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

Gene ID: 9097, updated on 12-Jun-2025
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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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

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. 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
  2. Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis in esophageal squamous cell carcinoma. Zhang B, et al. Thorac Cancer, 2017 Jul. PMID 28509417, Free PMC Article
  3. Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK/NF-κB signaling. Zhao Y, et al. Immun Inflamm Dis, 2021 Sep. PMID 34089575, Free PMC Article
  4. Functional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype. Turgut GT, et al. Clin Genet, 2022 Apr. PMID 35066879
  5. Knockdown of Ubiquitin-Specific Protease 14 (USP14) Inhibits the Proliferation and Tumorigenesis in Esophageal Squamous Cell Carcinoma Cells. Zhang J, et al. Oncol Res, 2017 Jan 26. PMID 27629392, Free PMC Article

See all (221) 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 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.
Submit: New GeneRIF Correction See all GeneRIFs (81)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

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 deubiquitinase activity IEA
Inferred from Electronic Annotation
more info
  
enables cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 PubMed 
enables cysteine-type peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables deubiquitinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables endopeptidase inhibitor activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activity IEA
Inferred from Electronic Annotation
more info
  
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
acts_upstream_of_or_within chemical synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
involved_in immune system process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
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 protein deubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in proteolysis IEA
Inferred from Electronic Annotation
more info
  
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 cytoplasm IEA
Inferred from Electronic Annotation
more info
  
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 endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in membrane IEA
Inferred from Electronic Annotation
more info
  
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in presynaptic cytosol IEA
Inferred from Electronic Annotation
more info
  
part_of proteasome complex IEA
Inferred from Electronic Annotation
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
more info
  
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

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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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