Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branch... See more...

Aliases for USP5 Gene

Aliases for USP5 Gene

  • Ubiquitin Specific Peptidase 5 2 3 5
  • Isopeptidase T 2 3 4
  • Ubiquitin-Specific-Processing Protease 5 3 4
  • Ubiquitin Carboxyl-Terminal Hydrolase 5 3 4
  • Deubiquitinating Enzyme 5 3 4
  • Ubiquitin Thioesterase 5 3 4
  • ISOT 3 4
  • Ubiquitin-Specific Protease-5 (Ubiquitin Isopeptidase T) 3
  • Ubiquitin Specific Peptidase 5 (Isopeptidase T) 2
  • Ubiquitin Specific Protease 5 (Isopeptidase T) 3
  • Testicular Tissue Protein Li 218 3
  • Ubiquitin Thiolesterase 5 3
  • Ubiquitin Isopeptidase T 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 50
  • USP5 5
  • IsoT 2

External Ids for USP5 Gene

Previous GeneCards Identifiers for USP5 Gene

  • GC12M006999
  • GC12M007084
  • GC12P006840
  • GC12P006831
  • GC12P006815
  • GC12P006978
  • GC12P006985
  • GC12P006991
  • GC12P006998
  • GC12P007006
  • GC12P007024
  • GC12P007047
  • GC12P007111
  • GC12P007137
  • GC12P006856
  • GC12P007850
  • GC12P008202
  • GC12P008985

Summaries for USP5 Gene

Entrez Gene Summary for USP5 Gene

  • Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]

GeneCards Summary for USP5 Gene

USP5 (Ubiquitin Specific Peptidase 5) is a Protein Coding gene. Among its related pathways are Protein ubiquitination and Deubiquitination. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and thiol-dependent ubiquitinyl hydrolase activity. An important paralog of this gene is USP13.

UniProtKB/Swiss-Prot Summary for USP5 Gene

  • Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition.

Gene Wiki entry for USP5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP5 Gene

Genomics for USP5 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for USP5 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 USP5 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP5

Top Transcription factor binding sites by QIAGEN in the USP5 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for USP5 Gene

Latest Assembly
chr12:6,852,148-6,866,632
(GRCh38/hg38)
Size:
14,485 bases
Orientation:
Plus strand

Previous Assembly
chr12:6,961,314-6,975,796
(GRCh37/hg19 by Entrez Gene)
Size:
14,483 bases
Orientation:
Plus strand

chr12:6,961,292-6,975,796
(GRCh37/hg19 by Ensembl)
Size:
14,505 bases
Orientation:
Plus strand

Genomic View for USP5 Gene

Genes around USP5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP5 Gene

Proteins for USP5 Gene

  • Protein details for USP5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P45974-UBP5_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 5
    Protein Accession:
    P45974
    Secondary Accessions:
    • D3DUS7
    • D3DUS8
    • Q96J22

    Protein attributes for USP5 Gene

    Size:
    858 amino acids
    Molecular mass:
    95786 Da
    Quaternary structure:
    • Interacts with TRIML1.
    Miscellaneous:
    • The UBP-type zinc finger domain crystallizes as a dimer linked by a disulfide bond between the Cys-195 residues of both molecules, but there is no evidence that the full-length USP5 exists as a dimer.

    Three dimensional structures from OCA and Proteopedia for USP5 Gene

    Alternative splice isoforms for USP5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP5 Gene

Selected DME Specific Peptides for USP5 Gene

P45974:
  • NRQQDAQEFFLHL
  • KEGRWVI
  • CGHYVCHIKK
  • NLGNSCY
  • ENLWLNLTDG
  • QIKKFTFGLDWVPKK
  • ACRKAVY
  • SFPDYLV
  • ERAVDWI
  • LFAFISHMGTSTM
  • GGNNHAVEHY
  • GSSGPGS
  • LAIGVEGGF
  • VKLGTIT
  • VFRFLVEE

Post-translational modifications for USP5 Gene

  • Ubiquitination at Lys20, Lys163, Lys184, Lys318, Lys353, Lys357, Lys360, Lys391, Lys423, Lys553, Lys586, Lys743, Lys793, and Lys836
  • Modification sites at PhosphoSitePlus

Domains & Families for USP5 Gene

Gene Families for USP5 Gene

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

Protein Domains for USP5 Gene

InterPro:
Blocks:
  • Ubiquitin-associated domain
  • Ubiquitin thiolesterase, family 2
  • Zn-finger in ubiquitin thiolesterase

Suggested Antigen Peptide Sequences for USP5 Gene

GenScript: Design optimal peptide antigens:
  • Ubiquitin-specific-processing protease 5 (UBP5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P45974

UniProtKB/Swiss-Prot:

UBP5_HUMAN :
  • The UBP-type zinc finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin. Both UBA domains are involved in polyubiquitin recognition.
  • Belongs to the peptidase C19 family.
Domain:
  • The UBP-type zinc finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin. Both UBA domains are involved in polyubiquitin recognition.
Family:
  • Belongs to the peptidase C19 family.
genes like me logo Genes that share domains with USP5: view

Function for USP5 Gene

Molecular function for USP5 Gene

UniProtKB/Swiss-Prot Function:
Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition.
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;.
GENATLAS Biochemistry:
ubiquitin specific protease 5,100kDa,expressed in brain,deubiquitin enzyme family

Enzyme Numbers (IUBMB) for USP5 Gene

Phenotypes From GWAS Catalog for USP5 Gene

Gene Ontology (GO) - Molecular Function for USP5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity TAS,IBA 21873635
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA 24424410
GO:0005515 protein binding IPI 16189514
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with USP5: view
genes like me logo Genes that share phenotypes with USP5: view

Animal Models for USP5 Gene

MGI Knock Outs for USP5:
  • Usp5 Usp5<tm1a(EUCOMM)Hmgu>

Animal Models for research

  • Taconic Biosciences Mouse Models for USP5

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP5

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for USP5 Gene

Localization for USP5 Gene

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 USP5 gene
Compartment Confidence
nucleus 4
cytosol 4
lysosome 4
cytoskeleton 3
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for USP5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005764 lysosome TAS 9827704
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with USP5: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for USP5 Gene

Pathways & Interactions for USP5 Gene

genes like me logo Genes that share pathways with USP5: view

Pathways by source for USP5 Gene

1 Qiagen pathway for USP5 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis

Gene Ontology (GO) - Biological Process for USP5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0016567 protein ubiquitination TAS --
GO:0016579 protein deubiquitination IDA,TAS --
GO:0018215 protein phosphopantetheinylation IEA --
genes like me logo Genes that share ontologies with USP5: view

No data available for SIGNOR curated interactions for USP5 Gene

Drugs & Compounds for USP5 Gene

(5) Drugs for USP5 Gene - From: ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
Vialinin A Pharma USP/isopeptidase T (IsoT)/UCH-L1 DUB inhibitor 0
WP1130 Pharma Deubiquitinase (DUB) inhibitor, Cell permeable 0

(2) ApexBio Compounds for USP5 Gene

Compound Action Cas Number
Vialinin A USP/isopeptidase T (IsoT)/UCH-L1 DUB inhibitor 858134-23-3
WP1130 Deubiquitinase (DUB) inhibitor, Cell permeable 856243-80-6
genes like me logo Genes that share compounds with USP5: view

Drug products for research

Transcripts for USP5 Gene

mRNA/cDNA for USP5 Gene

6 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP5

Alternative Splicing Database (ASD) splice patterns (SP) for USP5 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21a · 21b · 21c
SP1:
SP2: -
SP3:

Relevant External Links for USP5 Gene

GeneLoc Exon Structure for
USP5

Expression for USP5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for USP5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Lymph (Hematopoietic System)
  • Testis (Reproductive System)

Protein differential expression in normal tissues from HIPED for USP5 Gene

This gene is overexpressed in Lymph node (8.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for USP5 Gene



Protein tissue co-expression partners for USP5 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for USP5

SOURCE GeneReport for Unigene cluster for USP5 Gene:

Hs.631661

Evidence on tissue expression from TISSUES for USP5 Gene

  • Kidney(4.5)
  • Liver(4.4)
  • Lung(4.4)
  • Nervous system(4.2)
  • Skin(3.1)
  • Muscle(2.5)
  • Intestine(2.5)
  • Blood(2.3)
  • Eye(2.3)
  • Heart(2.2)
genes like me logo Genes that share expression patterns with USP5: view

Primer products for research

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP5 Gene

Orthologs for USP5 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for USP5 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia USP5 29 30
  • 98.75 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia USP5 29 30
  • 93.67 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia USP5 29 30
  • 92.42 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia USP5 30
  • 92 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Usp5 29 16 30
  • 91.96 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Usp5 29
  • 91.65 (n)
Chicken
(Gallus gallus)
Aves USP5 29 30
  • 81.33 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia USP5 30
  • 89 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia usp5 29
  • 73.92 (n)
Str.4101 29
Zebrafish
(Danio rerio)
Actinopterygii usp5 29 30
  • 66.87 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012248 29
  • 58.94 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG12082 29 30 31
  • 58.62 (n)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea usp-5 30
  • 37 (a)
OneToMany
T27A3.2 31
  • 35 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP14 30 32
  • 29 (a)
OneToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons UBP14 29
  • 55.85 (n)
Rice
(Oryza sativa)
Liliopsida Os01g0177200 29
  • 55.39 (n)
Os.7173 29
Barley
(Hordeum vulgare)
Liliopsida Hv.1989 29
Corn
(Zea mays)
Liliopsida Zm.5738 29
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9810 30
  • 49 (a)
OneToMany
Species where no ortholog for USP5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • 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)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 USP5 Gene

ENSEMBL:
Gene Tree for USP5 (if available)
TreeFam:
Gene Tree for USP5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for USP5: view image
Alliance of Genome Resources:
Additional Orthologs for USP5

Paralogs for USP5 Gene

(1) SIMAP similar genes for USP5 Gene using alignment to 2 proteins:

  • UBP5_HUMAN
  • F5H571_HUMAN

Pseudogenes.org Pseudogenes for USP5 Gene

genes like me logo Genes that share paralogs with USP5: view

Variants for USP5 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP5 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
rs143249320 Benign: not provided 6,852,233(+) C/T
NM_001098536.2(USP5):c.54C>T (p.Val18=)
SYNONYMOUS
rs143986399 Benign: not provided 6,861,073(+) C/T
NM_001098536.2(USP5):c.1465C>T (p.Leu489=)
SYNONYMOUS
rs145733981 Benign: not provided 6,855,778(+) C/T
NM_001098536.2(USP5):c.261C>T (p.Gly87=)
SYNONYMOUS
rs35165406 Benign: not provided 6,863,250(+) C/T
NM_001098536.2(USP5):c.1827C>T (p.Pro609=)
SYNONYMOUS
rs76083908 Benign: not provided 6,860,158(+) C/T
NM_001098536.2(USP5):c.1138C>T (p.Leu380=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for USP5 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for USP5 Gene

Variant ID Type Subtype PubMed ID
esv3580405 CNV gain 25503493
nsv557261 CNV loss 21841781
nsv832323 CNV loss 17160897
nsv832324 CNV loss 17160897

Variation tolerance for USP5 Gene

Residual Variation Intolerance Score: 2.39% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.50; 29.19% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for USP5 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP5
Leiden Open Variation Database (LOVD)
USP5

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP5 Gene

Disorders for USP5 Gene

Additional Disease Information for USP5

No disorders were found for USP5 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for USP5 Gene

Publications for USP5 Gene

  1. A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13. (PMID: 8723724) Ansari-Lari MA … Gibbs RA (Genome research 1996) 2 3 4 22
  2. Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53. (PMID: 19098288) Dayal S … Saville MK (The Journal of biological chemistry 2009) 3 4 22
  3. Recognition of polyubiquitin isoforms by the multiple ubiquitin binding modules of isopeptidase T. (PMID: 18482987) Reyes-Turcu FE … Wilkinson KD (The Journal of biological chemistry 2008) 3 4 22
  4. The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin. (PMID: 16564012) Reyes-Turcu FE … Wilkinson KD (Cell 2006) 3 4 22
  5. Domain analysis reveals that a deubiquitinating enzyme USP13 performs non-activating catalysis for Lys63-linked polyubiquitin. (PMID: 22216260) Zhang YH … Hu HY (PloS one 2011) 3 4

Products for USP5 Gene

Sources for USP5 Gene