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Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L1

Gene

Uchl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.1 Publication

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).

Kineticsi

  1. KM=116 nM for Ub-AMC1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei90 – 901NucleophileCurated
    Active sitei161 – 1611Proton donorPROSITE-ProRule annotation
    Sitei176 – 1761Important for enzyme activityBy similarity

    GO - Molecular functioni

    GO - Biological processi

    • adult walking behavior Source: MGI
    • axonogenesis Source: MGI
    • axon target recognition Source: MGI
    • axon transport of mitochondrion Source: MGI
    • cell proliferation Source: MGI
    • eating behavior Source: MGI
    • muscle fiber development Source: MGI
    • negative regulation of MAP kinase activity Source: MGI
    • neuromuscular process Source: MGI
    • protein deubiquitination Source: UniProtKB
    • response to ischemia Source: MGI
    • sensory perception of pain Source: Ensembl
    • 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

    BRENDAi3.4.19.12. 3474.

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 5

    Organism-specific databases

    MGIiMGI:103149. Uchl1.

    Subcellular locationi

    GO - Cellular componenti

    • axon Source: MGI
    • cytoplasm Source: UniProtKB
    • cytosol Source: MGI
    • endoplasmic reticulum membrane Source: UniProtKB-SubCell
    • extracellular exosome Source: MGI
    • myelin sheath Source: UniProtKB
    • neuronal cell body Source: MGI
    • neuron projection terminus Source: MGI
    • nucleoplasm Source: MGI
    • plasma membrane Source: Ensembl
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice show sensory ataxia at an early stage, followed by motor ataxia at a later stage. They have reduced levels of monoubiquitin in the nervous system, and increased resistance to retinal ischemia.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi30 – 301D → K: Abolishes enzymatic activity and ubiquitin binding. 1 Publication
    Mutagenesisi90 – 901C → S: Abolishes enzymatic activity, but does not affect ubiquitin binding. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 220220Ubiquitin carboxyl-terminal hydrolase isozyme L1PRO_0000211058Add
    BLAST
    Propeptidei221 – 2233Removed in mature formBy similarityPRO_0000414313

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi220 – 2201S-farnesyl cysteineBy similarity

    Post-translational modificationi

    O-glycosylated.By similarity

    Keywords - PTMi

    Glycoprotein, Lipoprotein, Prenylation

    Proteomic databases

    MaxQBiQ9R0P9.
    PaxDbiQ9R0P9.
    PRIDEiQ9R0P9.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00313962.
    Q9R0P9.
    UCD-2DPAGEQ9R0P9.

    PTM databases

    PhosphoSiteiQ9R0P9.

    Expressioni

    Tissue specificityi

    Expressed in brain, where it is found in neurons but not in oligodendrocytes or astrocytes. Found in the ganglion cell layer and the inner nuclear layer of the retina (at protein level). Expressed in brain and testis. In the brain, expression is at its lowest in replaceable neurons of hippocampus and olfactory bulb. Highly expressed in senescent pituitary.5 Publications

    Gene expression databases

    BgeeiQ9R0P9.
    CleanExiMM_UCHL1.
    ExpressionAtlasiQ9R0P9. baseline and differential.
    GenevisibleiQ9R0P9. MM.

    Interactioni

    Subunit structurei

    Monomer. Homodimer. Interacts with COPS5 and SNCA (By similarity).By similarity

    Protein-protein interaction databases

    BioGridi204423. 9 interactions.
    IntActiQ9R0P9. 5 interactions.
    MINTiMINT-4139420.
    STRINGi10090.ENSMUSP00000031131.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9R0P9.
    SMRiQ9R0P9. Positions 1-223.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni5 – 106Interaction with ubiquitinBy similarity
    Regioni151 – 1566Interaction with ubiquitinBy similarity
    Regioni211 – 2166Interaction with ubiquitinBy similarity

    Sequence similaritiesi

    Belongs to the peptidase C12 family.Curated

    Phylogenomic databases

    eggNOGiNOG327708.
    GeneTreeiENSGT00510000046640.
    HOVERGENiHBG075483.
    InParanoidiQ9R0P9.
    KOiK05611.
    OMAiMEWKPME.
    OrthoDBiEOG7S7SFK.
    PhylomeDBiQ9R0P9.
    TreeFamiTF316166.

    Family and domain databases

    Gene3Di3.40.532.10. 1 hit.
    InterProiIPR001578. Peptidase_C12_UCH.
    IPR030297. UCHL1.
    [Graphical view]
    PANTHERiPTHR10589. PTHR10589. 1 hit.
    PTHR10589:SF19. PTHR10589:SF19. 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.

    Q9R0P9-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MQLKPMEINP EMLNKVLAKL GVAGQWRFAD VLGLEEETLG SVPSPACALL
    60 70 80 90 100
    LLFPLTAQHE NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA
    110 120 130 140 150
    NNQDKLEFED GSVLKQFLSE TEKLSPEDRA KCFEKNEAIQ AAHDSVAQEG
    160 170 180 190 200
    QCRVDDKVNF HFILFNNVDG HLYELDGRMP FPVNHGASSE DSLLQDAAKV
    210 220
    CREFTEREQG EVRFSAVALC KAA
    Length:223
    Mass (Da):24,838
    Last modified:May 1, 2000 - v1
    Checksum:iF1402BF7B0C077EA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti149 – 1491E → K in AAD51029 (PubMed:12559414).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB025313 mRNA. Translation: BAA84083.1.
    AF172334 mRNA. Translation: AAD51029.1.
    AK013729 mRNA. Translation: BAB28976.1.
    BC039177 mRNA. Translation: AAH39177.1.
    CCDSiCCDS19315.1.
    RefSeqiNP_035800.2. NM_011670.2.
    UniGeneiMm.29807.

    Genome annotation databases

    EnsembliENSMUST00000031131; ENSMUSP00000031131; ENSMUSG00000029223.
    GeneIDi22223.
    KEGGimmu:22223.
    UCSCiuc008xpf.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB025313 mRNA. Translation: BAA84083.1.
    AF172334 mRNA. Translation: AAD51029.1.
    AK013729 mRNA. Translation: BAB28976.1.
    BC039177 mRNA. Translation: AAH39177.1.
    CCDSiCCDS19315.1.
    RefSeqiNP_035800.2. NM_011670.2.
    UniGeneiMm.29807.

    3D structure databases

    ProteinModelPortaliQ9R0P9.
    SMRiQ9R0P9. Positions 1-223.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi204423. 9 interactions.
    IntActiQ9R0P9. 5 interactions.
    MINTiMINT-4139420.
    STRINGi10090.ENSMUSP00000031131.

    Chemistry

    BindingDBiQ9R0P9.

    Protein family/group databases

    MEROPSiC12.001.

    PTM databases

    PhosphoSiteiQ9R0P9.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00313962.
    Q9R0P9.
    UCD-2DPAGEQ9R0P9.

    Proteomic databases

    MaxQBiQ9R0P9.
    PaxDbiQ9R0P9.
    PRIDEiQ9R0P9.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000031131; ENSMUSP00000031131; ENSMUSG00000029223.
    GeneIDi22223.
    KEGGimmu:22223.
    UCSCiuc008xpf.2. mouse.

    Organism-specific databases

    CTDi7345.
    MGIiMGI:103149. Uchl1.

    Phylogenomic databases

    eggNOGiNOG327708.
    GeneTreeiENSGT00510000046640.
    HOVERGENiHBG075483.
    InParanoidiQ9R0P9.
    KOiK05611.
    OMAiMEWKPME.
    OrthoDBiEOG7S7SFK.
    PhylomeDBiQ9R0P9.
    TreeFamiTF316166.

    Enzyme and pathway databases

    BRENDAi3.4.19.12. 3474.

    Miscellaneous databases

    ChiTaRSiUchl1. mouse.
    NextBioi302243.
    PROiQ9R0P9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9R0P9.
    CleanExiMM_UCHL1.
    ExpressionAtlasiQ9R0P9. baseline and differential.
    GenevisibleiQ9R0P9. MM.

    Family and domain databases

    Gene3Di3.40.532.10. 1 hit.
    InterProiIPR001578. Peptidase_C12_UCH.
    IPR030297. UCHL1.
    [Graphical view]
    PANTHERiPTHR10589. PTHR10589. 1 hit.
    PTHR10589:SF19. PTHR10589:SF19. 1 hit.
    PfamiPF01088. Peptidase_C12. 1 hit.
    [Graphical view]
    PRINTSiPR00707. UBCTHYDRLASE.
    PROSITEiPS00140. UCH_1. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice."
      Saigoh K., Wang Y.-L., Suh J.G., Yamanishi T., Sakai Y., Kiyosawa H., Harada T., Ichihara N., Wakana S., Kikuchi T., Wada K.
      Nat. Genet. 23:47-51(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
      Tissue: Brain.
    2. "Age-related alterations in the protein expression profile of C57BL/6J mouse pituitaries."
      Marzban G., Grillari J., Reisinger E., Hemetsberger T., Grabherr R., Katinger H.
      Exp. Gerontol. 37:1451-1460(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-10, TISSUE SPECIFICITY.
      Strain: C57BL/6J.
      Tissue: Pituitary.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Hippocampus.
    4. "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: Retina.
    5. Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M.
      Submitted (JUL-2007) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 20-27; 66-78; 116-123; 136-153 AND 158-199, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6.
      Tissue: Brain and Hippocampus.
    6. Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-30 AND CYS-90, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE.
    7. "Role of ubiquitin carboxy terminal hydrolase-L1 in neural cell apoptosis induced by ischemic retinal injury in vivo."
      Harada T., Harada C., Wang Y.-L., Osaka H., Amanai K., Tanaka K., Takizawa S., Setsuie R., Sakurai M., Sato Y., Noda M., Wada K.
      Am. J. Pathol. 164:59-64(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. "Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels."
      Lombardino A.J., Li X.-C., Hertel M., Nottebohm F.
      Proc. Natl. Acad. Sci. U.S.A. 102:8036-8041(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiUCHL1_MOUSE
    AccessioniPrimary (citable) accession number: Q9R0P9
    Secondary accession number(s): Q9R122
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: May 1, 2000
    Last modified: July 22, 2015
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.By similarity

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.