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Protein

Ubiquitin carboxyl-terminal hydrolase 46

Gene

usp-46

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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)DescriptionActionsGraphical viewLength
Active sitei36NucleophilePROSITE-ProRule annotation1
Active sitei342Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • ionotropic glutamate receptor binding Source: WormBase
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  • anterior/posterior axis specification, embryo Source: WormBase
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of locomotion involved in locomotory behavior Source: UniProtKB
  • protein deubiquitination involved in ubiquitin-dependent protein catabolic process Source: WormBase
  • regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Source: WormBase
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-CEL-5689880. Ub-specific processing proteases.

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
Proteomesi
  • UP000001940 Componenti: 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

  • cytoplasm Source: WormBase
  • endosome Source: WormBase
  • neuronal cell body Source: WormBase
  • perikaryon Source: UniProtKB-SubCell
Complete GO annotation...

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)DescriptionActionsGraphical viewLength
Mutagenesisi36C → 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 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedSequence analysis
ChainiPRO_00000806842 – 426Ubiquitin carboxyl-terminal hydrolase 46Add BLAST425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineSequence analysis1

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

EPDiP34547.
PaxDbiP34547.
PeptideAtlasiP34547.

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

Gene expression databases

BgeeiWBGene00011216.

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

GO - Molecular functioni

  • ionotropic glutamate receptor binding Source: WormBase

Protein-protein interaction databases

BioGridi41576. 2 interactors.
STRINGi6239.R10E11.3a.2.

Structurei

3D structure databases

ProteinModelPortaliP34547.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 406USPAdd BLAST380

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1864. Eukaryota.
ENOG410XQ81. LUCA.
GeneTreeiENSGT00850000132276.
HOGENOMiHOG000231498.
InParanoidiP34547.
KOiK11842.
OMAiDANIQMP.
OrthoDBiEOG091G0FC5.
PhylomeDBiP34547.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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. AlignAdd to basket

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

        10         20         30         40         50
MGATGSSQLE KEISTTESVN NANEHYYGLV NFGNTCYCNS VIQALFFCRP
60 70 80 90 100
FREKVLNYKQ TLKKSGASKD NLVTCLADLF HSIASQKRRV GTIAPKRFIT
110 120 130 140 150
KLKKENELFD NYMQQDAHEF FNYLINTISE TLIQEKIAER EKASRHGTLK
160 170 180 190 200
KGNVTVNLAP ATAGLPRSDE KGTSERNGGI TVEGNEFLNK SDTTTWIHEI
210 220 230 240 250
FQGILTNETR CLSCETVSSK DEDFLDLSID VEQNTSISHC LRVFSETETL
260 270 280 290 300
CGDQKYFCET CSSKQEAQKR MRIKKPPQLL ALHLKRFKFV EPLNRHTKLS
310 320 330 340 350
YRVVFPLELR LFNVSDDAEY GDRMYDLVAT VVHCGATPNR GHYITLVKSN
360 370 380 390 400
SFWLVFDDDI VEKLEVSSME EFSGMSTDAN IQMPPGNQSA PQKNSESAYI
410 420
LFYQARDYAA DDPNHNHKGK NSTHSV
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00526832 – 43Missing in isoform b. CuratedAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP34547.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi41576. 2 interactors.
STRINGi6239.R10E11.3a.2.

Protein family/group databases

MEROPSiC19.A37.

Proteomic databases

EPDiP34547.
PaxDbiP34547.
PeptideAtlasiP34547.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi176381.
WormBaseiR10E11.3a; CE41150; WBGene00011216; usp-46.
R10E11.3b; CE41151; WBGene00011216; usp-46.

Phylogenomic databases

eggNOGiKOG1864. Eukaryota.
ENOG410XQ81. LUCA.
GeneTreeiENSGT00850000132276.
HOGENOMiHOG000231498.
InParanoidiP34547.
KOiK11842.
OMAiDANIQMP.
OrthoDBiEOG091G0FC5.
PhylomeDBiP34547.

Enzyme and pathway databases

ReactomeiR-CEL-5689880. Ub-specific processing proteases.

Miscellaneous databases

PROiP34547.

Gene expression databases

BgeeiWBGene00011216.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[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]
ProtoNetiSearch...

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: November 30, 2016
This is version 123 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

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 one 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.