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	current	GRCh38.p12 (GCF_000001405.38)	18	NC_000018.10 (158483..213739)
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 FunctionsWhat's a GeneRIF?

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.
Usp14 and Ube3c cycle together on and off proteasomes, and the presence of ubiquitinated substrates promotes their association. This mechanism enables proteasome activity to adapt to the supply of substrates.
Title: Ubiquitinated proteins promote the association of proteasomes with the deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c.
our results demonstrated that vimentin in human GC tissues and cell lines was upregulated due to its de-ubiquitination after interactions with USP14 and miR-320a, which could promote the aggressiveness of GC cells.
Title: USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells.
Study detected elevated USP14 expression at both mRNA and protein levels, and was significantly associated with distant metastasis.
Title: Overexpression of ubiquitin specific peptidase 14 predicts unfavorable prognosis in esophageal squamous cell carcinoma.
These findings suggested that USP14 induces NF-kappaB activity and ERK1/2 phosphorylation triggered by microbial infection.
Title: Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation.
Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma
Title: Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma.
our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant Waldenstrom macroglobulinemia (WM) and carries a high potential for clinical translation
Title: Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.
USP14 promotes prostate cancer progression.
Title: Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.
without a ubiquitinated substrate present, Usp14 suppresses multiple proteasomal activities, especially basal ATP consumption and degradation of non-ubiquitinated proteins. These allosteric effects thus reduce ATP hydrolysis by inactive proteasomes and nonspecific proteolysis and enhance proteasomal specificity for ubiquitinated proteins.
Title: The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal activities and ubiquitin-independent proteolysis.
USP14 regulates autophagy by negatively controlling K63 ubiquitination of Beclin 1
Title: USP14 regulates autophagy by suppressing K63 ubiquitination of Beclin 1.

Submit: New GeneRIF Correction See all GeneRIFs (33)

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)

Pathways from BioSystems

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Deubiquitination, organism-specific biosystem (from REACTOME)
Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Post-translational protein modification, organism-specific biosystem (from REACTOME)
Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...

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: 252 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
tRNA guanylyltransferase activity	TAS Traceable Author Statement 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
tRNA 5'-end processing	IEA Inferred from Electronic Annotation more info
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_001037334.1 → 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, 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, ENST00000261601.7

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 ...