UBP46_CAEEL
ID UBP46_CAEEL Reviewed; 426 AA.
AC P34547;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 3.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 46;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme;
DE AltName: Full=Ubiquitin thioesterase;
DE AltName: Full=Ubiquitin-specific-processing protease;
GN Name=usp-46; ORFNames=R10E11.3;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, INTERACTION WITH GLR-1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-36.
RX PubMed=21273419; DOI=10.1523/jneurosci.4765-10.2011;
RA Kowalski J.R., Dahlberg C.L., Juo P.;
RT "The deubiquitinating enzyme USP-46 negatively regulates the degradation of
RT glutamate receptors to control their abundance in the ventral nerve cord of
RT Caenorhabditis elegans.";
RL J. Neurosci. 31:1341-1354(2011).
RN [4]
RP FUNCTION.
RX PubMed=23209443; DOI=10.1371/journal.pgen.1003092;
RA McCloskey R.J., Kemphues K.J.;
RT "Deubiquitylation machinery is required for embryonic polarity in
RT Caenorhabditis elegans.";
RL PLoS Genet. 8:E1003092-E1003092(2012).
RN [5]
RP INTERACTION WITH WDR-20 AND WDR-48, AND MUTAGENESIS OF CYS-36.
RX PubMed=24356955; DOI=10.1074/jbc.m113.507541;
RA Dahlberg C.L., Juo P.;
RT "The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the
RT deubiquitinating enzyme USP-46 to promote the abundance of the glutamate
RT receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans.";
RL J. Biol. Chem. 289:3444-3456(2014).
CC -!- FUNCTION: Regulates the abundance of the glr-1 glutamate receptor in
CC the ventral nerve cord by promoting its deubiquitination and preventing
CC its degradation in the lysosome. Contributes to the regulation of
CC embryonic polarity. {ECO:0000269|PubMed:21273419,
CC ECO:0000269|PubMed:23209443}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12;
CC -!- SUBUNIT: Interacts with wdr-20 and wdr-48; the catalytic activity of
CC usp-46 is increased in the presence of both wdr-20 and wdr-48.
CC Interacts with glr-1; the interaction results in deubiquitination of
CC glr-1. {ECO:0000269|PubMed:21273419, ECO:0000269|PubMed:24356955}.
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:21273419}.
CC Cytoplasm {ECO:0000269|PubMed:21273419}. Note=In ventral nerve cord
CC interneurons, localized to discrete puncta within the perikaryon. In
CC the ventral nerve cord, localized diffusely throughout the cytoplasm
CC and to punctate structures.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=P34547-1; Sequence=Displayed;
CC Name=b;
CC IsoId=P34547-2; Sequence=VSP_005268;
CC -!- TISSUE SPECIFICITY: Expressed in a number of tissues including the
CC nervous system, pharynx, body wall muscle, vulva muscle and intestine
CC and is detected in many head and ventral cord neurons.
CC {ECO:0000269|PubMed:21273419}.
CC -!- DISRUPTION PHENOTYPE: Decreased levels of glr-1 in the ventral nerve
CC cord and corresponding defects in glr-1-dependent behaviors including
CC reduced spontaneous reversal frequency and reduced responsiveness to
CC the nose touch assay which normally induces backward locomotion.
CC Increased levels of ubiquitinated glr-1. {ECO:0000269|PubMed:21273419}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; Z29095; CAB54286.2; -; Genomic_DNA.
DR EMBL; Z29095; CAB54287.2; -; Genomic_DNA.
DR PIR; S40715; S40715.
DR RefSeq; NP_499162.2; NM_066761.4. [P34547-1]
DR RefSeq; NP_499163.2; NM_066762.2. [P34547-2]
DR AlphaFoldDB; P34547; -.
DR SMR; P34547; -.
DR BioGRID; 41576; 4.
DR STRING; 6239.R10E11.3a.2; -.
DR MEROPS; C19.A37; -.
DR EPD; P34547; -.
DR PaxDb; P34547; -.
DR PeptideAtlas; P34547; -.
DR EnsemblMetazoa; R10E11.3a.1; R10E11.3a.1; WBGene00011216. [P34547-1]
DR EnsemblMetazoa; R10E11.3b.1; R10E11.3b.1; WBGene00011216. [P34547-2]
DR GeneID; 176381; -.
DR KEGG; cel:CELE_R10E11.3; -.
DR UCSC; R10E11.3a.1; c. elegans. [P34547-1]
DR CTD; 176381; -.
DR WormBase; R10E11.3a; CE41150; WBGene00011216; usp-46. [P34547-1]
DR WormBase; R10E11.3b; CE41151; WBGene00011216; usp-46. [P34547-2]
DR eggNOG; KOG1864; Eukaryota.
DR GeneTree; ENSGT00940000153284; -.
DR HOGENOM; CLU_008279_2_0_1; -.
DR InParanoid; P34547; -.
DR OMA; ATVVHCG; -.
DR OrthoDB; 378361at2759; -.
DR PhylomeDB; P34547; -.
DR Reactome; R-CEL-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-CEL-5689880; Ub-specific processing proteases.
DR PRO; PR:P34547; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00011216; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:WormBase.
DR GO; GO:0008595; P:anterior/posterior axis specification, embryo; IGI:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0090326; P:positive regulation of locomotion involved in locomotory behavior; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:WormBase.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; IMP:WormBase.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Hydrolase; Lipoprotein; Myristate;
KW Protease; Reference proteome; Thiol protease; Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..426
FT /note="Ubiquitin carboxyl-terminal hydrolase 46"
FT /id="PRO_0000080684"
FT DOMAIN 27..406
FT /note="USP"
FT REGION 162..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 36
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 342
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 32..43
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_005268"
FT MUTAGEN 36
FT /note="C->A: Abolishes the increased glr-1 expression
FT associated with coexpression of usp-46 with wdr-20 and wdr-
FT 48. Does not rescue the decreased glr-1 levels seen in usp-
FT 46 mutants. No effect on interaction with glr-1."
FT /evidence="ECO:0000269|PubMed:21273419,
FT ECO:0000269|PubMed:24356955"
SQ SEQUENCE 426 AA; 48277 MW; 1405021BDB5BA1AF CRC64;
MGATGSSQLE KEISTTESVN NANEHYYGLV NFGNTCYCNS VIQALFFCRP FREKVLNYKQ
TLKKSGASKD NLVTCLADLF HSIASQKRRV GTIAPKRFIT KLKKENELFD NYMQQDAHEF
FNYLINTISE TLIQEKIAER EKASRHGTLK KGNVTVNLAP ATAGLPRSDE KGTSERNGGI
TVEGNEFLNK SDTTTWIHEI FQGILTNETR CLSCETVSSK DEDFLDLSID VEQNTSISHC
LRVFSETETL CGDQKYFCET CSSKQEAQKR MRIKKPPQLL ALHLKRFKFV EPLNRHTKLS
YRVVFPLELR LFNVSDDAEY GDRMYDLVAT VVHCGATPNR GHYITLVKSN SFWLVFDDDI
VEKLEVSSME EFSGMSTDAN IQMPPGNQSA PQKNSESAYI LFYQARDYAA DDPNHNHKGK
NSTHSV
