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ATG4B autophagy related 4B cysteine peptidase [ Homo sapiens (human) ]

Gene ID: 23192, updated on 3-Apr-2024

Summary

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Official Symbol
ATG4Bprovided by HGNC
Official Full Name
autophagy related 4B cysteine peptidaseprovided by HGNC
Primary source
HGNC:HGNC:20790
See related
Ensembl:ENSG00000168397 MIM:611338; AllianceGenome:HGNC:20790
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
APG4B; AUTL1; HsAPG4B
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 different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 14.5), duodenum (RPKM 12.3) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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See ATG4B in Genome Data Viewer
Location:
2q37.3
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (241637693..241673857)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (242141021..242177191)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (242577108..242613272)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242490880-242491690 Neighboring gene BOK antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12543 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12544 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12545 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242509471-242510095 Neighboring gene BCL2 family apoptosis regulator BOK Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242515160-242515660 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:242518885-242519386 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:242519387-242519886 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242523714-242524242 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242529014-242529910 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242529911-242530805 Neighboring gene RNA, 5S ribosomal pseudogene 122 Neighboring gene THAP domain containing 4 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_58008 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242548955-242549456 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242549457-242549957 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242550174-242550694 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242554967-242555773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17429 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12548 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12547 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12549 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:242576729-242577656 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242578056-242578589 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242584167-242584667 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242584739-242585240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242596891-242597666 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242600039-242600540 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242600541-242601040 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242604899-242605504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242607599-242608100 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242608101-242608600 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12553 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:242626177-242626439 Neighboring gene deoxythymidylate kinase Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242640872-242641704 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242641943-242642572 Neighboring gene inhibitor of growth family member 5

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. The protease activity of human ATG4B is regulated by reversible oxidative modification. Zheng X, et al. Autophagy, 2020 Oct. PMID 31880198, Free PMC Article
  2. Activity-Based Protein Profiling Identifies ATG4B as a Key Host Factor for Enterovirus 71 Proliferation. Sun Y, et al. J Virol, 2019 Dec 15. PMID 31554687, Free PMC Article
  3. A new quinoline-based chemical probe inhibits the autophagy-related cysteine protease ATG4B. Bosc D, et al. Sci Rep, 2018 Aug 3. PMID 30076329, Free PMC Article
  4. Ablation of ATG4B Suppressed Autophagy and Activated AMPK for Cell Cycle Arrest in Cancer Cells. Liu PF, et al. Cell Physiol Biochem, 2017. PMID 29169176
  5. AKT-mediated phosphorylation of ATG4B impairs mitochondrial activity and enhances the Warburg effect in hepatocellular carcinoma cells. Ni Z, et al. Autophagy, 2018. PMID 29165041, Free PMC Article

See all (98) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FAT1 inhibits AML autophagy and proliferation via downregulating ATG4B expression.
    Title: FAT1 inhibits AML autophagy and proliferation via downregulating ATG4B expression.
  2. 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.
  3. ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
    Title: ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
  4. PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy.
    Title: PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy.
  5. The protease activity of human ATG4B is regulated by reversible oxidative modification.
    Title: The protease activity of human ATG4B is regulated by reversible oxidative modification.
  6. Distinct Mechanisms for Processing Autophagy Protein LC3-PE by RavZ and ATG4B.
    Title: Distinct Mechanisms for Processing Autophagy Protein LC3-PE by RavZ and ATG4B.
  7. Differential expression and prognostic relevance of autophagy-related markers ATG4B, GABARAP, and LC3B in breast cancer.
    Title: Differential expression and prognostic relevance of autophagy-related markers ATG4B, GABARAP, and LC3B in breast cancer.
  8. 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.
  9. Autophagy related 4B, upregulated by HIF-1alpha, attenuates the sensitivity to cisplatin in nasopharyngeal carcinoma cells.
    Title: Autophagy related 4B, upregulated by HIF-1α, attenuates the sensitivity to cisplatin in nasopharyngeal carcinoma cells.
  10. MiR-449a attenuates autophagy of T-cell lymphoma cells by downregulating ATG4B expression.
    Title: MiR-449a attenuates autophagy of T-cell lymphoma cells by downregulating ATG4B expression.
Submit: New GeneRIF Correction See all GeneRIFs (42)

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
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
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

  • MGC1353

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 endopeptidase activity TAS
Traceable Author Statement
more info
  
enables cysteine-type peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables endopeptidase 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 
enables scaffold protein binding IPI
Inferred from Physical Interaction
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 macroautophagy TAS
Traceable Author Statement
more info
  
involved_in microautophagy 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 otolith mineralization completed early in development ISS
Inferred from Sequence or Structural Similarity
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
  
acts_upstream_of_or_within protein delipidation IDA
Inferred from Direct Assay
more info
 PubMed 
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 autophagosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasmic vesicle IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
cysteine protease ATG4B
Names
APG4 autophagy 4 homolog B
ATG4 autophagy related 4 homolog B
AUT-like 1 cysteine endopeptidase
autophagin-1
autophagy-related cysteine endopeptidase 1
autophagy-related protein 4 homolog B
hAPG4B
NP_037457.3
NP_847896.1
XP_005247049.2
XP_047299694.1
XP_047299695.1
XP_047299696.1
XP_047299697.1
XP_047299698.1
XP_054197048.1
XP_054197049.1
XP_054197050.1
XP_054197051.1
XP_054197052.1
XP_054197053.1

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_013325.5 → NP_037457.3  cysteine protease ATG4B isoform a

    See identical proteins and their annotated locations for NP_037457.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is the predominant transcript and it encodes the longer isoform (a).
    Source sequence(s)
    AK123425, AK125277, AL080168, BC000719
    Consensus CDS
    CCDS46564.1
    UniProtKB/Swiss-Prot
    B7WNK2, Q53NU4, Q6ZUV8, Q8WYM9, Q96K07, Q96K96, Q96SZ1, Q9Y2F2, Q9Y4P1
    UniProtKB/TrEMBL
    B4DL29
    Related
    ENSP00000384259.3, ENST00000404914.8
    Conserved Domains (1) summary
    pfam03416
    Location:40 → 335
    Peptidase_C54; Peptidase family C54

  2. NM_178326.3 → NP_847896.1  cysteine protease ATG4B isoform b

    See identical proteins and their annotated locations for NP_847896.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1, that causes a frameshift. The resulting isoform (b) is shorter and has a distinct C-terminus compared to isoform a.
    Source sequence(s)
    AK027763, AK125277, AL080168, AL133638
    Consensus CDS
    CCDS46565.1
    UniProtKB/TrEMBL
    B4DNY2
    Related
    ENSP00000383964.3, ENST00000405546.7
    Conserved Domains (1) summary
    pfam03416
    Location:40 → 335
    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_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    241637693..241673857
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005246992.5 → XP_005247049.2  cysteine protease ATG4B isoform X1

    Conserved Domains (1) summary
    pfam03416
    Location:40 → 335
    Peptidase_C54; Peptidase family C54

  2. XM_047443738.1 → XP_047299694.1  cysteine protease ATG4B isoform X2

  3. XM_047443739.1 → XP_047299695.1  cysteine protease ATG4B isoform X3

  4. XM_047443741.1 → XP_047299697.1  cysteine protease ATG4B isoform X5

    Related
    ENSP00000384661.1, ENST00000402096.5

  5. XM_047443742.1 → XP_047299698.1  cysteine protease ATG4B isoform X4

  6. XM_047443740.1 → XP_047299696.1  cysteine protease ATG4B isoform X4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    242141021..242177191
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341075.1 → XP_054197050.1  cysteine protease ATG4B isoform X3

  2. XM_054341073.1 → XP_054197048.1  cysteine protease ATG4B isoform X1

  3. XM_054341074.1 → XP_054197049.1  cysteine protease ATG4B isoform X2

  4. XM_054341077.1 → XP_054197052.1  cysteine protease ATG4B isoform X5

    UniProtKB/TrEMBL
    B7ZA52

  5. XM_054341078.1 → XP_054197053.1  cysteine protease ATG4B isoform X4

  6. XM_054341076.1 → XP_054197051.1  cysteine protease ATG4B isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y4P1.2 GenPept UniProtKB/Swiss-Prot:Q9Y4P1

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