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

Summary

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
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
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

Genomic context

Location:: 18p11.32

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	18	NC_000018.10 (158557..214629)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (158483..213739)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

USP14 may function as a common denominator in the compensatory negative feedback between the two major proteolytic processes in the cell.
Title: Dual Function of USP14 Deubiquitinase in Cellular Proteasomal Activity and Autophagic Flux.
USP14 levels were significantly increased in gastric cancer (GC) tissues compared to the paired normal tissues. USP14 level was an independent prognostic factor for DFS in GC patients. Its knockdown sensitized GC cells to cisplatin by triggering cisplatin-induced apoptosis via impeding Akt and ERK signaling pathways.
Title: USP14 as a novel prognostic marker promotes cisplatin resistance via Akt/ERK signaling pathways in gastric cancer.
USP14 directly interacted with RNF168, which depended on the MIU1 domain of RNF168. These findings identify USP14 as a novel substrate of autophagy and regulation of RNF168-dependent Ubiquitination and TP53BP1 recruitment by USP14 as a critical link between DNA damage repair and autophagy.
Title: USP14 regulates DNA damage repair by targeting RNF168-dependent ubiquitination.
Data show that ubiquitin-specific protease 14 (USP14) is a direct target of hsa-miR-124a, and that hsa-miR-124a inhibits stemness.
Title: Tumor suppressive microRNA-124a inhibits stemness and enhances gefitinib sensitivity of non-small cell lung cancer cells by targeting ubiquitin-specific protease 14.
Our results provide a rationale for targeting the proteasome-associated DUB USP14 to treat and combat melanomas.
Title: Targeting the Proteasome-Associated Deubiquitinating Enzyme USP14 Impairs Melanoma Cell Survival and Overcomes Resistance to MAPK-Targeting Therapies.
genetic and pharmacological inhibition of USP14 promotes mitophagy.
Title: USP14 inhibition corrects an <i>in vivo</i> model of impaired mitophagy.
USP14 acts as a negative regulator in antiviral response through deubiquitinating K63-linked RIG-I
Title: USP14 promotes K63-linked RIG-I deubiquitination and suppresses antiviral immune responses.
High USP14 expression is associated with Osteoarthritis.
Title: USP14-mediated IκBα degradation exacerbates NF-κB activation and IL-1β-stimulated chondrocyte dedifferentiation.
The proteasome-associated deubiquitinating enzyme Usp14/UBP6 contains an N-terminal ubiquitin-like UBL domain and is an important regulator of proteasomal activity. Usp14 by itself represses multiple proteasomal activities but, upon binding a ubiquitin chain, Usp14 promotes ubiquitin-conjugate degradation. Usp14's UBL domain alone mimics this activation of proteasomes by ubiquitin chains.
Title: UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells.
By displacing USP14, TRIM11 changes proteasome composition and suppresses both catalytic and non-catalytic effects of USP14
Title: TRIM11 activates the proteasome and promotes overall protein degradation by regulating USP14.

Submit: New GeneRIF Correction See all GeneRIFs (42)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65814 (e-PCR)
- UniSTS:5382

RH65926 (e-PCR)
- UniSTS:52769

USP14__5036 (e-PCR)
- UniSTS:462943

D18S898E (e-PCR)
- UniSTS:71017

RH80953 (e-PCR)
- UniSTS:88960

D18S1294 (e-PCR)
- UniSTS:46746

D18S1244 (e-PCR)
- UniSTS:46747

RH47243 (e-PCR)
- UniSTS:37029

SHGC-30016 (e-PCR)
- UniSTS:12971

A003A48 (e-PCR)
- UniSTS:39639

D18S918E (e-PCR)
- UniSTS:150519

Homology

Homologs of the USP14 gene: The USP14 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 287 organisms have orthologs with human gene USP14
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cysteine-type endopeptidase activity	TAS Traceable Author Statement more info	PubMed
endopeptidase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
proteasome binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
thiol-dependent ubiquitin-specific protease activity	IDA Inferred from Direct Assay more info	PubMed
thiol-dependent ubiquitinyl hydrolase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
negative regulation of ER-associated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of endopeptidase activity	IEA Inferred from Electronic Annotation more info
protein deubiquitination	IDA Inferred from Direct Assay more info	PubMed
protein deubiquitination	TAS Traceable Author Statement more info
regulation of chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of proteasomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
extracellular exosome	HDA more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info
proteasome complex	IEA Inferred from Electronic Annotation more info
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

EC 3.4.19.12

NP_005142.1

EC 3.4.19.12

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)

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/Swiss-Prot

P54578

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
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

P54578

Related

ENSP00000261601.6, ENST00000261601.8

Conserved Domains (2) summary

smart00213
Location:5 → 74

UBQ; Ubiquitin homologues

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 ...