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ubiquitin thiolesterase L1; ubiquitin C-terminal hydrolase L1; UCH-L1; neuron cytoplasmic protein 9.5 (UCHL1, PARK5)
Function:
- ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors & of ubiquitinated proteins
- thiol protease that recognizes & hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin
- in contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8
- binding to free monoubiquitin may prevent its degradation in lysosomes
- homodimer may have ATP-independent ubiquitin ligase activity
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C- terminal Gly of ubiquitin
- interacts with SNCA (putative)
- interacts with COPS5
Kinetic parameters:
- KM=122 nM for Ub-AMC
- KM=1.20 uM for ubiquitin ethyl ester
- Vmax=0.47 umol/min/mg enzyme toward Ub-AMC
- Vmax=25 umol/min/mg enzyme toward ubiquitin ethyl ester
Structure:
- homodimer
- O-glycosylated (putative)
- belongs to the peptidase C12 family
Compartment: cytoplasm
Expression:
- found in neuronal cell bodies & processes throughout the neocortex (at protein level)
- expressed in neurons & cells of the neuroendocrine system & their tumors
- weakly expressed in ovary
Pathology:
- oxidation of Met-1, Met-6, Met-12, Met-124 & Met-179 to methionine sulfoxide, & oxidation of Cys-220 to cysteine sulfonic acid have been observed in brains from patients with Alzheimer disease (AD) & Parkinson disease (PD)
- in AD, UCHL1 was found to be associated with neurofibrillary tangles
Related
ubiquitin (UBCEP2, UBB, UBC)
General
ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme
Properties
SIZE: entity length = 223 aa
MW = 25 kD
COMPARTMENT: cytoplasm
MOTIF: methionine residue {1}
methionine residue {6}
methionine residue {12}
Ubiquitin binding 1 {37-54}
cysteine residue {C90}
methionine residue {124}
histidine residue {H161}
Ubiquitin binding 2 {170-178}
MOTIF: aspartate residue {D176}
methionine residue {179}
cysteine residue {220}
Database Correlations
OMIM 191342
UniProt P09936
Pfam PF01088
Kegg hsa:7345
References
- UniProt :accession P09936
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=UCHL1
- Wikipedia; Note: ubiquitin carboxy-terminal hydrolase L1 entry
http://en.wikipedia.org/wiki/ubiquitin_carboxy-terminal_hydrolase_L1