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    USP20 ubiquitin specific peptidase 20 [ Homo sapiens (human) ]

    Gene ID: 10868, updated on 3-May-2024

    Summary

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    Official Symbol
    USP20provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 20provided by HGNC
    Primary source
    HGNC:HGNC:12619
    See related
    Ensembl:ENSG00000136878 MIM:615143; AllianceGenome:HGNC:12619
    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
    VDU2; hVDU2; LSFR3A
    Summary
    This gene encodes a ubiquitin specific processing protease that was first identified as a substrate of the VHL (von Hippel-Lindau disease) protein E3 ubiquitin ligase complex. In addition to being ubiquitinated by the VHL-E3 ligase complex, this enzyme deubiquitinates hypoxia-inducible factor (HIF)-1 alpha and thereby causes increased expression of HIF-1alpha targeted genes which play a role in angiogenesis, glucose metabolism, cell proliferation and metastasis. The enzyme encoded by this gene also regulates G-protein coupled receptor signaling by mediating the deubiquitination of beta-2 adrenergic receptor (ADRB2). This enzyme is a ubiquitously expressed thiolester hydrolase. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jan 2013]
    Expression
    Ubiquitous expression in lymph node (RPKM 8.9), bone marrow (RPKM 8.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    9q34.11
    Exon count:
    26
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (129835458..129881828)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (142040029..142086556)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (132597737..132644107)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20390 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29122 Neighboring gene Sharpr-MPRA regulatory region 5710 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20391 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:132597987-132598487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:132601680-132602180 Neighboring gene torsin family 1 member A Neighboring gene chromosome 9 open reading frame 78 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29123 Neighboring gene Sharpr-MPRA regulatory region 12255 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:132632499-132632998 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:132636644-132637144 Neighboring gene Sharpr-MPRA regulatory region 12063 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:132647083-132647764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29125 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20393 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29126 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:132651249-132652136 Neighboring gene microRNA 6855 Neighboring gene Sharpr-MPRA regulatory region 3297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29128 Neighboring gene Sharpr-MPRA regulatory region 1290 Neighboring gene formin binding protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29129 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29130 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29131 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29132 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29133 Neighboring gene Sharpr-MPRA regulatory region 9235 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29134 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29135 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29136 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29137 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29139 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29140 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29142 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29143 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29144 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:132786300-132786450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29145 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29146 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:132796970-132797470 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:132797471-132797971 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29148 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20395 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20396 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20397 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:132811133-132811633 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20398 Neighboring gene G protein-coupled receptor 107 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:132878169-132878714 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:132881191-132882139 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20399 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29149

    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. Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2. Hu S, et al. Protein Expr Purif, 2021 May. PMID 33529762
    2. Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2. Li W, et al. Genes Dev, 2020 Oct 1. PMID 32943575, Free PMC Article
    3. USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization. Wu C, et al. Cell Death Differ, 2018 Nov. PMID 29867130, Free PMC Article
    4. USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis. Guan Y, et al. Pathol Res Pract, 2022 May. PMID 35405623
    5. Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins. Culver JA, et al. J Cell Biol, 2021 May 3. PMID 33792613, Free PMC Article

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1beta-evoked signaling in vascular smooth muscle cells and vascular inflammation.
      Title: Phosphorylation of USP20 on Ser334 by IRAK1 promotes IL-1β-evoked signaling in vascular smooth muscle cells and vascular inflammation.
    2. Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2.
      Title: Expression, purification and characterization of the second DUSP domain of deubiquitinase USP20/VDU2.
    3. Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins.
      Title: Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins.
    4. Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.
      Title: Deubiquitinase USP20 promotes breast cancer metastasis by stabilizing SNAI2.
    5. The Deubiquitinating Enzyme USP20 Regulates the TNFalpha-Induced NF-kappaB Signaling Pathway through Stabilization of p62.
      Title: The Deubiquitinating Enzyme USP20 Regulates the TNFα-Induced NF-κB Signaling Pathway through Stabilization of p62.
    6. Study revealed the molecular basis for the weak binding of USP20 N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP) to mono-ubiquitin and poly-ubiquitin. The solution structure of USP20 ZnF-UBP domain consists of a central beta-sheet with either one alpha-helix or two alpha-helices packed on each side of the sheet. The overall structure of USP20 ZnF-UBP domain is stabilized by three coordinated zinc ions.
      Title: Structural and functional studies of USP20 ZnF-UBP domain by NMR.
    7. USP20 is a positive regulator of beta-catenin in cancer cell migration, invasion and tumor growth in vivo. Mechanistically, USP20 deubiquitinates and stabilizes beta-catenin and is a potential biomarker for predicting chemoresistance in cancer.
      Title: USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization.
    8. our results demonstrate a role of the USP20 deubiquitinating enzyme in acting as a critical regulator of ULK1 and show a novel mechanism of the autophagy process in terms of ULK1 stability.
      Title: The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation.
    9. USP20 regulates actin cytoskeleton organization and cell migration in a manner dependent on ERK3 expression. The results identify USP20 as a bona fide regulator of ERK3 stability and physiological functions.
      Title: Deubiquitinating Enzyme USP20 Regulates Extracellular Signal-Regulated Kinase 3 Stability and Biological Activity.
    10. we investigated the inter-action between PKM2 and USP20. Our results suggest a new molecular pathway in cancer metabolism through the regulation of PKM2.
      Title: Regulation of pyruvate kinase isozyme M2 is mediated by the ubiquitin-specific protease 20.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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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    Replication interactions

    Interaction Pubs
    Knockdown of ubiquitin specific peptidase 20 (USP20) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Expression of HIV-1 Tat downregulates the abundance of ubiquitin specific peptidase 20 (USP20) in the nucleoli of Jurkat T-cells 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

    • KIAA1003

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables cysteine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in antiviral innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in endocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K48-linked deubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K63-linked deubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein deubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of G protein-coupled receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IC
    Inferred by Curator
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 20
    Names
    deubiquitinating enzyme 20
    pVHL-interacting deubiquitinating enzyme 2
    ubiquitin thioesterase 20
    ubiquitin thiolesterase 20
    ubiquitin-specific-processing protease 20
    NP_001008563.2
    NP_001103773.2
    NP_006667.3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_033097.2 RefSeqGene

      Range
      5030..51400
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_711

    mRNA and Protein(s)

    1. NM_001008563.5 → NP_001008563.2  ubiquitin carboxyl-terminal hydrolase 20

      See identical proteins and their annotated locations for NP_001008563.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has different 5' and 3' non-coding, terminal exons, compared to transcript variant 1. All three transcript variants encode the same protein.
      Source sequence(s)
      AL158207
      Consensus CDS
      CCDS43892.1
      UniProtKB/Swiss-Prot
      Q541F1, Q8IXQ1, Q96LG5, Q9UQN8, Q9UQP0, Q9Y2K6
      Related
      ENSP00000351122.1, ENST00000358355.5
      Conserved Domains (5) summary
      smart00695
      Location:810 → 895
      DUSP; Domain in ubiquitin-specific proteases
      cd02674
      Location:443 → 683
      Peptidase_C19R; A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl ...
      cl02553
      Location:144 → 291
      Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...
      pfam00443
      Location:144 → 682
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:30 → 90
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    2. NM_001110303.4 → NP_001103773.2  ubiquitin carboxyl-terminal hydrolase 20

      See identical proteins and their annotated locations for NP_001103773.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has a different 3' non-coding, terminal exon, compared to transcript variant 1. All three transcript variants encode the same protein.
      Source sequence(s)
      AL158207
      Consensus CDS
      CCDS43892.1
      UniProtKB/Swiss-Prot
      Q541F1, Q8IXQ1, Q96LG5, Q9UQN8, Q9UQP0, Q9Y2K6
      Related
      ENSP00000361506.3, ENST00000372429.8
      Conserved Domains (5) summary
      smart00695
      Location:810 → 895
      DUSP; Domain in ubiquitin-specific proteases
      cd02674
      Location:443 → 683
      Peptidase_C19R; A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl ...
      cl02553
      Location:144 → 291
      Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...
      pfam00443
      Location:144 → 682
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:30 → 90
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    3. NM_006676.8 → NP_006667.3  ubiquitin carboxyl-terminal hydrolase 20

      See identical proteins and their annotated locations for NP_006667.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. All three transcript variants encode the same protein.
      Source sequence(s)
      AL158207
      Consensus CDS
      CCDS43892.1
      UniProtKB/Swiss-Prot
      Q541F1, Q8IXQ1, Q96LG5, Q9UQN8, Q9UQP0, Q9Y2K6
      Related
      ENSP00000313811.4, ENST00000315480.9
      Conserved Domains (5) summary
      smart00695
      Location:810 → 895
      DUSP; Domain in ubiquitin-specific proteases
      cd02674
      Location:443 → 683
      Peptidase_C19R; A subfamily of peptidase C19. Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyze bonds involving the carboxyl ...
      cl02553
      Location:144 → 291
      Peptidase_C19; Peptidase C19 contains ubiquitinyl hydrolases. They are intracellular peptidases that remove ubiquitin molecules from polyubiquinated peptides by cleavage of isopeptide bonds. They hydrolyse bonds involving the carboxyl group of the C-terminal Gly ...
      pfam00443
      Location:144 → 682
      UCH; Ubiquitin carboxyl-terminal hydrolase
      pfam02148
      Location:30 → 90
      zf-UBP; Zn-finger in ubiquitin-hydrolases and other protein

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      129835458..129881828
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      142040029..142086556
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y2K6.2 GenPept UniProtKB/Swiss-Prot:Q9Y2K6

    Gene LinkOut

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