Ubiquitin carboxy-terminal hydrolase L1

Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) (EC number|3.1.2.15) is a deubiqutinating enzyme. PBB_Summary
section_title =
summary_text = 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 (Doran et al., 1983). [supplied by OMIM] cite web | title = Entrez Gene: UCHL1 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7345| accessdate = ]

Pathology

A point mutation (I93M) in the gene encoding this protein is implicated as the cause of Parkinson's disease in one kindred.

Furthermore, a polymorphism (S18Y) in this gene has been found to be associated with a reduced risk for Parkinson's disease.

The gene is also associated with the Alzheimer's disease, and required for normal synaptic and cognitive function. (Gong. et al 2006) [Gong,B, Cao,Z Zheng,P, Vitolo,O.P, Liu,S Staniszewski,A, Moolman,D Zhang,H Shelanski,M, and Arancio,O "Ubiquitin Hydrolase Uch-L1 Rescues β-Amyloid-Induced Decreases in Synaptic Function and Contextual Memory", Cell, Vol 126, 775-788, 25 August 2006]

Knot structure

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. [cite web
last = Peterson
first = Ivars
title = Knots in proteins
publisher = Science News
date = 2006-10-14
url = http://www.sciencenews.org/articles/20061014/mathtrek.asp
accessdate = 2008-09-11] [Cite journal
doi = 10.1371/journal.pcbi.0020122
volume = 2
issue = 9
pages = e122
last = Virnau
first = Peter
coauthors = Leonid A Mirny, Mehran Kardar
title = Intricate knots in proteins: Function and evolution
journal = PLoS Computational Biology
date = 2006-09-15
url = http://www.ncbi.nlm.nih.gov/pubmed/16978047]

ee also

* Ubiquitin carboxyl-terminal esterase L3 -- the gene UCHL3

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Healy DG, Abou-Sleiman PM, Wood NW |title=Genetic causes of Parkinson's disease: UCHL-1 |journal=Cell Tissue Res. |volume=318 |issue= 1 |pages= 189–94 |year= 2005 |pmid= 15221445 |doi= 10.1007/s00441-004-0917-3
*cite journal | author=Rasmussen HH, van Damme J, Puype M, "et al." |title=Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes |journal=Electrophoresis |volume=13 |issue= 12 |pages= 960–9 |year= 1993 |pmid= 1286667 |doi=
*cite journal | author=Edwards YH, Fox MF, Povey S, "et al." |title=The gene for human neurone specific ubiquitin C-terminal hydrolase (UCHL1, PGP9.5) maps to chromosome 4p14 |journal=Ann. Hum. Genet. |volume=55 |issue= Pt 4 |pages= 273–8 |year= 1992 |pmid= 1840236 |doi=
*cite journal | author=Honoré B, Rasmussen HH, Vandekerckhove J, Celis JE |title=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 |journal=FEBS Lett. |volume=280 |issue= 2 |pages= 235–40 |year= 1991 |pmid= 1849484 |doi= 10.1016/0014-5793(91)80300-R
*cite journal | author=Day IN, Hinks LJ, Thompson RJ |title=The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase |journal=Biochem. J. |volume=268 |issue= 2 |pages= 521–4 |year= 1990 |pmid= 2163617 |doi=
*cite journal | author=Day IN, Thompson RJ |title=Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells |journal=FEBS Lett. |volume=210 |issue= 2 |pages= 157–60 |year= 1987 |pmid= 2947814 |doi= 10.1016/0014-5793(87)81327-3
*cite journal | author=Doran JF, Jackson P, Kynoch PA, Thompson RJ |title=Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis |journal=J. Neurochem. |volume=40 |issue= 6 |pages= 1542–7 |year= 1983 |pmid= 6343558 |doi= 10.1111/j.1471-4159.1983.tb08124.x
*cite journal | author=Onno M, Nakamura T, Mariage-Samson R, "et al." |title=Human TRE17 oncogene is generated from a family of homologous polymorphic sequences by single-base changes |journal=DNA Cell Biol. |volume=12 |issue= 2 |pages= 107–18 |year= 1993 |pmid= 8471161 |doi=
*cite journal | author=Larsen CN, Price JS, Wilkinson KD |title=Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues |journal=Biochemistry |volume=35 |issue= 21 |pages= 6735–44 |year= 1996 |pmid= 8639624 |doi= 10.1021/bi960099f
*cite journal | author=Best CL, Pudney J, Welch WR, "et al." |title=Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause |journal=Hum. Reprod. |volume=11 |issue= 4 |pages= 790–7 |year= 1996 |pmid= 8671330 |doi=
*cite journal | author=D'Andrea V, Malinovsky L, Berni A, "et al." |title=The immunolocalization of PGP 9.5 in normal human kidney and renal cell carcinoma |journal=Il Giornale di chirurgia |volume=18 |issue= 10 |pages= 521–4 |year= 1998 |pmid= 9435142 |doi=
*cite journal | author=Larsen CN, Krantz BA, Wilkinson KD |title=Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases |journal=Biochemistry |volume=37 |issue= 10 |pages= 3358–68 |year= 1998 |pmid= 9521656 |doi= 10.1021/bi972274d
*cite journal | author=Leroy E, Boyer R, Auburger G, "et al." |title=The ubiquitin pathway in Parkinson's disease |journal=Nature |volume=395 |issue= 6701 |pages= 451–2 |year= 1998 |pmid= 9774100 |doi= 10.1038/26652
*cite journal | author=Wada H, Kito K, Caskey LS, "et al." |title=Cleavage of the C-terminus of NEDD8 by UCH-L3 |journal=Biochem. Biophys. Res. Commun. |volume=251 |issue= 3 |pages= 688–92 |year= 1998 |pmid= 9790970 |doi= 10.1006/bbrc.1998.9532
*cite journal | author=Leroy E, Boyer R, Polymeropoulos MH |title=Intron-exon structure of ubiquitin c-terminal hydrolase-L1 |journal=DNA Res. |volume=5 |issue= 6 |pages= 397–400 |year= 1999 |pmid= 10048490 |doi=
*cite journal | author=Lincoln S, Vaughan J, Wood N, "et al." |title=Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease |journal=Neuroreport |volume=10 |issue= 2 |pages= 427–9 |year= 1999 |pmid= 10203348 |doi= 10.1097/00001756-199902050-00040
*cite journal | author=Harhangi BS, Farrer MJ, Lincoln S, "et al." |title=The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease |journal=Neurosci. Lett. |volume=270 |issue= 1 |pages= 1–4 |year= 1999 |pmid= 10454131 |doi= 10.1016/S0304-3940(99)00465-6
*cite journal | author=Saigoh K, Wang YL, Suh JG, "et al." |title=Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice |journal=Nat. Genet. |volume=23 |issue= 1 |pages= 47–51 |year= 1999 |pmid= 10471497 |doi= 10.1038/12647
*cite journal | author=Mellick GD, Silburn PA |title=The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease |journal=Neurosci. Lett. |volume=293 |issue= 2 |pages= 127–30 |year= 2000 |pmid= 11027850 |doi= 10.1016/S0304-3940(00)01510-X
*cite journal | author=Sharma N, McLean PJ, Kawamata H, "et al." |title=Alpha-synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodies |journal=Acta Neuropathol. |volume=102 |issue= 4 |pages= 329–34 |year= 2002 |pmid= 11603807 |doi=

External links

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