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    USP21 ubiquitin specific peptidase 21 [ Homo sapiens (human) ]

    Gene ID: 27005, updated on 7-Apr-2024

    Summary

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    Official Symbol
    USP21provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 21provided by HGNC
    Primary source
    HGNC:HGNC:12620
    See related
    Ensembl:ENSG00000143258 MIM:604729; AllianceGenome:HGNC:12620
    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
    USP16; USP23
    Summary
    This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. The encoded protein is also able to release NEDD8, a ubiquitin-like protein, from NEDD8-conjugated proteins. This gene has been referred to as USP16 and USP23 but is now known as USP21. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]
    Expression
    Ubiquitous expression in ovary (RPKM 11.4), testis (RPKM 9.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    1q23.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (161159500..161165723)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (160296946..160303180)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (161129290..161135513)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA ACA64 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161120104-161120964 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:161123368-161124567 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1470 Neighboring gene ubiquitin-fold modifier conjugating enzyme 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161137271-161137934 Neighboring gene protoporphyrinogen oxidase Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1471 Neighboring gene beta-1,4-galactosyltransferase 3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:161146985-161147484 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161148623-161149124 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1981 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1982 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1983 Neighboring gene ADAM metallopeptidase with thrombospondin type 1 motif 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161162728-161163541 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1474 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1984 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161166678-161167583 Neighboring gene NADH:ubiquinone oxidoreductase core subunit S2

    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. USP21 accelerates the proliferation and glycolysis of esophageal cancer cells by regulating the STAT3/FOXO1 pathway. Wu Y, et al. Tissue Cell, 2022 Dec. PMID 36095935
    2. Deubiquitinating Enzyme USP21 Inhibits HIV-1 Replication by Downregulating Tat Expression. Gao W, et al. J Virol, 2021 Jun 10. PMID 33827943, Free PMC Article
    3. USP21 upregulation in cholangiocarcinoma promotes cell proliferation and migration in a deubiquitinase-dependent manner. Zhou P, et al. Asia Pac J Clin Oncol, 2021 Dec. PMID 33052017
    4. Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations. Prieto G, et al. Sci Rep, 2016 May 12. PMID 27174732, Free PMC Article
    5. USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1. Zhang Q, et al. Cell Death Dis, 2022 Aug 16. PMID 35974001, Free PMC Article

    See all (76) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Inhibition of USP21 leads to ovarian carcinoma cell death by suppressing MAPK signaling.
      Title: Inhibition of USP21 leads to ovarian carcinoma cell death by suppressing MAPK signaling.
    2. c-JUN-induced upregulation of LINC00174 contributes to colorectal cancer proliferation and invasion through accelerating USP21 expression.
      Title: c-JUN-induced upregulation of LINC00174 contributes to colorectal cancer proliferation and invasion through accelerating USP21 expression.
    3. Salt-like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin-specific protease 21 to stabilize Yin Yang 1.
      Title: Salt-like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin-specific protease 21 to stabilize Yin Yang 1.
    4. USP21 accelerates the proliferation and glycolysis of esophageal cancer cells by regulating the STAT3/FOXO1 pathway.
      Title: USP21 accelerates the proliferation and glycolysis of esophageal cancer cells by regulating the STAT3/FOXO1 pathway.
    5. USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1.
      Title: USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1.
    6. Ablation of USP21 in skeletal muscle promotes oxidative fibre phenotype, inhibiting obesity and type 2 diabetes.
      Title: Ablation of USP21 in skeletal muscle promotes oxidative fibre phenotype, inhibiting obesity and type 2 diabetes.
    7. USP21 regulates Hippo signaling to promote radioresistance by deubiquitinating FOXM1 in cervical cancer.
      Title: USP21 regulates Hippo signaling to promote radioresistance by deubiquitinating FOXM1 in cervical cancer.
    8. USP21 upregulation in cholangiocarcinoma promotes cell proliferation and migration in a deubiquitinase-dependent manner.
      Title: USP21 upregulation in cholangiocarcinoma promotes cell proliferation and migration in a deubiquitinase-dependent manner.
    9. USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma.
      Title: USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma.
    10. Deubiquitinating Enzyme USP21 Inhibits HIV-1 Replication by Downregulating Tat Expression.
      Title: Deubiquitinating Enzyme USP21 Inhibits HIV-1 Replication by Downregulating Tat Expression.
    Submit: New GeneRIF Correction See all GeneRIFs (29)

    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

    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

    Clone Names

    • MGC3394

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cysteine-type deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables cysteine-type deubiquitinase activity TAS
    Traceable Author Statement
    more info
    		  
    enables cysteine-type peptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables cysteine-type peptidase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables deNEDDylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transcription coactivator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in positive regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in transcription initiation-coupled chromatin remodeling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 21
    Names
    NEDD8-specific protease
    deubiquitinating enzyme 21
    ubiquitin specific protease 21
    ubiquitin thioesterase 21
    ubiquitin thiolesterase 21
    ubiquitin-specific processing protease 21
    ubiquitin-specific protease 16
    NP_001014443.1
    NP_001306776.1
    NP_001306777.1
    NP_036607.3
    XP_016856525.1
    XP_016856526.1
    XP_016856527.1
    XP_016856528.1
    XP_047273935.1
    XP_047273936.1
    XP_047273937.1
    XP_047273938.1
    XP_047273939.1
    XP_054191967.1
    XP_054191968.1
    XP_054191969.1
    XP_054191970.1
    XP_054191971.1
    XP_054191972.1
    XP_054191973.1
    XP_054191974.1

    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_001014443.3 → NP_001014443.1  ubiquitin carboxyl-terminal hydrolase 21 isoform c

      See identical proteins and their annotated locations for NP_001014443.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (c) is shorter at the N-terminus compared to isoform a. Variants 1 and 3 both encode the same isoform (c).
      Source sequence(s)
      AF177758, AI038040, BC090946, BI755746
      Consensus CDS
      CCDS30920.1
      UniProtKB/Swiss-Prot
      Q59H60, Q5BKT5, Q5VTW9, Q5VTX0, Q9BTV1, Q9HBS2, Q9NYN4, Q9UK80
      Related
      ENSP00000356981.3, ENST00000368002.8
      Conserved Domains (2) summary
      cd02674
      Location:213 → 556
      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 ...
      pfam00443
      Location:212 → 555
      UCH; Ubiquitin carboxyl-terminal hydrolase

    2. NM_001319847.2 → NP_001306776.1  ubiquitin carboxyl-terminal hydrolase 21 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) encodes the longest isoform (a).
      Source sequence(s)
      AI038040, AK310326, DA000829
      Conserved Domains (2) summary
      cd02674
      Location:242 → 585
      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 ...
      pfam00443
      Location:241 → 584
      UCH; Ubiquitin carboxyl-terminal hydrolase

    3. NM_001319848.2 → NP_001306777.1  ubiquitin carboxyl-terminal hydrolase 21 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence and uses an alternate in-frame splice junction in the 3' end compared to variant 4. The resulting isoform (b) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform a.
      Source sequence(s)
      AF217979, AF233442, AI038040, DA000829
      Consensus CDS
      CCDS81392.1
      UniProtKB/Swiss-Prot
      Q9UK80
      Related
      ENSP00000356980.1, ENST00000368001.1
      Conserved Domains (3) summary
      cd02674
      Location:213 → 542
      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:212 → 346
      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:212 → 541
      UCH; Ubiquitin carboxyl-terminal hydrolase

    4. NM_012475.5 → NP_036607.3  ubiquitin carboxyl-terminal hydrolase 21 isoform c

      See identical proteins and their annotated locations for NP_036607.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (c) is shorter at the N-terminus compared to isoform a. Variants 1 and 3 both encode the same isoform (c).
      Source sequence(s)
      AF177758, AI038040, BI755746
      Consensus CDS
      CCDS30920.1
      UniProtKB/Swiss-Prot
      Q59H60, Q5BKT5, Q5VTW9, Q5VTX0, Q9BTV1, Q9HBS2, Q9NYN4, Q9UK80
      Related
      ENSP00000289865.8, ENST00000289865.12
      Conserved Domains (2) summary
      cd02674
      Location:213 → 556
      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 ...
      pfam00443
      Location:212 → 555
      UCH; Ubiquitin carboxyl-terminal hydrolase

    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
      161159500..161165723
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047417980.1 → XP_047273936.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    2. XM_047417981.1 → XP_047273937.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X2

    3. XM_017001038.3 → XP_016856527.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    4. XM_017001037.3 → XP_016856526.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    5. XM_017001039.3 → XP_016856528.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    6. XM_047417982.1 → XP_047273938.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X3

    7. XM_017001036.2 → XP_016856525.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X5

    8. XM_047417979.1 → XP_047273935.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    9. XM_047417983.1 → XP_047273939.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      160296946..160303180
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054335996.1 → XP_054191971.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X2

    2. XM_054335997.1 → XP_054191972.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X3

    3. XM_054335995.1 → XP_054191970.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    4. XM_054335994.1 → XP_054191969.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    5. XM_054335993.1 → XP_054191968.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    6. XM_054335999.1 → XP_054191974.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X5

    7. XM_054335992.1 → XP_054191967.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X1

    8. XM_054335998.1 → XP_054191973.1  ubiquitin carboxyl-terminal hydrolase 21 isoform X4

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_016572.3: Suppressed sequence

      Description
      NM_016572.3: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UK80.1 GenPept UniProtKB/Swiss-Prot:Q9UK80

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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