The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another ... See more...

Aliases for UCHL3 Gene

Aliases for UCHL3 Gene

  • Ubiquitin C-Terminal Hydrolase L3 2 3 5
  • Ubiquitin Carboxyl-Terminal Esterase L3 (Ubiquitin Thiolesterase) 2 3
  • Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L3 3 4
  • Ubiquitin Thioesterase L3 3 4
  • Ubiquitin Thiolesterase 2 3
  • UCH-L3 3 4
  • Testicular Tissue Protein Li 221 3
  • EC 3.4.19.12 4

External Ids for UCHL3 Gene

Previous GeneCards Identifiers for UCHL3 Gene

  • GC13P074091
  • GC13P070118
  • GC13P075060
  • GC13P073921
  • GC13P075021
  • GC13P076123
  • GC13P056821

Summaries for UCHL3 Gene

Entrez Gene Summary for UCHL3 Gene

  • The protein encoded by this gene is a member of the deubiquitinating enzyme family. Members of this family are proteases that catalyze the removal of ubiquitin from polypeptides and are divided into five classes, depending on the mechanism of catalysis. This protein may hydrolyze the ubiquitinyl-N-epsilon amide bond of ubiquitinated proteins to regenerate ubiquitin for another catalytic cycle. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

GeneCards Summary for UCHL3 Gene

UCHL3 (Ubiquitin C-Terminal Hydrolase L3) is a Protein Coding gene. Among its related pathways are Metabolism of proteins and Deubiquitination. Gene Ontology (GO) annotations related to this gene include peptidase activity and ubiquitin binding. An important paralog of this gene is UCHL1.

UniProtKB/Swiss-Prot Summary for UCHL3 Gene

  • Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.

Gene Wiki entry for UCHL3 Gene

Additional gene information for UCHL3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for UCHL3 Gene

Genomics for UCHL3 Gene

GeneHancer (GH) Regulatory Elements for UCHL3 Gene

Promoters and enhancers for UCHL3 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 UCHL3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for UCHL3

Top Transcription factor binding sites by QIAGEN in the UCHL3 gene promoter:
  • HOXA9
  • HOXA9B
  • Meis-1
  • Meis-1a
  • Meis-1b
  • p53

Genomic Locations for UCHL3 Gene

Genomic Locations for UCHL3 Gene
chr13:75,548,867-75,606,020
(GRCh38/hg38)
Size:
57,154 bases
Orientation:
Plus strand
chr13:76,123,619-76,180,085
(GRCh37/hg19)
Size:
56,467 bases
Orientation:
Plus strand

Genomic View for UCHL3 Gene

Genes around UCHL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
UCHL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for UCHL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for UCHL3 Gene

Proteins for UCHL3 Gene

  • Protein details for UCHL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P15374-UCHL3_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase isozyme L3
    Protein Accession:
    P15374
    Secondary Accessions:
    • B2R970
    • Q5TBK8
    • Q6IBE9

    Protein attributes for UCHL3 Gene

    Size:
    230 amino acids
    Molecular mass:
    26183 Da
    Quaternary structure:
    • Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.
    Miscellaneous:
    • Identified as a tumor-specific antigen in colon cancer.

    Three dimensional structures from OCA and Proteopedia for UCHL3 Gene

neXtProt entry for UCHL3 Gene

Post-translational modifications for UCHL3 Gene

  • Ubiquitination at Lys121
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for UCHL3 Gene

Domains & Families for UCHL3 Gene

Gene Families for UCHL3 Gene

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

Protein Domains for UCHL3 Gene

Blocks:
  • Ubiquitin carboxyl-terminal hydrolase, family 1
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for UCHL3 Gene

GenScript: Design optimal peptide antigens:
  • Ubiquitin carboxyl-terminal esterase L3 (Ubiquitin thiolesterase) (Q5TBK7_HUMAN)
  • Ubiquitin thioesterase L3 (UCHL3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P15374

UniProtKB/Swiss-Prot:

UCHL3_HUMAN :
  • Belongs to the peptidase C12 family.
Family:
  • Belongs to the peptidase C12 family.
genes like me logo Genes that share domains with UCHL3: view

Function for UCHL3 Gene

Molecular function for UCHL3 Gene

UniProtKB/Swiss-Prot Function:
Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.
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={ECO:0000269 PubMed:15531586, ECO:0000269 PubMed:20380862, ECO:0000269 PubMed:9790970};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by monoubiquitin and diubiquitin.

Enzyme Numbers (IUBMB) for UCHL3 Gene

Phenotypes From GWAS Catalog for UCHL3 Gene

Gene Ontology (GO) - Molecular Function for UCHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA 9521656
GO:0005515 protein binding IPI 21453705
GO:0008233 peptidase activity IDA,IEA 21762696
GO:0008234 cysteine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with UCHL3: view
genes like me logo Genes that share phenotypes with UCHL3: view

Animal Models for UCHL3 Gene

MGI Knock Outs for UCHL3:

Animal Model Products

  • Taconic Biosciences Mouse Models for UCHL3

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for UCHL3

Clone Products

  • Addgene plasmids for UCHL3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for UCHL3 Gene

Localization for UCHL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for UCHL3 Gene

Cytoplasm.

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 UCHL3 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
extracellular 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for UCHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with UCHL3: view

Pathways & Interactions for UCHL3 Gene

genes like me logo Genes that share pathways with UCHL3: view

Pathways by source for UCHL3 Gene

1 Cell Signaling Technology pathway for UCHL3 Gene

Gene Ontology (GO) - Biological Process for UCHL3 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 TAS,IBA --
GO:0030163 protein catabolic process IDA 21762696
genes like me logo Genes that share ontologies with UCHL3: view

No data available for SIGNOR curated interactions for UCHL3 Gene

Drugs & Compounds for UCHL3 Gene

(4) Drugs for UCHL3 Gene - From: ApexBio and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
LDN 57444 Pharma UCH-L1 inhibitor,reversible competitve 0
TCID Pharma 0
WP1130 Pharma Deubiquitinase (DUB) inhibitor, Cell permeable 0

(3) ApexBio Compounds for UCHL3 Gene

Compound Action Cas Number
LDN 57444 UCH-L1 inhibitor,reversible competitve 668467-91-2
TCID 30675-13-9
WP1130 Deubiquitinase (DUB) inhibitor, Cell permeable 856243-80-6
genes like me logo Genes that share compounds with UCHL3: view

Transcripts for UCHL3 Gene

mRNA/cDNA for UCHL3 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for UCHL3

Clone Products

  • Addgene plasmids for UCHL3

Alternative Splicing Database (ASD) splice patterns (SP) for UCHL3 Gene

No ASD Table

Relevant External Links for UCHL3 Gene

GeneLoc Exon Structure for
UCHL3

Expression for UCHL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for UCHL3 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for UCHL3 Gene



Protein tissue co-expression partners for UCHL3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for UCHL3

SOURCE GeneReport for Unigene cluster for UCHL3 Gene:

Hs.162241

mRNA Expression by UniProt/SwissProt for UCHL3 Gene:

P15374-UCHL3_HUMAN
Tissue specificity: Highly expressed in heart, skeletal muscle, and testis.

Evidence on tissue expression from TISSUES for UCHL3 Gene

  • Lung(4.3)
  • Nervous system(4.3)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with UCHL3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for UCHL3 Gene

Orthologs for UCHL3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for UCHL3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia UCHL3 31 30
  • 100 (n)
OneToOne
dog
(Canis familiaris)
Mammalia UCHL3 31 30
  • 95.65 (n)
OneToOne
cow
(Bos Taurus)
Mammalia UCHL3 31 30
  • 94.93 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Uchl4 31
  • 94 (a)
OneToMany
Uchl3 17 31 30
  • 90.43 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia UCHL3 31
  • 93 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Uchl3 30
  • 88.7 (n)
oppossum
(Monodelphis domestica)
Mammalia UCHL3 31
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves UCHL3 31 30
  • 82.9 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia UCHL3 31
  • 83 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia uchl3 30
  • 74.93 (n)
zebrafish
(Danio rerio)
Actinopterygii uchl3 31 30
  • 68.41 (n)
OneToOne
Dr.16889 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.3304 30
fruit fly
(Drosophila melanogaster)
Insecta Uch 31 32 30
  • 55.11 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP012113 30
  • 50.68 (n)
worm
(Caenorhabditis elegans)
Secernentea ubh-1 31
  • 41 (a)
ManyToMany
F46E10.8 32
  • 40 (a)
ubh-3 31
  • 37 (a)
ManyToMany
ubh-2 31
  • 31 (a)
ManyToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E09967g 30
  • 51.36 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGL314C 30
  • 49.59 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes YUH1 33 31 30
  • 49.33 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons UCH3 30
  • 55.91 (n)
soybean
(Glycine max)
eudicotyledons Gma.11207 30
rice
(Oryza sativa)
Liliopsida Os02g0654500 30
  • 52.82 (n)
barley
(Hordeum vulgare)
Liliopsida Hv.6337 30
bread mold
(Neurospora crassa)
Ascomycetes NCU06372 30
  • 45.93 (n)
Species where no ortholog for UCHL3 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)
  • fission yeast (Schizosaccharomyces pombe)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for UCHL3 Gene

ENSEMBL:
Gene Tree for UCHL3 (if available)
TreeFam:
Gene Tree for UCHL3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for UCHL3: view image

Paralogs for UCHL3 Gene

Paralogs for UCHL3 Gene

(1) SIMAP similar genes for UCHL3 Gene using alignment to 4 proteins:

  • UCHL3_HUMAN
  • L8E899_HUMAN
  • L8EAH4_HUMAN
  • Q5TBK7_HUMAN
genes like me logo Genes that share paralogs with UCHL3: view

Variants for UCHL3 Gene

Additional dbSNP identifiers (rs#s) for UCHL3 Gene

Structural Variations from Database of Genomic Variants (DGV) for UCHL3 Gene

Variant ID Type Subtype PubMed ID
esv2747671 CNV deletion 23290073
esv2747672 CNV deletion 23290073
esv2747673 CNV deletion 23290073
esv2751152 CNV loss 17911159
esv2761803 CNV gain 21179565
esv3302852 CNV tandem duplication 20981092
nsv1090 CNV insertion 18451855
nsv521444 CNV gain 19592680
nsv562347 CNV loss 21841781
nsv983604 CNV duplication 23825009

Variation tolerance for UCHL3 Gene

Residual Variation Intolerance Score: 32.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.63; 13.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for UCHL3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
UCHL3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for UCHL3 Gene

Disorders for UCHL3 Gene

Additional Disease Information for UCHL3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for UCHL3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for UCHL3 Gene

Publications for UCHL3 Gene

  1. Molecular profiling of the immune response in colon cancer using protein microarrays: occurrence of autoantibodies to ubiquitin C-terminal hydrolase L3. (PMID: 14595809) Nam MJ … Hanash SM (Proteomics 2003) 3 4 23 54
  2. Cleavage of the C-terminus of NEDD8 by UCH-L3. (PMID: 9790970) Wada H … Kamitani T (Biochemical and biophysical research communications 1998) 3 4 23 54
  3. Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. (PMID: 9233788) Johnston SC … Hill CP (The EMBO journal 1997) 3 4 23 54
  4. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. (PMID: 2530630) Wilkinson KD … Pohl J (Science (New York, N.Y.) 1989) 2 3 4 54
  5. Mutant ubiquitin (UBB+1) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3). (PMID: 21762696) Dennissen FJ … van Leeuwen FW (FEBS letters 2011) 3 4 54

Products for UCHL3 Gene

  • Addgene plasmids for UCHL3

Sources for UCHL3 Gene