UBP14_MOUSE
ID UBP14_MOUSE Reviewed; 493 AA.
AC Q9JMA1; Q543U5; Q923F2; Q9D0L0;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 14;
DE EC=3.4.19.12 {ECO:0000250|UniProtKB:P54578};
DE AltName: Full=Deubiquitinating enzyme 14;
DE AltName: Full=Ubiquitin thioesterase 14;
DE AltName: Full=Ubiquitin-specific-processing protease 14;
GN Name=Usp14;
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 [MRNA].
RC TISSUE=Brain;
RA Hidaka T., Morishita T.;
RT "Mouse deubiquitinating enzyme-type TGT.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, Embryo, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP IDENTIFICATION, AND ASSOCIATION WITH THE 26S PROTEASOME.
RX PubMed=11566882; DOI=10.1093/emboj/20.18.5187;
RA Borodovsky A., Kessler B.M., Casagrande R., Overkleeft H.S.,
RA Wilkinson K.D., Ploegh H.L.;
RT "A novel active site-directed probe specific for deubiquitylating enzymes
RT reveals proteasome association of USP14.";
RL EMBO J. 20:5187-5196(2001).
RN [5]
RP FUNCTION, AND ASSOCIATION WITH THE 26S PROTEASOME.
RX PubMed=16190881; DOI=10.1111/j.1471-4159.2005.03409.x;
RA Anderson C., Crimmins S., Wilson J.A., Korbel G.A., Ploegh H.L.,
RA Wilson S.M.;
RT "Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice.";
RL J. Neurochem. 95:724-731(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP FUNCTION.
RX PubMed=19726649; DOI=10.1523/jneurosci.2635-09.2009;
RA Chen P.C., Qin L.N., Li X.M., Walters B.J., Wilson J.A., Mei L.,
RA Wilson S.M.;
RT "The proteasome-associated deubiquitinating enzyme Usp14 is essential for
RT the maintenance of synaptic ubiquitin levels and the development of
RT neuromuscular junctions.";
RL J. Neurosci. 29:10909-10919(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-52; SER-143 AND SER-148, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP STRUCTURE BY NMR OF 4-86.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the N-terminal ubiquitin-like domain of mouse
RT ubiquitin specific protease 14 (usp14).";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Proteasome-associated deubiquitinase which releases ubiquitin
CC from the proteasome targeted ubiquitinated proteins (PubMed:16190881).
CC Ensures the regeneration of ubiquitin at the proteasome. Is a
CC reversibly associated subunit of the proteasome and a large fraction of
CC proteasome-free protein exists within the cell. Required for the
CC degradation of the chemokine receptor CXCR4 which is critical for
CC CXCL12-induced cell chemotaxis. Serves also as a physiological
CC inhibitor of endoplasmic reticulum-associated degradation (ERAD) under
CC the non-stressed condition by inhibiting the degradation of unfolded
CC endoplasmic reticulum proteins via interaction with ERN1 (By
CC similarity). Indispensable for synaptic development and function at
CC neuromuscular junctions (NMJs) (PubMed:19726649). Plays a role in the
CC innate immune defense against viruses by stabilizing the viral DNA
CC sensor CGAS and thus inhibiting its autophagic degradation (By
CC similarity). {ECO:0000250|UniProtKB:P54578,
CC ECO:0000269|PubMed:16190881, ECO:0000269|PubMed:19726649}.
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:P54578};
CC -!- SUBUNIT: Homodimer (Potential). Associates with the 26S proteasome.
CC Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this
CC interaction recruits USP14 to cleave ubiquitin chains of CGAS (By
CC similarity). {ECO:0000250|UniProtKB:P54578}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6 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; AB034633; BAA93551.1; -; mRNA.
DR EMBL; AK011322; BAB27544.1; -; mRNA.
DR EMBL; AK029977; BAC26713.1; -; mRNA.
DR EMBL; AK045909; BAC32528.1; -; mRNA.
DR EMBL; BC005571; AAH05571.1; -; mRNA.
DR CCDS; CCDS37735.1; -.
DR RefSeq; NP_067497.2; NM_021522.4.
DR PDB; 1WGG; NMR; -; A=4-86.
DR PDBsum; 1WGG; -.
DR AlphaFoldDB; Q9JMA1; -.
DR BMRB; Q9JMA1; -.
DR SMR; Q9JMA1; -.
DR BioGRID; 208492; 53.
DR IntAct; Q9JMA1; 1.
DR MINT; Q9JMA1; -.
DR STRING; 10090.ENSMUSP00000089728; -.
DR MEROPS; C19.015; -.
DR iPTMnet; Q9JMA1; -.
DR PhosphoSitePlus; Q9JMA1; -.
DR SwissPalm; Q9JMA1; -.
DR EPD; Q9JMA1; -.
DR jPOST; Q9JMA1; -.
DR MaxQB; Q9JMA1; -.
DR PaxDb; Q9JMA1; -.
DR PeptideAtlas; Q9JMA1; -.
DR PRIDE; Q9JMA1; -.
DR ProteomicsDB; 300070; -.
DR Antibodypedia; 676; 320 antibodies from 35 providers.
DR DNASU; 59025; -.
DR Ensembl; ENSMUST00000092096; ENSMUSP00000089728; ENSMUSG00000047879.
DR GeneID; 59025; -.
DR KEGG; mmu:59025; -.
DR UCSC; uc008ean.1; mouse.
DR CTD; 9097; -.
DR MGI; MGI:1928898; Usp14.
DR VEuPathDB; HostDB:ENSMUSG00000047879; -.
DR eggNOG; KOG1872; Eukaryota.
DR GeneTree; ENSGT00390000009615; -.
DR InParanoid; Q9JMA1; -.
DR OMA; MCKGGIL; -.
DR OrthoDB; 600543at2759; -.
DR PhylomeDB; Q9JMA1; -.
DR TreeFam; TF314494; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 59025; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Usp14; mouse.
DR EvolutionaryTrace; Q9JMA1; -.
DR PRO; PR:Q9JMA1; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9JMA1; protein.
DR Bgee; ENSMUSG00000047879; Expressed in ectoplacental cone and 263 other tissues.
DR ExpressionAtlas; Q9JMA1; baseline and differential.
DR Genevisible; Q9JMA1; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISO:MGI.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; ISO:MGI.
DR GO; GO:0070628; F:proteasome binding; ISO:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1903070; P:negative regulation of ER-associated ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
DR GO; GO:0050920; P:regulation of chemotaxis; ISO:MGI.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; ISO:MGI.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR019954; Ubiquitin_CS.
DR InterPro; IPR044635; UBP14-like.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR PANTHER; PTHR43982; PTHR43982; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00299; UBIQUITIN_1; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 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 3D-structure; Acetylation; Cell membrane; Cytoplasm; Hydrolase; Immunity;
KW Innate immunity; Membrane; Phosphoprotein; Protease; Proteasome;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..493
FT /note="Ubiquitin carboxyl-terminal hydrolase 14"
FT /id="PRO_0000080637"
FT DOMAIN 4..80
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 105..482
FT /note="USP"
FT ACT_SITE 114
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 434
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 52
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 235
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54578"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54578"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54578"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54578"
FT MOD_RES 448
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54578"
FT CONFLICT 185
FT /note="Q -> R (in Ref. 1; BAA93551)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="L -> S (in Ref. 1; BAA93551)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="Q -> E (in Ref. 2; BAB27544)"
FT /evidence="ECO:0000305"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:1WGG"
FT STRAND 13..24
FT /evidence="ECO:0007829|PDB:1WGG"
FT HELIX 26..36
FT /evidence="ECO:0007829|PDB:1WGG"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:1WGG"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1WGG"
SQ SEQUENCE 493 AA; 56002 MW; 4E5F5DCB86057FF9 CRC64;
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN
IKMKNGMTVL MMGSADALPE EPSAKTVFVE DMTEEQLATA MELPCGLTNL GNTCYMNATV
QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH
MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSGRETDSSS APAVTPSKKK
SLIDQYFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDVYELCT
PELQEKMVSF RSKFKDLEDK KVNQQPNAND KNSPPKEIKY EPFSFADDIG SNNCGYYDLQ
AVLTHQGRSS SSGHYVSWVR RKQDEWIKFD DDKVSIVTPE DILRLSGGGD WHIAYVLLYG
PRRVEIMEEE SEQ
