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Literature summary for 3.4.19.12 extracted from

  • Liu, Z.; Meray, R.K.; Grammatopoulos, T.N.; Fredenburg, R.A.; Cookson, M.R.; Liu, Y.; Logan, T.; Lansbury, P.T.
    Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinsons disease (2009), Proc. Natl. Acad. Sci. USA, 106, 4635-4640.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine membrane-associated farnesylated UCH-L1 is a therapeutic target for Parkinson's disease Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
FLAG-tagged UCH-L1 overexpression in the SH-SY5Y human neuroblastoma cell line, which endogenously expresses UCH-L1 and alpha-synuclein, can be cytotoxic at high expression levels in these cells. Coexpression of wild-type UCH-L1, but not of the protective S18Y variant, in COS-7 cells increases levels of transfected alpha-synuclein by inhibiting its degradation, the amount of UCH-L1M in transfected cells correlates with the intracellular level of alpha-synuclein Homo sapiens

Protein Variants

Protein Variants Comment Organism
C220S the mutant has in vitro ubiquitin hydrolase activity comparable to the wild-type protein Homo sapiens
S18Y a naturally occuring polymorph, replacing the weak CKAA farnesylation motif with the optimal CVIM motif (S18Y/CVIM UCH-L1) leads to significantly increased accumulation of alpha-synuclein relative to S18Y Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
endoplasmic reticulum membrane membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with the membrane Mus musculus 5789
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endoplasmic reticulum membrane membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with the membrane Homo sapiens 5789
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membrane membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum Mus musculus 16020
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membrane membrane associated form UCH-L1M, C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum Homo sapiens 16020
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additional information UCH-L1 exists in a membrane-associated form, UCH-L1M, in addition to the commonly studied soluble form Mus musculus
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additional information UCH-L1 exists in a membrane-associated form, UCH-L1M, in addition to the commonly studied soluble form Homo sapiens
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plasma membrane the membrane-associated UCH-L1M form is associated with the plasma membrane of oocytes, C-terminal farnesylation promotes the association of UCH-L1 with the membrane Homo sapiens 5886
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plasma membrane the membrane-associated UCH-L1M form, C-terminal farnesylation promotes the association of UCH-L1 with the membrane Mus musculus 5886
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soluble soluble UCH-L1 form, UCH-L1S Mus musculus
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soluble soluble UCH-L1 form, UCH-L1S Homo sapiens
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-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the proteasomal pathway is partially inhibited by UCH-L1M ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
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-
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Mus musculus
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-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
lipoprotein C-terminal farnesylation promotes the association of UCH-L1 with membranes. Inhibition of UCH-L1 farnesylation by farnesyltransferase inhibitor FTI-277 Mus musculus
lipoprotein C-terminal farnesylation promotes the association of UCH-L1 with membranes. Inhibition of UCH-L1 farnesylation by farnesyltransferase inhibitor FTI-277 Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
brain cortex, UCH-L1M omprises about 30% of total UCH-L1 in diseased and normal human brain Homo sapiens
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brain in mouse brain regions, e.g. cortex, hippocampus, striatum, and midbrain, both UCH-L1M and UCH-L1S occur in varying relative amounts Mus musculus
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brain cortex
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Mus musculus
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corpus striatum
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Mus musculus
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hippocampus
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Mus musculus
-
midbrain
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Mus musculus
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neuron primary dopaminergic neurons Mus musculus
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oocyte UCH-L1 is associated with the plasma membrane of oocytes Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the proteasomal pathway is partially inhibited by UCH-L1M Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
ubiquitin C-terminal hydrolase-L1
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Mus musculus
ubiquitin C-terminal hydrolase-L1
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Homo sapiens
UCH-L1
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Mus musculus
UCH-L1
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Homo sapiens

General Information

General Information Comment Organism
metabolism the proteasomal pathway is partially inhibited by UCH-L1M Homo sapiens
additional information membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity, mechanism, overview Mus musculus
additional information membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity, mechanism, overview Homo sapiens