tamoxifen chemosensitivity by suppressing autophagy. Li Q, et al. Mol Med Rep, 2022 Mar. PMID 35088889, Free PMC Article
  3. The insufficiency of ATG4A in macroautophagy. Nguyen N, et al. J Biol Chem, 2020 Sep 25. PMID 32732290, Free PMC Article
  4. Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways. Yan C, et al. Mol Med Rep, 2020 Aug. PMID 32626969, Free PMC Article
  5. ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells. Yang SW, et al. Oncotarget, 2016 Jun 28. PMID 27276686, Free PMC Article

See all (44) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Loss of ATG4B and ATG4A results in two-stage cell cycle defects in pancreatic ductal adenocarcinoma cells.
    Title: Loss of ATG4B and ATG4A results in two-stage cell cycle defects in pancreatic ductal adenocarcinoma cells.
  2. Association of ATG4A single nucleotide polymorphism rs807185 on risk of microscopic polyangiitis in Chinese population.
    Title: Association of ATG4A single nucleotide polymorphism rs807185 on risk of microscopic polyangiitis in Chinese population.
  3. Alterations of ATG4A and LC3B in neurons derived from Alzheimer's disease patients.
    Title: Alterations of ATG4A and LC3B in neurons derived from Alzheimer's disease patients.
  4. ATG4A regulates human erythroid maturation and mitochondrial clearance.
    Title: ATG4A regulates human erythroid maturation and mitochondrial clearance.
  5. Knockdown of ATG4A inhibits breast cancer progression and promotes tamoxifen chemosensitivity by suppressing autophagy.
    Title: Knockdown of ATG4A inhibits breast cancer progression and promotes tamoxifen chemosensitivity by suppressing autophagy.
  6. Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans.
    Title: Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans.
  7. 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.
  8. Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.
    Title: Overexpression of ATG4a promotes autophagy and proliferation, and inhibits apoptosis in lens epithelial cells via the AMPK and Akt pathways.
  9. Long-noncoding RNA MALAT1 sponges microRNA-92a-3p to inhibit doxorubicin-induced cardiac senescence by targeting ATG4a.
    Title: Long-noncoding RNA MALAT1 sponges microRNA-92a-3p to inhibit doxorubicin-induced cardiac senescence by targeting ATG4a.
  10. The insufficiency of ATG4A in macroautophagy.
    Title: The insufficiency of ATG4A in macroautophagy.
Submit: New GeneRIF Correction See all GeneRIFs (24)

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 variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-phosphatidylethanolamide deconjugating activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein-phosphatidylethanolamide deconjugating activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in C-terminal protein lipidation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in aggrephagy IBA
Inferred from Biological aspect of Ancestor
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 lipid metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in mitophagy IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in piecemeal microautophagy of the nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein delipidation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein delipidation IDA
Inferred from Direct Assay
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
  

General protein information

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Preferred Names
cysteine protease ATG4A
Names
APG4 autophagy 4 homolog A
ATG4 autophagy related 4 homolog A
AUT-like 2, cysteine endopeptidase
autophagin 2
autophagy-related cysteine endopeptidase 2
autophagy-related protein 4 homolog A
hAPG4A
NP_001308216.1
NP_001308217.1
NP_001308218.1
NP_001308219.1
NP_443168.2
NP_840054.1
NP_840055.1
XP_011529144.1
XP_047297757.1
XP_047297758.1
XP_047297759.1
XP_054182398.1
XP_054182399.1
XP_054182400.1
XP_054182401.1

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)

  1. NM_001321287.2 → NP_001308216.1  cysteine protease ATG4A isoform c

    Status: REVIEWED

    Source sequence(s)
    AL031177
    UniProtKB/TrEMBL
    B4DEA4
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 258
    Peptidase_C54; Peptidase family C54

  2. NM_001321288.2 → NP_001308217.1  cysteine protease ATG4A isoform c

    Status: REVIEWED

    Source sequence(s)
    AL031177
    UniProtKB/TrEMBL
    B4DEA4
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 258
    Peptidase_C54; Peptidase family C54

  3. NM_001321289.2 → NP_001308218.1  cysteine protease ATG4A isoform d

    Status: REVIEWED

    Source sequence(s)
    AA648264, AK293533, AL031177, BC041862, BC061696
    UniProtKB/TrEMBL
    B4DEA4
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 196
    Peptidase_C54; Peptidase family C54

  4. NM_001321290.2 → NP_001308219.1  cysteine protease ATG4A isoform e

    Status: REVIEWED

    Source sequence(s)
    AL031177
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 163
    Peptidase_C54; Peptidase family C54

  5. NM_052936.5 → NP_443168.2  cysteine protease ATG4A isoform a

    See identical proteins and their annotated locations for NP_443168.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform (a).
    Source sequence(s)
    AA648264, BC041862, BC061696
    Consensus CDS
    CCDS14538.1
    UniProtKB/Swiss-Prot
    A6NCH2, B2RAZ7, D3DUY0, O95534, Q5JYY9, Q5JYZ0, Q86VE5, Q8WYN0, Q96KQ0, Q96KQ1
    Related
    ENSP00000361306.3, ENST00000372232.8
    Conserved Domains (1) summary
    pfam03416
    Location:42 → 335
    Peptidase_C54; Peptidase family C54

  6. NM_178270.4 → NP_840054.1  cysteine protease ATG4A isoform b

    See identical proteins and their annotated locations for NP_840054.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes isoform b.
    Source sequence(s)
    AA648264, AJ320509, BC041862, BC061696
    Consensus CDS
    CCDS14539.1
    UniProtKB/Swiss-Prot
    Q8WYN0
    Related
    ENSP00000298131.5, ENST00000345734.7
    Conserved Domains (1) summary
    pfam03416
    Location:43 → 273
    Peptidase_C54; Peptidase family C54

  7. NM_178271.3 → NP_840055.1  cysteine protease ATG4A isoform c

    Status: REVIEWED

    Source sequence(s)
    AA648264, BC041862, BM541631
    UniProtKB/TrEMBL
    B4DEA4
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 258
    Peptidase_C54; Peptidase family C54

RNA

  1. NR_135608.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL031177
    Related
    ENST00000343524.9

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    108088829..108154671
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441801.1 → XP_047297757.1  cysteine protease ATG4A isoform X1

  2. XM_047441802.1 → XP_047297758.1  cysteine protease ATG4A isoform X2

  3. XM_047441803.1 → XP_047297759.1  cysteine protease ATG4A isoform X3

  4. XM_011530842.2 → XP_011529144.1  cysteine protease ATG4A isoform X3

    See identical proteins and their annotated locations for XP_011529144.1

    UniProtKB/TrEMBL
    B4DEA4
    Conserved Domains (1) summary
    pfam03416
    Location:1 → 258
    Peptidase_C54; Peptidase family C54

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    106526530..106592262
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054326424.1 → XP_054182399.1  cysteine protease ATG4A isoform X2

  2. XM_054326423.1 → XP_054182398.1  cysteine protease ATG4A isoform X1

  3. XM_054326425.1 → XP_054182400.1  cysteine protease ATG4A isoform X3

  4. XM_054326426.1 → XP_054182401.1  cysteine protease ATG4A isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WYN0.1 GenPept UniProtKB/Swiss-Prot:Q8WYN0

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