General Information of Drug Therapeutic Target (DTT) (ID: TT23UD6)

DTT Name Ubiquitin thioesterase L3 (UCHL3)
Synonyms Ubiquitin carboxyl-terminal hydrolase isozyme L3; UCH-L3
Gene Name UCHL3
DTT Type
Literature-reported target
[1]
BioChemical Class
Peptidase
UniProt ID
UCHL3_HUMAN
TTD ID
T77181
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.4.19.12
Sequence
MEGQRWLPLEANPEVTNQFLKQLGLHPNWQFVDVYGMDPELLSMVPRPVCAVLLLFPITE
KYEVFRTEEEEKIKSQGQDVTSSVYFMKQTISNACGTIGLIHAIANNKDKMHFESGSTLK
KFLEESVSMSPEERARYLENYDAIRVTHETSAHEGQTEAPSIDEKVDLHFIALVHVDGHL
YELDGRKPFPINHGETSDETLLEDAIEVCKKFMERDPDELRFNAIALSAA
Function
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. Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins.
Reactome Pathway
Synthesis of active ubiquitin (R-HSA-8866652 )
Neddylation (R-HSA-8951664 )
UCH proteinases (R-HSA-5689603 )

References

1 Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's diseas... Clin Chim Acta. 2010 Jul 4;411(13-14):955-8.