Ubiquitin Carboxyl Terminal Hydrolase L1 (UCHL1)

PARK5; PGP9.5; Uch-L1; Neuron cytoplasmic protein 9.5; Ubiquitin thioesterase L1; Ubiquitin carboxyl-terminal hydrolase isozyme L1

SPN	P801
HGNC	12513
MGI	103149
PubMed	23064229
RGD	3928
UniProt	P09936
Wiki	UCHL1

UCHL1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. It is present in all neurons.

Human UCH-L1 and the closely related protein UCHL3 have the most complicated knot structure yet discovered for a protein, with five knot crossings. It is speculated that a knot structure may increase a protein's resistance to degradation in the proteasome.Ubiquitin carboxy-terminal hydrolase L1 has been shown to interact with COP9 constitutive photomorphogenic homolog subunit 5.

Reference

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase."
Biochem. J. 268:521-524(1990) [PubMed] [Europe PMC] [Abstract]

"Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases."
J. Biol. Chem. 279:13256-13264(2004) [PubMed] [Europe PMC] [Abstract]

, Submitted (DEC-2008) to UniProtKB

"Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells."
FEBS Lett. 210:157-160(1987) [PubMed] [Europe PMC] [Abstract]

"The ubiquitin pathway in Parkinson's disease."
Nature 395:451-452(1998) [PubMed] [Europe PMC] [Abstract]

"Neuronal protein gene product 9.5 (IEF SSP 6104) is expressed in cultured human MRC-5 fibroblasts of normal origin and is strongly down-regulated in their SV40 transformed counterparts."
FEBS Lett. 280:235-240(1991) [PubMed] [Europe PMC] [Abstract]

"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]

"Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues."
Biochemistry 35:6735-6744(1996) [PubMed] [Europe PMC] [Abstract]

"Cleavage of the C-terminus of NEDD8 by UCH-L3."
Biochem. Biophys. Res. Commun. 251:688-692(1998) [PubMed] [Europe PMC] [Abstract]

"The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility."
Cell 111:209-218(2002) [PubMed] [Europe PMC] [Abstract]

"Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)."
Oncogene 21:3003-3010(2002) [PubMed] [Europe PMC] [Abstract]

"Mechanistic studies of ubiquitin C-terminal hydrolase L1."
Biochemistry 45:2443-2452(2006) [PubMed] [Europe PMC] [Abstract]

"Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease."
Proc. Natl. Acad. Sci. U.S.A. 106:4635-4640(2009) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1."
Proc. Natl. Acad. Sci. U.S.A. 103:4675-4680(2006) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation."
Proc. Natl. Acad. Sci. U.S.A. 107:9117-9122(2010) [PubMed] [Europe PMC] [Abstract]

"Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants."
Biochem. Biophys. Res. Commun. 304:176-183(2003) [PubMed] [Europe PMC] [Abstract]

"The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease."
Neurosci. Lett. 270:1-4(1999) [PubMed] [Europe PMC] [Abstract]

"Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease."
NeuroReport 10:427-429(1999) [PubMed] [Europe PMC] [Abstract]

"The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease."
Neurosci. Lett. 293:127-130(2000) [PubMed] [Europe PMC] [Abstract]

"UCHL1 is a Parkinson's disease susceptibility gene."
Ann. Neurol. 55:512-521(2004) [PubMed] [Europe PMC] [Abstract]

Erratum
Ann. Neurol. 55:899-899(2004)

"UCHL-1 is not a Parkinson's disease susceptibility gene."
Ann. Neurol. 59:627-633(2006) [PubMed] [Europe PMC] [Abstract]

"The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells."
Hum. Mol. Genet. 17:2160-2171(2008) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts."
Ophthalmic Genet. 32:75-79(2011) [PubMed] [Europe PMC] [Abstract]

"Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration."
Proc. Natl. Acad. Sci. U.S.A. 110:3489-3494(2013) [PubMed] [Europe PMC] [Abstract]