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

Gene ID: 9097, updated on 7-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (158557..214629)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (312304..368380)
105.20220307 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
  • 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. Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC). Morgan EL, et al. Cell Death Differ, 2023 May. PMID 37055579, Free PMC Article
  2. USP14-regulated allostery of the human proteasome by time-resolved cryo-EM. Zhang S, et al. Nature, 2022 May. PMID 35477760, Free PMC Article
  3. 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
  4. 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
  5. Ubiquitin-specific protease 14 promotes radio-resistance and suppresses autophagy in oral squamous cell carcinoma. Xie W, et al. Exp Cell Res, 2021 Jan 15. PMID 33212146

See all (185) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. USP14 promotes the proliferation of cervical cancer via upregulating beta-catenin.
    Title: USP14 promotes the proliferation of cervical cancer via upregulating β-catenin.
  4. 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.
  5. 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.
  6. USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis.
    Title: USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis.
  7. SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.
    Title: SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1.
  8. Inhibition of USP14 promotes TNFalpha-induced cell death in head and neck squamous cell carcinoma (HNSCC).
    Title: Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC).
  9. Insulin Suppresses Ubiquitination via the Deubiquitinating Enzyme Ubiquitin-Specific Protease 14, Independent of Proteasome Activity in H4IIEC3 Hepatocytes.
    Title: Insulin Suppresses Ubiquitination via the Deubiquitinating Enzyme Ubiquitin-Specific Protease 14, Independent of Proteasome Activity in H4IIEC3 Hepatocytes.
  10. USP14 promotes colorectal cancer progression by targeting JNK for stabilization.
    Title: USP14 promotes colorectal cancer progression by targeting JNK for stabilization.
Submit: New GeneRIF Correction See all GeneRIFs (75)

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 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 deubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein deubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of chemotaxis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of proteasomal protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
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 plasma membrane IDA
Inferred from Direct Assay
more info
  
part_of proteasome complex IEA
Inferred from Electronic Annotation
more info
  
located_in synapse 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_2023_10

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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