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P34547

- UBP46_CAEEL

UniProt

P34547 - UBP46_CAEEL

Protein

Ubiquitin carboxyl-terminal hydrolase 46

Gene

usp-46

Organism
Caenorhabditis elegans
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 109 (01 Oct 2014)
      Sequence version 3 (04 Dec 2007)
      Previous versions | rss
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    Functioni

    Regulates the abundance of the glr-1 glutamate receptor in the ventral nerve cord by promoting its deubiquitination and preventing its degradation in the lysosome. Contributes to the regulation of embryonic polarity.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).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei36 – 361NucleophilePROSITE-ProRule annotation
    Active sitei342 – 3421Proton acceptorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ionotropic glutamate receptor binding Source: WormBase
    2. ubiquitin-specific protease activity Source: WormBase

    GO - Biological processi

    1. protein deubiquitination involved in ubiquitin-dependent protein catabolic process Source: WormBase
    2. regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Source: WormBase

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC19.A37.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 46 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme
    Ubiquitin thioesterase
    Ubiquitin-specific-processing protease
    Gene namesi
    Name:usp-46
    ORF Names:R10E11.3
    OrganismiCaenorhabditis elegans
    Taxonomic identifieri6239 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
    ProteomesiUP000001940: Chromosome III

    Organism-specific databases

    WormBaseiR10E11.3a; CE41150; WBGene00011216; usp-46.
    R10E11.3b; CE41151; WBGene00011216; usp-46.

    Subcellular locationi

    Perikaryon 1 Publication. Cytoplasm 1 Publication
    Note: In ventral nerve cord interneurons, localized to discrete puncta within the perikaryon. In the ventral nerve cord, localized diffusely throughout the cytoplasm and to punctate structures.

    GO - Cellular componenti

    1. cell body Source: WormBase
    2. cytoplasm Source: WormBase
    3. endosome Source: WormBase

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Decreased levels of glr-1 in the ventral nerve cord and corresponding defects in glr-1-dependent behaviors including reduced spontaneous reversal frequency and reduced responsiveness to the nose touch assay which normally induces backward locomotion. Increased levels of ubiquitinated glr-1.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi36 – 361C → A: Abolishes the increased glr-1 expression associated with coexpression of usp-46 with wdr-20 and wdr-48. Does not rescue the decreased glr-1 levels seen in usp-46 mutants. No effect on interaction with glr-1. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedSequence Analysis
    Chaini2 – 426425Ubiquitin carboxyl-terminal hydrolase 46PRO_0000080684Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineSequence Analysis

    Keywords - PTMi

    Lipoprotein, Myristate

    Proteomic databases

    PaxDbiP34547.
    PRIDEiP34547.

    Expressioni

    Tissue specificityi

    Expressed in a number of tissues including the nervous system, pharynx, body wall muscle, vulva muscle and intestine and is detected in many head and ventral cord neurons.1 Publication

    Interactioni

    Subunit structurei

    Interacts with wdr-20 and wdr-48; the catalytic activity of usp-46 is increased in the presence of both wdr-20 and wdr-48. Interacts with glr-1; the interaction results in deubiquitination of glr-1.2 Publications

    Protein-protein interaction databases

    BioGridi41576. 2 interactions.
    STRINGi6239.R10E11.3a.1.

    Structurei

    3D structure databases

    ProteinModelPortaliP34547.
    SMRiP34547. Positions 26-406.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 406380USPAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family.Curated
    Contains 1 USP domain.Curated

    Phylogenomic databases

    eggNOGiCOG5077.
    GeneTreeiENSGT00650000093027.
    HOGENOMiHOG000231498.
    InParanoidiP34547.
    KOiK11842.
    OMAiDANIQMP.
    PhylomeDBiP34547.

    Family and domain databases

    InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [Graphical view]
    PfamiPF00443. UCH. 1 hit.
    [Graphical view]
    PROSITEiPS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform a (identifier: P34547-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGATGSSQLE KEISTTESVN NANEHYYGLV NFGNTCYCNS VIQALFFCRP    50
    FREKVLNYKQ TLKKSGASKD NLVTCLADLF HSIASQKRRV GTIAPKRFIT 100
    KLKKENELFD NYMQQDAHEF FNYLINTISE TLIQEKIAER EKASRHGTLK 150
    KGNVTVNLAP ATAGLPRSDE KGTSERNGGI TVEGNEFLNK SDTTTWIHEI 200
    FQGILTNETR CLSCETVSSK DEDFLDLSID VEQNTSISHC LRVFSETETL 250
    CGDQKYFCET CSSKQEAQKR MRIKKPPQLL ALHLKRFKFV EPLNRHTKLS 300
    YRVVFPLELR LFNVSDDAEY GDRMYDLVAT VVHCGATPNR GHYITLVKSN 350
    SFWLVFDDDI VEKLEVSSME EFSGMSTDAN IQMPPGNQSA PQKNSESAYI 400
    LFYQARDYAA DDPNHNHKGK NSTHSV 426
    Length:426
    Mass (Da):48,277
    Last modified:December 4, 2007 - v3
    Checksum:i1405021BDB5BA1AF
    GO
    Isoform b (identifier: P34547-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         32-43: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:414
    Mass (Da):46,947
    Checksum:i7D7D0C014C061398
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei32 – 4312Missing in isoform b. CuratedVSP_005268Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z29095 Genomic DNA. Translation: CAB54286.2.
    Z29095 Genomic DNA. Translation: CAB54287.2.
    PIRiS40715.
    RefSeqiNP_499162.2. NM_066761.4. [P34547-1]
    NP_499163.2. NM_066762.2. [P34547-2]
    UniGeneiCel.6955.

    Genome annotation databases

    EnsemblMetazoaiR10E11.3a.1; R10E11.3a.1; WBGene00011216. [P34547-1]
    R10E11.3a.2; R10E11.3a.2; WBGene00011216. [P34547-1]
    GeneIDi176381.
    KEGGicel:CELE_R10E11.3.
    UCSCiR10E11.3a.1. c. elegans. [P34547-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z29095 Genomic DNA. Translation: CAB54286.2 .
    Z29095 Genomic DNA. Translation: CAB54287.2 .
    PIRi S40715.
    RefSeqi NP_499162.2. NM_066761.4. [P34547-1 ]
    NP_499163.2. NM_066762.2. [P34547-2 ]
    UniGenei Cel.6955.

    3D structure databases

    ProteinModelPortali P34547.
    SMRi P34547. Positions 26-406.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 41576. 2 interactions.
    STRINGi 6239.R10E11.3a.1.

    Protein family/group databases

    MEROPSi C19.A37.

    Proteomic databases

    PaxDbi P34547.
    PRIDEi P34547.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblMetazoai R10E11.3a.1 ; R10E11.3a.1 ; WBGene00011216 . [P34547-1 ]
    R10E11.3a.2 ; R10E11.3a.2 ; WBGene00011216 . [P34547-1 ]
    GeneIDi 176381.
    KEGGi cel:CELE_R10E11.3.
    UCSCi R10E11.3a.1. c. elegans. [P34547-1 ]

    Organism-specific databases

    CTDi 176381.
    WormBasei R10E11.3a ; CE41150 ; WBGene00011216 ; usp-46.
    R10E11.3b ; CE41151 ; WBGene00011216 ; usp-46.

    Phylogenomic databases

    eggNOGi COG5077.
    GeneTreei ENSGT00650000093027.
    HOGENOMi HOG000231498.
    InParanoidi P34547.
    KOi K11842.
    OMAi DANIQMP.
    PhylomeDBi P34547.

    Miscellaneous databases

    NextBioi 892334.
    PROi P34547.

    Family and domain databases

    InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR028889. UCH/PAN2.
    [Graphical view ]
    Pfami PF00443. UCH. 1 hit.
    [Graphical view ]
    PROSITEi PS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Bristol N2.
    2. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
      The C. elegans sequencing consortium
      Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
      Strain: Bristol N2.
    3. "The deubiquitinating enzyme USP-46 negatively regulates the degradation of glutamate receptors to control their abundance in the ventral nerve cord of Caenorhabditis elegans."
      Kowalski J.R., Dahlberg C.L., Juo P.
      J. Neurosci. 31:1341-1354(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH GLR-1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, MUTAGENESIS OF CYS-36.
    4. "Deubiquitylation machinery is required for embryonic polarity in Caenorhabditis elegans."
      McCloskey R.J., Kemphues K.J.
      PLoS Genet. 8:E1003092-E1003092(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans."
      Dahlberg C.L., Juo P.
      J. Biol. Chem. 289:3444-3456(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH WDR-20 AND WDR-48, MUTAGENESIS OF CYS-36.

    Entry informationi

    Entry nameiUBP46_CAEEL
    AccessioniPrimary (citable) accession number: P34547
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: December 4, 2007
    Last modified: October 1, 2014
    This is version 109 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programCaenorhabditis annotation project

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Caenorhabditis elegans
      Caenorhabditis elegans: entries, gene names and cross-references to WormBase
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3