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    USP14 ubiquitin specific peptidase 14 [ Homo sapiens (human) ]

    Gene ID: 9097, updated on 30-Oct-2024

    Summary

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    Official Symbol
    USP14provided by HGNC
    Official Full Name
    ubiquitin specific peptidase 14provided by HGNC
    Primary source
    HGNC:HGNC:12612
    See related
    Ensembl:ENSG00000101557 MIM:607274; AllianceGenome:HGNC:12612
    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
    TGT; Ubp6
    Summary
    This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in brain (RPKM 16.7), prostate (RPKM 15.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See USP14 in Genome Data Viewer
    Location:
    18p11.32
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (158557..214629)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (312304..368380)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (158557..214629)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene Rho associated coiled-coil containing protein kinase 1 pseudogene 1 Neighboring gene microRNA 8078 Neighboring gene uncharacterized LOC105371951 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9236 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9237 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:185973-186474 Neighboring gene THO complex subunit 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13019 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9238 Neighboring gene collectin subfamily member 12 Neighboring gene uncharacterized LOC107985155 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr18:394012-395211 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:419844-420037 Neighboring gene OCT4 hESC enhancer GRCh37_chr18:420584-421135 Neighboring gene Sharpr-MPRA regulatory region 14658 Neighboring gene ReSE screen-validated silencer GRCh37_chr18:505812-505991 Neighboring gene long intergenic non-protein coding RNA 1925

    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 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. Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation. Dash R, et al. Cells, 2024 May 31. PMID 38891087, Free PMC Article
    2. Targeting the Proteasome-Associated Deubiquitinating Enzyme USP14 Impairs Melanoma Cell Survival and Overcomes Resistance to MAPK-Targeting Therapies. Didier R, et al. Mol Cancer Ther, 2018 Jul. PMID 29703842
    3. Function of Deubiquitinating Enzyme USP14 as Oncogene in Different Types of Cancer. Zhu Y, et al. Cell Physiol Biochem, 2016. PMID 26938858
    4. USP14-regulated allostery of the human proteasome by time-resolved cryo-EM. Zhang S, et al. Nature, 2022 May. PMID 35477760, Free PMC Article
    5. USP14 as a novel prognostic marker promotes cisplatin resistance via Akt/ERK signaling pathways in gastric cancer. Fu Y, et al. Cancer Med, 2018 Nov. PMID 30296012, Free PMC Article

    See all (212) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Usp14 deficiency removes alpha-synuclein by regulating S100A8/A9 in Parkinson's disease.
      Title: Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson's disease.
    2. Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.
      Title: Deubiquitination of CIB1 by USP14 promotes lenvatinib resistance via the PAK1-ERK1/2 axis in hepatocellular carcinoma.
    3. Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation.
      Title: Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation.
    4. The regulatory role and mechanism of USP14 in endothelial cell pyroptosis induced by coronary heart disease.
      Title: The regulatory role and mechanism of USP14 in endothelial cell pyroptosis induced by coronary heart disease.
    5. Mechanistic insights into the role of USP14 in adipose tissue macrophage recruitment and insulin resistance in obesity.
      Title: Mechanistic insights into the role of USP14 in adipose tissue macrophage recruitment and insulin resistance in obesity.
    6. GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4.
      Title: GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4.
    7. Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.
      Title: Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.
    8. USP14 promotes the proliferation of cervical cancer via upregulating beta-catenin.
      Title: USP14 promotes the proliferation of cervical cancer via upregulating β-catenin.
    9. USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy.
      Title: USP14 Regulates ATF2/PIK3CD Axis to Promote Microvascular Endothelial Cell Proliferation, Migration, and Angiogenesis in Diabetic Retinopathy.
    10. USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1.
      Title: USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1.
    Submit: New GeneRIF Correction See all GeneRIFs (80)

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables K63-linked deubiquitinase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables cysteine-type deubiquitinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cysteine-type deubiquitinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables deubiquitinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables endopeptidase inhibitor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables proteasome binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables proteasome binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of ERAD pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of ERAD pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein K48-linked deubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of proteasomal protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in presynaptic cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of proteasome complex IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin carboxyl-terminal hydrolase 14
    Names
    deubiquitinating enzyme 14
    tRNA-guanine transglycosylase, 60-kD subunit
    ubiquitin specific peptidase 14 (tRNA-guanine transglycosylase)
    ubiquitin specific protease 14 (tRNA-guanine transglycosylase)
    ubiquitin thioesterase 14
    ubiquitin thiolesterase 14
    ubiquitin-specific processing protease 14
    NP_001032411.1
    NP_005142.1

    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_001037334.2 → NP_001032411.1  ubiquitin carboxyl-terminal hydrolase 14 isoform b

      See identical proteins and their annotated locations for NP_001032411.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon, compared to variant 1, but maintains the reading frame. The resulting protein (isoform b) is shorter than isoform a.
      Source sequence(s)
      AK098497, AP000845, BC003556, BG717018, BU161860, CA438203, CR976282
      Consensus CDS
      CCDS32781.1
      UniProtKB/TrEMBL
      A6NJA2
      Related
      ENSP00000464447.1, ENST00000582707.5
      Conserved Domains (3) summary
      cd02657
      Location:71 → 446
      Peptidase_C19A; 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 hydrolyse bonds involving the carboxyl ...
      pfam00443
      Location:69 → 445
      UCH; Ubiquitin carboxyl-terminal hydrolase
      cl00155
      Location:5 → 68
      UBQ; Ubiquitin-like proteins

    2. NM_005151.4 → NP_005142.1  ubiquitin carboxyl-terminal hydrolase 14 isoform a

      See identical proteins and their annotated locations for NP_005142.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AK098497, AP000845, BC003556, BU161860, CA438203
      Consensus CDS
      CCDS32780.1
      UniProtKB/Swiss-Prot
      B7Z4N8, J3QRZ5, P54578, Q53XY5
      UniProtKB/TrEMBL
      B2RD79
      Related
      ENSP00000261601.6, ENST00000261601.8
      Conserved Domains (2) summary
      cd02657
      Location:106 → 481
      Peptidase_C19A; 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 hydrolyse bonds involving the carboxyl ...
      cd16104
      Location:4 → 76
      Ubl_USP14_like; ubiquitin-like (Ubl) domain found in ubiquitin carboxyl-terminal hydrolase 14 (USP14) and similar proteins

    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_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      158557..214629
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      312304..368380
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P54578.3 GenPept UniProtKB/Swiss-Prot:P54578

    Gene LinkOut

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