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ATG4C autophagy related 4C cysteine peptidase [ Homo sapiens (human) ]

Gene ID: 84938, updated on 11-Apr-2024

Summary

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Official Symbol
ATG4Cprovided by HGNC
Official Full Name
autophagy related 4C cysteine peptidaseprovided by HGNC
Primary source
HGNC:HGNC:16040
See related
Ensembl:ENSG00000125703 MIM:611339; AllianceGenome:HGNC:16040
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
APG4C; AUTL1; AUTL3; APG4-C; HsAPG4C
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. Alternate transcriptional splice variants, encoding the same protein, have been characterized. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 4.0), placenta (RPKM 3.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
1p31.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (62784132..62865516)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (62662283..62743647)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (63249803..63331187)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 946 Neighboring gene Sharpr-MPRA regulatory region 4934 Neighboring gene DOCK7 divergent transcript Neighboring gene uncharacterized LOC124904194 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:63220743-63221288 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:63221289-63221835 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:63221836-63222381 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1119 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1120 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1121 Neighboring gene Sharpr-MPRA regulatory region 3967 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1122 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1123 Neighboring gene NANOG hESC enhancer GRCh37_chr1:63347799-63348356 Neighboring gene VISTA enhancer hs311 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:63432364-63432864 Neighboring gene VISTA enhancer hs168 Neighboring gene VISTA enhancer hs169 Neighboring gene long intergenic non-protein coding RNA 1739 Neighboring gene MPRA-validated peak269 silencer Neighboring gene uncharacterized LOC105378770 Neighboring gene long intergenic non-protein coding RNA 466 Neighboring gene RNA, 5S ribosomal pseudogene 49

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. Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression. Liu P, et al. Bioengineered, 2021 Dec. PMID 34699312, Free PMC Article
  2. Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux. Wen ZP, et al. J Exp Clin Cancer Res, 2019 Jul 10. PMID 31291988, Free PMC Article
  3. Genetic association, mRNA and protein expression analysis identify ATG4C as a susceptibility gene for Kashin-Beck disease. Wu C, et al. Osteoarthritis Cartilage, 2017 Feb. PMID 27742532
  4. Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer. Zeng Y, et al. PLoS One, 2020. PMID 32401768, Free PMC Article
  5. ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy. Antonelli M, et al. Oncotarget, 2017 Mar 28. PMID 28423511, Free PMC Article

See all (29) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MicroRNA-142-3p inhibits autophagy and promotes intracellular survival of Mycobacterium tuberculosis by targeting ATG16L1 and ATG4c.
    Title: MicroRNA-142-3p inhibits autophagy and promotes intracellular survival of Mycobacterium tuberculosis by targeting ATG16L1 and ATG4c.
  2. Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression.
    Title: Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression.
  3. 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.
  4. CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC
    Title: Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer.
  5. 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.
  6. our results suggested that increased ATG4C expression was associated with worse prognosis in glioma patients. Knockdown of ATG4C suppressed glioma progression by inducing cell cycle arrest and promoting apoptosis of glioma cells possibly through increasing ROS production.
    Title: Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux.
  7. association between SNPs and Kashin-Beck disease
    Title: Genetic association, mRNA and protein expression analysis identify ATG4C as a susceptibility gene for Kashin-Beck disease.
  8. We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.
    Title: ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.
  9. miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.
    Title: miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1.
Submit: New GeneRIF Correction

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

EBI GWAS Catalog

Description
Genetic Loci Associated with Circulating Levels of Very Long-Chain Saturated Fatty Acids.
EBI GWAS Catalog
Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women.
EBI GWAS Catalog
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.
EBI GWAS Catalog

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

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ14867

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 endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
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
  
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 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 cellular_component ND
No biological Data available
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
cysteine protease ATG4C
Names
APG4 autophagy 4 homolog C
ATG4 autophagy related 4 homolog C
AUT-like 1, cysteine endopeptidase
AUT-like 3 cysteine endopeptidase
autophagin-3
autophagy-related cysteine endopeptidase 3
autophagy-related protein 4 homolog C
epididymis secretory sperm binding protein
NP_116241.2
NP_835739.1

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_032852.4 → NP_116241.2  cysteine protease ATG4C

    See identical proteins and their annotated locations for NP_116241.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is the predominant transcript. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC099794, BC033024, BI518482, BM146035, BQ777265
    Consensus CDS
    CCDS623.1
    UniProtKB/Swiss-Prot
    A6NLR8, D3DQ58, Q96DT6, Q96K04
    UniProtKB/TrEMBL
    A0A384MTY5, Q05D29
    Related
    ENSP00000322159.4, ENST00000317868.9
    Conserved Domains (1) summary
    pfam03416
    Location:77 → 394
    Peptidase_C54; Peptidase family C54

  2. NM_178221.3 → NP_835739.1  cysteine protease ATG4C

    See identical proteins and their annotated locations for NP_835739.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses a different splice site in the 5' UTR as compared to variant 1. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC099794, BC008395, BC033024, BM146035, BM720875, BQ777265, DB183325
    Consensus CDS
    CCDS623.1
    UniProtKB/Swiss-Prot
    A6NLR8, D3DQ58, Q96DT6, Q96K04
    UniProtKB/TrEMBL
    A0A384MTY5, Q05D29
    Related
    ENSP00000360161.3, ENST00000371120.7
    Conserved Domains (1) summary
    pfam03416
    Location:77 → 394
    Peptidase_C54; Peptidase family C54

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    62784132..62865516
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    62662283..62743647
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96DT6.1 GenPept UniProtKB/Swiss-Prot:Q96DT6

Gene LinkOut

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