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Q9JKB1

- UCHL3_MOUSE

UniProt

Q9JKB1 - UCHL3_MOUSE

Protein

Ubiquitin carboxyl-terminal hydrolase isozyme L3

Gene

Uchl3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 2 (26 Sep 2001)
      Previous versions | rss
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    Functioni

    Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome.6 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).

    Enzyme regulationi

    Inhibited by monoubiquitin and diubiquitin.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei95 – 951NucleophilePROSITE-ProRule annotation
    Active sitei169 – 1691Proton donorPROSITE-ProRule annotation
    Sitei184 – 1841Important for enzyme activityBy similarity

    GO - Molecular functioni

    1. peptidase activity Source: UniProtKB
    2. ubiquitin-specific protease activity Source: InterPro

    GO - Biological processi

    1. adult walking behavior Source: MGI
    2. cellular response to insulin stimulus Source: UniProtKB
    3. eating behavior Source: MGI
    4. positive regulation of fat cell differentiation Source: UniProtKB
    5. protein catabolic process Source: UniProtKB
    6. protein deubiquitination Source: MGI
    7. retina development in camera-type eye Source: MGI
    8. ubiquitin-dependent protein catabolic process Source: InterPro

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    BRENDAi3.4.19.12. 3474.

    Protein family/group databases

    MEROPSiC12.003.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase isozyme L3 (EC:3.4.19.12)
    Short name:
    UCH-L3
    Alternative name(s):
    Ubiquitin thioesterase L3
    Gene namesi
    Name:Uchl3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 14

    Organism-specific databases

    MGIiMGI:1355274. Uchl3.

    Subcellular locationi

    Cytoplasm 2 Publications

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Mice have no developmental defects, are fertile, and show normal T-cell differentiation. They have normal anxiety, locomotor behavior, motor function and synaptic transmission, but show defects in spatial learning and working memory. Exhibit stress-related effects with profound apoptosis-mediated germ cell loss and also, prominent retinal degeneration with photoreceptor cell apoptosis and mitochondrial oxidative stress. Mice show reduced capacity for adipocyte differentiation and impaired insulin responses.5 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi95 – 951C → S: No increase in phosphorylation of AKT1, FOXO1 and INSR. No increased expression of SLC2A1, FABP4 nor ADIPOQ. Impaired formation of large lipid droplets. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 230230Ubiquitin carboxyl-terminal hydrolase isozyme L3PRO_0000211062Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei130 – 1301PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9JKB1.
    PaxDbiQ9JKB1.
    PRIDEiQ9JKB1.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00311369.
    Q9JKB1.

    PTM databases

    PhosphoSiteiQ9JKB1.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with highest levels in brain, liver, heart, thymus, kidney and testis. Highly expressed in the cauda epididymidis, in meiotic pachytene spermatocytes and post-meiotic spematids. In the retina, enriched in the photoreceptor inner segment.4 Publications

    Developmental stagei

    Expressed at E8.5 in structures required for skeletal patterning. Highly expressed at E11, and decreases markedly from E15.2 Publications

    Gene expression databases

    BgeeiQ9JKB1.
    GenevestigatoriQ9JKB1.

    Interactioni

    Subunit structurei

    Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.By similarity

    Protein-protein interaction databases

    BioGridi206165. 1 interaction.
    IntActiQ9JKB1. 2 interactions.
    MINTiMINT-1856010.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JKB1.
    SMRiQ9JKB1. Positions 2-230.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni8 – 136Interaction with ubiquitinBy similarity
    Regioni152 – 1598Interaction with ubiquitinBy similarity
    Regioni219 – 2246Interaction with ubiquitinBy similarity

    Sequence similaritiesi

    Belongs to the peptidase C12 family.Curated

    Phylogenomic databases

    eggNOGiNOG327708.
    GeneTreeiENSGT00510000046640.
    HOGENOMiHOG000182400.
    HOVERGENiHBG075483.
    InParanoidiQ9JKB1.
    KOiK05609.
    OrthoDBiEOG7S7SFK.
    PhylomeDBiQ9JKB1.
    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.

    Q9JKB1-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEGQRWLPLE ANPEVTNQFL KQLGLHPNWQ FVDVYGMEPE LLSMVPRPVC    50
    AVLLLFPITE KYEVFRTEEE EKIKSQGQDV TSSVYFMKQT ISNACGTIGL 100
    IHAIANNKDK MHFESGSTLK KFLEESVSMS PEERAKFLEN YDAIRVTHET 150
    SAHEGQTEAP SIDEKVDLHF IALVHVDGHL YELDGRKPFP INHGKTSDET 200
    LLEDAIEVCK KFMERDPDEL RFNAIALSAA 230
    Length:230
    Mass (Da):26,152
    Last modified:September 26, 2001 - v2
    Checksum:iF147991F3ED69AC3
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti205 – 2073AIE → VIK in AAF64193. (PubMed:10713173)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF247358 mRNA. Translation: AAF64193.1.
    AB033370 mRNA. Translation: BAB20094.1.
    BC048481 mRNA. Translation: AAH48481.1.
    CCDSiCCDS27313.1.
    PIRiJC7688.
    RefSeqiNP_057932.2. NM_016723.2.
    UniGeneiMm.275970.

    Genome annotation databases

    EnsembliENSMUST00000002289; ENSMUSP00000002289; ENSMUSG00000022111.
    GeneIDi50933.
    KEGGimmu:50933.
    UCSCiuc007uvw.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF247358 mRNA. Translation: AAF64193.1 .
    AB033370 mRNA. Translation: BAB20094.1 .
    BC048481 mRNA. Translation: AAH48481.1 .
    CCDSi CCDS27313.1.
    PIRi JC7688.
    RefSeqi NP_057932.2. NM_016723.2.
    UniGenei Mm.275970.

    3D structure databases

    ProteinModelPortali Q9JKB1.
    SMRi Q9JKB1. Positions 2-230.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 206165. 1 interaction.
    IntActi Q9JKB1. 2 interactions.
    MINTi MINT-1856010.

    Chemistry

    BindingDBi Q9JKB1.

    Protein family/group databases

    MEROPSi C12.003.

    PTM databases

    PhosphoSitei Q9JKB1.

    2D gel databases

    REPRODUCTION-2DPAGE IPI00311369.
    Q9JKB1.

    Proteomic databases

    MaxQBi Q9JKB1.
    PaxDbi Q9JKB1.
    PRIDEi Q9JKB1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000002289 ; ENSMUSP00000002289 ; ENSMUSG00000022111 .
    GeneIDi 50933.
    KEGGi mmu:50933.
    UCSCi uc007uvw.1. mouse.

    Organism-specific databases

    CTDi 7347.
    MGIi MGI:1355274. Uchl3.

    Phylogenomic databases

    eggNOGi NOG327708.
    GeneTreei ENSGT00510000046640.
    HOGENOMi HOG000182400.
    HOVERGENi HBG075483.
    InParanoidi Q9JKB1.
    KOi K05609.
    OrthoDBi EOG7S7SFK.
    PhylomeDBi Q9JKB1.
    TreeFami TF316166.

    Enzyme and pathway databases

    BRENDAi 3.4.19.12. 3474.

    Miscellaneous databases

    NextBioi 307977.
    PROi Q9JKB1.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9JKB1.
    Genevestigatori Q9JKB1.

    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. "Expression and functional analysis of Uch-L3 during mouse development."
      Kurihara L.J., Semenova E., Levorse J.M., Tilghman S.M.
      Mol. Cell. Biol. 20:2498-2504(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
      Strain: Swiss Webster / NIH.
    2. "Cloning, expression, and mapping of a mouse gene, Uchl4, highly homologous to human and mouse Uchl3."
      Osawa Y., Wang Y.-L., Osaka H., Aoki S., Wada K.
      Biochem. Biophys. Res. Commun. 283:627-633(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Strain: C57BL/6J.
      Tissue: Kidney and Liver.
    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: Testis.
    4. Cited for: DEVELOPMENTAL STAGE.
    5. "Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory."
      Wood M.A., Kaplan M.P., Brensinger C.M., Guo W., Abel T.
      Hippocampus 15:610-621(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    6. "Photoreceptor cell apoptosis in the retinal degeneration of Uchl3-deficient mice."
      Sano Y., Furuta A., Setsuie R., Kikuchi H., Wang Y.L., Sakurai M., Kwon J., Noda M., Wada K.
      Am. J. Pathol. 169:132-141(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
    7. "The new function of two ubiquitin C-terminal hydrolase isozymes as reciprocal modulators of germ cell apoptosis."
      Kwon J.
      Exp. Anim. 56:71-77(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.
    8. "The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel."
      Butterworth M.B., Edinger R.S., Ovaa H., Burg D., Johnson J.P., Frizzell R.A.
      J. Biol. Chem. 282:37885-37893(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ENAC RECYCLING, SUBCELLULAR LOCATION.
    9. "Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis."
      Suzuki M., Setsuie R., Wada K.
      Endocrinology 150:5230-5239(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION IN ADIPOGENESIS AND INSULIN SIGNALING, MUTAGENESIS OF CYS-95.
    10. "Skeletal muscles of Uchl3 knockout mice show polyubiquitinated protein accumulation and stress responses."
      Setsuie R., Suzuki M., Tsuchiya Y., Wada K.
      Neurochem. Int. 56:911-918(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    11. "Mutant ubiquitin (UBB(+1)) associated with neurodegenerative disorders is hydrolyzed by ubiquitin C-terminal hydrolase L3 (UCH-L3)."
      Dennissen F.J., Kholod N., Hermes D.J., Kemmerling N., Steinbusch H.W., Dantuma N.P., van Leeuwen F.W.
      FEBS Lett. 585:2568-2574(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiUCHL3_MOUSE
    AccessioniPrimary (citable) accession number: Q9JKB1
    Secondary accession number(s): Q9EQX7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: September 26, 2001
    Last modified: October 1, 2014
    This is version 118 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, 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