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P09936

- UCHL1_HUMAN

UniProt

P09936 - UCHL1_HUMAN

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
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    • History
      Entry version 167 (01 Oct 2014)
      Sequence version 2 (01 Nov 1990)
      Previous versions | rss
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    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. protein binding Source: IntAct
    6. ubiquitin binding Source: UniProtKB
    7. ubiquitin-specific protease activity Source: InterPro
    8. 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

    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 membrane Source: UniProtKB-SubCell
    5. extracellular vesicular exosome Source: UniProt
    6. neuronal cell body Source: Ensembl
    7. nucleus Source: HPA

    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

    ArrayExpressiP09936.
    BgeeiP09936.
    CleanExiHS_UCHL1.
    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. 47 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 – 1910
    Beta strandi24 – 318
    Helixi36 – 405
    Beta strandi46 – 549
    Helixi57 – 7014
    Turni71 – 744
    Beta strandi86 – 883
    Helixi90 – 10011
    Turni101 – 1055
    Helixi113 – 1208
    Turni121 – 1233
    Helixi126 – 1349
    Helixi137 – 14711
    Beta strandi160 – 1689
    Beta strandi171 – 1755
    Beta strandi179 – 1813
    Beta strandi183 – 1875
    Helixi190 – 1923
    Helixi193 – 20715
    Helixi211 – 2133
    Beta strandi215 – 2217

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    MQLKPMEINP EMLNKVLSRL GVAGQWRFVD VLGLEEESLG SVPAPACALL    50
    LLFPLTAQHE NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA 100
    NNQDKLGFED GSVLKQFLSE TEKMSPEDRA KCFEKNEAIQ AAHDAVAQEG 150
    QCRVDDKVNF HFILFNNVDG HLYELDGRMP FPVNHGASSE DTLLKDAAKV 200
    CREFTEREQG EVRFSAVALC KAA 223
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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. 47 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

    ArrayExpressi P09936.
    Bgeei P09936.
    CleanExi HS_UCHL1.
    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

    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: October 1, 2014
    This is version 167 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

    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