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

    Gene ID: 23192, updated on 10-Dec-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (241637693..241673857)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (242141021..242177191)
    RS_2024_09 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

    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. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition. Bortnik S, et al. Oncotarget, 2016 Oct 11. PMID 27556700, Free PMC Article
    3. 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
    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. [The expression, purification and characterization of human His-ATG4B protein]. Huang R, et al. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2015 Feb. PMID 25652856

    See all (106) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TDP-43 regulates LC3ylation in neural tissue through ATG4B cryptic splicing inhibition.
      Title: TDP-43 regulates LC3ylation in neural tissue through ATG4B cryptic splicing inhibition.
    2. FAT1 inhibits AML autophagy and proliferation via downregulating ATG4B expression.
      Title: FAT1 inhibits AML autophagy and proliferation via downregulating ATG4B expression.
    3. 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.
    4. ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
      Title: ATG4B antagonizes antiviral immunity by GABARAP-directed autophagic degradation of TBK1.
    5. PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy.
      Title: PFKP facilitates ATG4B phosphorylation during amino acid deprivation-induced autophagy.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (43)

    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)

    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 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 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_2024_08

    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

      UniProtKB/TrEMBL
      B4DL29

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

      UniProtKB/TrEMBL
      B4DL29
      Related
      ENSP00000384661.1, ENST00000402096.5

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

      UniProtKB/TrEMBL
      B4DL29

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

      UniProtKB/TrEMBL
      B4DL29

    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

      UniProtKB/TrEMBL
      B4DL29

    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
      B4DL29, B7ZA52

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

      UniProtKB/TrEMBL
      B4DL29

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

      UniProtKB/TrEMBL
      B4DL29
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y4P1.2 GenPept UniProtKB/Swiss-Prot:Q9Y4P1

    Gene LinkOut

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