UBP46_MOUSE
ID UBP46_MOUSE Reviewed; 366 AA.
AC P62069; Q3ULU5; Q80V95; Q9H7U4; Q9H9T8;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF LYS-92.
RX PubMed=19465912; DOI=10.1038/ng.344;
RA Tomida S., Mamiya T., Sakamaki H., Miura M., Aosaki T., Masuda M., Niwa M.,
RA Kameyama T., Kobayashi J., Iwaki Y., Imai S., Ishikawa A., Abe K.,
RA Yoshimura T., Nabeshima T., Ebihara S.;
RT "Usp46 is a quantitative trait gene regulating mouse immobile behavior in
RT the tail suspension and forced swimming tests.";
RL Nat. Genet. 41:688-695(2009).
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 (PubMed:19465912). 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:0000269|PubMed:19465912}.
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. Interacts with WDR20.
CC {ECO:0000250|UniProtKB:P62068}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46 subfamily.
CC {ECO:0000305}.
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DR EMBL; AK145298; BAE26353.1; -; mRNA.
DR EMBL; BC039916; AAH39916.1; -; mRNA.
DR CCDS; CCDS39112.1; -.
DR RefSeq; NP_808229.1; NM_177561.3.
DR AlphaFoldDB; P62069; -.
DR SMR; P62069; -.
DR BioGRID; 213641; 9.
DR STRING; 10090.ENSMUSP00000070554; -.
DR MEROPS; C19.052; -.
DR iPTMnet; P62069; -.
DR PhosphoSitePlus; P62069; -.
DR SwissPalm; P62069; -.
DR MaxQB; P62069; -.
DR PaxDb; P62069; -.
DR PRIDE; P62069; -.
DR ProteomicsDB; 298106; -.
DR Antibodypedia; 1722; 133 antibodies from 26 providers.
DR DNASU; 69727; -.
DR Ensembl; ENSMUST00000068058; ENSMUSP00000070554; ENSMUSG00000054814.
DR GeneID; 69727; -.
DR KEGG; mmu:69727; -.
DR UCSC; uc008xtg.1; mouse.
DR CTD; 64854; -.
DR MGI; MGI:1916977; Usp46.
DR VEuPathDB; HostDB:ENSMUSG00000054814; -.
DR eggNOG; KOG1864; Eukaryota.
DR GeneTree; ENSGT00940000153284; -.
DR InParanoid; P62069; -.
DR OMA; NKYFCDV; -.
DR OrthoDB; 378361at2759; -.
DR PhylomeDB; P62069; -.
DR TreeFam; TF314144; -.
DR BioGRID-ORCS; 69727; 1 hit in 72 CRISPR screens.
DR PRO; PR:P62069; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P62069; protein.
DR Bgee; ENSMUSG00000054814; Expressed in secondary oocyte and 225 other tissues.
DR ExpressionAtlas; P62069; baseline and differential.
DR Genevisible; P62069; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
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:0101005; F:deubiquitinase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008343; P:adult feeding behavior; IMP:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0048149; P:behavioral response to ethanol; IMP:MGI.
DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; IDA:MGI.
DR GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; ISO:MGI.
DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IMP:UniProtKB.
DR GO; GO:0060013; P:righting reflex; IMP:MGI.
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_0000080675"
FT DOMAIN 35..365
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 313
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
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 92
FT /note="Missing: In CS; shows negligible immobility in the
FT tail suspension test (TST) and forced swimming test (FST).
FT Both male and female CS mice show virtually no immobile
FT posture immobility in the TST and FST."
FT /evidence="ECO:0000269|PubMed:19465912"
SQ SEQUENCE 366 AA; 42442 MW; 67BB113FC4081C46 CRC64;
MTVRNIASIC NMGTNASALE KDIGPEQFPI NEHYFGLVNF GNTCYCNSVL QALYFCRPFR
ENVLAYKAQQ KKKENLLTCL ADLFHSIATQ KKKVGVIPPK KFISRLRKEN DLFDNYMQQD
AHEFLNYLLN TIADILQEEK KQEKQNGKLK NGNMNEPAEN NKPELTWVHE IFQGTLTNET
RCLNCETVSS KDEDFLDLSV DVEQNTSITH CLRDFSNTET LCSEQKYYCE TCCSKQEAQK
RMRVKKLPMI LALHLKRFKY MEQLHRYTKL SYRVVFPLEL RLFNTSSDAV NLDRMYDLVA
VVVHCGSGPN RGHYITIVKS HGFWLLFDDD IVEKIDAQAI EEFYGLTSDI SKNSESGYIL
FYQSRE
