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

Gene ID: 9097, updated on 3-Nov-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
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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. Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma. Chen X, et al. Int J Biochem Cell Biol, 2016 Oct. PMID 27592452
  2. USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro. Han KH, et al. Int J Mol Sci, 2019 Oct 24. PMID 31653087, Free PMC Article
  3. Ubiquitin-specific protease 14 expression associated with intrahepatic cholangiocarcinoma cell differentiation. Chuensumran U, et al. Asian Pac J Cancer Prev, 2011. PMID 21627382
  4. Compensatory increase in USP14 activity accompanies impaired proteasomal proteolysis during aging. Ponnappan S, et al. Mech Ageing Dev, 2013 Jan-Feb. PMID 23291607, Free PMC Article
  5. UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells. Kim HT, et al. Proc Natl Acad Sci U S A, 2018 Dec 11. PMID 30487212, Free PMC Article

See all (216) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Deubiquitinase USP14 is upregulated in Crohn's disease and inhibits the NOD2 pathway mediated inflammatory response in vitro.
    Title: Deubiquitinase USP14 is upregulated in Crohn's disease and inhibits the NOD2 pathway mediated inflammatory response in vitro.
  2. Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.
    Title: Biallelic USP14 variants cause a syndromic neurodevelopmental disorder.
  3. 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.
  4. 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.
  5. Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation.
    Title: Structural Dynamics Analysis of USP14 Activation by AKT-Mediated Phosphorylation.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. USP14 promotes the proliferation of cervical cancer via upregulating beta-catenin.
    Title: USP14 promotes the proliferation of cervical cancer via upregulating β-catenin.
Submit: New GeneRIF Correction See all GeneRIFs (82)

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

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