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
ID:UCHL3_HUMAN DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L3; Short=UCH-L3; EC=22.214.171.124; 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. SUBCELLULAR LOCATION: Cytoplasm. 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:
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.
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.
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.
ModBase Predicted Comparative 3D Structure on P15374
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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.