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   24-JAN-2024, entry version 138.
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. Interacts with
CC       DMWD. Component of the USP46/WDR20/WDR48 deubiquitinating complex.
CC       {ECO:0000250|UniProtKB:P62068}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P62068}.
CC       Note=USP46/WDR48/WDR20 complex is predominantly cytoplasmic.
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; 10090-ENSMUSP00000070554; -.
DR   ProteomicsDB; 298106; -.
DR   Pumba; P62069; -.
DR   Antibodypedia; 1722; 146 antibodies from 26 providers.
DR   DNASU; 69727; -.
DR   Ensembl; ENSMUST00000068058.14; ENSMUSP00000070554.8; ENSMUSG00000054814.15.
DR   GeneID; 69727; -.
DR   KEGG; mmu:69727; -.
DR   UCSC; uc008xtg.1; mouse.
DR   AGR; MGI:1916977; -.
DR   CTD; 64854; -.
DR   MGI; MGI:1916977; Usp46.
DR   VEuPathDB; HostDB:ENSMUSG00000054814; -.
DR   eggNOG; KOG1864; Eukaryota.
DR   GeneTree; ENSGT00940000153284; -.
DR   InParanoid; P62069; -.
DR   OMA; ANFGNTC; -.
DR   OrthoDB; 227085at2759; -.
DR   PhylomeDB; P62069; -.
DR   TreeFam; TF314144; -.
DR   BioGRID-ORCS; 69727; 1 hit in 78 CRISPR screens.
DR   PRO; PR:P62069; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P62069; Protein.
DR   Bgee; ENSMUSG00000054814; Expressed in secondary oocyte and 228 other cell types or tissues.
DR   ExpressionAtlas; P62069; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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: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; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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   CDD; cd02663; Peptidase_C19G; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
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   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF714; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 46; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; P62069; MM.
PE   1: Evidence at protein level;
KW   Behavior; Cytoplasm; Hydrolase; Metal-binding; Protease;
KW   Reference proteome; 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
//