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Chen, H. UCHL1 Gene. Encyclopedia. Available online: https://encyclopedia.pub/entry/4047 (accessed on 20 April 2024).
Chen H. UCHL1 Gene. Encyclopedia. Available at: https://encyclopedia.pub/entry/4047. Accessed April 20, 2024.
Chen, Hongliu. "UCHL1 Gene" Encyclopedia, https://encyclopedia.pub/entry/4047 (accessed April 20, 2024).
Chen, H. (2020, December 23). UCHL1 Gene. In Encyclopedia. https://encyclopedia.pub/entry/4047
Chen, Hongliu. "UCHL1 Gene." Encyclopedia. Web. 23 December, 2020.
UCHL1 Gene
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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/uchl1

Ubiquitin C-terminal hydrolase L1.

genes

1. Normal Function

The UCHL1 gene provides instructions for making an enzyme called ubiquitin carboxyl-terminal esterase L1. This enzyme is found in nerve cells throughout the brain. Ubiquitin carboxyl-terminal esterase L1 is probably involved in the cell machinery that breaks down (degrades) unneeded proteins. In cells, damaged or excess proteins are tagged with molecules called ubiquitin. Ubiquitin serves as a signal to move these unneeded proteins into specialized structures known as proteasomes, where the proteins are degraded. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins.

Although the exact function of ubiquitin carboxyl-terminal esterase L1 is not fully understood, it appears to have two types of enzyme activity. One of these, called hydrolase activity, removes and recycles ubiquitin molecules from degraded proteins. This recycling step is important to sustain the degradation process. The other enzyme function, known as ligase activity, links together ubiquitin molecules for use in tagging proteins for disposal.

2. Health Conditions Related to Genetic Changes

2.1. Parkinson Disease

A relatively common variation (polymorphism) in the UCHL1 gene may reduce the risk of developing Parkinson disease, a condition characterized by progressive problems with movement and balance. The variation leads to a change in one of the building blocks (amino acids) used to make ubiquitin carboxyl-terminal esterase L1. Instead of serine at position 18 in the enzyme's chain of amino acids, people with the polymorphism have the amino acid tyrosine (written as Ser18Tyr or S18Y). This change is most common in Chinese and Japanese populations and occurs less frequently in European populations. The polymorphism reduces the ligase activity of ubiquitin carboxyl-terminal esterase L1 but has little effect on the hydrolase activity. Some studies suggest that having the S18Y polymorphism may help protect against Parkinson disease, particularly in young adults. However, other studies have not shown this effect. It remains unclear how this amino acid variation might reduce the risk of developing Parkinson disease.

A different change in the UCHL1 gene may increase the risk of Parkinson disease. This mutation has been reported in two siblings with the disease. The mutation replaces the amino acid isoleucine with the amino acid methionine at position 93 in ubiquitin carboxyl-terminal esterase L1 (written as Ile93Met or I93M). The mutation leads to decreased hydrolase activity, which may disrupt the ubiquitin-proteasome system. Instead of being degraded, unneeded proteins could accumulate to toxic levels that impair or kill nerve cells in the brain. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement. It is unclear whether this UCHL1 gene mutation is a true risk factor for Parkinson disease, because it has been identified in only one family.

3. Other Names for This Gene

  • MSY1

  • neuron cytoplastic protein 9.5

  • PARK5

  • PGP9.5

  • ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)

  • ubiquitin thiolesterase

  • UBL1

  • UCHL-1

  • UCHL1_HUMAN

References

  1. Facheris M, Strain KJ, Lesnick TG, de Andrade M, Bower JH, Ahlskog JE,Cunningham JM, Lincoln S, Farrer MJ, Rocca WA, Maraganore DM. UCHL1 is associatedwith Parkinson's disease: a case-unaffected sibling and case-unrelated controlstudy. Neurosci Lett. 2005 Jun 10-17;381(1-2):131-4.
  2. Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM,Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, Wood NW. UCHL-1 is not a Parkinson's disease susceptibilitygene. Ann Neurol. 2006 Apr;59(4):627-33.
  3. Hutter CM, Samii A, Factor SA, Nutt JG, Higgins DS, Bird TD, Griffith A,Roberts JW, Leis BC, Montimurro JS, Kay DM, Edwards KL, Payami H, Zabetian CP.Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease.Eur J Neurol. 2008 Feb;15(2):134-9.
  4. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodestwo opposing enzymatic activities that affect alpha-synuclein degradation andParkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18.
  5. Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Krüger R,Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, deAndrade M, Rocca WA; UCHL1 Global Genetics Consortium. UCHL1 is a Parkinson'sdisease susceptibility gene. Ann Neurol. 2004 Apr;55(4):512-21. Erratum in: AnnNeurol. 2004 Jun;55(6):899. Toda, Taksushi [corrected to Toda, Tatsushi].
  6. Ragland M, Hutter C, Zabetian C, Edwards K. Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y variant and Parkinson's Disease: a HuGE review and meta-analysis. Am J Epidemiol. 2009 Dec 1;170(11):1344-57. doi:10.1093/aje/kwp288.
  7. Tan EK, Puong KY, Fook-Chong S, Chua E, Shen H, Yuen Y, Pavanni R, Wong MC,Puvan K, Zhao Y. Case-control study of UCHL1 S18Y variant in Parkinson's disease.Mov Disord. 2006 Oct;21(10):1765-8.
  8. Wintermeyer P, Krüger R, Kuhn W, Müller T, Woitalla D, Berg D, Becker G, LeroyE, Polymeropoulos M, Berger K, Przuntek H, Schöls L, Epplen JT, Riess O. Mutationanalysis and association studies of the UCHL1 gene in German Parkinson's disease patients. Neuroreport. 2000 Jul 14;11(10):2079-82.
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Subjects: Genetics & Heredity
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Hongliu Chen
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Update Date: 23 Dec 2020
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