UBP46_DANRE
ID UBP46_DANRE Reviewed; 370 AA.
AC A5WWB0;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 07-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 46;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:P62068};
DE AltName: Full=Deubiquitinating enzyme 46;
DE AltName: Full=Ubiquitin thioesterase 46;
DE AltName: Full=Ubiquitin-specific-processing protease 46;
GN Name=usp46; ORFNames=ch73-16a12.1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Deubiquitinating enzyme that plays a role in behavior,
CC possibly by regulating GABA action (By similarity). Has almost no
CC deubiquitinating activity by itself and requires the interaction with
CC wdr48 to have a high activity (By similarity).
CC {ECO:0000250|UniProtKB:P62068, ECO:0000250|UniProtKB:P62069}.
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; Evidence={ECO:0000250|UniProtKB:P62068};
CC -!- SUBUNIT: Interacts with WDR48. {ECO:0000250|UniProtKB:P62068}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAN88313.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CT827859; CAN88313.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001231910.1; NM_001244981.1.
DR AlphaFoldDB; A5WWB0; -.
DR SMR; A5WWB0; -.
DR STRING; 7955.ENSDARP00000066677; -.
DR MEROPS; C19.052; -.
DR PaxDb; A5WWB0; -.
DR Ensembl; ENSDART00000132093; ENSDARP00000116502; ENSDARG00000045343.
DR GeneID; 100148916; -.
DR KEGG; dre:100148916; -.
DR CTD; 64854; -.
DR ZFIN; ZDB-GENE-070705-213; usp46.
DR eggNOG; KOG1864; Eukaryota.
DR GeneTree; ENSGT00940000153284; -.
DR HOGENOM; CLU_008279_2_0_1; -.
DR InParanoid; A5WWB0; -.
DR OMA; NKYFCDV; -.
DR OrthoDB; 378361at2759; -.
DR PhylomeDB; A5WWB0; -.
DR PRO; PR:A5WWB0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000045343; Expressed in retina and 18 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007610; P:behavior; IEA:UniProtKB-KW.
DR GO; GO:0016579; P:protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
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 3: Inferred from homology;
KW Behavior; Hydrolase; Metal-binding; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway; Zinc.
FT CHAIN 1..370
FT /note="Ubiquitin carboxyl-terminal hydrolase 46"
FT /id="PRO_0000378995"
FT DOMAIN 35..369
FT /note="USP"
FT ACT_SITE 44
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 233
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
SQ SEQUENCE 370 AA; 42905 MW; E0FAEF5A62DD6FDA CRC64;
MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR
ENVLAYKVQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD
AHEFLNYLLN TVADILQEER KQEKQNGRLK NNGTAIATDT EPEQNKIDPT WVHEIFQGTL
TNETRCLNCE TVSSKDEDFL DLSVDVEQNT SITHCLRDFS NTETLCSEYK YYCEMCCSKQ
EAQKRMRVKK LPMILALHLK RFKYMEQLHR YTKLSYRVVF PLELRLFNTS GDAVNLDRMY
DLVAVVVHCG SGPNRGHYIT IVKSHGFWLL FDDDIVEKID AQAIEEFYGL TSDISKNSES
GYILFYQSRE
