Ubiquitin carboxy-terminal hydrolase L1

Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)

PDB rendering based on 2etl.
Identifiers
Symbols UCHL1; PARK5; PGP 9.5; PGP9.5; PGP95; Uch-L1
External IDs OMIM: 191342 MGI: 103149 HomoloGene: 37894 GeneCards: UCHL1 Gene
EC number 3.4.19.12
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 7345 22223
Ensembl ENSG00000154277 ENSMUSG00000029223
UniProt P09936 Q3TCH2
RefSeq (mRNA) NM_004181.4 NM_011670.2
RefSeq (protein) NP_004172.2 NP_035800.2
Location (UCSC) Chr 4:
41.26 – 41.27 Mb		 Chr 5:
67.07 – 67.08 Mb
PubMed search [1] [2]

Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) (EC 3.1.2.15) is a deubiqutinating enzyme. 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.[1][2]

Contents

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.[3]

Knot structure

Human UCH-L1 and the closely related protein UCHL3 have one of 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.[4] [5]

Interactions

Ubiquitin carboxy-terminal hydrolase L1 has been shown to interact with COP9 constitutive photomorphogenic homolog subunit 5.[6]

See also

References

  1. ^ Doran JF, Jackson P, Kynoch PA, Thompson RJ (June 1983). "Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis". J. Neurochem. 40 (6): 1542–1547. doi:10.1111/j.1471-4159.1983.tb08124.x. PMID 6343558. 
  2. ^ "Entrez Gene: UCHL1 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7345. 
  3. ^ Gong B, Cao Z, Zheng P et al. (August 2006). "Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory". Cell 126 (4): 775–788. doi:10.1016/j.cell.2006.06.046. PMID 16923396. http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(06)00963-9. 
  4. ^ Peterson, Ivars (2006-10-14). "Knots in proteins". Science News. Archived from the original on 2008-04-21. http://web.archive.org/web/20080421150458/http://www.sciencenews.org/articles/20061014/mathtrek.asp. Retrieved 2008-09-11. 
  5. ^ Virnau, Peter; Leonid A Mirny, Mehran Kardar (2006-09-15). "Intricate knots in proteins: Function and evolution". PLoS Computational Biology 2 (9): e122. doi:10.1371/journal.pcbi.0020122. PMC 1570178. PMID 16978047. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1570178. 
  6. ^ Caballero, Otávia L; Resto Vicente, Patturajan Meera, Meerzaman Daoud, Guo Ming Zhou, Engles James, Yochem Robert, Ratovitski Edward, Sidransky David, Jen Jin (May. 2002). "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)". Oncogene (England) 21 (19): 3003–3010. doi:10.1038/sj.onc.1205390. ISSN 0950-9232. PMID 12082530. 

Further reading

  • Healy DG, Abou-Sleiman PM, Wood NW (2005). "Genetic causes of Parkinson's disease: UCHL-1". Cell Tissue Res. 318 (1): 189–194. doi:10.1007/s00441-004-0917-3. PMID 15221445. 
  • Rasmussen HH, van Damme J, Puype M et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis 13 (12): 960–969. doi:10.1002/elps.11501301199. PMID 1286667. 
  • Edwards YH, Fox MF, Povey S et al. (1992). "The gene for human neurone specific ubiquitin C-terminal hydrolase (UCHL1, PGP9.5) maps to chromosome 4p14". Ann. Hum. Genet. 55 (Pt 4): 273–278. doi:10.1111/j.1469-1809.1991.tb00853.x. PMID 1840236. 
  • Honoré B, Rasmussen HH, Vandekerckhove J, Celis JE (1991). "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 (2): 235–240. doi:10.1016/0014-5793(91)80300-R. PMID 1849484. 
  • Day IN, Hinks LJ, Thompson RJ (1990). "The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase". Biochem. J. 268 (2): 521–4. PMC 1131465. PMID 2163617. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1131465. 
  • Day IN, Thompson RJ (1987). "Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells". FEBS Lett. 210 (2): 157–160. doi:10.1016/0014-5793(87)81327-3. PMID 2947814. 
  • Doran JF, Jackson P, Kynoch PA, Thompson RJ (1983). "Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis". J. Neurochem. 40 (6): 1542–1547. doi:10.1111/j.1471-4159.1983.tb08124.x. PMID 6343558. 
  • Onno M, Nakamura T, Mariage-Samson R et al. (1993). "Human TRE17 oncogene is generated from a family of homologous polymorphic sequences by single-base changes". DNA Cell Biol. 12 (2): 107–118. doi:10.1089/dna.1993.12.107. PMID 8471161. 
  • Larsen CN, Price JS, Wilkinson KD (1996). "Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues". Biochemistry 35 (21): 6735–6744. doi:10.1021/bi960099f. PMID 8639624. 
  • Best CL, Pudney J, Welch WR et al. (1996). "Localization and characterization of white blood cell populations within the human ovary throughout the menstrual cycle and menopause". Hum. Reprod. 11 (4): 790–7. PMID 8671330. 
  • D'Andrea V, Malinovsky L, Berni A et al. (1998). "The immunolocalization of PGP 9.5 in normal human kidney and renal cell carcinoma". Il Giornale di chirurgia 18 (10): 521–4. PMID 9435142. 
  • Larsen CN, Krantz BA, Wilkinson KD (1998). "Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases". Biochemistry 37 (10): 3358–3368. doi:10.1021/bi972274d. PMID 9521656. 
  • Leroy E, Boyer R, Auburger G et al. (1998). "The ubiquitin pathway in Parkinson's disease". Nature 395 (6701): 451–452. doi:10.1038/26652. PMID 9774100. 
  • Wada H, Kito K, Caskey LS et al. (1998). "Cleavage of the C-terminus of NEDD8 by UCH-L3". Biochem. Biophys. Res. Commun. 251 (3): 688–692. doi:10.1006/bbrc.1998.9532. PMID 9790970. 
  • Leroy E, Boyer R, Polymeropoulos MH (1999). "Intron-exon structure of ubiquitin c-terminal hydrolase-L1". DNA Res. 5 (6): 397–400. doi:10.1093/dnares/5.6.397. PMID 10048490. 
  • Lincoln S, Vaughan J, Wood N et al. (1999). "Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease". Neuroreport 10 (2): 427–429. doi:10.1097/00001756-199902050-00040. PMID 10203348. 
  • Harhangi BS, Farrer MJ, Lincoln S et al. (1999). "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): 1–4. doi:10.1016/S0304-3940(99)00465-6. PMID 10454131. 
  • Saigoh K, Wang YL, Suh JG et al. (1999). "Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice". Nat. Genet. 23 (1): 47–51. doi:10.1038/12647. PMID 10471497. 
  • Mellick GD, Silburn PA (2000). "The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease". Neurosci. Lett. 293 (2): 127–130. doi:10.1016/S0304-3940(00)01510-X. PMID 11027850. 
  • Sharma N, McLean PJ, Kawamata H et al. (2002). "Alpha-synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodies". Acta Neuropathol. 102 (4): 329–34. PMID 11603807. 

External links

3.1.1: Carboxylic ester hydrolases
3.1.2: Thioesterase
Palmitoyl protein thioesterase · Ubiquitin carboxy-terminal hydrolase L1
3.1.3: Phosphatase
3.1.4: Phosphodiesterase
3.1.6: Sulfatase
Nuclease (includes
deoxyribonuclease and
ribonuclease)
either deoxy- or ribo-
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6