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P09936 (UCHL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L1

Short name=UCH-L1
EC=3.4.19.12
EC=6.-.-.-
Alternative name(s):
Neuron cytoplasmic protein 9.5
PGP 9.5
Short name=PGP9.5
Ubiquitin thioesterase L1
Gene names
Name:UCHL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length223 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.12 Ref.13 Ref.28

Catalytic activity

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.20

Subunit structure

Monomer. Homodimer. Interacts with SNCA By similarity. Interacts with COPS5. Ref.14 Ref.19

Subcellular location

Cytoplasm. Endoplasmic reticulum membrane; Lipid-anchor. Note: About 30% of total UCHL1 is associated with membranes in brain. Ref.16

Tissue specificity

Found in neuronal cell bodies and processes throughout the neocortex (at protein level). Expressed in neurons and cells of the diffuse neuroendocrine system and their tumors. Weakly expressed in ovary. Down-regulated in brains from Parkinson disease and Alzheimer disease patients. Ref.5 Ref.12

Post-translational modification

O-glycosylated By similarity.

Involvement in disease

Parkinson disease 5 (PARK5) [MIM:613643]: A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.13 Ref.21 Ref.27

Neurodegeneration with optic atrophy, childhood-onset (NDGOA) [MIM:615491]: A progressive neurodegenerative syndrome characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfuction, and spasticity with upper motor neuron dysfunction.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27 Ref.30

Miscellaneous

Oxidation of Met-1, Met-6, Met-12, Met-124 and Met-179 to methionine sulfoxide, and oxidation of Cys-220 to cysteine sulfonic acid have been observed in brains from Alzheimer disease (AD) and Parkinson disease (PD) patients. In AD, UCHL1 was found to be associated with neurofibrillary tangles. In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.

Sequence similarities

Belongs to the peptidase C12 family.

Caution

Ref.8 reports the association of mutation Ile93Met with Parkinson disease. However, according to Ref.27 this association is uncertain and UCHL1 is not a susceptibility gene for Parkinson disease.

Biophysicochemical properties

Kinetic parameters:

KM=122 nM for Ub-AMC Ref.8 Ref.11 Ref.21

KM=1.20 µM for ubiquitin ethyl ester

Vmax=0.47 µmol/min/mg enzyme toward Ub-AMC

Vmax=25 µmol/min/mg enzyme toward ubiquitin ethyl ester

Sequence caution

The sequence CAA28443.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
   Molecular functionHydrolase
Ligase
Protease
Thiol protease
   PTMGlycoprotein
Lipoprotein
Oxidation
Prenylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

axon target recognition

Inferred from electronic annotation. Source: Ensembl

axon transport of mitochondrion

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from electronic annotation. Source: Ensembl

eating behavior

Inferred from electronic annotation. Source: Ensembl

muscle fiber development

Inferred from electronic annotation. Source: Ensembl

negative regulation of MAP kinase activity

Inferred from direct assay PubMed 19477270. Source: BHF-UCL

neuromuscular process

Inferred from electronic annotation. Source: Ensembl

protein deubiquitination

Inferred from direct assay PubMed 9521656. Source: UniProtKB

response to ischemia

Inferred from electronic annotation. Source: Ensembl

sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxon

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionalpha-2A adrenergic receptor binding

Inferred from physical interaction PubMed 19477270. Source: BHF-UCL

cysteine-type endopeptidase activity

Inferred from direct assay Ref.11. Source: UniProtKB

ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

omega peptidase activity

Inferred from direct assay PubMed 9521656. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.14PubMed 20029029. Source: IntAct

ubiquitin binding

Inferred from direct assay PubMed 9521656. Source: UniProtKB

ubiquitin thiolesterase activity

Traceable author statement PubMed 9521656. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

COPS5Q929053EBI-714860,EBI-594661
EGFRP005332EBI-714860,EBI-297353

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 220220Ubiquitin carboxyl-terminal hydrolase isozyme L1
PRO_0000211055
Propeptide221 – 2233Removed in mature form Probable
PRO_0000414311

Regions

Region5 – 106Interaction with ubiquitin
Region211 – 2166Interaction with ubiquitin

Sites

Active site901Nucleophile Ref.11 Ref.15 Ref.20
Active site1611Proton donor Ref.11 Ref.15 Ref.20
Site11Susceptible to oxidation
Site61Susceptible to oxidation
Site121Susceptible to oxidation
Site1241Susceptible to oxidation
Site1761Important for enzyme activity
Site1791Susceptible to oxidation
Site2201Susceptible to oxidation

Amino acid modifications

Lipidation2201S-farnesyl cysteine Ref.16

Natural variations

Natural variant71E → A in NDGOA; has decreased binding to ubiquitin and significantly decreased hydrolase activity compared to wild-type. Ref.30
VAR_070875
Natural variant181S → Y Found in patients with cataract; unknown pathological significance; loss of dimerization ability; impaired ligase activity; confers an antioxidant protective function when expressed at physiological levels in neuroblastoma cells and primary cortical neurons. Ref.13 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29
Corresponds to variant rs5030732 [ dbSNP | Ensembl ].
VAR_015677
Natural variant931I → M in PARK5; impaired enzymatic hydrolase activity; has about a 50% reduction in catalytic activity compared to wild-type protein. Ref.8 Ref.13 Ref.20 Ref.21 Ref.22
VAR_015678

Experimental info

Mutagenesis731Q → R: No effect on enzymatic parameters. Ref.11
Mutagenesis901C → S: Abolishes enzymatic activity. Ref.11 Ref.20 Ref.21
Mutagenesis971H → Q or N: 2-fold increase in affinity for ubiquitin ethyl ester, slight reduction in enzymatic activity. Ref.11
Mutagenesis1611H → D: 10000-fold decrease in enzymatic activity; no change in affinity for ubiquitin ethyl ester. Ref.11
Mutagenesis1611H → K, Q, N or Y: Abolishes enzymatic activity. Ref.11
Mutagenesis1761D → N: 6-fold decrease in affinity for ubiquitin ethyl ester; 97.5% decrease in enzymatic activity. Ref.11
Mutagenesis2041F → A: Almost complete loss of activity. Ref.20

Secondary structure

....................................... 223
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09936 [UniParc].

Last modified November 1, 1990. Version 2.
Checksum: C9E972AC4DA5DA8A

FASTA22324,824
        10         20         30         40         50         60 
MQLKPMEINP EMLNKVLSRL GVAGQWRFVD VLGLEEESLG SVPAPACALL LLFPLTAQHE 

        70         80         90        100        110        120 
NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA NNQDKLGFED GSVLKQFLSE 

       130        140        150        160        170        180 
TEKMSPEDRA KCFEKNEAIQ AAHDAVAQEG QCRVDDKVNF HFILFNNVDG HLYELDGRMP 

       190        200        210        220 
FPVNHGASSE DTLLKDAAKV CREFTEREQG EVRFSAVALC KAA 

« Hide

References

« Hide 'large scale' references
[1]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung and Muscle.
[4]"The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase."
Day I.N.M., Hinks L.J., Thompson R.J.
Biochem. J. 268:521-524(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-15.
[5]"Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's diseases."
Choi J., Levey A.I., Weintraub S.T., Rees H.D., Gearing M., Chin L.-S., Li L.
J. Biol. Chem. 279:13256-13264(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-15 AND 214-221, SUSCEPTIBILITY TO OXIDATION, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
[6]Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-15; 20-27; 66-78; 84-129; 136-195 AND 214-221, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[7]"Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel cytoplasmic marker for neurones and neuroendocrine cells."
Day I.N.M., Thompson R.J.
FEBS Lett. 210:157-160(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-223, PARTIAL PROTEIN SEQUENCE.
[8]"The ubiquitin pathway in Parkinson's disease."
Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., Brownstein M.J., Jonnalagada S., Chernova T., Dehejia A., Lavedan C., Gasser T., Steinbach P.J., Wilkinson K.D., Polymeropoulos M.H.
Nature 395:451-452(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-223, VARIANT PARK5 MET-93, CHARACTERIZATION OF VARIANT PARK5 MET-93, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"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."
Honore B., Rasmussen H.H., Vandekerckhove J., Celis J.E.
FEBS Lett. 280:235-240(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-25; 79-81; 106-121 AND 134-151.
[10]"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-25; 79-91; 106-123 AND 136-151.
[11]"Substrate binding and catalysis by ubiquitin C-terminal hydrolases: identification of two active site residues."
Larsen C.N., Price J.S., Wilkinson K.D.
Biochemistry 35:6735-6744(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE, MUTAGENESIS OF GLN-73; CYS-90; HIS-97; HIS-161 AND ASP-176, BIOPHYSICOCHEMICAL PROPERTIES.
[12]"Cleavage of the C-terminus of NEDD8 by UCH-L3."
Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T.
Biochem. Biophys. Res. Commun. 251:688-692(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[13]"The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility."
Liu Y., Fallon L., Lashuel H.A., Liu Z., Lansbury P.T. Jr.
Cell 111:209-218(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT PARK5 MET-93, CHARACTERIZATION OF VARIANT TYR-18.
[14]"Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)."
Caballero O.L., Resto V., Patturajan M., Meerzaman D., Guo M.Z., Engles J., Yochem R., Ratovitski E., Sidransky D., Jen J.
Oncogene 21:3003-3010(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COPS5.
[15]"Mechanistic studies of ubiquitin C-terminal hydrolase L1."
Case A., Stein R.L.
Biochemistry 45:2443-2452(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE.
[16]"Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease."
Liu Z., Meray R.K., Grammatopoulos T.N., Fredenburg R.A., Cookson M.R., Liu Y., Logan T., Lansbury P.T. Jr.
Proc. Natl. Acad. Sci. U.S.A. 106:4635-4640(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-220.
[17]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Structural basis for conformational plasticity of the Parkinson's disease-associated ubiquitin hydrolase UCH-L1."
Das C., Hoang Q.Q., Kreinbring C.A., Luchansky S.J., Meray R.K., Ray S.S., Lansbury P.T., Ringe D., Petsko G.A.
Proc. Natl. Acad. Sci. U.S.A. 103:4675-4680(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), SUBUNIT.
[20]"Ubiquitin vinyl methyl ester binding orients the misaligned active site of the ubiquitin hydrolase UCHL1 into productive conformation."
Boudreaux D.A., Maiti T.K., Davies C.W., Das C.
Proc. Natl. Acad. Sci. U.S.A. 107:9117-9122(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF VARIANTS TYR-18 AND MET-93 IN COMPLEX WITH UBIQUITIN, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF CYS-90 AND PHE-204.
[21]"Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants."
Nishikawa K., Li H., Kawamura R., Osaka H., Wang Y.-L., Hara Y., Hirokawa T., Manago Y., Amano T., Noda M., Aoki S., Wada K.
Biochem. Biophys. Res. Commun. 304:176-183(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PARK5 MET-93, CHARACTERIZATION OF VARIANT TYR-18, MUTAGENESIS OF CYS-90, BIOPHYSICOCHEMICAL PROPERTIES.
[22]"The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene is not observed in European cases with familial Parkinson's disease."
Harhangi B.S., Farrer M.J., Lincoln S., Bonifati V., Meco G., De Michele G., Brice A., Durr A., Martinez M., Gasser T., Bereznai B., Vaughan J.R., Wood N.W., Hardy J., Oostra B.A., Breteler M.M.
Neurosci. Lett. 270:1-4(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-93.
[23]"Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease."
Lincoln S., Vaughan J., Wood N., Baker M., Adamson J., Gwinn-Hardy K., Lynch T., Hardy J., Farrer M.
NeuroReport 10:427-429(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-18.
[24]"The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does not confer protection against idiopathic Parkinson's disease."
Mellick G.D., Silburn P.A.
Neurosci. Lett. 293:127-130(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-18.
[25]"UCHL1 is a Parkinson's disease susceptibility gene."
UCHL1 global genetics consortium
Maraganore D.M., Lesnick T.G., Elbaz A., Chartier-Harlin M.-C., Gasser T., Krueger R., Hattori N., Mellick G.D., Quattrone A., Satoh J., Toda T., Wang J., Ioannidis J.P.A., de Andrade M., Rocca W.A.
Ann. Neurol. 55:512-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-18.
[26]Erratum
UCHL1 global genetics consortium
Maraganore D.M., Lesnick T.G., Elbaz A., Chartier-Harlin M.-C., Gasser T., Krueger R., Hattori N., Mellick G.D., Quattrone A., Satoh J., Toda T., Wang J., Ioannidis J.P.A., de Andrade M., Rocca W.A.
Ann. Neurol. 55:899-899(2004)
[27]"UCHL-1 is not a Parkinson's disease susceptibility gene."
Healy D.G., Abou-Sleiman P.M., Casas J.P., Ahmadi K.R., Lynch T., Gandhi S., Muqit M.M., Foltynie T., Barker R., Bhatia K.P., Quinn N.P., Lees A.J., Gibson J.M., Holton J.L., Revesz T., Goldstein D.B., Wood N.W.
Ann. Neurol. 59:627-633(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-18, LACK OF ASSOCIATION OF VARIANT TYR-18 WITH PARKINSON DISEASE.
[28]"The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells."
Kyratzi E., Pavlaki M., Stefanis L.
Hum. Mol. Genet. 17:2160-2171(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT TYR-18, ANTIOXIDANT FUNCTION IN NEURONAL CELLS.
[29]"Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts."
Rudolph T., Sjolander A., Palmer M.S., Minthon L., Wallin A., Andreasen N., Tasa G., Juronen E., Blennow K., Zetterberg H., Zetterberg M.
Ophthalmic Genet. 32:75-79(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-18.
[30]"Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration."
Bilguvar K., Tyagi N.K., Ozkara C., Tuysuz B., Bakircioglu M., Choi M., Delil S., Caglayan A.O., Baranoski J.F., Erturk O., Yalcinkaya C., Karacorlu M., Dincer A., Johnson M.H., Mane S., Chandra S.S., Louvi A., Boggon T.J. expand/collapse author list , Lifton R.P., Horwich A.L., Gunel M.
Proc. Natl. Acad. Sci. U.S.A. 110:3489-3494(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NDGOA ALA-7, CHARACTERIZATION OF VARIANT NDGOA ALA-7.
+Additional computationally mapped references.

Web resources

Wikipedia

Ubiquitin carboxy-terminal hydrolase L1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC095043 Genomic DNA. Translation: AAY40923.1.
CH471069 Genomic DNA. Translation: EAW92983.1.
BC000332 mRNA. Translation: AAH00332.1.
BC005117 mRNA. Translation: AAH05117.1.
BC006305 mRNA. Translation: AAH06305.1.
X17377 Genomic DNA. Translation: CAA35249.1.
X04741 mRNA. Translation: CAA28443.1. Different initiation.
AH007277 Genomic DNA. Translation: AAD09172.1.
CCDSCCDS3462.1.
PIRA25856.
RefSeqNP_004172.2. NM_004181.4.
UniGeneHs.518731.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ETLX-ray2.40A/B1-223[»]
2LENNMR-A1-223[»]
3IFWX-ray2.40A1-223[»]
3IRTX-ray2.80A/B1-223[»]
3KVFX-ray2.80A1-223[»]
3KW5X-ray2.83A1-223[»]
4DM9X-ray2.35A/B1-223[»]
ProteinModelPortalP09936.
SMRP09936. Positions 1-223.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113192. 46 interactions.
DIPDIP-36620N.
IntActP09936. 15 interactions.
MINTMINT-1378022.
STRING9606.ENSP00000284440.

Chemistry

BindingDBP09936.
ChEMBLCHEMBL6159.

Protein family/group databases

MEROPSC12.001.

PTM databases

PhosphoSiteP09936.

Polymorphism databases

DMDM136681.

2D gel databases

DOSAC-COBS-2DPAGEP09936.
UCD-2DPAGEP09936.

Proteomic databases

MaxQBP09936.
PaxDbP09936.
PeptideAtlasP09936.
PRIDEP09936.

Protocols and materials databases

DNASU7345.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284440; ENSP00000284440; ENSG00000154277.
ENST00000503431; ENSP00000422542; ENSG00000154277.
GeneID7345.
KEGGhsa:7345.
UCSCuc003gvo.3. human.

Organism-specific databases

CTD7345.
GeneCardsGC04P041174.
GeneReviewsUCHL1.
HGNCHGNC:12513. UCHL1.
HPACAB002580.
HPA005993.
MIM191342. gene.
613643. phenotype.
615491. phenotype.
neXtProtNX_P09936.
Orphanet352654. Early-onset progressive neurodegeneration - blindness - ataxia - spasticity.
2828. Young adult-onset Parkinsonism.
PharmGKBPA37160.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327708.
HOGENOMHOG000182400.
HOVERGENHBG075483.
InParanoidP09936.
KOK05611.
PhylomeDBP09936.
TreeFamTF316166.

Enzyme and pathway databases

BRENDA3.1.2.15. 2681.
SABIO-RKP09936.

Gene expression databases

ArrayExpressP09936.
BgeeP09936.
CleanExHS_UCHL1.
GenevestigatorP09936.

Family and domain databases

Gene3D3.40.532.10. 1 hit.
InterProIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERPTHR10589. PTHR10589. 1 hit.
PfamPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSPR00707. UBCTHYDRLASE.
PROSITEPS00140. UCH_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUCHL1. human.
EvolutionaryTraceP09936.
GeneWikiUbiquitin_carboxy-terminal_hydrolase_L1.
GenomeRNAi7345.
NextBio28756.
PROP09936.
SOURCESearch...

Entry information

Entry nameUCHL1_HUMAN
AccessionPrimary (citable) accession number: P09936
Secondary accession number(s): Q4W5K6, Q71UM0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 165 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM