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 ... See more...

Aliases for USP14 Gene

Aliases for USP14 Gene

  • Ubiquitin Specific Peptidase 14 2 3 5
  • Ubiquitin Specific Peptidase 14 (TRNA-Guanine Transglycosylase) 2 3
  • Ubiquitin Specific Protease 14 (TRNA-Guanine Transglycosylase) 2 3
  • Ubiquitin Carboxyl-Terminal Hydrolase 14 3 4
  • Deubiquitinating Enzyme 14 3 4
  • Ubiquitin Thioesterase 14 3 4
  • TGT 3 4
  • TRNA-Guanine Transglycosylase, 60-KD Subunit 3
  • Ubiquitin-Specific Processing Protease 14 3
  • Ubiquitin-Specific-Processing Protease 14 4
  • Ubiquitin Thiolesterase 14 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 52

External Ids for USP14 Gene

Previous GeneCards Identifiers for USP14 Gene

  • GC18P000442
  • GC18P000146
  • GC18P000148

Summaries for USP14 Gene

Entrez Gene Summary for USP14 Gene

  • 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]

GeneCards Summary for USP14 Gene

USP14 (Ubiquitin Specific Peptidase 14) is a Protein Coding gene. Diseases associated with USP14 include Ovarian Serous Cystadenocarcinoma and Autosomal Dominant Cerebellar Ataxia. Among its related pathways are Metabolism of proteins and Ubiquitin-Proteasome Dependent Proteolysis. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is USP8.

UniProtKB/Swiss-Prot Summary for USP14 Gene

  • Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation.

Tocris Summary for USP14 Gene

  • Deubiquitinating enzymes (DUBs) are a group of proteases that catalyze the cleavage of protein-ubiquitin bonds. By removing these modifications, DUBs counteract the activity of ubiquitin ligases, which add ubiquitin molecules to target proteins.

Gene Wiki entry for USP14 Gene

Additional gene information for USP14 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP14 Gene

Genomics for USP14 Gene

GeneHancer (GH) Regulatory Elements for USP14 Gene

Promoters and enhancers for USP14 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around USP14 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP14

Top Transcription factor binding sites by QIAGEN in the USP14 gene promoter:
  • AP-1
  • CUTL1
  • FOXD1
  • HNF-1
  • HNF-1A
  • LCR-F1
  • MIF-1
  • NF-E2
  • NF-E2 p45
  • RREB-1

Genomic Locations for USP14 Gene

Genomic Locations for USP14 Gene
chr18:158,383-214,629
(GRCh38/hg38)
Size:
56,247 bases
Orientation:
Plus strand
chr18:158,383-214,629
(GRCh37/hg19)
Size:
56,247 bases
Orientation:
Plus strand

Genomic View for USP14 Gene

Genes around USP14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP14 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP14 Gene

Proteins for USP14 Gene

  • Protein details for USP14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P54578-UBP14_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 14
    Protein Accession:
    P54578
    Secondary Accessions:
    • B7Z4N8
    • J3QRZ5
    • Q53XY5

    Protein attributes for USP14 Gene

    Size:
    494 amino acids
    Molecular mass:
    56069 Da
    Quaternary structure:
    • Homodimer (Potential). Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this interaction recruits USP14 to cleave ubiquitin chains of CGAS.
    SequenceCaution:
    • Sequence=CR976282; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for USP14 Gene

    Alternative splice isoforms for USP14 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP14 Gene

Selected DME Specific Peptides for USP14 Gene

P54578:
  • NLGNTCYMN
  • PPMVFKAQLFALT
  • SGGGDWH
  • QMMRVLQQKLEAIEDD
  • LMMGSADALPEEPSAKTVFVEDMTEEQLA

Post-translational modifications for USP14 Gene

  • Ubiquitination at Lys49, Lys62, Lys130, Lys214, Lys291, Lys300, Lys348, Lys441, Lys443, and Lys449
  • Modification sites at PhosphoSitePlus

Domains & Families for USP14 Gene

Gene Families for USP14 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for USP14 Gene

Blocks:
  • Ubiquitin domain
  • Ubiquitin thiolesterase, family 2
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for USP14 Gene

GenScript: Design optimal peptide antigens:
  • Ubiquitin carboxyl-terminal hydrolase (A6NJA2_HUMAN)
  • Ubiquitin carboxyl-terminal hydrolase (B7Z4N8_HUMAN)
  • Ubiquitin carboxyl-terminal hydrolase (D3DUG9_HUMAN)
  • Ubiquitin-specific-processing protease 14 (UBP14_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P54578

UniProtKB/Swiss-Prot:

UBP14_HUMAN :
  • Belongs to the peptidase C19 family. USP14/UBP6 subfamily.
Family:
  • Belongs to the peptidase C19 family. USP14/UBP6 subfamily.
genes like me logo Genes that share domains with USP14: view

Function for USP14 Gene

Molecular function for USP14 Gene

UniProtKB/Swiss-Prot Function:
Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence=. ;.
GENATLAS Biochemistry:
ubiquitin specific protease 14,deubiquitin enzyme family

Enzyme Numbers (IUBMB) for USP14 Gene

Phenotypes From GWAS Catalog for USP14 Gene

Gene Ontology (GO) - Molecular Function for USP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity TAS 9827704
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA 23958854
GO:0004866 endopeptidase inhibitor activity IMP 18162577
GO:0005515 protein binding IEA,IPI 19106094
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with USP14: view
genes like me logo Genes that share phenotypes with USP14: view

Animal Models for USP14 Gene

MGI Knock Outs for USP14:
  • Usp14 Usp14<tm2b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for USP14

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for USP14 Gene

Localization for USP14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP14 Gene

Cytoplasm. Cell membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for USP14 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
extracellular 1
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for USP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000502 proteasome complex IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA,TAS --
GO:0005886 plasma membrane IEA --
GO:0009986 cell surface IDA 19106094
genes like me logo Genes that share ontologies with USP14: view

Pathways & Interactions for USP14 Gene

genes like me logo Genes that share pathways with USP14: view

Pathways by source for USP14 Gene

1 Qiagen pathway for USP14 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis
1 Cell Signaling Technology pathway for USP14 Gene

Gene Ontology (GO) - Biological Process for USP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0007268 chemical synaptic transmission IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
genes like me logo Genes that share ontologies with USP14: view

No data available for SIGNOR curated interactions for USP14 Gene

Drugs & Compounds for USP14 Gene

(8) Drugs for USP14 Gene - From: DrugBank, ApexBio, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Phenethyl isothiocyanate Investigational Pharma Target 14
HBX 41108 Pharma 0
IU1 Pharma Usp14 inhibitor 0
WP1130 Pharma Deubiquitinase (DUB) inhibitor, Cell permeable 0

(2) Additional Compounds for USP14 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
NSC 624206
13116-77-3

(3) Tocris Compounds for USP14 Gene

Compound Action Cas Number
NSC 624206 Ubiquitin-activating enzyme (E1) inhibitor 13116-77-3
PYR 41 Ubiquitin-activating enzyme (E1) inhibitor 418805-02-4
PYZD 4409 Ubiquitin-activating enzyme (E1) inhibitor 423148-78-1

(3) ApexBio Compounds for USP14 Gene

Compound Action Cas Number
HBX 41108 924296-39-9
IU1 Usp14 inhibitor 314245-33-5
WP1130 Deubiquitinase (DUB) inhibitor, Cell permeable 856243-80-6
genes like me logo Genes that share compounds with USP14: view

Transcripts for USP14 Gene

mRNA/cDNA for USP14 Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for USP14

Alternative Splicing Database (ASD) splice patterns (SP) for USP14 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15 ^ 16 ^ 17a · 17b ^ 18 ^ 19a · 19b
SP1: - -
SP2: - - -
SP3: -
SP4:
SP5:
SP6: -
SP7:

Relevant External Links for USP14 Gene

GeneLoc Exon Structure for
USP14

Expression for USP14 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for USP14 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for USP14 Gene



Protein tissue co-expression partners for USP14 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for USP14

SOURCE GeneReport for Unigene cluster for USP14 Gene:

Hs.464416

Evidence on tissue expression from TISSUES for USP14 Gene

  • Nervous system(4.9)
  • Liver(4.6)
  • Skin(4.5)
  • Blood(4.3)
  • Lung(2.7)
genes like me logo Genes that share expression patterns with USP14: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP14 Gene

Orthologs for USP14 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for USP14 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia USP14 31 30
  • 99.73 (n)
OneToOne
dog
(Canis familiaris)
Mammalia USP14 31 30
  • 94.26 (n)
OneToOne
cow
(Bos Taurus)
Mammalia USP14 31 30
  • 93.12 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia USP14 31
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia USP14 31
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Usp14 17 31 30
  • 91.48 (n)
rat
(Rattus norvegicus)
Mammalia Usp14 30
  • 91.48 (n)
chicken
(Gallus gallus)
Aves USP14 31 30
  • 82.66 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia USP14 31
  • 90 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia usp14 30
  • 79.18 (n)
zebrafish
(Danio rerio)
Actinopterygii usp14 31 30
  • 73.57 (n)
OneToOne
wufk63d09 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5646 30
fruit fly
(Drosophila melanogaster)
Insecta CG5384 31 32 30
  • 57.51 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009348 30
  • 56.29 (n)
worm
(Caenorhabditis elegans)
Secernentea usp-14 31 30
  • 51.88 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP6 33 31 30
  • 47.78 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0A10791g 30
  • 45.5 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AEL029W 30
  • 45.28 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons UBP6 30
  • 53.38 (n)
rice
(Oryza sativa)
Liliopsida Os01g0550100 30
  • 52.95 (n)
Os.9089 30
barley
(Hordeum vulgare)
Liliopsida Hv.4282 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 54 (a)
OneToOne
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes ubp6 30
  • 51.85 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU01919 30
  • 50.29 (n)
Species where no ortholog for USP14 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for USP14 Gene

ENSEMBL:
Gene Tree for USP14 (if available)
TreeFam:
Gene Tree for USP14 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for USP14: view image

Paralogs for USP14 Gene

Variants for USP14 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP14 Gene

SNP ID Clinical significance and condition Chr 18 pos Variation AA Info Type
718575 Benign: not provided 163,396(+) G/A SYNONYMOUS_VARIANT
722595 Benign: not provided 210,453(+) T/C SYNONYMOUS_VARIANT
736870 Likely Benign: not provided 210,474(+) A/G SYNONYMOUS_VARIANT
739467 Likely Benign: not provided 211,185(+) T/C SYNONYMOUS_VARIANT
742955 Likely Benign: not provided 204,585(+) T/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for USP14 Gene

Structural Variations from Database of Genomic Variants (DGV) for USP14 Gene

Variant ID Type Subtype PubMed ID
dgv1534n106 CNV deletion 24896259
dgv3300n100 CNV gain 25217958
dgv3301n100 CNV gain 25217958
dgv3302n100 CNV gain 25217958
esv2658900 CNV deletion 23128226
esv2675103 CNV deletion 23128226
esv3554936 CNV deletion 23714750
esv3573886 CNV gain 25503493
esv3641472 CNV loss 21293372
esv3641473 CNV gain 21293372
esv3641475 CNV gain 21293372
esv3641476 CNV loss 21293372
esv3641477 CNV loss 21293372
nsv1064150 CNV gain 25217958
nsv1071821 CNV deletion 25765185
nsv1160503 CNV duplication 26073780
nsv482935 CNV loss 15286789
nsv512512 CNV loss 21212237
nsv518642 CNV gain 19592680
nsv576227 CNV gain 21841781
nsv576228 CNV loss 21841781

Variation tolerance for USP14 Gene

Residual Variation Intolerance Score: 36.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.91; 67.73% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for USP14 Gene

Human Gene Mutation Database (HGMD)
USP14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP14

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP14 Gene

Disorders for USP14 Gene

MalaCards: The human disease database

(3) MalaCards diseases for USP14 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
ovarian serous cystadenocarcinoma
  • serous cystadenoma
autosomal dominant cerebellar ataxia
  • spinocerebellar ataxia
myeloma, multiple
  • multiple myeloma, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search USP14 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for USP14

genes like me logo Genes that share disorders with USP14: view

No data available for UniProtKB/Swiss-Prot and Genatlas for USP14 Gene

Publications for USP14 Gene

  1. Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation. (PMID: 19106094) Mines MA … Fan GH (The Journal of biological chemistry 2009) 3 4 54
  2. USP14 inhibits ER-associated degradation via interaction with IRE1alpha. (PMID: 19135427) Nagai A … Ichijo H (Biochemical and biophysical research communications 2009) 3 4 54
  3. Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. (PMID: 18162577) Koulich E … DeMartino GN (Molecular biology of the cell 2008) 3 4 54
  4. Ubiquitin-specific protease 14 expression in colorectal cancer is associated with liver and lymph node metastases. (PMID: 16465409) Shinji S … Tajiri T (Oncology reports 2006) 3 23 54
  5. Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. (PMID: 16211010) Hu M … Shi Y (The EMBO journal 2005) 3 4 54

Products for USP14 Gene

Sources for USP14 Gene