Sequence information
Variant position: 93 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 223 The length of the canonical sequence.
Location on the sequence:
QEVSPKVYFMKQTIGNSCGT
I GLIHAVANNQDKLGFEDGSV
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLGFEDGSV
Mouse QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLEFEDGSV
Rat QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLEFEDGSV
Pig QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLEFEDGSV
Bovine QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLEFEDGSV
Horse QEVSPKVYFMKQTIGNSCGTI GLIHAVANNQDKLEFEDGSV
Sequence annotation in neighborhood: The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:Type: the type of sequence feature. Positions: endpoints of the sequence feature. Description: contains additional information about the feature.
Type Positions Description
Chain
1 – 220
Ubiquitin carboxyl-terminal hydrolase isozyme L1
Active site
90 – 90
Nucleophile
Mutagenesis
73 – 73
Q -> R. No effect on enzymatic parameters.
Mutagenesis
90 – 90
C -> S. Abolishes enzymatic activity.
Mutagenesis
97 – 97
H -> QN. 2-fold increase in affinity for ubiquitin ethyl ester, slight reduction in enzymatic activity.
Helix
90 – 100
Literature citations
The ubiquitin pathway in Parkinson's disease.
Leroy E.; Boyer R.; Auburger G.; Leube B.; Ulm G.; Mezey E.; Harta G.; Brownstein M.J.; Jonnalagada S.; Chernova T.; Dehejia A.; Lavedan C.; Gasser T.; Steinbach P.J.; Wilkinson K.D.; Polymeropoulos M.H.;
Nature 395:451-452(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-223; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; VARIANT PARK5 MET-93; CHARACTERIZATION OF VARIANT PARK5 MET-93;
The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility.
Liu Y.; Fallon L.; Lashuel H.A.; Liu Z.; Lansbury P.T. Jr.;
Cell 111:209-218(2002)
Cited for: FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT PARK5 MET-93; CHARACTERIZATION OF VARIANT TYR-18;
Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration.
Bilguvar K.; Tyagi N.K.; Ozkara C.; Tuysuz B.; Bakircioglu M.; Choi M.; Delil S.; Caglayan A.O.; Baranoski J.F.; Erturk O.; Yalcinkaya C.; Karacorlu M.; Dincer A.; Johnson M.H.; Mane S.; Chandra S.S.; Louvi A.; Boggon T.J.; Lifton R.P.; Horwich A.L.; Gunel M.;
Proc. Natl. Acad. Sci. U.S.A. 110:3489-3494(2013)
Cited for: FUNCTION; CATALYTIC ACTIVITY; VARIANTS SPG79 ALA-7 AND MET-93; CHARACTERIZATION OF VARIANT SPG79 ALA-7; MUTAGENESIS OF CYS-90;
Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation.
Boudreaux D.A.; Maiti T.K.; Davies C.W.; Das C.;
Proc. Natl. Acad. Sci. U.S.A. 107:9117-9122(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF VARIANTS TYR-18 AND MET-93 IN COMPLEX WITH UBIQUITIN; CATALYTIC ACTIVITY; ACTIVE SITE; MUTAGENESIS OF CYS-90 AND PHE-204;
Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants.
Nishikawa K.; Li H.; Kawamura R.; Osaka H.; Wang Y.-L.; Hara Y.; Hirokawa T.; Manago Y.; Amano T.; Noda M.; Aoki S.; Wada K.;
Biochem. Biophys. Res. Commun. 304:176-183(2003)
Cited for: CHARACTERIZATION OF VARIANT PARK5 MET-93; CHARACTERIZATION OF VARIANT TYR-18; MUTAGENESIS OF CYS-90; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES;
The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease.
Harhangi B.S.; Farrer M.J.; Lincoln S.; Bonifati V.; Meco G.; De Michele G.; Brice A.; Durr A.; Martinez M.; Gasser T.; Bereznai B.; Vaughan J.R.; Wood N.W.; Hardy J.; Oostra B.A.; Breteler M.M.;
Neurosci. Lett. 270:1-4(1999)
Cited for: VARIANT MET-93;
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Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.