Ubiquitin carboxyl-terminal hydrolase isozyme L1

Details

Name
Ubiquitin carboxyl-terminal hydrolase isozyme L1
Synonyms
  • 3.4.19.12
  • Neuron cytoplasmic protein 9.5
  • PGP 9.5
  • PGP9.5
  • Ubiquitin thioesterase L1
  • UCH-L1
Gene Name
UCHL1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009794|Ubiquitin carboxyl-terminal hydrolase isozyme L1
MQLKPMEINPEMLNKVLSRLGVAGQWRFVDVLGLEEESLGSVPAPACALLLLFPLTAQHE
NFRKKQIEELKGQEVSPKVYFMKQTIGNSCGTIGLIHAVANNQDKLGFEDGSVLKQFLSE
TEKMSPEDRAKCFEKNEAIQAAHDAVAQEGQCRVDDKVNFHFILFNNVDGHLYELDGRMP
FPVNHGASSEDTLLKDAAKVCREFTEREQGEVRFSAVALCKAA
Number of residues
223
Molecular Weight
24824.17
Theoretical pI
Not Available
GO Classification
Functions
alpha-2A adrenergic receptor binding / cysteine-type endopeptidase activity / ligase activity / omega peptidase activity / ubiquitin binding / ubiquitin protein ligase binding / ubiquitin-specific protease activity
Processes
adult walking behavior / axon target recognition / axon transport of mitochondrion / cell proliferation / eating behavior / muscle fiber development / negative regulation of MAP kinase activity / neuromuscular process / proteasome-mediated ubiquitin-dependent protein catabolic process / protein deubiquitination / response to ischemia / sensory perception of pain
Components
axon / cytoplasm / cytosol / endoplasmic reticulum membrane / extracellular exosome / myelin sheath / neuron projection terminus / neuronal cell body / nucleoplasm
General Function
Ubiquitin-specific protease activity
Specific Function
Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020904|Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1)
ATGCAGCTCAAGCCGATGGAGATCAACCCCGAGATGCTGAACAAAGTGCTGTCCCGGCTG
GGGGTCGCCGGCCAGTGGCGCTTCGTGGACGTGCTGGGGCTGGAAGAGGAGTCTCTGGGC
TCGGTGCCAGCGCCTGCCTGCGCGCTGCTGCTGCTGTTTCCCCTCACGGCCCAGCATGAG
AACTTCAGGAAAAAGCAGATTGAAGAGCTGAAGGGACAAGAAGTTAGTCCTAAAGTGTAC
TTCATGAAGCAGACCATTGGGAATTCCTGTGGCACAATCGGACTTATTCACGCAGTGGCC
AATAATCAAGACAAACTGGGATTTGAGGATGGATCAGTTCTGAAACAGTTTCTTTCTGAA
ACAGAGAAAATGTCCCCTGAAGACAGAGCAAAATGCTTTGAAAAGAATGAGGCCATACAG
GCAGCCCATGATGCCGTGGCACAGGAAGGCCAATGTCGGGTAGATGACAAGGTGAATTTC
CATTTTATTCTGTTTAACAACGTGGATGGCCACCTCTATGAACTTGATGGACGAATGCCT
TTTCCGGTGAACCATGGCGCCAGTTCAGAGGACACCCTGCTGAAGGACGCTGCCAAGGTC
TGCAGAGAATTCACCGAGCGTGAGCAAGGAGAAGTCCGCTTCTCTGCCGTGGCTCTCTGC
AAGGCAGCCTAA
Chromosome Location
4
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP09936
UniProtKB Entry NameUCHL1_HUMAN
HGNC IDHGNC:12513
General References
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  3. Day IN, Hinks LJ, Thompson RJ: The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase. Biochem J. 1990 Jun 1;268(2):521-4. [Article]
  4. Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin LS, Li L: Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases. J Biol Chem. 2004 Mar 26;279(13):13256-64. Epub 2004 Jan 13. [Article]
  5. Day IN, Thompson RJ: Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells. FEBS Lett. 1987 Jan 5;210(2):157-60. [Article]
  6. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH: The ubiquitin pathway in Parkinson's disease. Nature. 1998 Oct 1;395(6701):451-2. [Article]
  7. Honore B, Rasmussen HH, Vandekerckhove J, Celis JE: 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. 1991 Mar 25;280(2):235-40. [Article]
  8. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. Electrophoresis. 1992 Dec;13(12):960-9. [Article]
  9. Larsen CN, Price JS, Wilkinson KD: Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues. Biochemistry. 1996 May 28;35(21):6735-44. [Article]
  10. Wada H, Kito K, Caskey LS, Yeh ET, Kamitani T: Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochem Biophys Res Commun. 1998 Oct 29;251(3):688-92. [Article]
  11. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr: The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18. [Article]
  12. Caballero OL, Resto V, Patturajan M, Meerzaman D, Guo MZ, Engles J, Yochem R, Ratovitski E, Sidransky D, Jen J: Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Oncogene. 2002 May 2;21(19):3003-10. [Article]
  13. Case A, Stein RL: Mechanistic studies of ubiquitin C-terminal hydrolase L1. Biochemistry. 2006 Feb 21;45(7):2443-52. [Article]
  14. Liu Z, Meray RK, Grammatopoulos TN, Fredenburg RA, Cookson MR, Liu Y, Logan T, Lansbury PT Jr: 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. 2009 Mar 24;106(12):4635-40. doi: 10.1073/pnas.0806474106. Epub 2009 Mar 4. [Article]
  15. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  17. Das C, Hoang QQ, Kreinbring CA, Luchansky SJ, Meray RK, Ray SS, Lansbury PT, Ringe D, Petsko GA: Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4675-80. Epub 2006 Mar 13. [Article]
  18. Boudreaux DA, Maiti TK, Davies CW, Das C: 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. 2010 May 18;107(20):9117-22. doi: 10.1073/pnas.0910870107. Epub 2010 May 3. [Article]
  19. Nishikawa K, Li H, Kawamura R, Osaka H, Wang YL, Hara Y, Hirokawa T, Manago Y, Amano T, Noda M, Aoki S, Wada K: Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem Biophys Res Commun. 2003 Apr 25;304(1):176-83. [Article]
  20. Harhangi BS, Farrer MJ, Lincoln S, Bonifati V, Meco G, De Michele G, Brice A, Durr A, Martinez M, Gasser T, Bereznai B, Vaughan JR, Wood NW, Hardy J, Oostra BA, Breteler MM: The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease. Neurosci Lett. 1999 Jul 23;270(1):1-4. [Article]
  21. Lincoln S, Vaughan J, Wood N, Baker M, Adamson J, Gwinn-Hardy K, Lynch T, Hardy J, Farrer M: Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease. Neuroreport. 1999 Feb 5;10(2):427-9. [Article]
  22. Mellick GD, Silburn PA: The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease. Neurosci Lett. 2000 Oct 27;293(2):127-30. [Article]
  23. Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA: UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 2004 Apr;55(4):512-21. [Article]
  24. 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 susceptibility gene. Ann Neurol. 2006 Apr;59(4):627-33. [Article]
  25. Kyratzi E, Pavlaki M, Stefanis L: The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells. Hum Mol Genet. 2008 Jul 15;17(14):2160-71. doi: 10.1093/hmg/ddn115. Epub 2008 Apr 14. [Article]
  26. Rudolph T, Sjolander A, Palmer MS, Minthon L, Wallin A, Andreasen N, Tasa G, Juronen E, Blennow K, Zetterberg H, Zetterberg M: Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts. Ophthalmic Genet. 2011 Jun;32(2):75-9. doi: 10.3109/13816810.2010.544360. Epub 2011 Jan 26. [Article]
  27. Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, Delil S, Caglayan AO, Baranoski JF, Erturk O, Yalcinkaya C, Karacorlu M, Dincer A, Johnson MH, Mane S, Chandra SS, Louvi A, Boggon TJ, Lifton RP, Horwich AL, Gunel M: Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3489-94. doi: 10.1073/pnas.1222732110. Epub 2013 Jan 28. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12695Phenethyl IsothiocyanateinvestigationalunknownDetails