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P09936

- UCHL1_HUMAN

UniProt

P09936 - UCHL1_HUMAN

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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L1

Gene

UCHL1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

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).1 Publication

Kineticsi

  1. KM=122 nM for Ub-AMC3 Publications
  2. KM=1.20 µM for ubiquitin ethyl ester3 Publications

Vmax=0.47 µmol/min/mg enzyme toward Ub-AMC3 Publications

Vmax=25 µmol/min/mg enzyme toward ubiquitin ethyl ester3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei1 – 11Susceptible to oxidation
Sitei6 – 61Susceptible to oxidation
Sitei12 – 121Susceptible to oxidation
Active sitei90 – 901Nucleophile
Sitei124 – 1241Susceptible to oxidation
Active sitei161 – 1611Proton donor
Sitei176 – 1761Important for enzyme activity
Sitei179 – 1791Susceptible to oxidation
Sitei220 – 2201Susceptible to oxidation

GO - Molecular functioni

  1. alpha-2A adrenergic receptor binding Source: BHF-UCL
  2. cysteine-type endopeptidase activity Source: UniProtKB
  3. ligase activity Source: UniProtKB-KW
  4. omega peptidase activity Source: UniProtKB
  5. ubiquitin binding Source: UniProtKB
  6. ubiquitin-specific protease activity Source: InterPro
  7. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. adult walking behavior Source: Ensembl
  2. axon target recognition Source: Ensembl
  3. axon transport of mitochondrion Source: Ensembl
  4. cell death Source: UniProtKB-KW
  5. cell proliferation Source: Ensembl
  6. eating behavior Source: Ensembl
  7. muscle fiber development Source: Ensembl
  8. negative regulation of MAP kinase activity Source: BHF-UCL
  9. neuromuscular process Source: Ensembl
  10. protein deubiquitination Source: UniProtKB
  11. response to ischemia Source: Ensembl
  12. sensory perception of pain Source: Ensembl
  13. ubiquitin-dependent protein catabolic process Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Ligase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi3.1.2.15. 2681.
SABIO-RKP09936.

Protein family/group databases

MEROPSiC12.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase isozyme L1 (EC:3.4.19.12, EC:6.-.-.-)
Short name:
UCH-L1
Alternative name(s):
Neuron cytoplasmic protein 9.5
PGP 9.5
Short name:
PGP9.5
Ubiquitin thioesterase L1
Gene namesi
Name:UCHL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:12513. UCHL1.

Subcellular locationi

Cytoplasm 1 Publication. Endoplasmic reticulum membrane 1 Publication; Lipid-anchor 1 Publication
Note: About 30% of total UCHL1 is associated with membranes in brain.

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: Ensembl
  4. endoplasmic reticulum Source: UniProtKB-KW
  5. extracellular vesicular exosome Source: UniProt
  6. membrane Source: UniProtKB-KW
  7. neuronal cell body Source: Ensembl
  8. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti93 – 931I → M in PARK5; impaired enzymatic hydrolase activity; has about a 50% reduction in catalytic activity compared to wild-type protein. 2 Publications
VAR_015678
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71E → A in NDGOA; has decreased binding to ubiquitin and significantly decreased hydrolase activity compared to wild-type. 1 Publication
VAR_070875

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi73 – 731Q → R: No effect on enzymatic parameters. 1 Publication
Mutagenesisi90 – 901C → S: Abolishes enzymatic activity. 3 Publications
Mutagenesisi97 – 971H → Q or N: 2-fold increase in affinity for ubiquitin ethyl ester, slight reduction in enzymatic activity. 1 Publication
Mutagenesisi161 – 1611H → D: 10000-fold decrease in enzymatic activity; no change in affinity for ubiquitin ethyl ester. 1 Publication
Mutagenesisi161 – 1611H → K, Q, N or Y: Abolishes enzymatic activity. 1 Publication
Mutagenesisi176 – 1761D → N: 6-fold decrease in affinity for ubiquitin ethyl ester; 97.5% decrease in enzymatic activity. 1 Publication
Mutagenesisi204 – 2041F → A: Almost complete loss of activity. 1 Publication

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

MIMi613643. phenotype.
615491. phenotype.
Orphaneti352654. Early-onset progressive neurodegeneration - blindness - ataxia - spasticity.
2828. Young adult-onset Parkinsonism.
PharmGKBiPA37160.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 220220Ubiquitin carboxyl-terminal hydrolase isozyme L1PRO_0000211055Add
BLAST
Propeptidei221 – 2233Removed in mature formCuratedPRO_0000414311

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi220 – 2201S-farnesyl cysteine1 Publication

Post-translational modificationi

O-glycosylated.By similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Oxidation, Prenylation

Proteomic databases

MaxQBiP09936.
PaxDbiP09936.
PeptideAtlasiP09936.
PRIDEiP09936.

2D gel databases

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

PTM databases

PhosphoSiteiP09936.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiP09936.
CleanExiHS_UCHL1.
ExpressionAtlasiP09936. baseline and differential.
GenevestigatoriP09936.

Organism-specific databases

HPAiCAB002580.
HPA005993.

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with SNCA (By similarity). Interacts with COPS5.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
COPS5Q929053EBI-714860,EBI-594661
EGFRP005332EBI-714860,EBI-297353

Protein-protein interaction databases

BioGridi113192. 48 interactions.
DIPiDIP-36620N.
IntActiP09936. 15 interactions.
MINTiMINT-1378022.
STRINGi9606.ENSP00000284440.

Structurei

Secondary structure

1
223
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 1910Combined sources
Beta strandi22 – 309Combined sources
Helixi36 – 383Combined sources
Beta strandi39 – 424Combined sources
Beta strandi46 – 549Combined sources
Helixi57 – 7014Combined sources
Turni71 – 744Combined sources
Beta strandi86 – 883Combined sources
Helixi90 – 10011Combined sources
Turni101 – 1055Combined sources
Helixi113 – 1208Combined sources
Turni121 – 1233Combined sources
Helixi126 – 1349Combined sources
Helixi137 – 14711Combined sources
Beta strandi160 – 1689Combined sources
Beta strandi171 – 1755Combined sources
Beta strandi179 – 1813Combined sources
Beta strandi183 – 1875Combined sources
Helixi190 – 1923Combined sources
Helixi193 – 20715Combined sources
Helixi211 – 2133Combined sources
Beta strandi215 – 2217Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4JKJX-ray2.15A/B1-223[»]
ProteinModelPortaliP09936.
SMRiP09936. Positions 1-223.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09936.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni5 – 106Interaction with ubiquitin
Regioni211 – 2166Interaction with ubiquitin

Sequence similaritiesi

Belongs to the peptidase C12 family.Curated

Phylogenomic databases

eggNOGiNOG327708.
HOGENOMiHOG000182400.
HOVERGENiHBG075483.
InParanoidiP09936.
KOiK05611.
PhylomeDBiP09936.
TreeFamiTF316166.

Family and domain databases

Gene3Di3.40.532.10. 1 hit.
InterProiIPR001578. Peptidase_C12_UCH.
[Graphical view]
PANTHERiPTHR10589. PTHR10589. 1 hit.
PfamiPF01088. Peptidase_C12. 1 hit.
[Graphical view]
PRINTSiPR00707. UBCTHYDRLASE.
PROSITEiPS00140. UCH_1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09936-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MQLKPMEINP EMLNKVLSRL GVAGQWRFVD VLGLEEESLG SVPAPACALL
60 70 80 90 100
LLFPLTAQHE NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA
110 120 130 140 150
NNQDKLGFED GSVLKQFLSE TEKMSPEDRA KCFEKNEAIQ AAHDAVAQEG
160 170 180 190 200
QCRVDDKVNF HFILFNNVDG HLYELDGRMP FPVNHGASSE DTLLKDAAKV
210 220
CREFTEREQG EVRFSAVALC KAA
Length:223
Mass (Da):24,824
Last modified:November 1, 1990 - v2
Checksum:iC9E972AC4DA5DA8A
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71E → A in NDGOA; has decreased binding to ubiquitin and significantly decreased hydrolase activity compared to wild-type. 1 Publication
VAR_070875
Natural varianti18 – 181S → 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. 5 Publications
Corresponds to variant rs5030732 [ dbSNP | Ensembl ].
VAR_015677
Natural varianti93 – 931I → M in PARK5; impaired enzymatic hydrolase activity; has about a 50% reduction in catalytic activity compared to wild-type protein. 2 Publications
VAR_015678

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3462.1.
PIRiA25856.
RefSeqiNP_004172.2. NM_004181.4.
UniGeneiHs.518731.

Genome annotation databases

EnsembliENST00000284440; ENSP00000284440; ENSG00000154277.
ENST00000503431; ENSP00000422542; ENSG00000154277.
GeneIDi7345.
KEGGihsa:7345.
UCSCiuc003gvo.3. human.

Polymorphism databases

DMDMi136681.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Ubiquitin carboxy-terminal hydrolase L1 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS3462.1.
PIRi A25856.
RefSeqi NP_004172.2. NM_004181.4.
UniGenei Hs.518731.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2ETL X-ray 2.40 A/B 1-223 [» ]
2LEN NMR - A 1-223 [» ]
3IFW X-ray 2.40 A 1-223 [» ]
3IRT X-ray 2.80 A/B 1-223 [» ]
3KVF X-ray 2.80 A 1-223 [» ]
3KW5 X-ray 2.83 A 1-223 [» ]
4DM9 X-ray 2.35 A/B 1-223 [» ]
4JKJ X-ray 2.15 A/B 1-223 [» ]
ProteinModelPortali P09936.
SMRi P09936. Positions 1-223.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113192. 48 interactions.
DIPi DIP-36620N.
IntActi P09936. 15 interactions.
MINTi MINT-1378022.
STRINGi 9606.ENSP00000284440.

Chemistry

BindingDBi P09936.
ChEMBLi CHEMBL6159.

Protein family/group databases

MEROPSi C12.001.

PTM databases

PhosphoSitei P09936.

Polymorphism databases

DMDMi 136681.

2D gel databases

DOSAC-COBS-2DPAGE P09936.
UCD-2DPAGE P09936.

Proteomic databases

MaxQBi P09936.
PaxDbi P09936.
PeptideAtlasi P09936.
PRIDEi P09936.

Protocols and materials databases

DNASUi 7345.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000284440 ; ENSP00000284440 ; ENSG00000154277 .
ENST00000503431 ; ENSP00000422542 ; ENSG00000154277 .
GeneIDi 7345.
KEGGi hsa:7345.
UCSCi uc003gvo.3. human.

Organism-specific databases

CTDi 7345.
GeneCardsi GC04P041174.
GeneReviewsi UCHL1.
HGNCi HGNC:12513. UCHL1.
HPAi CAB002580.
HPA005993.
MIMi 191342. gene.
613643. phenotype.
615491. phenotype.
neXtProti NX_P09936.
Orphaneti 352654. Early-onset progressive neurodegeneration - blindness - ataxia - spasticity.
2828. Young adult-onset Parkinsonism.
PharmGKBi PA37160.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG327708.
HOGENOMi HOG000182400.
HOVERGENi HBG075483.
InParanoidi P09936.
KOi K05611.
PhylomeDBi P09936.
TreeFami TF316166.

Enzyme and pathway databases

BRENDAi 3.1.2.15. 2681.
SABIO-RK P09936.

Miscellaneous databases

ChiTaRSi UCHL1. human.
EvolutionaryTracei P09936.
GeneWikii Ubiquitin_carboxy-terminal_hydrolase_L1.
GenomeRNAii 7345.
NextBioi 28756.
PROi P09936.
SOURCEi Search...

Gene expression databases

Bgeei P09936.
CleanExi HS_UCHL1.
ExpressionAtlasi P09936. baseline and differential.
Genevestigatori P09936.

Family and domain databases

Gene3Di 3.40.532.10. 1 hit.
InterProi IPR001578. Peptidase_C12_UCH.
[Graphical view ]
PANTHERi PTHR10589. PTHR10589. 1 hit.
Pfami PF01088. Peptidase_C12. 1 hit.
[Graphical view ]
PRINTSi PR00707. UBCTHYDRLASE.
PROSITEi PS00140. UCH_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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. 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. 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. 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. Cited for: VARIANT TYR-18.
  26. Cited for: VARIANT TYR-18, LACK OF ASSOCIATION OF VARIANT TYR-18 WITH PARKINSON DISEASE.
  27. "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.
  28. "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.
  29. Cited for: VARIANT NDGOA ALA-7, CHARACTERIZATION OF VARIANT NDGOA ALA-7.

Entry informationi

Entry nameiUCHL1_HUMAN
AccessioniPrimary (citable) accession number: P09936
Secondary accession number(s): Q4W5K6, Q71UM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 1, 1990
Last modified: November 26, 2014
This is version 169 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Caution

PubMed:9774100 reports the association of mutation Ile93Met with Parkinson disease. However, according to PubMed:16450370 this association is uncertain and UCHL1 is not a susceptibility gene for Parkinson disease.Curated
The oxidation forms of Met-1, Met-6, Met-12, Met-124, Met-179 and Cys-220 are subject of controversy and could be the artifactual results of sample handling.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3