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Ubiquitin carboxyl-terminal hydrolase 46 (EC 3.4.19.12) (Deubiquitinating enzyme 46) (Ubiquitin thioesterase 46) (Ubiquitin-specific-processing protease 46)

 UBP46_MOUSE             Reviewed;         366 AA.
P62069; Q3ULU5; Q80V95; Q9H7U4; Q9H9T8;
21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
21-JUN-2004, sequence version 1.
10-OCT-2018, entry version 112.
RecName: Full=Ubiquitin carboxyl-terminal hydrolase 46;
EC=3.4.19.12 {ECO:0000250|UniProtKB:P62068};
AltName: Full=Deubiquitinating enzyme 46;
AltName: Full=Ubiquitin thioesterase 46;
AltName: Full=Ubiquitin-specific-processing protease 46;
Name=Usp46;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Mammary gland;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=FVB/N; TISSUE=Mammary tumor;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
FUNCTION, AND MUTAGENESIS OF LYS-92.
PubMed=19465912; DOI=10.1038/ng.344;
Tomida S., Mamiya T., Sakamaki H., Miura M., Aosaki T., Masuda M.,
Niwa M., Kameyama T., Kobayashi J., Iwaki Y., Imai S., Ishikawa A.,
Abe K., Yoshimura T., Nabeshima T., Ebihara S.;
"Usp46 is a quantitative trait gene regulating mouse immobile behavior
in the tail suspension and forced swimming tests.";
Nat. Genet. 41:688-695(2009).
-!- FUNCTION: Deubiquitinating enzyme that plays a role in behavior,
possibly by regulating GABA action. May act by mediating the
deubiquitination of GAD1/GAD67 (PubMed:19465912). Has almost no
deubiquitinating activity by itself and requires the interaction
with WDR48 to have a high activity. Not involved in
deubiquitination of monoubiquitinated FANCD2 (By similarity).
{ECO:0000250|UniProtKB:P62068, ECO:0000269|PubMed:19465912}.
-!- CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester,
thioester, amide, peptide and isopeptide bonds formed by the C-
terminal Gly of ubiquitin (a 76-residue protein attached to
proteins as an intracellular targeting signal).
{ECO:0000250|UniProtKB:P62068}.
-!- SUBUNIT: Interacts with WDR48. Interacts with WDR20.
{ECO:0000250|UniProtKB:P62068}.
-!- SIMILARITY: Belongs to the peptidase C19 family. USP12/USP46
subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AK145298; BAE26353.1; -; mRNA.
EMBL; BC039916; AAH39916.1; -; mRNA.
CCDS; CCDS39112.1; -.
RefSeq; NP_808229.1; NM_177561.3.
UniGene; Mm.473866; -.
UniGene; Mm.48795; -.
ProteinModelPortal; P62069; -.
SMR; P62069; -.
BioGrid; 213641; 1.
STRING; 10090.ENSMUSP00000070554; -.
MEROPS; C19.052; -.
iPTMnet; P62069; -.
PhosphoSitePlus; P62069; -.
SwissPalm; P62069; -.
MaxQB; P62069; -.
PaxDb; P62069; -.
PRIDE; P62069; -.
Ensembl; ENSMUST00000068058; ENSMUSP00000070554; ENSMUSG00000054814.
GeneID; 69727; -.
KEGG; mmu:69727; -.
UCSC; uc008xtg.1; mouse.
CTD; 64854; -.
MGI; MGI:1916977; Usp46.
eggNOG; KOG1864; Eukaryota.
eggNOG; ENOG410XQ81; LUCA.
GeneTree; ENSGT00890000139367; -.
HOGENOM; HOG000231498; -.
HOVERGEN; HBG054038; -.
InParanoid; P62069; -.
KO; K11842; -.
OMA; SYKAQQK; -.
OrthoDB; EOG091G0FC5; -.
PhylomeDB; P62069; -.
TreeFam; TF314144; -.
PRO; PR:P62069; -.
Proteomes; UP000000589; Chromosome 5.
Bgee; ENSMUSG00000054814; Expressed in 242 organ(s), highest expression level in secondary oocyte.
CleanEx; MM_USP46; -.
ExpressionAtlas; P62069; baseline and differential.
Genevisible; P62069; MM.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
GO; GO:0005634; C:nucleus; ISO:MGI.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0004843; F:thiol-dependent ubiquitin-specific protease activity; ISS:UniProtKB.
GO; GO:0036459; F:thiol-dependent ubiquitinyl hydrolase activity; ISS:UniProtKB.
GO; GO:0101005; F:ubiquitinyl hydrolase activity; IDA:MGI.
GO; GO:0008343; P:adult feeding behavior; IMP:MGI.
GO; GO:0001662; P:behavioral fear response; IMP:MGI.
GO; GO:0048149; P:behavioral response to ethanol; IMP:MGI.
GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISO:MGI.
GO; GO:0016579; P:protein deubiquitination; IDA:MGI.
GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IEA:Ensembl.
GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IMP:UniProtKB.
GO; GO:0060013; P:righting reflex; IMP:MGI.
GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
InterPro; IPR038765; Papain_like_cys_pep_sf.
InterPro; IPR001394; Peptidase_C19_UCH.
InterPro; IPR018200; USP_CS.
InterPro; IPR028889; USP_dom.
Pfam; PF00443; UCH; 1.
SUPFAM; SSF54001; SSF54001; 1.
PROSITE; PS00972; USP_1; 1.
PROSITE; PS00973; USP_2; 1.
PROSITE; PS50235; USP_3; 1.
1: Evidence at protein level;
Behavior; Complete proteome; Hydrolase; Metal-binding; Protease;
Reference proteome; Thiol protease; Ubl conjugation pathway; Zinc.
CHAIN 1 366 Ubiquitin carboxyl-terminal hydrolase 46.
/FTId=PRO_0000080675.
DOMAIN 35 365 USP.
ACT_SITE 44 44 Nucleophile. {ECO:0000255|PROSITE-
ProRule:PRU10092, ECO:0000255|PROSITE-
ProRule:PRU10093}.
ACT_SITE 313 313 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU10092, ECO:0000255|PROSITE-
ProRule:PRU10093}.
METAL 182 182 Zinc. {ECO:0000250|UniProtKB:P62068}.
METAL 185 185 Zinc. {ECO:0000250|UniProtKB:P62068}.
METAL 229 229 Zinc. {ECO:0000250|UniProtKB:P62068}.
METAL 232 232 Zinc. {ECO:0000250|UniProtKB:P62068}.
MUTAGEN 92 92 Missing: In CS; shows negligible
immobility in the tail suspension test
(TST) and forced swimming test (FST).
Both male and female CS mice show
virtually no immobile posture immobility
in the TST and FST.
{ECO:0000269|PubMed:19465912}.
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


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