UCHL3

UCHL3 is deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. UCHL3 is thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. UCHL3 has a 10-fold preference for Arg and Lys at position P3". Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. UCHL3 indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. UCHL3 is required for stress-response retinal, skeletal muscle and germ cell maintenance. UCHL3 may be involved in working memory. UCHL3 can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.

UCHL3 Related Areas

Neuroscience>>Neurodegenerative Disease>>Ubiquitin-proteasome pathway>>UCHL3

UCHL3 Alternative Names

UCHL3, UCH-L3, RP11-173B14.3 [Homo sapiens]

Uchl3, UCH-L3 [Mus musculus]

Summaries for UCHL3

Wikipedia summary for UCHL3:

Ubiquitin carboxyl-terminal hydrolase isozyme L3 is an enzyme that in humans is encoded by the UCHL3 gene.

Human UCHL3 Protein General Information

 

• Protein names: Ubiquitin carboxyl-terminal hydrolase isozyme L3
  Short name=UCHL3
• Sequence length: 230 AA.
• Enzyme regulation: Inhibited by monoubiquitin and diubiquitin.
• Sequence similarities: Belongs to the peptidase C12 family.
• Post-translational modification: Phosphorylated upon DNA damage, probably by ATM or ATR.
• Subunit structure: 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.
• 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).
• Miscellaneous: Identified as a tumor-specific antigen in colon cancer.

General information above from UniProt

Function for UCHL3 Protein

UniProtKB:

UCHL3 is deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. UCHL3 is thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. UCHL3 has a 10-fold preference for Arg and Lys at position P3". Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. UCHL3 indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. UCHL3 is required for stress-response retinal, skeletal muscle and germ cell maintenance. UCHL3 may be involved in working memory. UCHL3 can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.

Genatlas:

• UCHL3 is involved both in the processing of ubiquitin precursors and of ubiquinated proteins
• UCHL3 is required to maintain a stable apical membrane ENaC (epithelial sodium channel) population by facilitating the dynamic recycling of ENaC at the apical surface
• UCHL3 regulates the apical membrane recycling of the epithelial sodium channel
• UCHL3 may promotes adipogenesis by enhancing insulin signaling in a hydrolase activity-dependent manner
• UCHL3 has potential functions as a de-ubiquitinating enzyme where lack of its hydrolase activity may result in the prominent accumulation of ubiquitinated proteins and subsequent induction of stress responses in skeletal muscle
• UCHL3 is deubiquitinating enzyme, upregulated in BMP2-induced osteoblast differentiation
• UCHL3 enhances osteoblast differentiation through the stabilization of SMAD1 signaling, acting to fine-tune the process of SMAD1 activation
• Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development

Homology for human UCHL3

• homolog to murine Uchl3 and Uchl4
• homolog to UCHL1