UBP46_RAT
ID UBP46_RAT Reviewed; 366 AA.
AC F1M625; G8ACC6;
DT 13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 46;
DE EC=3.4.19.12 {ECO:0000269|PubMed:22043315};
DE AltName: Full=Deubiquitinating enzyme 46;
DE AltName: Full=Ubiquitin thioesterase 46;
DE AltName: Full=Ubiquitin-specific-processing protease 46;
GN Name=Usp46 {ECO:0000312|RGD:1564808};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|EMBL:ADV57650.1}
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF
RP CYS-44 AND LYS-92, AND TISSUE SPECIFICITY.
RC STRAIN=Wistar {ECO:0000312|EMBL:ADV57650.1};
RC TISSUE=Brain {ECO:0000312|EMBL:ADV57650.1};
RX PubMed=22043315; DOI=10.1371/journal.pone.0026297;
RA Zhang W., Tian Q.B., Li Q.K., Wang J.M., Wang C.N., Liu T., Liu D.W.,
RA Wang M.W.;
RT "Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral
RT despair' in mice, influences the deubiquitinating enzyme activity.";
RL PLoS ONE 6:E26297-E26297(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
CC -!- FUNCTION: Deubiquitinating enzyme that plays a role in behavior,
CC possibly by regulating GABA action. May act by mediating the
CC deubiquitination of GAD1/GAD67 (By similarity). Has almost no
CC deubiquitinating activity by itself and requires the interaction with
CC WDR48 to have a high activity. Not involved in deubiquitination of
CC monoubiquitinated FANCD2 (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:0000269|PubMed:22043315};
CC -!- SUBUNIT: Interacts with WDR48. Interacts with WDR20.
CC {ECO:0000250|UniProtKB:P62068}.
CC -!- TISSUE SPECIFICITY: Detected in lung and spleen, and at lower levels in
CC brain, kidney, testis and liver. {ECO:0000269|PubMed:22043315}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GU455413; ADV57650.1; -; mRNA.
DR EMBL; AABR07072397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001178525.1; NM_001191596.1.
DR AlphaFoldDB; F1M625; -.
DR SMR; F1M625; -.
DR STRING; 10116.ENSRNOP00000002879; -.
DR MEROPS; C19.052; -.
DR PaxDb; F1M625; -.
DR PRIDE; F1M625; -.
DR GeneID; 289584; -.
DR KEGG; rno:289584; -.
DR CTD; 64854; -.
DR RGD; 1564808; Usp46.
DR VEuPathDB; HostDB:ENSRNOG00000002106; -.
DR eggNOG; KOG1864; Eukaryota.
DR HOGENOM; CLU_008279_2_0_1; -.
DR InParanoid; F1M625; -.
DR OMA; NKYFCDV; -.
DR OrthoDB; 378361at2759; -.
DR TreeFam; TF314144; -.
DR PRO; PR:F1M625; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002106; Expressed in brain and 19 other tissues.
DR ExpressionAtlas; F1M625; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0101005; F:deubiquitinase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008343; P:adult feeding behavior; ISO:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0048149; P:behavioral response to ethanol; ISO:RGD.
DR GO; GO:0016579; P:protein deubiquitination; ISO:RGD.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISO:RGD.
DR GO; GO:0060013; P:righting reflex; ISO:RGD.
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 1: Evidence at protein level;
KW Behavior; Hydrolase; Metal-binding; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation pathway; Zinc.
FT CHAIN 1..366
FT /note="Ubiquitin carboxyl-terminal hydrolase 46"
FT /id="PRO_0000435846"
FT DOMAIN 35..365
FT /note="USP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT ACT_SITE 44
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035,
FT ECO:0000305|PubMed:22043315"
FT ACT_SITE 313
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01035"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT BINDING 232
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P62068"
FT MUTAGEN 44
FT /note="C->S: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:22043315"
FT MUTAGEN 92
FT /note="Missing: Mildly decreases enzyme activity."
FT /evidence="ECO:0000269|PubMed:22043315"
SQ SEQUENCE 366 AA; 42415 MW; E09EC218E1DDC550 CRC64;
MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR
ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD
AHEFLNYLLN TIADILQEEK KQEKQNGKLK NGNMNEPAEN SKPELTWVHE IFQGTLTNET
RCLNCETVSS KDEDFLDLSV DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK
RMRVKKLPMI LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA
VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI SKNSESGYIL
FYQSRE
