UCHL1, UCHL3 (UCHL3) Antibody – Rabbit Polyclonal

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.12

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

By similarity.

Subunit structure: Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates

By similarity.

Subcellular location: Cytoplasm Ref.2 Ref.8.

Tissue specificity: Ubiquitously expressed, with highest levels in brain, liver, heart, thymus, kidney and testis. Highly expressed in the cauda epididymidis, in meiotic pachytene spermatocytes and post-meiotic spematids. In the retina, enriched in the photoreceptor inner segment. Ref.1 Ref.2 Ref.6 Ref.7

Developmental stage: Expressed at E8.5 in structures required for skeletal patterning. Highly expressed at E11, and decreases markedly from E15. Ref.1 Ref.4

Disruption phenotype: Mice have no developmental defects, are fertile, and show normal T-cell differentiation. They have normal anxiety, locomotor behavior, motor function and synaptic transmission, but show defects in spatial learning and working memory. Exhibit stress-related effects with profound apoptosis-mediated germ cell loss and also, prominent retinal degeneration with photoreceptor cell apoptosis and mitochondrial oxidative stress. Mice show reduced capacity for adipocyte differentiation and impaired insulin responses. Ref.5 Ref.6 Ref.7 Ref.10 Ref.11

Sequence similarities: Belongs to the peptidase C12 family.