UniProtKB/Swiss-Prot P09936: Variant p.Ser18Tyr

Ubiquitin carboxyl-terminal hydrolase isozyme L1
Gene: UCHL1
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Variant information Variant position:

18 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Serine (S) to Tyrosine (Y) at position 18 (S18Y, p.Ser18Tyr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from small size and polar (S) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

It confers protection from oxidative stress when expressed at physiological levels in neuroblastoma cells and primary cortical neurons; loss of dimerization ability; impaired ligase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs5030732 [ dbSNP | Ensembl ]

Sequence information Variant position:

18 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:

MQLKPMEINPEMLNKVL S RLGVAGQWRFVDVLGLEEES 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                         MQLKPMEINPEMLNKVLSRLGVAGQWRFVDVLGLEEES

Mouse                         MQLKPMEINPEMLNKVLAKLGVAGQWRFADVLGLEEET

Rat                           MQLKPMEINPEMLNKVLAKLGVAGQWRFADVLGLEEET

Pig                           MQLKPMEINPEMLNKVLTRLGVAGHWRFADVLGLEEES

Bovine                        MQLKPMEINPEMLNKVLTRLGVAGQWRFEDVLGLEEES

Horse                         MQLKPMEINPEMLNKVLARLGVAGQWRFVDVLGLEEET

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
Domain	5 – 205	UCH
Site	1 – 1	Susceptible to oxidation
Site	6 – 6	Susceptible to oxidation
Site	12 – 12	Susceptible to oxidation
Helix	10 – 19

Literature citations
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; 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; Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease.
Lincoln S.; Vaughan J.; Wood N.; Baker M.; Adamson J.; Gwinn-Hardy K.; Lynch T.; Hardy J.; Farrer M.;
NeuroReport 10:427-429(1999)
Cited for: VARIANT TYR-18; The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease.
Mellick G.D.; Silburn P.A.;
Neurosci. Lett. 293:127-130(2000)
Cited for: VARIANT TYR-18; UCHL1 is a Parkinson's disease susceptibility gene.
Maraganore D.M.; Lesnick T.G.; Elbaz A.; Chartier-Harlin M.-C.; Gasser T.; Krueger R.; Hattori N.; Mellick G.D.; Quattrone A.; Satoh J.; Toda T.; Wang J.; Ioannidis J.P.A.; de Andrade M.; Rocca W.A.;
Ann. Neurol. 55:512-521(2004)
Cited for: VARIANT TYR-18; UCHL-1 is not a Parkinson's disease susceptibility gene.
Healy D.G.; Abou-Sleiman P.M.; Casas J.P.; Ahmadi K.R.; Lynch T.; Gandhi S.; Muqit M.M.; Foltynie T.; Barker R.; Bhatia K.P.; Quinn N.P.; Lees A.J.; Gibson J.M.; Holton J.L.; Revesz T.; Goldstein D.B.; Wood N.W.;
Ann. Neurol. 59:627-633(2006)
Cited for: VARIANT TYR-18; LACK OF ASSOCIATION OF VARIANT TYR-18 WITH PARKINSON DISEASE; The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells.
Kyratzi E.; Pavlaki M.; Stefanis L.;
Hum. Mol. Genet. 17:2160-2171(2008)
Cited for: CHARACTERIZATION OF VARIANT TYR-18; ANTIOXIDANT FUNCTION IN NEURONAL CELLS; Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts.
Rudolph T.; Sjolander A.; Palmer M.S.; Minthon L.; Wallin A.; Andreasen N.; Tasa G.; Juronen E.; Blennow K.; Zetterberg H.; Zetterberg M.;
Ophthalmic Genet. 32:75-79(2011)
Cited for: VARIANT TYR-18;

Disclaimer: 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.