Human Gene UCHL3 (uc001vjq.4) Description and Page Index
  Description: Homo sapiens ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) (UCHL3), transcript variant 2, mRNA.
RefSeq Summary (NM_006002): 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].
Transcript (Including UTRs)
   Position: hg19 chr13:76,123,886-76,180,156 Size: 56,271 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg19 chr13:76,123,957-76,179,948 Size: 55,992 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr13:76,123,886-76,180,156)mRNA (may differ from genome)Protein (230 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L3; Short=UCH-L3; EC=; AltName: Full=Ubiquitin thioesterase L3;
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.
CATALYTIC ACTIVITY: 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).
ENZYME REGULATION: Inhibited by monoubiquitin and diubiquitin.
SUBUNIT: Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.
TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, and testis.
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
MISCELLANEOUS: Identified as a tumor-specific antigen in colon cancer.
SIMILARITY: Belongs to the peptidase C12 family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): UCHL3
CDC HuGE Published Literature: UCHL3
Positive Disease Associations: Fibrinogen
Related Studies:
  1. Fibrinogen
    Qiong Yang et al. BMC medical genetics 2007, Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903294]
    Using genome-wide association methodology, we have successfully identified a SNP in complete LD with a sequence variant previously shown to be strongly associated with factor VII, providing proof of principle for this approach. Further study of additional strongly associated SNPs and linked regions may identify novel variants that influence the inter-individual variability in hemostatic factors and hematological phenotypes.

-  MalaCards Disease Associations
  MalaCards Gene Search: UCHL3
Diseases sorted by gene-association score: colonic benign neoplasm (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.10 RPKM in Adrenal Gland
Total median expression: 382.43 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -37.0071-0.521 Picture PostScript Text
3' UTR -32.74208-0.157 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001578 - Peptidase_C12

Pfam Domains:
PF01088 - Ubiquitin carboxyl-terminal hydrolase, family 1

SCOP Domains:
54001 - Cysteine proteinases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P15374
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene Details  Gene DetailsGene DetailsGene Details
Gene Sorter  Gene SorterGene SorterGene Sorter
  Protein SequenceProtein SequenceProtein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004843 thiol-dependent ubiquitin-specific protease activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008234 cysteine-type peptidase activity
GO:0016787 hydrolase activity
GO:0019784 NEDD8-specific protease activity
GO:0036459 thiol-dependent ubiquitinyl hydrolase activity
GO:0043130 ubiquitin binding

Biological Process:
GO:0006508 proteolysis
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0016579 protein deubiquitination
GO:0030163 protein catabolic process
GO:0043687 post-translational protein modification

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  AK313665 - Homo sapiens cDNA, FLJ94247, Homo sapiens ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) (UCHL3), mRNA.
BC018125 - Homo sapiens ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase), mRNA (cDNA clone MGC:9190 IMAGE:3887201), complete cds.
HM005534 - Homo sapiens clone HTL-T-221 testicular tissue protein Li 221 mRNA, complete cds.
M30496 - Human ubiquitin carboxyl-terminal hydrolase (PGP 9.5, UCH-L3) isozyme L3 mRNA, complete cds.
CU676190 - Synthetic construct Homo sapiens gateway clone IMAGE:100016834 5' read UCHL3 mRNA.
HQ447110 - Synthetic construct Homo sapiens clone IMAGE:100070395; CCSB000721_01 ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) (UCHL3) gene, encodes complete protein.
KJ892351 - Synthetic construct Homo sapiens clone ccsbBroadEn_01745 UCHL3 gene, encodes complete protein.
CR456855 - Homo sapiens full open reading frame cDNA clone RZPDo834H096D for gene UCHL3, ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase); complete cds, incl. stopcodon.
BT019359 - Homo sapiens ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) mRNA, complete cds.
BC045576 - Homo sapiens cDNA clone IMAGE:4836799, **** WARNING: chimeric clone ****.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P15374 (Reactome details) participates in the following event(s):

R-HSA-8951644 Release of mature NEDD8
R-HSA-5690319 UCHL1, UCHL3 cleave ubiquitin adducts
R-HSA-5690808 UCHL3, SENP8 cleave NEDD8
R-HSA-8853503 UCHL3,USP7,USP9X cleaves RPS27A yielding ubiquitin
R-HSA-8853514 UCHL3,USP7,USP9X cleaves UBA52 yielding ubiquitin
R-HSA-8951664 Neddylation
R-HSA-5689603 UCH proteinases
R-HSA-597592 Post-translational protein modification
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-5688426 Deubiquitination
R-HSA-392499 Metabolism of proteins
R-HSA-8852135 Protein ubiquitination

-  Other Names for This Gene
  Alternate Gene Symbols: B2R970, NM_006002, NP_001257881, P15374, Q5TBK8, Q6IBE9, uc001vjq.3, UCHL3_HUMAN
UCSC ID: uc001vjq.4
RefSeq Accession: NM_006002
Protein: P15374 (aka UCHL3_HUMAN or UCL3_HUMAN)
CCDS: CCDS9453.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_006002.4
exon count: 9CDS single in 3' UTR: no RNA size: 972
ORF size: 693CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1586.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.